637

IndexAAbsolute Asymmetric Synthesis

Autocatalysis, Pyrimidine Carboxaldehydes,360–361

Pyrimidine Carboxaldehydes, 360–361Absorbed Catalysts, 522–524Achiral Additive, Phosphine Oxide, Hydrocyanation

of Aldehydes, 387–388Achiral Ligands

Atropisomers, BIPHEN, 210In Ketone Reduction, 382–386With Hydrogen Bonds, 207–208

Achiral Salen Complexes, in Cyclopropanation, 223Activation Modes, 376Activation of Lewis Acids, by Lewis Bases, 352–355Acyl Anion Equivalent

From Acyl Silane, 60–61From Aldehyde, 59

Acylation, AlcoholsDesymmetrization, 309–310Enantiotopic Group Differentiation, 612Enzymatic, Dynamic Kinetic Resolution, 280–284Kinetic Resolution, 57, 488–489Planar Chiral DMAP Analog, 57

Acylation, C-Acylation, 4Solvent Effect, 15

Acylation, Propargylic Alcohol, 56–57Planar Chiral DMAP Analog, 57, 72

Acylation Catalyst, 260–262Enzymes, with DKR, 283

Acylation of Phenols, in Desymmetrization of MesoBisphenols, 310

Acyl-DMAP complex, 56–57Additives, 15

Achiral, 629–630Amines, 207Autoinduction, in Diels–Alder, 364Diels–Alder Reaction, 629–630Impact on Direct Aldol, 366N-Methylimidazole, with Proline, 407

AD-mix, 248; see DihydroxylationAlanine, 578ALB Catalysts; see Heterobimetallic Catalysts, Al, LiAlcohol

Synthesis of, 343–347Via Kinetic Resolution, 612

Alcohol, Chiral, in Aldehyde Alkylation, 220–223Alcohol, from Aldehyde

Alkyl Lithium, 17Diorganozinc, 2–4, 7–8, 381–382, 469–470, 480, 586,

589, 600Grignard, 17

Alcohol, from Ketone, Reduction, 51, 201–204,379–381, 556–557

Alcohol, PropargylicReduction, 556–557, 568–569, 572–573Via Kinetic Resolution, 57

Aldehyde, Allylation; see AllylationAldehyde, from α,β-Unsaturated Aldehyde, Transfer

HydrogenationAldehyde, Hydrocyanation; see HydrocyanationAldehyde, Via Hydroformylation, 12–14, 99–100, 553Aldehyde, β-Chiral Additions, 430–431Aldehyde Dimerization, Via Aldol with Proline,

394–395Aldehydes vs. Ketones, Binding to Lewis Acids, 389Aldol Reaction, 393–394

Aldolase, 377–378Atropisomer Formation, 627Axial Chirality, 627Bifunctional Catalysts, 179–183, 386–387Boron Enolate, 450–451Desymmetrization, 52, 67Diastereoselection, 428–429Dinuclear Zinc Catalyst, 364–366Direct, Intermolecular, 8–9, 73–74, 572–574Double Diastereoselective, 572–574Dynamic Kinetic Resolution, 282–283Enantioface Differentiation, 627Glycine Imine Enolates, 78Hajos–Parrish–Eder–Sauer–Weichert Reaction, 52,

67, 392–393Heterobimetallic Catalyst, 73–74, 418–419, 572–574In a Multistep Reaction, 463–466, 475–477Intramolecular, 52, 67

In a Multistep Reaction, 471–472, 489–490With Proline, 393–394

Isocyanoacetates, 179–183Mukaiyama, 178, 340

α-Benzyloxyaldehyde with Silyl Ketene Acetals,35–38, 601

Comparison to Direct Aldol Reaction, 418–420Copper Catalysts, 6, 16, 35–38, 442–444, 601, 606,

624–625, 631Diastereoselection, 6311,2-Diketones with Silyl Ketene Acetals, 606, 631Double Diastereoselection, 442–444Enantioface Differentiation, 624–625Energy Diagram, 340α-Ketoesters with Silyl Ketene Acetals, 6Nonlinear Effects, 340Phosphoramide Catalysts, 47–50Regioselection, 606, 631Solvent Effect, 16Synthesis of Carbohydrates, 395Temperature Effects, 6Tin Catalysts, 606, 631Titanium Catalysts, 37–38

18_index.qxp 6/30/08 12:02 PM Page 637

Trichlorosilyl Enolates, 48Vinylogous Silyl Ketene Acetals, 49

Phase-Transfer Catalysis, 184–187Proline-Catalyzed, 8–9, 52, 67, 393–394, 627Solvent Effect, 16Stoichiometric, 450–452Synthesis of Epothilone, 572–574Synthesis of Fostriecin, 572–573Triple Diastereoselection, 450–451Vs. Mannich Reaction, Chemoselection, 607–608

Aldolase, in a Multistep Reaction, 475–477Aldolase, Types I and II, 377–378Alkaloids

Psycholeine, 319–320, 566–567Quadrigemine C, 319–320, 566–567

Alkene Addition, Re vs. Si, 598Alkene Diboration; see DiborationAlkene Metathesis; see MetathesisAlkoxides, in Bifunctional Catalysis, 378–382Alkylation, Diazoesters, Imines, 70Alkylation, of Aldehydes

Alkyl Lithium, 17Amino Alcohol Catalysts, 343–347Bis(Sulfonamide)Ti Catalysts, 142Diorganozinc, 2–4, 7–8, 381–382, 469–470, 480, 586,

589, 600Grignard, 17In a Multistep Reaction, 480Mechanism with Titanium Catalysts, 336Nonlinear Effects, 343–347Solvent Effect, 15TADDOL Complexes as Catalysts, 136

Alkylation, of AnhydridesDesymmetrization, 621–622Enantiotopic Group Differentiation, 621–622

Alkylation, of Enals, in a Multistep Reaction, 469–471Alkylation, of Enolates, PTC Catalysis, 78–79Alkylation, of Enones

Dialkyl Zinc, 469–471In a Multistep Reaction, 469–470

Alkylation, of IminesDiazoesters, 70Umpolung, 70

Alkylation, of α-Iminoesters, in a Multistep Reaction,472–474

Alkylation, of α-Ketoesters, 607–608Alkylidene Cyclohexanes

Axial chirality, 586–588Generation of, 616–617

Alkyne Cross Coupling, 484–485Allenes, Axial Chirality, 586–588Allenes, Generation of, 616–617Allenes, Via Chirality Exchange, 603Alleve, Synthesis of, 25Allose, Synthesis of, with Proline, 397Allyl, Via SN2’ Displacement, 459–460Allyl Amine, Via π-Allylation, 102, 554, 555Allyl Azide, Via π-Allylation, 102Allyl Ether, Via π-Allylation, 554Allyl Indium, 473–474

Allyl Phenol, Via π-Allylation, 571–572Allyl Sulfonyl, Via π-Allylation, 102Allyl Trichlorosilanes, 353–354α-Allylation

Aldehydes, 56SOMO Catalysis, 56

AllylationBifunctional Catalysts, 401Conformationally Dynamic Ligands, 152–153,

155–156Allylation, C–C, C–N, C–O, C–S Bond Formation, 325Allylation, Mechanism, 322Allylation, of Aldehydes, 49, 435

Catalyzed by Lewis Bases, 352–3551,4-Diastereoselection, 435Double Diastereoselective, 572–573In a Multistep Reaction, 473–474Synthesis of Fostriecin, 572–573

Allylic AlcoholsFrom Allylic Epoxides, 266–267Hydrogenation, 195Synthesis of, Isomerization of Meso Epoxides,

349–352Via Elimination, 74Via Enal Alkylation, 469–471Via Epoxide Elimination, 74Via Sharpless–Katsuki Asymmetric Epoxidation,

242–246Allylic Diesters, in Desymmetrization, 323–325Allylic Epoxides, Ring Opening with Organozinc

Reagents, 266–267Allylic Substitution

Copper Catalysts, 459–460Desymmetrization, 321–322In a Multistep Reaction, 459–460

Allylsilanes, 56, 572–573Aldehyde Allylation, 352–355Carbonyl Addition; see AllylationSynthesis of, 284–286

Aluminosilicates, Zeolites, 506–508Aluminum Catalysts, 196

Aldehyde Hydrocyanation, 387–388Bifunctional Catalyst, 558–559BINOL Derivative Complex, 32, 558–559Binolate, [2+2] Cycloadditions, 411–412Conjugate Addition of Cyanide, to Unsaturated

Imides, 405–406Cyclophane Ligand, [2+2] Cycloadditions,

411–412Diels–Alder Reaction, 41, 362–364Metal–Organic Coordination Networks, in

Conjugate Additions, 519–520Salen Complex, Conjugate Addition of HCN, 405Silylcyanation, 558–559Synthesis of Epothilone, 558–559Vaulted Biaryl Complex, 41

Amidinium, pKa, 67Amidocarbonylation, η2-Coordination, 94α-Amination, 53

Regioselection, 606–607

638 Index

Aldol Reaction (cont.)

18_index.qxp 6/30/08 12:02 PM Page 638

Amine CatalystsDiamine, Enolate Protonation, 71Lewis Base, 50, 53, 54, 71Pyrrolidine Derivative

Conjugation Addition, 53Hetero-Diels–Alder Reaction, 54

Triamine, Enolate Protonation, 50Amines, Achiral Additives, 207Amines, Via Hydroamination, 103Amines, Via Kinetic Resolution of Imines, with

Hydrosilylation, 246–247Amino Acid Derivatives

Synthesis of, 275, 278Via Dynamic Kinetic Resolution, 279

Amino Acids2-Naphthol Oxidation, 536–538Proline, in Nonlinear Effects, 355–357Synthesis of, 184–187Tryptophan, 176–178

Amino Alcohols, Nonlinear Effects, 343–347Amino Ketones, Synthesis of, Via

Aza–Morita–Balis–Hillman Reaction, 400Amino Phosphine Ligands, Cross-Coupling, in DKR,

284–286Amino Zinc Alkoxide, Aldehyde Alkylation, 2–4,

7–8, 337, 469–471, 600α-Amino Acid

Cyclopropanation Catalyst, 81–82From Enamide, Hydrogenation, 9–11, 25–26, 98–99,

435–436From Glycine Imine Enolate, 78–79, 446–447Synthesis of, 9–11, 25–26, 67, 78–79, 98–99, 184–187,

435–436, 446–447, 457–459, 472–473, 480–481,485–486, 551, 586, 602, 609–610, 623

Via Alkylation, 78–79Via Anhydride Methanolysis, 76–77Via Hydrogenation, Enamide, 9–11, 25–26, 98–99,

435–436, 457–459, 480–481, 551, 586, 602, 623Via Kinetic Resolution, 76–77Via Phase-Transfer Catalysis, 78–79, 446–447,

609–610Via β-Lactam Cleavage, 485–486

β-Amino Acid, Synthesis of, 485–486β-Amino Acid Derivatives, Chromatographic

Resolution, 333β-Amino Alcohol

In Aldehyde Alkylation, 2–4, 7–8, 469–471, 600Via Ketone Reduction, 560–561

β-Amino Carbonyl Compounds, Synthesis of,420–421

α-Amino Ketone, Via α-Amination of Ketones,606–607

β-Amino Ketone, Via Mannich-Type Reaction, 68,608

α-Aminonitrile, Via Imine Hydrocyanation, 611α-Aminoxylation, Under Heterogeneous Conditions,

355–357Amplification, 478–479, 482–483, 563–567, 615Anhydrides

Alcoholysis, 264–266

Hydrolysis, 264–266Kinetic Resolution, 76–77Methanolysis, 76–77Parallel Kinetic Resolution, 264–266Ring Opening, 264–266

Anilino OxazolineChromium Catalyst, 450–452Nozaki–Hiyama–Kishi Reaction, 450–452

Anion CaptureImmobilization Method, 527–529With Triflates, 527–529

Ansa MetallocenesCatalysts, 126Ethylene-1,2-Bis(H5-4,5,6,7-Tetrahydro-1-Indenyl),

EBTHI, 126Imine Reduction, 126In Hydrosilylation of Imines, Kinetic Resolution

aR, 586–587Arene Complexes, as Catalysts, 149Arrhenius, 6

Equation, 11aS, 586–587Aspartic Acid, 554–555Asymmetric Activation

Of Achiral Catalysts, 223–227Of Enantioenriched Catalysts, 205Of Racemic Catalysts, 198, 200

Asymmetric Allylation, in Dynamic KineticAsymmetric Transformation, 287, 291

Asymmetric Amplification; see AmplificationAsymmetric Catalysis

Definition, 2With Unresolvable Ligands, 212–216

Asymmetric Complexation; see ComplexationAsymmetric Deactivation; see DeactivationAsymmetric Diminution; see DiminutionAsymmetric Substitution; see SubstitutionAtropisomeric Amides, 588, 616Atropisomeric Amides, Kinetic Resolution via

Dihydroxylation, 247–248Atropisomeric Biaryls, 92, 579, 587–588Atropisomeric Conformations, 151Atropisomeric Ligands, 154Atropisomerism, Definition, 579Atropisomerization, 23, 211Atropisomers

BIPHEN, 213Generation of, 614–616Via Desymmetrization, 320–321

Autocatalysis, 197, 357–361Autocatalysis, with Nonlinear Effects, 357–360Autoinduction, 361–369

With Non-Enantiopure Catalysts, 366–367Axial Chirality, 586–588

Generation of, 614–618Via Desymmetrization, 316

Azadiene, Asymmetric Metal Complexation, 618Aza-Morita–Baylis–Hillman Reaction, 399Azetidinone, Industrial Synthesis of, 274β-Azido Alcohol, Via Epoxide Opening, 448–449

Index 639

18_index.qxp 6/30/08 12:02 PM Page 639

Aziridination, 87Aziridination, with Copper Catalysts, 156–157Azodicarboxylates, in Amination of Aldehydes, 396

BBack Bonding, 93–94Background Reaction, 199

Absence, 2–4Catalyzed, 6, 9, 18Uncatalyzed, 17

Baeyer–Villiger, 418–419Bait-and-Switch, in Epoxide Desymmetrization,

299–300Bark Beetle Pheromone, 587BBMPP

Enamide Hydrogenation, Temperature Effect, 11Rhodium Complex, 11

Benazepril, ACE Inhibitor, from PlatinumHydrogenation, 522–524

Benzofuran, Via Wacker Reaction, 96, 628Benzopyran, Via Wacker Reaction, 460–461Benzoylquinine, [2+2] Cycloadditions, Nucleophilic

Catalysts, 409–413Berry Pseudorotation, 584Biaryl Formation

Chirality Exchange, 604[2+2+2] Cycloaddition, 105–106Via Kumada Coupling, 615Via Oxidative Coupling, 484–485, 562, 614–615Via Suzuki Reaction, 92–93, 614, 615

Biaryl Phosphine, Synthesis of, 321Biaryls

Axial chirality, 586–588Via Desymmetrization, 320–321, 619

Bifunctional Catalysis, 9–10, 67, 558–559, 572–573,607

Interdependent, 386–402Intramolecular, 378–385

Bifunctional CatalystsAddition to Aldehydes, 381–382Addition to α-Ketoester, 390–392Aldol, 179–183, 386–387Allylation, Relative Rates, 403Allylic Alkylation, 401–403Aza-Morita–Baylis–Hillman Reaction, 399Charge–Charge Interactions, 386–387Counterion Dependency, 403Cross-Aldol Reaction, with Proline, 393–394Dependent, 376Dual Catalysts, 404Electronically Coupled, 378–382Epoxide Desymmetrization, with Zirconium,

299–300Ferrocene-Based Ligands, Aldol, 386–387Hajos–Parrish–Eder–Sauer–Wiechert Reaction, 52,

67, 392–393Hydrogen Bonding in, 382–386Indium/Nucleophilic Catalysts, [2+2]

Cycloadditions, 411–412Lanthanides, 405–406

Lewis Acidic and Basic Groups, 387–390Lewis Acid–Brønsted Base Catalysts, Aldol,

386–387Lewis Base–Lewis Base, 407–408Mechanism

Ketone Reduction, 385With Proline, 395–396

Morita–Baylis–Hillman Reaction, 399Proline, 392–398Reduction of Imines, Ruthenium Catalysts, 382–386Reduction of Ketones

Ruthenium Catalysts, 382–386With CBS Catalyst, 379–381

(Salen)CoX Complexes, 238–239Bifunctional Enzymes, Aldolase, 377–378BINAP, 579

Allylation of Aldehydes, 572–573π-Allylation, 103, 616–617Conformation, 129–130Conjugate Addition, 465–466, 489–490[5+2] Cycloaddition, 105Heck Reaction, 98, 318, 566–567Hydrogenation, 194

Alkynyl Ketone, 568–569Allyl Alcohol, 551, 568–569, 605α-Amino Ketone, 560–561Enamide, 480–481α-Hydroxy Ketone, 551β-Ketoester, 480–481, 551, 626–627α,β-Unsaturated Acid, 551

Hydrometallation, 103Isomerization, 433, 552Ketone Reduction, 201–204, 273–278Kinetic Resolutions, of Enynes, 250–252Palladium Complex, 95, 98,103, 566–567, 616–617Rhodium Complex, 105, 433, 465–466, 480–481,

489–490, 552Ruthenium Complex, 551, 560–561, 568–569, 605,

626–627Silver Complex, 572–573Stereoview, 131Wacker Reaction, 95

BINAP Derivatives, Ketone Reduction, 382–386BINAPHOS, Rhodium Complex, Hydroformylation,

99–100, 553Binaphthalene, PTC Catalysts, 78–79, 446–447, 581Binaphthol; see BINOL1,1’-Binaphthyl, 579Binaphthyl Bisoxazoline; see BisoxazolineBINAPO, π-Allylation, Palladium Complex, 555BINOL, 215–216

Aldehyde Alkylation, 335–336, 538–540Aldol Reaction, 73–74, 572–574Atropisomerization, 123Axial Chirality, 587Bifunctional, 387–388Conjugate Addition, 559Diels–Alder Reaction, 347–348, 629–630Enantiomer Self-Disproportionation, 334Ene Reaction, 34, 199–200, 306, 552

640 Index

18_index.qxp 6/30/08 12:02 PM Page 640

Two-Directional, 478Epoxide Rearrangements, 249–250Henry Reaction, 479Heterobimetallic Catalyst, 73–74, 413–422, 463–465,

479, 553, 558–559, 572–574, 584–585Hydrocyanation, 479, 558–559In Metal–Organic Coordination Networks,

519–520Lanthanide Catalysts, 206–207Michael Reaction, 463–465, 553Morita–Baylis–Hillman Reaction, 399–400Mukaiyama Aldol Reaction, 37–38Nitroaldol, 479Organocatalyst, 68–69pKa, 67Racemization, 123Titanium Complex, 34, 37–38, 306, 335–336, 478,

552Ytterbium Complex, 629–630λ vs. δ Arrangement, 584–585

BINOL Derivatives3,3’-Ar, Metathesis, 91Aldehyde Alkylation, 480Aluminum Complex, 32, 558–559As Bifunctional Catalysts, 399–400Bifunctional Catalyst, 558–559Hetero-Diels–Alder Reaction, 480Lewis Acid from, 32Metathesis, 90–91Molybdenum Catalyst, 90–91Morita–Baylis–Hillman Reaction, Hydrogen

Bonding Catalyst, 68–693,3-Ph2, 217–219Silylcyanation, 558–5593,3’-SiPh3 Substituted, 196Synthesis of, 484–485, 562, 614–615With Pendent Groups, 558–559Zinc Catalyst, 480

BINOL Phosphoramidite, 459–460, 464–465, 467–468BINOL Phosphoric Acid, 69–70, 80–81

Conjugate Addition, 80Counterion Catalysis, 80–81Cycloisomerization, 81Diazoester Nucleophile, 70Imine Addition, 70pKa, 67Transfer Hydrogenation, 80

BINOLate (BINOL dianion); see BINOLBINOL-Based Lewis Acids, 123BINOL-Phosphine Catalyst, Organocatalysis, in Aza-

Morita–Baylis–Hillman Reaction, 401BINOL-Pyridine Derivatives, Organocatalysis, in

Morita–Baylis–Hillman Reaction, 399–400Biotin, Synthesis of, 444–445BIPHEN, 210BIPHEP

Bis(Phosphine), 210–216Copper Complex, Reduction of Ketones, 51

BIPHEPHOS, Rhodium Complex, EnamideHydrogenation, 458–459

1,4-Bis(Acyloxy)-2-Ene, in Desymmetrization, 323Bisimine, Zinc Catalyst, Hetero-Diels–Alder

Reaction/Aldehyde Alkylation, 480BISOX, 582–583Bisoxazoline, 118

π-Allylation, Stereoinduction, 122–123α-Amination, 468–469Aziridination, 156–157Conjugate Addition, 468–469Copper Complex, 6, 38–39, 44, 119, 439–444, 462,

468–469, 481–482, 487, 606, 625–626, 629–631Cyclopropanation, 481–482Diels–Alder Reaction

Double Diastereoselection, 439–441Intermolecular, 44, 629–630Intramolecular, 44

Hetero-Diels–Alder Reaction, 38–39, 462, 487,625–626

Mukaiyama Aldol Reaction, 6, 606, 631Double Diastereoselection, 442–444

Palladium Complex, 96, 460–461Semicorrin, 118Wacker Reaction, 96, 460–461

Bisphosphines, 179, 185DIOP, 314–316In π-Allylation, 401–403In Dynamic Kinetic Asymmetric Transformation,

288Bisphosphoramidates, Allylation of Aldehydes,

353–354Bispidine, Asymmetric Deprotonation, 75Bite Angle, Bidentate Phosphines, 322Boiling Point, Racemate vs. Enantioenriched, 331Boltzmann Distribution, Bisoxazoline, Spiro, 7–9Boron Catalysts

CBS Reductions, 379–381Diels–Alder Reaction, 41–42Mukaiyama Aldol Reaction, 178Oxazaborolidines, 379–381

Box; see BisoxazolineBOXAX; see Bisoxazoline, BinaphthylBPPM

Enamide Hydrogenation, Temperature Effects, 11Rhodium Complex, 11

β-Bromohydrin, Synthesis of, 299–300Brønsted Acid Catalysis

α-Amination of Ketones, 606–607Asymmetric Protonation, 70–73, 567–568BINOL, 67BINOL Derivative, 69BINOL Phosphoric Acid, 67, 70Chiral Proton Source, 71, 72Concepts, 66–67Diamine, 71Diels–Alder Reaction, 69Hetero-Diels–Alder Reaction, 69α-Hydroxy Acid, 606–607α-Hydroxylation of Ketones, 606–607Lewis Acid Assisted, 71–72, 567–568Mannich-Type Reaction, 68

Index 641

BINOL (cont.)

18_index.qxp 6/30/08 12:02 PM Page 641

Morita–Baylis–Hillman Reaction, 69Multifunctional Catalysts

Aldol Reaction, 67Diketopiperazine, 67Hydrocyanation, 67Proline, 67

N-Acyl Imine Addition, 70pKa Values, 67Planar Chiral DMAP, 71–72Polycyclization, 72, 567–568Proline, 67Quininium, 67TADDOL, 67, 69, 606–607Umpolung Addition, 70Urea, 67–68Vs. Nucleophilic Catalysis, 72–73

Brønsted Base Catalysis, Multifunctional Catalysts,73–74

Brook Rearrangement[1,2], 60–61Retro-[1,4], 60–61

Bryostatin 7, Synthesis of, with HeterobimetallicCatalysts, 419

Butenolides, Dynamic Kinetic AsymmetricTransformation with, 287–288

tert-Butyl Hydroperoxide, in Sharpless–KatsukiAsymmetric Epxoidation, 242–246

CC1 Symmetry, 27C2-Symmetric, PTC Catalysts, 78–79, 446–447, 581C-Acylation, of Silyl Ketene Acetals, 4Cahn–Ingold–Prelog Convention, 580, 586Callipeltoside A, Synthesis of, 571–572CAMP, P-Chirogenic Phosphines, 582Capnellene, Toward the Synthesis of, 318Carbapenems, Industrial Synthesis of, 274Carbene Catalysts, Stetter Reaction, 59Carbene Intermediates, in Cyclopropanation,

256–257Carbene, Rhodium Catalyst, 304Carbenoids, in C–H Insertions, 303–306Carbohydrates

Synthesis of, with Proline, 394Synthetic Precursors, 553Via Dihydroxylation, 475–477Via Organocatalysis, 397

Carbometalation, Enone, in a Multistep Reaction,489–490

Carbon, Centrochirality, 578–580Carbonyl Addition, Re vs. Si, 598Carbopalladation, 306–307

In a Multistep Reaction, 468–469Carboxyanhydrides, Alcoholysis, Dynamic Kinetic

Resolution, 279Cascade Processes; see Domino Processes

Definition; see Multistep Asymmetric Catalysis,456

Catalyst Compatibility, 458–460, 481–483, 490Catalyst Heterogenization, 497–508

Catalyst Interactions, with Supported Catalysts,502–503

Catalyst Loading, on Silica Support, 536–538Catalyst Optimization

Activation and Deactivation Strategies, 192–206With Achiral Additives, 206

Via Hydrogen Bonding, 208–209With Ligands with Chiral Conformations, Via

Hydrogen Bonding, 216–219Catalyst Recycling, 542

Ionic Exchange Supported, 525Silica-Supported Epoxidation, 505–506Silica-Supported HKR, 502–503

Catalyst Supports, an Overview, 498–508Catalyst–Surface Interactions, 536–538Catalytic Cycles, Competing, 19Cation Exchange Resin, 524–526CBS Reduction, of Ketones, 379–381C-Chirogenicity, 578–580Central Chirality; see CentrochiralityCentrochirality, 580–585

Carbon, 578–580Generation of, 614Metals, 583–586Nitrogen, 581Phosphorous, 582Silicon, 580–581Sulfur, 582–583

Centrosymmetric Bis(Epoxide), Desymmetrization,311

C–H Activation, 258–259Desymmetrization, 300–301Radical Intermediates, 300–301

C–H Activation/Cope Rearrangement, 258–259C–H Insertion

Asymmetric Amplification, 564–565C–C Bond-Forming Reactions, 303–306Desymmetrization, 564–565, 619–621Diastereoselection, Simple, 619–621Double Diastereoselection, 441–442, 449–450Enantioface Differentiation, 619–621Enantiotopic Group Differentiation, 619–621Group Transfer Catalysis, 89–90Intramolecular, with Metal Carbenoids,

303–306Regiocontrol, 449–450Rhodium Catalyst, 89–90, 441–442, 449–450,

564–565, 619–621With Metal Carbenoids, 303–306

Charge Transfer Complex, 177Charge–Charge Interactions, 179

In Bifunctional Catalysis, 386–387Charge-Transfer Interactions, Ketone Reduction,

173Chelation

α-Chiral Carbonyl, 430β-Chiral Carbonyl, 430–431

Chemoselection, Definition, 607–608Chemoselectivity, Additions to α-Ketoester, with

Bifunctional Catalysts, 390–392

642 Index

Brønsted Acid Catalysis (cont.)

18_index.qxp 6/30/08 12:02 PM Page 642

α-ChlorinationImidazolidinone Catalyst, 53–54Of Aldehydes, 53–54

α-Chloroaldehyde, Via α-Chlorination, 53α-Chloroepoxide, Via Kinetic Resolution, 557–558Chirality, Definition, 578Chirality Exchange, Definition, 603–604Chirality Transfer; see Chirality ExchangeChiraphos, Enamide Hydrogenation

Curtin–Hammett, 26Temperature Effect, 11π-Coordination, 99

Chiraphos, Rhodium Complex, 11, 26, 99ChiroCLEC-PC, 260Chirons, 556Chlorohydrins, Via Wacker Reaction, 94–95Chromatography

Of Enantioenriched Compounds, 333–334Separation of Diastereomers, 333

Chromium CatalystsAnilino Oxazoline Complexes, 450–452Diels–Alder Reaction, 41–42Double Diastereoselection, 447–449Epoxide Desymmetrization, 300Epoxide Opening

Azide, 448–449Bifunctional Catalysts, 404

Hetero-Diels–Alder Reaction, 34–35, 447–449,556–558

Nozaki–Hiyama–Kishi Coupling, 450–452Pinacol Coupling, 624Salen Complexes, 448–449, 557–558Salen Complexes, Nonlinear Effects, 338–339Schiff Base Complexes, 34–35, 41–42, 447–449,

556–557Sulfonamide Oxazoline Complexes, 450–452Synthesis of FR901464, 556–557Synthesis of Muconin, 557–558TBoxH Complexes, 624Triple Diastereoselection, 450–452

C–H-π-Interactions, 168, 169Computation, 170Ketone Reduction, 173–174Transfer Hydrogenation, 170, 173

Cilastatin, Synthesis of, viiCinchona Alkaloids, 67, 184–187, 278, 580–581, 592

Anhydride Alcoholyis, 76Brønsted Base Catalyst, Enolate Alkylation, 76Catalyzed Synthesis of β-Lactams, 535–536[2+2] Cycloaddition, 54–55, 485–486, 552Dihydroxylation, 19–20, 83, 247–248, 445–446,

475–477, 481–482, 552, 559–560, 565–566, 605,616, 628–629

Hydrogenation, 522–524Hydrogenation, α-Ketoester, 551In a Multistep Reaction, 485–486Ion-Pair Catalyst, Enolate Alkylation, 78, 581, 610,

613Kinetic Resolution, 76, 264–266β-Lactam Formation, 54–55, 485–486

β-Lactone Formation, 552Lewis Base Catalyst, 54–55, 485–486, 552Ligand, Platinum Catalyst, 551Linked, 19–20, 76, 83, 445–446, 475–477, 552,

559–560, 565–566, 605, 616, 628–629Organocatalyst, Supported, 540–541Osmium Complex, 19–20, 83, 445–446, 475–477,

481–482, 552, 559–560, 565–566, 605, 616,628–629

pKa, 67PTC Catalyst, Enolate Alkylation, 78, 581, 610, 613Supported Catalysts, 522–524

Cinchonine, 184–187cis-Decalin, 579Citreoviridin, Synthesis of, Via Desymmetrization,

563Citronellal, Synthesis of, 80, 433Claisen Rearrangement, Copper Catalyst, 38–39Cn Space Groups, 578Cn-Rotation Axis, 594, 596[Co(H2N–CH2–CH2–NH2)3]3+, 584–585[Co(NH3)2(H2O)2(CN)2], 583–584Cobalt Catalysts

Alkylation of Aldehydes, 586Dynamic Kinetic Resolution, 284EDTA Complex, 586Epoxide Opening, 236–237, 311–312

Desymmetrization, 311–312Epoxide Opening, with Water, 552, 557–558Kinetic Resolution of Epoxides, Bifunctional

Catalysts, 404Large Scale, 552Salen Complexes, 552, 557–558Supported Complexes, Epoxide Opening, 501–503Synthesis of Muconin, 557–558

Colloidal Catalysts, Palladium, in π-Allylation,515–516

Colloids, 508–509Colombiasin A, Synthesis of, 258Complexation, Asymmetric, 618Concentration Effects, 16–17Concentration Effects, Enantiomeric Excess in

Aldehyde Allylation, 352–355Concurrent Processes, 484–485, 485–486, 488–489

Definition, 456Conduritol B, Synthesis of, 22Confinement Effects

Impact on Enantioselectivity, 533–535With Supported Catalysts, 533–535

Conformational Isomers; see AtropisomerismConformations, Chiral

Atropisomers, 210Bis(Phosphine), 210–216In Meso Ligands, 216

Conjugate AdditionAllenes, Formation, 616–617, 619–621Amines to Enones, 420–421Aryl Boronic Acid, 465–466Bifunctional Catalysts, 405–406, 420–421Boron Catalyst, 42

Index 643

18_index.qxp 6/30/08 12:02 PM Page 643

Copper Catalyst, 14, 464–465, 467–469Diazo Compounds, 468–469Diorganozinc, 464–465, 467Enol Ether, 42Enolate, 53Enones, 506–508, 519–520Epothilone, Synthesis of, 558–559Heterobimetallic Catalyst, 558–559Hydrogen Cyanide, with Bifunctional Catalysts,

405In a Multistep Reaction, 464–469, 472–473, 489–490Malonate, 468–469Organocatalyst, 53, 59, 60–61, 78–79, 80Parallel Kinetic Resolution, 489–490PTC Catalysis, 78–79Pyrrolidine Catalyst, 53Rhodium Catalyst, 14, 465–466, 489–490, 616–617Scandium Catalyst, 45Silyl Ketene Acetals, 42, 45Silyl Nitronate, 78–79Stetter Reaction, 59Temperature Effects, 14Thiols, 558–559Transfer Hydrogenation, 80α,β-Unsaturated Aldehydes, 78–79α,β-Unsaturated Amides, 60–61α,β-Unsaturated Ketones, 42, 59, 464–466, 467,

616–617α,β-Unsaturated Nitro, 53

Consecutive Processes; see Sequential ProcessesDefinition; see Multistep Asymmetric Catalysis, 456

Contact Ion Pair, in Phase-Transfer Catalysis,184–187

Continuous Flow Processes, 497, 510–511Coordination Polymers, 498Cope Rearrangement, 258–259Copper Catalysts, 120, 148, 266–267, 340

Allyic Substitution, 459–460α-Amination, 468–469BIPHEP Complex, 51Bisoxazoline Complex, 6, 38–39, 44, 439–444, 462,

468–469, 481–482, 487, 625–626, 629–631Claisen Rearrangement, 38–39Complex Substrates, 561–562Conjugate Addition, 14, 464–465, 467–468–469Cyclopropanation, vii, 481–482Diaza–cis-Decalin Complex, 484–485, 561–562,

614–615Diels–Alder Reaction

Double Diastereoselection, 439–441Intermolecular, 18–19, 44, 629–630Intramolecular, 44, 462

Glaser–Hay Coupling, 484–485Hetero-Diels–Alder Reaction, 38–39, 462, 487,

625–626In a Kinetic Resolution, 487In a Multistep Reaction, 459–460, 462, 467–468,

481–482, 484–485, 487Mukaiyama Aldol Reaction, 6, 35–38, 601, 624–625,

630–631

Double Diastereoselection, 442–444Regiocontrol, 606

Oxidative Biaryl Coupling, 484–485, 561–562,614–615

Peptide Complex, 467Phosphino Peptide Complex, 14Phosphoramidite Complex, 459–460, 464–465, 468Pyridine Bisoxazoline Complex, 18–19, 35–38, 601,

624–625Reduction of Ketones, 51Schiff Base Complex, viiSN2’ Displacement, 459–460Transetherification, 462

Counterion CatalysisAnion, 68, 79–81Cation, 77–79

Counterion Effects, 400Cross Coupling, 284–286

Anhydride Alkylation, 621–622Copper Catalyst, 484–485, 562, 614–615Desymmetrization, 320–321Kumada, 613, 615Palladium Catalyst, 92–93, 484–485, 562, 614–615,

621–622Phosphine Synthesis, 288–290Suzuki, 92–93, 614, 619

Cross-Linked PolymersMass Transport, 497Swelling, 497

Cross-Linking, Impact on Catalysis, 497Cross-Linking Agents, 509, 510–511

Impact on Enantioselectivity, 510–511Crossover Experiments, 36–37Cryptophycin, 569–571Crystal Packing, Racemate vs. Enantioenriched, 331Curtin–Hammett, 25, 139, 177, 182

Dynamic Kinetic Asymmetric Transformation,Phosphination, 291

Enamide Hydrogenation, 98–99Energy Diagram, 25Equation, 25

β-Cyano Imides, Synthesis of, from UnsaturatedImides, 405

γ-Cyano-γ-Hydroxy-α-Amino Acids, ViaMannich/Hydrocyanation Sequence,472–473

CyanohydrinFrom Aldehyde, 67, 479, 558–559From Ketone, 572–573

Cyanosilylation, 558–559[2+2] Cycloaddition, 43

Cinchona Alkaloid Catalyst, 54–55, 485–486, 552

In a Multistep Reaction, 485–486β-Lactam Formation, 54–55, 409–410, 485–486Large Scale, 552

[2+2+2] CycloadditionDouble η2-Coordination, 105–106Iridium Catalyst, 105–106

[3+2] Cycloaddition, 43, 58

644 Index

Conjugate Addition (cont.)

18_index.qxp 6/30/08 12:02 PM Page 644

[4+1] CycloadditionAllene with Carbon Monoxide, 104–105η4-Coordination, 104–105Rhodium Catalyst, 104–105

[4+3] Cycloaddition, 58[5+2] Cycloaddition

Double η2-Coordination, 105Rhodium Catalyst, 105

Cycloalkene, Via Metathesis, 90–91Cyclobutanone

Via Wagner Meerwein Shift, 103Via Parallel Kinetic Resolution, 263–264

Cycloheptene, [5+2] Cycloaddition, 105Cyclohexanone

Via Michael/Aldol Sequence, 471–472Via Diels–Alder Reaction, 68–69

CycloisomerizationChiral Counterion Catalysis, 80–81Of Allenes, Gold Catalyst, 80–81Of Cyclopropanes, Rhodium Catalyst, 105Of Enynes, Kinetic Resolution, 250–252Palladium Catalyst, 611

Cyclopentenone[4+1] Cycloaddition, 104Generation of, in Parallel Kinetic Resolution, 263–264

Cyclophane Ligands, with Aluminum, 411Cyclophellitol, 22, 23Cyclopropanation, 58, 87, 223

Copper Catalyst, vii, 481–482Directed Electrostatic Activation, 81–82In a Multistep Reaction, 467–468, 470–471, 481–482In Parallel Kinetic Resolutions, 256–257Intramolecular, 256–257Large Scale, viiOrganocatalyst, 81–82Substrate Directed, 432To Cilastatin, viiwith an Ylide, 81–82α,β-Unsaturated Aldehyde, 81–82

CycphosEnamide Hydrogenation, Temperature Effect, 11Rhodium Complex, 11

Cytochrome P450, C–H Oxidations, 301

Dδ, 584–585δ-Hydroxy Ester, Via Mukaiyama Aldol Reaction,

Vinylogous Silyl Ketene Acetals, 49Δ, 584–585Δ-[Na3(THF)6[(R)-BINOLate]3La, 584–586ΔG; see Energy DifferenceΔG‡; see Free EnergyΔH‡; see EnthalpyΔS‡; see EntropyDAIB

Aldehyde Alkylation, 2–4, 7–8Zinc Complex, 7

DAIPENHydrogenation, α-Aminoketone, 560–561Ruthenium Complex, 560–561

DBU, Isomerization of Meso Epoxides, 349–352de; see Diastereomeric ExcessDeactivation, of Racemic Catalysts, 192–198, 200Decarboxylative Allylation, 24–25, 555Dendrimers, as Supports, 513–515Dendronized Catalysts, for Hydrogenation,

513–515Denopamine, 560–561Dependent Bifunctional Catalysts, 376Deprotonation

Asymmetric, 73–76Meso-Epoxides, 73–75N-Boc Pyrrolidine, 75–76

Diastereoselective, 429Of Epoxides, 74

Desymmetrization, 298–325, 466–467Acylation of Phenols, 310Alcohol Phosphonylation, 621–622Alkene Metathesis, 90–91Alkylation of Aldehydes, 600Anhydride Alkylation, 621–622C–H Insertions, 303–306, 565, 619–621Combined with Kinetic Resolution, 309–310,

320–321Complex Natural Product Synthesis, 319–320Dihydroxylation, 566Dynamic Kinetic Asymmetric Transformation, 293Enantiotopic Group Differentiation, 610Generation of Atropisomers, 320–321Heck Reaction, 567Late-Stage Synthesis, 319–320Multiple Stereocenters, To Establish, 313Natural Product Synthesis, 308, 323–325Intramolecular, Synthesis of Quadrigemine C,

319–320, 566–567Intramolecular Aldol, 52, 67Of Biaryls, 320–321Of Centrosymmetric Bis(Epoxide), 311–312Of Complex Substrates, 313, 567Of Compounds with One Functional Group,

298–306Of Dienes, Via Hydrosilylation, 316Of Divinyl Carbinols, Via Sharpless–Katsuki

Epoxidation, 312–313Of Epoxides, Nonlinear Effects, 349–352Of Meso Dienes, Via Heck Reaction, 317–318Of Meso Diols, 313Of Meso Epoxides, 73–75, 298–300Of Meso Heterocycles, by Hydroxylation, 302–303Of Meso Compound, 621–622Of Oxabicyclic Alkenes, 306–308Of Siloxydienes, Via Hydrosilylation, 314–315Of Tetrahydrofuran, in C–H Hydroxylations,

302–303Of Tetrahydropyran, in C–H Hydroxylations,

302–303Quadrigemine, C, Synthesis, 319–320Remote Stereocenters, 310Ring-Closing Metathesis, Using Supported

Catalysts, 512–513

Index 645

18_index.qxp 6/30/08 12:02 PM Page 645

Sharpless–Katsuki Epoxidation, 562–564Suzuki Coupling, 618–619Wacker Reaction, 95–96

Deuterium Labeling, C–H Hydroxylation,Desymmetrization, 303

(DHQ)2PHAL; see Dihydroxylation(DHQD)2PHAL; see DihydroxylationDiamines

Asymmetric Deprotonation, 75Asymmetric Protonation, 71DPEN, Ketone Reduction, 382–386Epoxide Elimination, 74Epoxide Rearrangement, 75Ketone Reduction, 382–386

Diastereocontrol1,2-, 429–4331,3-, 430–4331,4-, 434–4351,5-, 434–4351,6-, 4341,7-, 4341,9-, 4351,23-, 435Allylic Strain, 431Axial, 435Centrochiral to Axial, 435Distal Stereocenters, 435–436Functional Groups; see Diastereoselection,

Directed ReactionsDiastereofaces; see Diastereotopic FacesDiastereomeric Catalyst Combinations, Dual

Catalysts, 408Diastereomeric Catalysts

In Ketone Reduction, 384Relative Rates, 201

Diastereomeric Complexes, 217–218(Pybox)2Cu2+, 343

Diastereomeric Excess, Equation, 593Diastereomeric Interactions

Giving Rise to Different Species, 334In Chemistry, 331–335

Diastereomeric Ratio, Equation, 593Diastereomers

Atropisomers, 213Definition, 592–593

DiastereoselectionAldol Reaction with Proline, 397Definition, 601–602Diastereofacial Selectivity, 429Diastereotopic Group Selectivity, 429Directed Reactions, 432–434, 605Double, 436–450, 557, 563–567

Additive Effects, 436–440Aldol Reaction, 572–574Allylation, 572–573Catalyst Control, 435–436, 444–448, 475, 478Catalyst Regiocontrol vs. Diastereocontrol,

448–450C–H Insertion, 441–442, 449–450Diels–Alder Reaction, 439–441, 447–448

Dihydroxylation, 445–446Energetic Analysis, 436–439Epoxidation, 569–571Epoxide Opening, 448–449Hydrogenation, 435–436, 444–445, 568–569,

572–573Hydrosilylation, 616–618In Synthesis, 568–574Kinetic Resolution, 250–252, 441–442Matched, 428, 434, 436–450Mechanism Insight, 443–444Mismatched, 428, 434, 436–450Mixed Control, 442–443Mukaiyama Aldol, 442–444Nozaki–Hiyama–Kishi Reaction, 450–452Phase-Transfer Catalysis, 446–447Reaction Coordinate Diagrams, 438Substrate Control, 440–441π-Allylation, 571–572

Internal StereocontrolDeprotonationKetone AlkylationKetone Reduction, 428–429Torsional Control, 429

Remote Stereocontrol, 434–436Simple, 428–436

Aldol Reaction, 428–429Diels–Alder Reaction, 428–429

Triple, 450–452Aldol Reaction, 450–451Catalytic, 450–452Nozaki–Hiyama–Kishi Reaction, 450–452Stoichiometric, 450–451

With Chiral Substrates, Internal Stereocontrol,428–436, 475

Diastereoselective Synthesis, Number ofStereoisomers, 553–554

Diastereospecific, Definition, 602Diastereotopic, Definition, 594–595Diastereotopic Faces, Definition, 598–600Diastereotopic Groups

Definition, 598–600Sulfonyls, 156–157

Diaza–cis-Decalin, Copper Complex, OxidativeBiaryl Coupling, 484–485, 562, 614–615

Diazo CompoundsC–H Insertion, 89–90, 303–306

Asymmetric Amplification, 564–565Double Diastereoselection, 449–450Enantiotopic Group Differentiation, 619–621Kinetic Resolution, 441–442

Conjugate Addition, 69–70Cyclopropanation, viiFormation, 70Umpolung, 69–70

Diazo Decomposition, in C–H Insertion, 303–306

DiazoestersAddition to N-Acyl Imines, 69–70Cyclopropanation, 223

646 Index

Desymmetrization (cont.)

18_index.qxp 6/30/08 12:02 PM Page 646

DIBAL-H, Hydride Source, Desymmetrization,307–308

Diborate, Via Alkene Diboration, 460–461Diboration, Alkene

In a Multistep Reaction, 460–461Rhodium Catalyst, 460–461

Dibromides, Via Wacker Reaction, 94–951,4-Dicarbonyl

Brook Rearrangement, 60–61Umpolung Addition, 60–61Via Anhydride Desymmetrization, 621–622

1,5-DicarbonylVia Conjugate Addition, 42Via Michael Reaction, 9–10, 553

1,4-Dicarbonyls, Formation, 56, 60Diels–Alder Reaction, 166–8, 176–8, 196

(Binolate)Ti ComplexesAchiral Additives, 629–630Aluminum Catalyst, 41Background Reaction, 18Boron Lewis Acid, 41, 125, 166–168, 510–511Chromium Catalyst, 34–35, 41, 447–448, 556–557Copper Catalyst, 18, 38–39, 44, 120, 439–441, 462,

487, 625–626, 629–630Counterion Effect, 18Diastereoselection, 428–429, 431, 629–630Diastereoselection, Simple, 630–631Dipole–Induced-Dipole Interactions, 166, 176Double Diastereoselection, 439–441Electrostatic Interactions, 166Endo vs. Exo, 630–631Hetero, 34–35, 38–39, 54, 68–69, 196, 447–448, 462,

480, 487, 556–558Double Diastereoselection, 447–448Enantioface Differentiation, 625–626In a Multistep Reaction, 462, 480, 487

Imidazolidinone, 56–58Iminium Catalysis, 56–58In a Multistep Reaction, 480, 487, 488–489Intramolecular, 44, 58

In a Multistep Reaction, 487, 488–489α-Ketophosphonates, 38–39, 625–626Kinetic Resolution, 487Methacrolein, 18, 68–69Molecular Orbital Diagram, 40Organocatalyst, 54Osmium Catalyst, 150Pyrrolidine Catalyst, 54Quinones, 41–42, 44, 125Ruthenium Catalyst, 150Solvent Effect, 15–16Supported Oxazaborolidinone Catalyst,

510–511Synthesis of (+)-Diepoxin σ, 126Synthesis of FR901464, 556–557TADDOL Catalyst, 68–69TADDOLate–Ti Catalyst, 136–143Titanium Catalyst, 15–16, 43, 136–143, 347–348α,β-Unsaturated Aldehyde, 41α,β-Unsaturated Ester, 41–42

α,β-Unsaturated Ketones, 54, 56–58, 462, 487,625–626

α,β-Unsaturated Oxazolidinone, 15–16, 43–44,629–631, 629–630

Via Enamine, 54With 3,3’-DiphenylBINOL, 125With BINAPO, 150With Chiral Relay Catalysts, 147–148With Chiral Relay Substrates, 157Ytterbium Catalyst, 629–630Zinc Catalyst, 121

(+)-Diepoxin s, Synthesis of, 126Dihydrofuran

Via Heck Reaction, 98Via Metathesis, 553

Dihydropyran, Via Hetero-Diels–Alder Reaction,34–35, 38–39, 54, 68–69, 447–448, 462, 487,556–55, 625–626

DihydroxylationAlkene, 19–20, 83–84, 247–249, 445–446, 481–482,

552, 565–566, 605, 616, 628–629Atropisomer Generation, 616Atropisomeric Amides, 247–249Diastereocontrol, 431Double Diastereoselection, 445–446Enveloped Catalyst, 531–532In a Multistep Reaction, 475–477, 481–482Large-Scale, 552Osmium Catalyst, 19–20, 83,445–446, 481–482, 552,

559–560, 565–566, 605, 616, 628–629Osmium Catalyst, Supported, 526Pseudoenantiomers, 628–629Regioselection, 605Squalene, 565–566, 605Supported Dual Catalysts, 540–541Synthesis of Zaragozic Acid, 559–560

Diketopiperazine, Hydrocyanation, 67Dimeric Catalysts, 35Dimers of Dimers, Autocatalysis, 357–360Diminution, 337Dinuclear Catalyst, with Zinc, 364–3661,5-Diol, Via Double Ene Reaction, 478Diols

Dynamic Kinetic Resolution, 281Via Alkene Dihydroxylation, 19–20, 83–84,

445–446, 475–477, 481–482, 552, 559–560, 605,616, 628–629

Via Epoxide Opening, 552, 557–558Via Kinetic Resolution of Epoxides, 237–238,

501–503Via Pinacol Coupling, 624Via α-Hydroxylation/Aldehyde Allylation

Sequence, 4741,3-Diols, Synthesis, 314–315Dioncophylline C, 593DIOP, 129

Enamide Hydrogenation, Temperature Effects, 11

Hydrosilylation, 314–315Rhodium Complex, 11

Index 647

18_index.qxp 6/30/08 12:02 PM Page 647

DiorganozincAldehyde Alkylation, 2–4, 7–8, 15, 469–471, 480,

586, 589, 600Autocatalysis, 357–360Bis(Sulfonamide)Ti Complex, 136, 142Conjugate Addition, 14, 464–465, 467–468Cross-Coupling, 621–622Desymmetrization, Oxabicyclic Alkenes,

307–308α-Ketoester Alkylation, 607

Dioxiranes, 86–88, 569–571Dioxop

Enamide Hydrogenation, Temperature Effects, 11Rhodium Complex, 11

DIPAMPEnamide Hydrogenation, viiP-Chirogenic Phosphines, 582Rhodium Complex, vii

Dipeptide CatalystAutoinduction, 368Hydrocyanation of Aldehydes, 368Hydrocyanation, 67

1,3-Dipolar Cycloaddition, 168–171Dipole–Induced-Dipole Interactions, 166, 176Directed Electrostatic Activation, 81–82Dirhodium Catalysts, Diazo Decomposition, 303–306Disproportionation of Enantiomers, 333Diyne, Synthesis, 484–485Dizinc Catalyst, 364–366DMAP

Planar Chiral Analogs, 589–590Alcohol Acylation, 56–57, 72C-Acylation, 4Ketene Alcoholysis, 72

Dn Space Groups, 578DNA, as a Ligand, 225Dolichols, Synthesis of, 605Domino Processes, 318, 460–466, 471–473, 477–478,

487–490Definition; see Multistep Asymmetric Catalysis, 456

DOPA, Synthesis of, vii, 25DOSP, Rhodium Complex

Asymmetric Amplification, 564–565C–H Insertion, 89–90, 441–442, 449–450, 564–565,

619–621, 619–621Double Diastereoselection, 449–450Enantiotopic Group Differentiation, 619–621Kinetic Resolution, 441–442

Double Diastereoselection; see Diastereoselection,Double

DPEN, Diamine, Ketone Reduction, 276DPPBA

Palladium Complex, 21–24, 101–103, 552–554, 561,571–572

π-AllylationCallipeltoside A Synthesis, 571–572Complex Substrates, 561, 571–572Double Diastereoselection, 571–572Dynamic Kinetic Asymmetric Transformation,

23–24

Generation of Small Components, 552–554Kinetic Resolution, 21–22η3-Coordination, 101–103

dr; see Diastereomeric RatioDual Activation Mechanism, Aldehyde Alkylation,

381–382Dual Activation Strategy, 376Dual Catalysis, 107Dual Catalysts

Autoinduction, in Diels–Alder, 362–364BINOL, 411[2+2] Cycloadditions, 410–413Diastereomeric Combinations, 408In Conjugate Addition of Cyanide, 405–406Lanthanide/Aluminum, 405–407Nucleophilic/Lewis Acid, 410–413Proline/Peptide, Morita–Baylis–Hillman Reaction,

407–409(Salen)CoX Complexes, 239Supported, 497Systems, 403–412

Dual Hydrogen-Bonding, 68DuPHOS

[2+2+2] Cycloaddition, 105–106[4+1] Cycloaddition, 104Hydrogenation, 435–436, 457–459, 551, 602, 623Iridium Catalyst, 105–106Parallel Kinetic Resolution, 262–264Rhodium Catalyst, 104, 435–436, 457–459, 551, 602,

623Dynamic Kinetic Asymmetric Transformation

(DyKAT), 23–24Comparison with Dynamic Kinetic Resolution, 286Definition, 286Reaction Coordinate Diagrams, 22Type A, 287Type B, 291With Two Racemic Substrates, in Allylation,

929–293Dynamic Kinetic Resolution (DKR), 21–25, 272–293

Comparison to Kinetic Resolution, 272Comparison with Dynamic Kinetic Asymmetric

Transformations, 286Coupling, 613Dual Catalysts, 280–284Enantiotopic Group Differentiation, 613Enzymes, 280–284Hydrogenation, 626–627Proline, 398Reaction Coordinate Diagrams, 22, 488–489Stereoselective vs. Stereospecific, 603Via Basic Substrate Racemization, 273–277

EEarly Metal Catalysts, Structure, 306EBTHI

Diels–Alder Reaction, 15–16Planar Chirality, 589–590Titanium Complex, 15–16, 589–590

Edge–Face Interactions, Phosphines, 130, 144

648 Index

18_index.qxp 6/30/08 12:02 PM Page 648

EDTA, Cobalt Complex, 586ee; see Enantiomeric Excess

As a Function of Conversion, 349As a Function of Time, 364–366

ee Dependence, on Concentration, 352–355Electron Transfer, in C–H Hydroxylation, 303Electronic Asymmetry, 143–144Electrophile Activation; see also Lewis Acids, 56–58Electrophilic Alkene Activation, η2-Coordination,

94–95Electrostatic Activation, 81–82Electrostatic Forces, 179–184Electrostatic Interactions, 176, 179–184

Phase-Transfer Catalysis, 184Elimination, E2 Reaction, 603Elimination, Epoxide, 74Enamide Intermediates, in

Hajos–Parrish–Ender–Sauer–WiechertReaction, 392–393

Enamine, from Allyl Amine, 433, 552Enamine Catalysis, 52, 53–56, 67, 471–474, 482–483Enamine Oxidation, 55–56Enantioconvergent, 24–25Enantioenriched; see Enantiomerically EnrichedEnantiofaces; see Enantiotopic FacesEnantiomer Imbalance, Absolute Asymmetric

Synthesis, 360–361Enantiomer Self-Disproportionation, 333

Of Binols, 334Of Helical Compounds, 334Of Sulfoxides, 334

Enantiomeric Catalysts, 628–631Enantiomeric Enrichment

During Purification, 334Via Achiral Chromatography, 333

Enantiomeric Excess, viEnergy Difference, 3, 5–6, 590–591Equation, 5–6, 591

Enantiomeric Ratio, vi, 3, 5, 590–591Equation, 591

Enantiomerically Enriched, Definition, 591Enantiomerization, Definition, 591Enantiopure, Definition, 590–591Enantiopure Compounds, Physical Properties,

331–335Enantioselective, Definition, 601–602Enantioselective Catalysis; see Asymmetric CatalysisEnantioselectivity-Determing Step (eds), 12–13, 17Enantiospecific, Definition, 602Enantiotopic, Definition, 594–595Enantiotopic Face

Definition, 597–598Differentiation, 561, 610–611, 623–625

Re, 598Si, 598To Yield Centrochiral Units, 598To Yield Planar Chiral Units, 598

Enantiotopic Group and Homotopic Groups in thesame compound, 597

Definition, 596–597

Differentiation, 561, 609–610, 619–623Re, 596Si, 596

Encapsulated Catalyst, for Epoxidation, 529–531Ene Reaction, 199

(BIPHEN)Rh Catalyst, 215In a Multistep Reaction, 478In Desymmetrization, 306Intermolecular, 34Intramolecular, 34Large-Scale, 552Titanium Catalyst, 34, 552To α-Ketoester, 519–520

Energy Diagrams; see Reaction Coordinate DiagramsEnergy Difference

Enantiomeric Excess, 3, 5–6, 590–591Selectivity, Double Diastereoselection, 436–439

Eniphos, Rhodium Complex, EnamideHydrogenation, 551

Enolα-Allylation, 55–56Formation of 1,4-Dicarbonyls, 56

Enolates, 179–183α-Alkylation, 77–79, 446–447, 467–468, 609–610,

613–614Alkylation in Amino Acid Synthesis, 184–187Amination, in a Multistep Reaction, 468–469Asymmetric Protonation, 70–73From Ketene, 409–413Glycine Imine, 77–79, 446–447, 609–610Lithium, 50With Nucleophilic Catalysts, 409–413

Enones, Synthesis of, Via Hajos–Parrish–Ender–Sauer–Wiechert Reaction, 52, 67, 392–393

Enthalpy, of Activation, 11, 13Entropy, of Activation, 11, 13Envelopment, in Polymer Support, 531–532Enynes, 250–252Enzyme Catalysts

Aldolase, 377–378Dynamic Kinetic Resolution, 280–284Ketone Reduction, Kinetic Resolution, 268

Epichlorohydrin, Kinetic Resolution SupportedCatalysts, 501

Epi-Hygromycin, Toward the Synthesis of, 232Epimerization, in Dynamic Kinetic Asymmetric

Transformation, 286Epothilone, 558–559, 572–574Epothilone A, Synthesis of, 234–235, 418–419Epothilone C, Synthesis on Solid Support, 498Epoxidation, 58

1,4-Diastereoselection, 434–435Asymmetric Amplification, 564Complex Substrates, 562–564, 569–571Cryptophycin 52 Synthesis, 569–571Desymmetrization, 562–564Dioxiranes, 86–88, 569–571Double Diastereoselective, 569–571Enantioface Differentiation, 625–626Encapsulated Catalyst, 529–531

Index 649

18_index.qxp 6/30/08 12:02 PM Page 649

In a Multistep Reaction, 469–470Kinetic Resolution, 242–246, 564, 599–600, 625–626Large-Scale, 552Manganese Catalysts, 84, 86–87, 552, 569–571Organocatalysts, 86–88, 569–571Salen Catalysts, 84, 86–87, 569–571Sharpless–Katsuki, vii, 84–85, 433, 552, 562–564,

569–571, 599–600, 625–626Kinetic Resolution, 242–246Mechanism, 243Stereoinduction in, 246–248Synthesis of Epoxy Alcohols, 242

Substrate Directed, 432, 433Titanium Catalyst, vii, 84–85, 433, 552, 562–564,

569–571, 599–600, 625–626Epoxide Elimination

To Allylic Alcohol, 74Via Deprotonation, 74

Epoxide Glycidol, Via DKR, 284Epoxide Opening, 266–267

Centrosymmetric Bis(Epoxide), 311–312Chromium Catalyst, 448–449Cobalt Catalyst, 552, 557–558Dual Catalysts, 404Salen Catalysts, Supported, 501With Azide, 298–299

Double Diastereoselection, 448–449Nonlinear Effects, 338–339Regiocontrol, 448–449

With Bromide, 299–300With Cyanide, Bifunctional Catalysts, 405With Iodide, 299–300With Supported Catalysts, 501–503With Water

Dendrimeric Salen Catalysts, 239Large Scale, 552, 557–558Mechanism, 239(Salen)CoX Catalysts, 237–240

Epoxide Rearrangement, 75Epoxy Alcohol

Via Desymmetrization, 312–313Via Sharpless–Katsuki Epoxidation, vii, 84–85,

242–246, 433, 552, 562–564, 569–571, 599–600,625–626

Equilibrating Intermediates; see Curtin–HammettEquilibria, in Epoxide Opening, 238er; see Enantiomeric RatioEsomeprazole, Synthesis of; see NexiumEuropium Catalyst

Dual Catalysts, 405–407Epoxide Opening, 405–406

External Stereocontrol, 428, 436, 444–448Eyring, Equation, 11Eyring, Plot, 10, 13, 14

FFalse Positive Nonlinear Effects, 338, 349[Fe(bipyridine)3]2+, 584–585Fecht acid, 587Felkin–Anh Model, Carbonyl Additions, 430

Ferrocene, Planar Chiral DMAPAlcohol Acylation, 56–57, 72C-Acylation, 4Ketene Alcoholysis, 72Kinetic Resolutions, 234–236

Ferrocenyl PhosphineBifunctional, Aldol, 386–387Kumada Reaction, 613Planar Chirality, 579Suzuki Reaction, 92–93, 619

First-Order Catalyst, Anhydride Methanolysis, 76Fischer, Emil, 428, 553FK506, Via Desymmetrization, 563Flow Reactor, with Supported Catalysts, 541–543α-Fluorination

In a Multistep Reaction, 482–483Of Aldehydes, 53, 482–483

α-Fluoroaldehyde, Via α-Fluorination, 53, 482–483Fluoxetine, Synthesis of, Via Hydrogenation, 384Formyl C–H•••O Interactions

Electrostatic Interactions, 175–176Lewis Acids, 175Mukaiyama Aldol, 178

Fostriecin, Synthesis of, 572–573FR901464, Synthesis of, 556–557Free Energy of Activation, 3, 11, 590–591Friedel–Crafts Reactions

Imidazolidinone Catalyst, 58, 472–473In a Multistep Reaction, 472–473α,β-Ketophosphonates, 45Scandium Catalyst, 45

Fructose-Derived Catalysts, Epoxidation, 86–88

GGadolinium Catalysts

Diels–Alder Reaction, 44Pyridine Bisoxazoline Complex, 44

General Acid Catalysis, 66Geometry-Induced Ligand Acceleration, Aldehyde

Alkylation, 219–220Glaser–Hay Coupling, 484–485Glycidol, by Sharpless–Katsuki Epoxidation, viiGold Catalysts, 179–183

Aldol, Bifunctional Catalysts, 386–387Chiral Counterion, 80–81Cycloisomerization, 80–81

Grignard Reagents, in Cross-Coupling, in DKR,284–286

Group-Transfer Catalysis, 82–91Alkene Metathesis, 90Aziridination, 87C–H Insertion, 89–90Cyclopropanation, 87Dihydroxylation, 83–84Epoxidation, 84–88

Hη4-Iron Complex, 618η4-Iron Complex, Chirality Exchange, 604η4-Iron-Dienyldialdehyde, 600

650 Index

Epoxidation (cont.)

18_index.qxp 6/30/08 12:02 PM Page 650

η6-Arene–Cr Complex, Planar Chirality, 589–590η6-Tricarbonylchromium Complex, 618–619Hajos–Parrish–Eder–Sauer–Weichert Reaction, 52, 67,

392–393Linear Behavior, 397Proline, 392–393

Halichondrin, Synthesis of, 452, 563–564Heck Reaction

η2-Coordination, 94, 96–98Diastereoselective, 555In a Multistep Reaction, 460–461Intermolecular, 96–97Intramolecular, 98Palladium Catalysts, 97–98, 566–567Palladium Nanoparticles, 540–541Psycholeine Synthesis, 319–320, 566–567Quadrigemine C Synthesis , 319–320, 566–567

Helical Arrangements, of Ligands, 584–585Helical Chirality, 588–589Helicene, 579HELOL, Zinc Complex, Aldehyde Alkylation, 589Hemibrevetoxin B, Disconnection of, 311Hemilabile Ligands, 92–93Henry Reaction; see NitroaldolHeterobimetallic Catalysts

Al, LiIn a Multistep Reaction, 463–464Large-Scale Reaction, 553Michael Reaction, 463–464, 553

Cs, Ni, Michael Reaction, 9–10La,Li

Aldol Reaction, 74, 572–574Epothilone Synthesis, 572–574Fostriecin Synthesis, 572–573

Ln, Chirality at, 415Multifunctional Catalysts, 413–422Sm,Na

Conjugate Addition, 558–559Epothiolone Synthesis, 558–559

Y,Li, in a Multistep Reaction, 479Heterochiral Dimers, Zinc Catalysts, 343–347Hetero-Diels–Alder Reaction; see Diels–Alder

ReactionHeterogeneous Mixtures, in Nonlinear Effects,

355–357Heterogeneous vs. Homogeneous Catalysts, 496–497Heterogenization of Catalysts, 497–508

Catalyst Construction in Pores, 499Coordination Polymers, 498Of Salens on Silica, 501–503Via Charge–Charge Interactions, 499Via Polymer Derivatization, 498Via Tethering, 499

Heterolytic Cleavage of Hydrogen, by Ruthenium,385

Heterotopic, Definition, 594–595Homoallylic Alcohols

Synthesis of, 306, 352–355Via Allylation of Aldehydes, 572–573Via Ene Reaction, 34

Homochiral, 591Homochiral Dimers, Zinc Catalysts, 343–347Homochirality, Origin of, 360–361Homoleptic Ligands, 584Homotopic, Definition, 594–595Homotopic Groups and Enantiotopic Groups in the

Same Compound, 597Hydroacylation

(BINAP)Ru, 131–135Kinetic Resolution, 262Mechanism, 132Parallel Kinetic Resolution, 262–264

Hydroalkoxylation, Allene, 80–81Hydroamination

Diene, 103–104Styrene, 103–104η2-Coordination, 94

Hydrocarbonylation, η2-Coordination, 94Hydrocyanation, 388–389

Aluminum Catalyst, 558–559Epothilone Synthesis, 558–559, 572–573Fostriecin Synthesis, 572–573Heterobimetallic Catalyst Y,Li, 479Imine, Enantioface Differentiation, 611In a Multistep Reaction, 472–473, 479Of Aldehydes, 67, 367–368, 472–473, 479, 558–559Of Imines, 611Of Ketones, 572–573Organocatalyst, 67, 611Titanium Catalyst, 572–573

Hydrofluorination, Enal, Organocatalyst, 482–483Hydroformylation, vii

π-Activation, 99–100η2-Coordination, 94, 99–100In a Multistep Reaction, 458–459Large-Scale, 553Mechanism Shift, 12–14Platinum Catalyst, 12–14Rhodium Catalyst, 99–100, 553

Hydrogen Abstraction, in Hydroxylations, 300–301Hydrogen Bonding, 66–67, 207

Bifunctional Catalysis, 382–386, 396Catalysis, 66–70C–H•••O Interactions, 175Formyl C–H, 175–179Homochiral vs. Heterochiral, 332–333Hydrogenation β-Ketoester, 275Nonlinear Behavior, 355–357Platinum–Cinchonidine-Catalyzed Hydrogenation,

524Proline with Chloroform, 355–357Racemate vs. Enantioenriched, 332–333Transfer Hydrogenations, 170–172

Hydrogen Transfer Mechanism, 386Hydrogenation

Alkene, 551Double Diastereoselection, 444–445, 568–569, 605Regioselection, 605

Alkynyl Ketones, 556–557Double Diastereoselection, 445

Index 651

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Anion Capture Supports, 527–529BINAP, Directed, 131Chiral Counterion Catalysis, 80Conformationally Dynamic Ligands, 154η2-Coordination, 94Denopamine Synthesis, 560–561Dolichols Synthesis, 605Enamide, vii, 551, 586, 589

η2-Coordination, 98–99Curtin–Hammett, 25–26, 98–99, 444–445Double Diastereocontrol, 435–436Enantioface Differentiation, 623In a Multistep Reaction, 457–459, 480–481Pressure Effect, 16–17Stereospecific, 602, 623Temperature Effect, 10–13

Fostriecin Synthesis, 572–573FR901464 Synthesis, 556–557Iminium Catalysis, 58, 80In a Multistep Reaction, 480–481, 482–483Ketone, 200, 273–278, 382–383, 508–509, 517–519,

551, 556–557, 560–561Double Diastereoselective, 568–569, 572–573

Ketone vs. Alkene, 386Large-Scale, vii, 551α-Ketoester, 551β-Ketoester,

Dynamic Kinetic Resolution, 626–627Enantioface Differentiation, 626–627In a Multistep Reaction, 480–481

Ketoesters, 131, 533–535Organocatalyst, 58, 80Platinum Catalyst, 551Resin-Bound Catalysts, 524Rhodium Catalyst, vii, 10–13, 16–17, 25–26, 98–99,

144, 435–436, 444–445, 457–459, 551, 586,589, 602, 624

Ruthenium Catalyst, 445, 480–481, 488, 551,556–557, 560–561, 568–569, 572–573, 605,626–627

Silica-Supported Catalysts, 506–508Substrate Directed, 131, 432, 605Supported Catalysts, 503–504Taurospongin A Synthesis, 568–569Trimethyldodecanol Synthesis, 568–569Transfer, 58, 80, 445, 482–483, 488, 556–557,

560–561, 568–569, 572–573, 610α,β-Unsaturated Aldehyde, Transfer, 80Zeolite-Supported Catalysts, 506–508

Hydrolytic Kinetic Resolution (HKR); see EpoxideOpening

Hydrometallation, to a π-Benzyl Complex, 103–104Hydropalladation, Enantioface Differentiation,

611Hydrosilane, 581Hydrosilylation, 581

Alkene Desymmetrization, 314Ansa-Metallocenes, Stereoinduction, 128Double Diastereoselection, 616–618Ketone, 50–51, 140

Imine, 127, 246Mechanism, 127

Intramolecular, Desymmetrization, 314Membrane Encapsulation, 532–533S-Chirogenicity, 316To Spiranes, 616–618Zinc Catalysts, 140

4β-Hydroxyalatol, Disconnection of, ViaDesymmetrization, 313

α-Hydroxy AcidOrganocatalyst, α-Hydroxylation, 606Via Hydrogenation, 551

β-Hydroxy Aldehydesα-Hydroxy Ester

Via Alkylation, α-Ketoesters, 607Via Ene Reaction, 552Via Mukaiyama Aldol Reaction, α-Ketoesters with

Silyl Ketene Acetals, 6, 606, 631β-Hydroxy Ester

Via Ketone Reduction, 626–627Via Mukaiyama Aldol Reaction, with Silyl Ketene

Acetals, 6, 36–38, 49, 442–444, 601, 624–625α-Hydroxy Esters, Synthesis of, 390–392β-Hydroxy Esters, Synthesis of, Via DKR, 283α-Hydroxy Ketone

Via Aldol Reaction, with Proline, 8–9Via α-Hydroxylation of Ketones, 606–607

β-Hydroxy KetoneVia Aldol Reaction

Aldehydes with Ketones, 74, 572–574, 627Heterobimetallic Catalyst, 74, 572–574

Via Ene Reaction, 478Via Morita–Baylis–Hillman Reaction, 69Via Mukaiyama Aldol Reaction

Trichlorosilyl Enolates, 48α-Benzyloxyaldehyde with Enol Ethers, 35–38,

442–444α-Hydroxy Ketones, Synthesis of, 249–250β-Hydroxy Nitro, Via Henry Reaction, 479α-Hydroxylation, 53

In a Multistep Reaction, 474Proline Catalyst, 474Regioselection, 606–607

β-Hydroxy Carbonyls, Synthesis of, 364–366β-Hydroxy Ketones, Synthesis of, from Direct Aldol,

364–366Hydroxylation, of C–H Bonds, 301–302Hypercages, in Zeolites, 529Hyperconjugation, 560Hypercoordinate Silicon, in Allylation of Aldehydes,

352–355Hypervalent Aluminum, in Diels–Alder, 362–364Hypervalent Silicon, 46–50

Ii, Center of Symmetry, 596Imidazolidine, Michael Reaction, in a Multistep

Reaction, 471–472Imidazolidinone

Aldehyde α-Allylation, 55–56

652 Index

Hydrogenation (cont.)

18_index.qxp 6/30/08 12:02 PM Page 652

Aldehyde α-Chlorination, 53Aldehyde α-Fluorination, 482–483Diels–Alder Reaction, 56–58Enamine Catalysis, 53, 482–483Friedel–Crafts Reaction, 472–473Iminium Catalysis, 56–58, 482–483In a Multistep Reaction, 472–473, 482–483SOMO Catalysis, 55–56Transfer Hydrogenation, 482–483

IminesAlkylation, 1,5-Diastereoselection, 435N-Acyl

Diazoester Addition, 69–70Silyl Ketene Acetal Addition, 68

β-Lactam Synthesis, 409–413Reduction, 126–127

Iminium Catalysis, 56–58, 79–80, 81–82, 471–473,482–483

Immobilized Catalysts, 498–543Imprinted Catalysts, 107Inclusion Complexes, 107Indentical Catalysts, Dual Catalysts, 404Independent Bifunctional Catalysts, 376

Aldol, 386–387Allylation, 401–403Charge–Charge Interactions, 386–387Hydrocyanation of Aldehydes, 387–388Hydrocyanation of Ketones, 388–390Salen Derivatives, Additions to α-Ketoester,

390–392Indirect Activation

Lewis Acid Catalysis, 39–45Lewis Base Catalysis, 56–61

Indium, in Bifunctional Catalysis, [2+2]Cycloadditions, 411–412

Industrial-Scale Synthesis, vi–vii, 550–553β-Iodohydrin, Synthesis of, 299–300Inorganic Supports, 497

Alumina, 497Silica, 497Zeolites, 497–498

Inositol, Desymmetrization, 621–622Interdependent Bifunctional Catalysts, 378–382Intermolecular Associations, in Solution, 332Internal Stereocontrol, 428, 429–435, 436, 475Intrinsic Selectivity, 26Inversion at Phosphorus, in Phosphines, 290Inversion Temperature, 12Ion Exchange, with Layered Double Hydroxides,

526Ion Exchange Resins, as Catalyst Supports, 524–526Ionic Interactions, in Supported Catalysts, 524Ionic Radius, Impact on ee, in Lanthanide-Based

Catalysts, 417Ionomycin, Fragment Synthesis, Via

Desymmetrization, 308–309Ion-Pair Mediated Reactions, 184–187Ion-Pairing Catalysis, 77–82

Anion, 79–81Cation, 72–73,77–79

General Schematic, 77In Phase-Transfer Catalysis, 184–187

Ion-Pairing, Aldol Reaction, 179–183Iridium Catalysts

[2+2+2] Cycloaddition, 105–1061,3-Dipolar Cycloaddition, 168DuPHOS Complex, 105–106Hydrogenation, 551Large-Scale, 551Phosphino-Oxazoline Complex, 551

IsomerizationAllylamine to Enamine, 433, 552Large-Scale, 552Of Meso Epoxides, Nonlinear Effects, 349–352Substrate Directed, 433

Isosparteine, Epoxide Rearrangement, 75Iterative Processes; see Sequential Processes

Definition; see Multistep Asymmetric Catalysis, 456

JJahn–Teller Distortion, Copper(II), 120, 341JOSIPHOS, 593

Anhydride Desymmetrization, 621–622Enamide Hydrogenation, 444–445Palladium Complex, 619, 621–622Rhodium Complex, 444–445Suzuki Coupling, 619

K(+)-K[Co(EDTA)], 586Ketenes

Alcoholysis, 54, 72–73[2+2] Cycloaddition, 409–413, 485–486, 552From Acid Chlorides, 54–55, 485–486

β-Ketoester, Via C-Acylation of Silyl Ketene Acetals,4

β-Ketoesters, Reduction of, with SupportedCatalysts, 532–533

KetonesAlkylation, Diastereoselection, 429α-Amination, Regioselection, 606–607α-Chiral, Additions, 430β-Chiral, Additions, 429–431Hajos–Parrish–Ender–Sauer–Wiechert Reaction, 52,

67, 392–393α-Hydroxylation, Regioselection, 606–607Reduction; see Reduction, KetonesVia Asymmetric Protonation, 50Via Kinetic Resolution, 26–27Via Oxidation, 26–27

Ketones vs. Aldehydes, Binding to Lewis Acids, 389

Kinetic Isotope EffectsAldol Reaction, 418Anhydride Methanolysis, 76C–H Hydroxylation, 303C–H Insertion, 90

Kinetic Resolution, 20–22, 232–253, 563–564Additional Stereocenter Generation, 242–249,

625–627

Index 653

Imidazolidinone (cont.)

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Alcohol Acylation, Enantiotopic GroupDifferentiation, 612

Aldol Reaction, 572–574, 627Alkene Metathesis, 90Atropisomer Generation, 616Basic Concepts, 232Benzylic Alcohol Oxidation, 26–27Bifunctional Catalysts, 404C–H Insertion, 441–442Chiral Nanoparticles, 515–516Conversion vs. ee, Graph, 233Desymmetrization, 309–310, 320–321Dihydroxylation, 247–249Double Diastereoselection, 441–442Dynamic; see Dynamic Kinetic ResolutionEnergy Diagram, 233Epoxidation, 599–600, 625–626Epoxide Opening, 557–558Generating No New Stereocenters, 234Mathematical Description, 232–233Multistep Asymmetric Catalysis, 487–490Of Alcohols

Mechanism, 236With Planar Chiral Catalysts, 234–235

Of Allylic AlcoholsEpoxidation, 312–313Via Hydrogenation, 195

Of Allylic Epoxides, Via Ring Opening, 266–267Of Amines, with Planar Chiral Catalysts, 236–237Of Anhydrides, 76–77Of Butenolides, 287–288Of Enol–Ester Epoxides, 249–250Of Epoxides

With (Salen)CoX Catalysts, 237–240With Supported Catalysts, 501–530

Of β-Ketoester, 273Of Mixtures of Diastereomers, 250–252Of N-Carboxyanhydrides, 278Of Propargylic Alcohols, 56–57Parallel; see Parallel Kinetic ResolutionPlanar Chiral DMAP Analogs, 56–57Reaction Coordinate Diagrams, 21(Salen)CoX, Bifunctional Catalysts, Impact of X, 404Stereoselective vs. Stereospecific, 603

Knipholone, 587Knowles, William S., vkrel, 232, 256

Intrinsic, 26Kumada Coupling, 320–321

Atropisomer, 615Axial Chirality, 615Desymmetrization, 615Enantiotopic Group Differentiation, 613, 615Palladium Catalyst, 613, 615

Lλ, 584–585Λ, 584–585β-Lactams

Dual Supported Catalysts, 541–543

Supported Catalysts, 535–536Synthesis of, 54–55, 409–410, 485–486, 554–555Via [2+2] Cycloaddition, 54–55, 485–486

β-Lactone, Via [2+2] Cycloaddition, 552Lactones, Synthesis by C–H Insertions, 304–306Lanthanide Contraction, 415

Impact on ee, 417Lanthanides

Common Coordination Number, 413Conjugate Addition of Cyanide, to Unsaturated

Imides, 405–406Lewis Acids, 206–207Multifunctional Catalysts, 413–422Oxidation State, 413

Large-Scale Synthesis, vi–vii, 550–553Layered Double Hydroxides, as Supports, for

Osmium, 526LDA, Epoxides Isomerization, 73–74, 349–352Le Châtelier’s Principle, 23, 613Leaching, in Polymer Supports, 532Leukocyte Elastase, Synthesis of Inhibitor,

β-Lactams, 411Lewis Acid, Ligand Complexation, 19Lewis Acid Catalysis, 4, 32–45

Activation Via a Conjugated System (IndirectActivation)

One-Point Binding, 39–42Two-Point Binding, 43–45

Chiral Modifying Ligand, 32–33Coordination Modes, 40–42Direct Activation

One-Point Binding, 34–35Two-Point Binding, 35–39

LUMO Orbital Energies, 33, 34, 40Substrate Activation, 33

Lewis Acid–Brønsted Base Catalysts, Bifunctional Catalysts, Aldol, 386–387

Lewis Base Catalysis, 45–61Activation Modes, 45–46Activation Via a Conjugated System (Indirect

Activation), 56–58, 79–80, 81–82Acyl Activation, 56–57Allylation, 352–355Covalent Activation, 45–46, 51–61Derived from Peptides, 310Desymmetrization of Meso Diols, 309–310Electrophile Activation, 4, 56–58Enamine Activation, 52, 53–56, 67, 471–474, 482–483Iminium Activation, 56–58, 79–80, 81–82, 471–473,

482–483Noncovalent, 45–46, 46–51Nucleophile Activation, 53–55Oxidative Activation, 55–56Phosphine, 260–262Silicon Activation, 46–50Umpolung, 58–61

Lewis Base–Lewis Base Catalysis, BifunctionalCatalysts, 407–408

LigandAchiral, 215–216

654 Index

Kinetic Resolution (cont.)

18_index.qxp 6/30/08 12:02 PM Page 654

Amino Acid, 1762-Naphthol Oxidation, 536–538

Amino Alcohol, 170–175CBS Ketone Reduction, 379–381Dialkylzinc Reagents, 381–382Nonlinear Effects, 343–347

β-Amino Alcohol, in Aldehyde Alkylation, 2–4,7–8, 469–471, 600

Amino Phosphine, Cross-Coupling, 320–321Anilino Oxazoline

Chromium Catalyst, 450–452Nozaki–Hiyama–Kishi Reaction, 450–452

Atropisomeric, 154BIPHEN, 214

Atropisomeric Conformations, 151Amides, 155Induced Axial Chirality, 151–156

Azadiene, Asymmetric Metal Complexation, 618BBMPP

Enamide Hydrogenation, 11Rhodium Complex, 11

BINAP, 123–125, 273–278, 319–320, 579Allylation of Aldehydes, 572–573Conjugate Addition, 465–466, 489–490[5+2] Cycloaddition, 105Desymmetrization, 307–308Heck Reaction, 98, 318, 566–567Hydrogenation, 480–481, 551, 560–561, 568–569,

605, 626–627Hydrometallation, 103Isomerization, 433, 552Ketone Reduction, 203–205, 382–386, 520–521Kinetic Resolution, 250–252Metal–Organic Coordination Networks, 517–519Palladium Complex, 95, 98,103, 566–567, 616–617Parallel Kinetic Resolution, 263π-Allylation, 103, 616–617Rhodium Complex, 105, 433, 465–466, 480–481,

489–490, 552Ruthenium Complex, 551, 560–561, 568–569, 605,

626–627Silver Complex, 572–573Soluble Polymeric Supports, 513–515Supported Hydrogenations, 508–509, 538–540Wacker Reaction, 95

BINAPHOS, Rhodium Complex, 99–100, 553Binaphthyl Bisoxazoline; see BisoxazolineBINAPO, 150

π-Allylation, 555Binding of Diastereotopic Groups, 142BINOL

Aldehyde Alkylation, 335–336, 538–540Aldol Reaction, 73–74, 572–574Axial Chirality, 587Bifunctional, 387–388Conjugate Addition, 559Diels–Alder Reaction, 347–348, 629–630Ene Reaction, 34, 478, 552, 199–200, 306Epoxide Rearrangements, 249–250Henry Reaction, 479

Heterobimetallic Catalyst, 73–74, 413–422,463–465, 479, 553, 558–559, 572–574, 584–585

Hydrocyanation, 479, 558–559λ vs. δ Arrangement, 584–585Lanthanide Catalysts, 206–207Metal–Organic Coordination Networks, 519–520Michael Reaction, 463–465, 553Morita–Baylis–Hillman Reaction, 399–400Mukaiyama Aldol Reaction, 37–38Nitroaldol Reaction, 479pKa, 67Racemization, 123Titanium Complex, 34, 37–38, 306, 335–336, 478,

552Ytterbium Complex, 629–630

BINOL Derivatives3,3’-Ar, 91Aldehyde Alkylation, 480Aluminum Complex, 32, 558–559Bifunctional Catalyst, 558–559Hetero-Diels–Alder Reaction, 480Lewis Acid From, 32Metathesis, 90–91Molybdenum Catalyst, 90–91Silylcyanation, 558–559With Pendent Groups, 558–559Zinc Catalyst, 480

BINOL Phosphoramidite, 459–460, 464–465,467–468

BINOLate, (BINOL dianion); see BINOLBIPHEN, 210Biphenyl-Based, 151–154BIPHEP, 210–216

Copper Complex, 51Ketone Reduction, 51

BIPHEPHOSEnamide Hydrogenation, 458–459Rhodium Complex, 458–459

Bipyridine Derivatives, 225–226Bisimine, Zinc Catalyst, 480BISOX, 582–583Bisoxazoline

α-Amination, 468–469Binaphthyl, 96, 460–461Conjugate Addition, 468–469Copper Complex, 6, 38–39, 44, 439–444, 462,

468–469, 481–482, 487, 606, 625–626, 629–631Cyclopropanation, 481–482Diels–Alder Reaction, 44, 439–441, 629–630Hetero-Diels–Alder Reaction, 38–39, 462, 487,

625–626Mukaiyama Aldol Reaction, 6, 442–444, 606, 631Palladium Complex, 96, 460–461Spiro, 96

BisphosphineAllylation, 291–293Bifunctional, 386–387BPPM (Pyrrolidine-Based), 503–504Dynamic Kinetic Asymmetric Transformation, 288PPM (Pyrrolidine-Based), 503–504

Index 655

Ligand (cont.)

18_index.qxp 6/30/08 12:02 PM Page 655

Bisphosphoramidates, 353–354Bispidine, Asymmetric Deprotonation, 75Bite Angle, in Phosphines, 322Box; see BisoxazolineBOXAX; see Bisoxazoline, BinaphthylBPPM

Enamide Hydrogenation, 11Rhodium Complex, 11

C3-Symmetric, Amino Alcohol, 298–300CAMP

P-Chirogenic Phosphines, 582Phorphorus Stereocenter, 129

Carbohydrate Derived, in Bifunctional Catalysts,389–390

Carboxamidates, in Cyclopropanation, 256–257Chiral Conformations, 205Chiral Relays, 147–148Chiraphos

Enamide Hydrogenation, 11, 26, 99Rhodium Complex, 11, 26, 99

Cinchona Alkaloids, 247–248Osmium Complex, 19–20, 83, 445–446, 475–477,

481–482, 552, 559–560, 565–566, 605, 616,628–629

Platinum Catalyst, 551Configurationally Dynamic, 147Coordination of Diastereotopic Lone Pairs, 140Cycphos

Enamide Hydrogenation, 11Rhodium Complex, 11

DAIB, 381–382Aldehyde Alkylation, 2–4, 7–8Nonlinear Effects, 343–347Zinc Complex, 7

DAIPENHydrogenation, 560–561Ruthenium Complex, 560–561

(DHQ)2PHAL; see Dihydroxylation(DHQD)2PHAL; see DihydroxylationDiamine, 140, 533–535

Achiral, 216–218DINAM, 195DPEN, 210–216Hydrogenation, 506–508Isomerization of Meso Epoxides, 349–352Ketone Reduction, 382–386Metal–Organic Coordination Networks, 517–519Nanoparticle Supported Hydrogenations,

508–509Diaza–cis-decalin, Copper Complex, 484–485, 562,

614–615Diimine, Achiral, 216–218Diimines, in Aziridination, 156–157Diisopropyl Tartrate, 312

Sharpless–Katsuki Asymmetric Epoxidation,242–246

DIOP, 129, 314–316Alkene Hydrogenation, 524Enamide Hydrogenation, 11Rhodium Complex, 11

DioxopEnamide Hydrogenation, 11Rhodium Complex, 11

DIPAMPEnamide Hydrogenation, viiP-Chirogenic Phosphines, 582Rhodium Complex, vii

Dipodal, 401–403DOSP, Rhodium Complex, 89–90, 441–442,

449–450, 564–565, 619–621, 619–621DPEN, in Ketone Reduction, 201–204DPPBA

Palladium Complex, 21–24, 101–103, 552–554,561, 571–572

π-Allylation, 23–24, 101–103, 552–554, 561, 571–572DuPHOS, 262–264, 532–533

[2+2+2] Cycloaddition, 105–106[4+1] Cycloaddition, 104Hydrogenation, 435–436, 457–459, 551, 602, 623Iridium Catalyst, 105–106Phosphine Synthesis, 288–290Rhodium Catalyst, 104, 435–436, 457–459, 551,

602, 623With Anion Capture Support, 527–529

EBTHIDiels–Alder Reaction, 15–16Planar Chirality, 589–590Titanium Complex, 15–16, 589–590

Edge-Face Interactions, 130, 144EDTA, Cobalt Complex, 586Eniphos, Rhodium Complex, 551Ferrocene-Based Ligands, Bifunctional, 386–387Ferrocene, Planar Chiral, 284–286Ferrocenyl Phosphine

Kumada Reaction, 613Planar Chirality, 579Suzuki Reaction, 92–93, 619

Fluxional, 147HELOL, Zinc Complex, 589JOSIPHOS, 593

Anhydride Desymmetrization, 621–622Enamide Hydrogenation, 444–445Palladium Complex, 619, 621–622Rhodium Complex, 444–445Suzuki Coupling, 619

Meso, 215–216Methylene Bis(Phenol), 220MIB

In Nonlinear Effects, 343–347Zinc Catalyst, 469–471

P/N Ligands, Desymmetrization, 307PHANEPHOS, 589–590Phelix, Rhodium Complex, 589Phephos, in Desymmetrization, 320–321Phosphine Ligands, Enamide Hydrogenation, 11Phosphoramidates, Allylation of Aldehydes,

352–355Phosphoramidite

Allylic Substitution, 459–460Conjugate Addition, 464–465, 468

656 Index

Ligand (cont.)

18_index.qxp 6/30/08 12:02 PM Page 656

Copper Catalyst, 459–460, 464–465Kinetic Resolution, 266

Phox; see Phosphino OxazolinePlanar Chiral Ferrocene, 307–308Privileged Structures, 123, 237Proline Derivative

Aldol Reaction, 364–366Cyclopropanation, 258–259

ProphosEnamide Hydrogenation, 11

Rhodium Complex, 11PyBox; see Pyridine bisoxazolinePyridine Bisoxazoline

Copper Catalyst, 18, 35–38, 442–444, 601,624–625, 631

Diels–Alder Reaction, 18, 44–45Friedel–Crafts Reaction, 45Gadolinium Complex, 44–45Mukaiyama Aldol Reaction, 35–38, 340, 442–444,

601, 606, 624–625, 631Scandium Complex, 45Tin Complex, 606, 631

QUINAPDiboration, 460–461Rhodium Complex, 460–461

SalenAlkylation, 607Bifunctional Catalyst, 404, 607Bifunctional Ni,Cs Catalyst, 9–10C–H Hydroxylation, 301–302Chromium Complex, 448–449, 557–558Cobalt Complex, 552, 557–558Dynamic Kinetic Resolution, 284Epoxidation, 84, 86–87, 505–506, 552, 569–571Epoxide Opening, 237–240, 300, 311–312,

448–449, 552, 557–558Hetero-Diels–Alder Reaction, 557–558Manganese Catalyst, 84, 86–87, 552, 569–571Michael Reaction, 9–10Nonlinear Effects, 338–339Titanium Catalyst, 607

Salen Derivatives, with Pendent Bases, 390–392Schiff Base

Chromium Complex, 34–35, 41, 447–448, 556–557

Conjugate Addition, 467–468Copper Complex, vii, 467–468Cyclopropanation, viiDiels–Alder Reaction, 41Hetero-Diels–Alder Reaction, 34–35, 556–557

SEGPHOSConjugate Addition, 616–617Cycloisomerization, 611Formation of Axial Chiral Allenes, 616–617Hydrometallation, 103Palladium Complex, 103, 611Rhodium Complex, 616–617

Semicorrin, 118Siam, S-Chirogenicity, 582–583SILOP, Bisphosphine, 316

SparteineAlkyl Lithium Adduct, 17, 75–76Alkylation of Aldehydes, 17Deprotonation, 75–76Grignard Adduct, 17Kinetic Resolution, 26–27Oxidation of Alcohols, 26–27Palladium Complex, 26–27, 628Wacker Reaction, 628

Spiro Bisoxazoline; see BisoxazolineStereodynamic, Dihydropyrazole, 147–148Sugar-Based Diphosphite, in Allylation, 515–516Sulfoxides, in Cyclopropanation, 224Sulfoximines, 582TADDOL, 135–140

Diels–Alder Reaction, 43, 68–69Hetero-Diels–Alder Reaction, 68–69pKa, 67Titanium Complex, 43

TADDOLate, (TADDOL dianion); see TADDOLTartrate, 592, 625–626

Sharpless–Katsuki Epoxidation, vii, 84–85, 433,552, 562–564, 569–571, 599–600, 625–626

Sulfide Oxidation, 552, 609Titanium Complex, vii, 84–85, 433, 552, 562–564,

569–571, 599–600, 609, 625–626TBoxH, Chromium Catalyst, 624Tetrapodal, 401–403TMBTP, Bis(Phosphine), 525Trialkanolamine, 298–300Tunephos, 275VAPOL, in Diels–Alder, 362–364Vaulted Biaryl

Aluminum Complex, 41Diels–Alder Reaction, 41

Ligand-Accelerated Catalysis, 2, 17, 20, 32–33, 51, 83

Ligand Complexation, 19Ligand-Deccelerated Catalysis, 17–19, 32–33, 51Linked Catalysts; see Tethered CatalystsLipase, 260, 283

Dynamic Kinetic Resolution, in a MultistepReaction, 488–489

Supported, 281Lithium Catalysts, 73–76

Heterobimetallic, 413–422Isomerization of Meso Epoxides, 349–352

Lithium Enolate, Asymmetric Protonation, 50, 70–71

MM, Axial chirality, 587M, Helical chirality, 589M, Planar chirality, 590Manganese Catalysts

C–H Hydroxylations, 301–302Cryptophycin Synthesis 52, 569–571Epoxidation, 84, 86–87, 552, 569–571Epoxidation, Inside Zeolites, 529–531Epoxidation, on Mesoporous Silica, 505–506

Index 657

Ligand (cont.)

18_index.qxp 6/30/08 12:02 PM Page 657

Large-Scale, 552Salen Complexes, 84, 86–87, 552, 569–571

Mannich ReactionIn a Multistep Reaction, 473–474N-Boc Imine, 68Proline Catalyst, 473–474, 608Silyl Ketene Acetal, 68Thiourea Catalyst, 68Vs. Aldol Reaction, Chemoselection, 607–608

Mannostatin, Synthesis of, Via Allylation, 324Matched, 428, 434, 436–450MCM-41, Mesoporous Silica, 505–506MCM-41 Support, with Anion Capture, 527–529Measurement of Nonlinear Effects, 337–338

Common Mistakes, 337–338Mechanism

Alcohol AcylationKinetic Resolution, 57Planar Chiral DMAP Analogs, 57, 72

Alcohol OxidationKinetic Resolution, 27Palladium Catalysts, 27

Aldehyde Alkylation, 3, 8, 336, 343–347, 381–382Catalyzed by Phosphoramidates, 353In a Multistep Process, 474

Aldehyde Hydrocyanation, with DipeptideCatalyst, 67

Aldol ReactionGold Catalyzed, 181–182, 386–387Heterobimetallic Catalyst, 74, 420In a Multistep Process, 472Proline Catalyzed, 9, 395–396

AldolaseType I, 377–378Type II, 377–378

Alkene Metathesis, 91α-Allylation, Via Enamine, 56α-Amination of Aldehydes, Proline Catalyzed,

395–396Anhydride Alcoholysis, Parallel Kinetic

Resolution, 266Asymmetric Deprotonation

Epoxides, 74–75N-Boc Pyrrolidine, 75

Asymmetric Protonation, 50, 71, 72Autocatalysis, 357–360Autoinduction

Generic, 361In Diels–Alder, 362–364

Aza-Morita–Baylis–Hillman Reaction, 400Back Bonding, 94Benzannulation, 604Biaryl Formation, 604, 614–615Bifunctional Catalysis, Gold Catalyst, 181–182Bifunctional Catalysts, Additions to α-Ketoester,

390–392Brønsted Acid Catalysis, 72Brook Rearrangement, 61C-Acylation, with Planar Chiral DMAP Analogs,

4

Carboxy Anhydride Alcoholysis, HydrogenBonding, 76

CBS Reduction of Ketones, 380–381C–H Activation/Cope Rearrangement, 259C–H Hydroxylation, 301, 303C–H Insertion, 303–304

Rhodium Carbenoid, 89α-Chelation Control, 430β-Chelation Control, 431Chirality Exchange, 604α-Chlorination, Via Enamine, 53Conjugate Addition

Heterobimetallic Catalysts, 421In a Multistep Process, 473, 483PTC, 79Via Enamine, 53Via Umpolung, 61

Counterion Catalysis, 80–81Cross-Coupling, 93, 614–615

With DKR, 284–286Curtin–Hammett, 26, 99[2+2] Cycloaddition, 55

In a Multistep Process, 486[2+2+2] Cycloaddition, 106[4+1] Cycloaddition, 104[5+2] Cycloaddition, 105Cycloisomerization, 104–105, 252, 612

Counterion Catalysis, 81Gold Catalyzed, 81

CyclopropanationDirected, 432With an Ylide, 82

Decarboxylative Allylation, 24Deprotonation, 75Desymmetrization, Oxabicyclic Alkenes, 308Diels–Alder Reaction

Stereotransfer, 626Via Enamine, 54Via Iminium, 58

Dihydroxylation, 19, 84Dioxirane, 881,3-Dipolar Cycloaddition, 171Directed Electrostatic Activation, 82Dynamic Kinetic Asymmetric Transformation of

Butenolides, 287–288Dynamic Kinetic Resolution, with Proline, 398Electron Transfer, in Hydroxylation, 303Electrophile Activation, 57Electrophilic Alkene Activation, 95–97Enamide Hydrogenation, 26, 99Enamine Catalysis, 53–56, 474, 483Enamine Oxidation, 56Ene Reaction, 34

Two-Directional, 478Enolate Alkylation, PTC, 78, 610Epoxidation

Dioxirane, 88Directed, 432Manganese Salen, 87Titanium Catalyst, 85

658 Index

Manganese Catalysts (cont.)

18_index.qxp 6/30/08 12:02 PM Page 658

Epoxide Desymmetrization, by Azide, 299Epoxide Elimination, 74–75Epoxide Opening, with Nonlinear Effects, 338–339Felkin–Anh Addition, 430α-Fluorination, in a Multistep Process, 483Friedel–Crafts Reaction, in a Multistep Process,

473Glycine Imine Enolate Alkylation, PTC, 610Hajos–Parrish–Eder–Sauer–Weichert Reaction,

52Heck Reaction, 317Heterobimetallic Catalyst, 74Hetero-Diels–Alder Reaction, Hydrogen Bonding,

69Hydroacylation, 132, 263Hydrocyanation of Aldehydes, Bifunctional

Catalyst, 388Hydrocyanation of Ketones, with Bifunctional

Catalysts, 389–390Hydroformylation, 13, 100Hydrogenation

Counterion Catalysis, 80Transfer, 80

Hydrosilylation, 618Of Imines, 127Of Siloxydienes, 315

α-Hydroxylation, in a Multistep Process, 474Imine Alkylation, Hydrogen Bonding, 70Imine Formation, in a Multistep Process, 486Iminium Catalysis, 58, 82, 473, 483Intramolecular Cyclopropanation, 257Isomerization

Allyl Amine to Enamine, 433Of Meso Epoxides, 351–351

Ketene Alcoholysis, 72Ketolactone Reduction, 277Ketone Reduction, 385

Directed, 434α-Ketoester Alkylation, 607Kinetic Resolution, Alcohol Acylation, 57Kumada Coupling, 615β-Lactam Cleavage, in a Multistep Process, 486β-Lactam Formation, in a Multistep Process, 486Lewis Acid Assisted Brønsted Acid, 72Lewis Base/Indium (LA), [2+2] Cycloadditions,

411–412Mannich Reaction, Proline Catalyzed, 395–396Metathesis, 91Michael Reaction, in a Multistep Process, 472Morita–Baylis–Hillman Reaction, 399

Hydrogen Bonding, 69Mukaiyama Aldol Reaction, 37, 178, 341

Stereotransfer, 444, 606, 625With Silicon Tetrachloride, 50With Trichlorosilyl Enolate, 48

N-Acyl Intermediate, Planar Chiral DMAP Analog,57, 72

Nitroaldol Reaction, 416Nucleophilic Catalyst, β-Lactam Synthesis, 410Oxidative Biaryl Coupling, 615

α-Oxyamination of Aldehydes, Proline Catalyzed,395–396

Phase-Transfer Catalysis, 78–79, 185, 610Phosphination, 290π-Allylation, 101–103

Desymmetrization, 322Dynamic Kinetic Asymmetric Transformation,

23, 102Kinetic Resolution, 22Selective Enantiotopic Face Coordination, 102Via Hydrometallation, 103

π-Coordination, 94Pinacol Coupling, 624Platinum-Cinchonidine-Catalyzed Hydrogenation,

524Polycyclization, 72Probing with Nonlinear Effects, 349–352Proline Catalyzed, 395–396Proline/Peptide Dual Catalyst System, 409Racemization of Alcohols, Ruthenium Catalyzed,

281Racemization of N-Carboxyanhydrides, 279Remote Stereocontrol, 434Rhodium Carbenoid, 89Ring-Closing Metathesis, 241Sharpless–Katsuki Epoxidation, 85, 243SOMO Catalysis, 56Spirane Formation, 6181,7-Stereocontrol, 434Stetter Reaction, 59Suzuki Reaction, 93, 614Termolecular Ring-Opening, of

Carboxyanhydrides, 278Transfer Hydrogenation, 80, 172

In a Multistep Process, 483Umpolung, 61, 70Wacker Reaction, 95–97Zinc-Catalyzed Hydrosilylation of Ketones, 141

Mechanism Shift, 11–13Melting Point, Racemate vs. Enantioenriched, 331Membrane-Encapsulated Catalysts, in

Hydrogenation, 532–533Menthol, Synthesis of, 433Mercury, Test for Colloids, 515–516Meso, Definition, 592Meso Enediol Ester, in Allylation, in

Desymmetrization, 321–322Metal Alkoxides, in Bifunctional Catalysis, 378–382Metal Carbenoids, in C–H Insertions, 303–306Metal Chirality, 139, 149, 583–586

Asymmetric Catalysis, 585–586Heterobimetallic Catalysts, 413–422Iridium, 169Rhodium, 169Titanium, 139

Metal Complexation, Asymmetric, 618Metal Complexes, Chiral, from Chiral Ligands, 118Metal Geometries

Changes in, 387–388Octahedral, 583

Index 659

Mechanism (cont.)

18_index.qxp 6/30/08 12:02 PM Page 659

Square Pyramidal, 583Tetrahedral, 583Trigonal Bipyramidal, 583

Metal Geometry-Induced Ligand Asymmetry,219–223

Metal Oxo, in Hydroxylations, 301Metallocene Catalysts, Asymmetric Induction with,

126Metallocenes, in Hydrosilylation of Imines, Kinetic

Resolution, 246–248Metal–Organic Coordination Networks, as

Supported Catalysts, 516–521Metal–Organic Coordination Polymers, in Ketone

Reduction, 520–521Metals, Centrochirality, 583–586Metathesis, Alkene

Desymmetrization, 90–91, 553In a Multistep Reaction, 90, 459–460, 467–468Kinetic Resolution, 90, 240–242Large-Scale Reaction, 553Molybdenum Catalysts, 90–91Ruthenium Catalysts, 90–91Supported Catalysts, 512–513Tungsten Catalysts, 90

Methods for HeterogenizationMethylene Bis(Phenol)

Geometry-Induced Ligand Acceleration, 220Isomerization, 220

MIB, Zinc Catalyst, Aldehyde Alkylation, 469–471Michael Reaction

Bifunctional Ni,Cs Catalyst, 9–10Carbene Catalyst, 58Glycine-Imine Enolates, 78Heterobimetallic Al,Li Catalyst, 463–464, 553Imidazolidine Catalyst, 471–472In a Multistep Reaction, 463–464, 471–472,

482–483Ketones, 207–209Large-Scale Reaction, 553Nitroalkanes, 207–209

Microencapsulated Catalysts, 529–531Microenvironment Modification, 107Mismatched, 428, 434, 436–450ML2, Nonlinear Effects, 340–343Molecular Sieves, as Solid Supports, 506–508Molybdenum Catalysts

BINOL Derivative Complex, 90–91Biphenol Complex, 553Large-Scale Reaction, 553Metathesis, 90–91, 553Ring-Closing Metathesis, 240–242, 512–513

Monodentate PhosphineIn Hydrosilylation, 321Synthesis of, Via DKR, 321

Morita–Baylis–Hillman Reaction, 399, 407–408BINOL Derivative Catalyst, 68–69

Muconin, 557–558Mukaiyama Aldol Reaction; see Aldol ReactionMultifunctional Catalysis, 81–82, 107

Henry Reaction, 416–417

Mukaiyama Aldol Reaction, 413–421Nitroaldol, 416–417

Multiple Catalysts, on One Support, 538–541Multistep Asymmetric Catalysis, 456–491

Asymmetric Catalysis in First Step, 457–461Asymmetric Catalysis in Later Step, 461–62Asymmetric Catalysis in Several Steps, 484–487Dynamic Kinetic Resolution, 488–489Independent Enantioselective Reactions,

475–483Kinetic Resolution, 487Parallel Kinetic Resolution, 489–490Stereochemistry in Several Steps, 462–475

Multistep Processes, Definition; see MultistepAsymmetric Catalysis

NN,N-Diethylgeranylamine, Synthesis of, 433NADH Mimic, Transfer Hydrogenation, 80Nanoparticles

As Supports, 508–509Chiral Palladium, in Allylation, 515–516Heck Reaction, 540–541

Naphthoquinones, Diels–Alder Reaction, 41, 44Naphthylisoquinoline Alkaloid, 593Naproxen

Synthesis of, 25With Supported Catalysts, 513–515

Natural Product Synthesis, Via Desymmetrization,323–325

Nazarov Reaction, 73N-Chirogenicity, 581Negative Nonlinear Effects; see Nonlinear EffectsNexium, Synthesis of, 582, 609Nickel Catalysts

BINAP, 307–308Conjugate Additions to Enones, 506–508

Nitrene, Aziridination, 156–157Nitroaldol

Heterobimetallic Catalysts, 416–417In a Multistep Reaction, Heterobimetallic Catalyst,

479Nitrogen, Centrochirality, 581Nitrogen Inversion, 147, 157Nitronate, in the Nitroaldol, 416NMR

15N, in Isomerization of Meso Epoxides, 3516Li, in Isomerization of Meso Epoxides, 351Observation of Diastereomeric Interactions, 332

Nobel Prize, vNoncovalent Interactions, in Supported Catalysts,

522–533Nonlinear Effects, 194, 197, 335–357

Absolute Asymmetric Synthesis, 360–361Aldehyde Alkylation, 343–347Aldehyde Allylation, 352–355

Phosphoramidates, 352–355Aldehyde Hydrocyanation, 368Aldol Reaction, 365α-Aminoxylation, 355–357

660 Index

Metal Geometries (cont.)

18_index.qxp 6/30/08 12:02 PM Page 660

Autocatalysis, 357–360Benefits of, 337(BINOLate)Ti Catalysts, 335–336Catalyst Preparation Dependency, 347–348Desymmetrization of Epoxides, 338–339Determination of, 337–338Epoxide Opening, 338–339Epoxide Opening, Energy Diagrams, 339False Positive, 338, 349Hajos–Parrish–Eder–Sauer–Wiechert Reaction, 393Heterogeneous Mixtures, 355–357Hexose Formation, with Proline, 397Homochirality Origin, 360–361Hydrocyanation, 368Isomerization of Meso Epoxides, 349–352Lewis Base Catalysis, Allylation of Aldehydes,

352–355Mechanistic Probes, 335–339, 349–354Mukaiyama Aldol Reaction, 342Negative

Definition, 337With (BINOLate)Ti, 335–336

Origins of, 337–338Phase Behavior, 355–357Positive, Definition, 337Precipitation, 349Proline, in Hexose Formation, 397Reservoir Effect, (ML)2, 343–347Reservoir Effect, ML2, 340–343Salen–Chromium Catalysts, 338–339Second-Order in Catalyst, 338–339Solubility Problems, 338, 349, 355–357Substrate Dependence, 346–347

Noyori, Ryoji, vNozaki–Hiyama–Kishi Reaction

Double Diastereoselection, 450–452Triple Diastereoselection, 450–452

Nucleophile Activation, 53–55Nucleophile Trajectory, 119Nucleophiles, in Allylation, 325Nucleophilic Catalysis; see Lewis Base Catalysis vs.

Brønsted Acid Catalysis, 72–73Aldehydes, 216, 218

Achiral Ligands, 215–216Autocatalysis, 197BINOLate Ligands, 217–219Chiral Activation, 205Relative Rates, 218–219

OOlean, 580Olefin Metathesis; see MetathesisOlive Fruit Fly Pheromone; see OleanOmeprazole, Synthesis of; see PrilosecOne-Point Binding, Lewis Acid Catalysis, 34–35, 39–42Optical Purity, 591Optical Rotations

Importance of Polar Solvents, 332Substrates That Hydrogen Bond, 332–333

Organic Supports, 497

Organocatalysis, vSupported Catalysts, 535–536

Organocatalystsα-Amino Acid, Cyclopropanation, 81–82Azadiene, Metal Complexation, 618Binaphthalene-Derived Ammonium

Conjugate Addition, 79Enolate Alkylation, 79, 446–447PTC Catalysts, 79, 446–447

BINOL Derivative, Morita–Baylis–HillmanReaction, 69

BINOL Phosphoric AcidConjugate Addition, 80Counterion Catalysis, 80–81Cycloisomerization, 81Diazoester Nucleophile, 70Imine Addition, 70Transfer Hydrogenation, 80

BINOL-Phosphine Catalyst, in Aza-Morita–Baylis–Hillman Reaction, 401

BINOL-Pyridine Derivatives, inMorita–Baylis–Hillman Reaction, 399–400

CarbeneStetter Reaction, 59Umpolung Reaction, 59

Cinchona Alkaloids, 264–266Anhydride Alcoholysis, 76[2+2] Cycloaddition, 54, 485–486, 552Enolate Alkylation, 78, 581, 610, 613In a Multistep Reaction, 485–486Ion-Pair Catalysis, 78, 581, 610, 613Kinetic Resolution, 76Large-Scale, 552PTC Catalysis, 78, 581, 610, 613

DiamineAsymmetric Deprotonation, 75Asymmetric Protonation, 71Epoxide Elimination, 74Epoxide Rearrangement, 75

Diketopiperazine, Hydrocyanation, 67Dipeptide, Hydrocyanation, 67Epoxidation, Via Dioxirane, 87–88Fructose Derived, Epoxidation, 87–88, 569–571α-Hydroxy Acid, α-Amination, 606Imidazolidine

In a Multistep Reaction, 471–472Michael Reaction, 471–472

ImidazolidinoneAldehyde α-Allylation, 56Aldehyde α-Chlorination, 53Aldehyde α-Fluorination, 482–483Diels–Alder Reaction, 56–58Enamine Catalysis, 53, 482–483Friedel–Crafts Reaction, 472–473Iminium Catalysis, 56–58, 472–473, 482–483In a Multistep Reaction, 472–474, 482–483SOMO Catalysis, 56Transfer Hydrogenation, 482–483

Ketone, Dioxirane Epoxidation, 87–88, 569–571Nucleophilic Catalysts, 409–413

Index 661

Nonlinear Effects (cont.)

18_index.qxp 6/30/08 12:02 PM Page 661

PeptideAlcohol Acylation, 612Alcohol Phosphorylation, 621–622

Phosphine, Acylation of Alcohols, 260–262Phosphite

Brook Rearrangement, 60–61Umpolung Reaction, 60–61

Phosphoramides, Mukaiyama Aldol Reaction,48–49

ProlineAldol Reaction, 8–9, 392–398, 627Hajos–Parrish–Eder–Sauer–Weichert Reaction,

52, 67, 392–393α-Hydroxylation, 474In a Multistep Reaction, 472Mannich Reaction, 472–474, 608

Proline, Morita–Baylis–Hillman Reaction, 407–409Proline Derivatives, 207–208Pyrrolidine Derivative

Conjugate Addition, 53Hetero-Diels–Alder Reaction, 54

Synthesis of Cryptophycin 52, 569–571TADDOL

α-Amination, 606Diels–Alder Reaction, 68–69Hetero-Diels–Alder Reaction, 68–69

ThioureaImine Substrate, 68Mannich-Type Reaction, 68

Triamine, Enolate Protonation, 50Urea, Strecker Reaction, 611

Organometallic Catalysts, vOrganozinc Reagents, Reaction with Allylic

Epoxides, 266–267Osmium Catalysts, 247–249

Cinchona Alkaloid, 19–20, 83–84, 445–446, 475–477, 481–482, 552, 559–560, 565–566, 605, 616, 628–629

Dihydroxylation, 19–20, 83–84, 445–446, 475–477,481–482, 552, 559–560, 565–566, 605, 616,628–629

Large-Scale, 552Layered Double Hydroxides, 526Multistep Reaction, 475–477, 481–482Squalene, 565–566, 605Synthesis of Zaragozic Acid, 559–560

Oxazaborolidines, Ketone Reduction, 379–381Oxazaborolidinone, Supported on Polystyrene, in

Diels–Alder, 510–511Oxaziridines, 581Oxidation

AlcoholsDesymmetrization, 610Enantiotopic Group Differentiation, 610Ruthenium Catalyst, 610

Benzylic Alcohols, Palladium Catalyst, 26–27Kinetic Resolution, Palladium Catalyst, 26–27Sulfide

Large-Scale, 552, 609Titanium Catalyst, 552, 609

Oxidative Activation, 55–56, 484–485, 562, 614–615

Oxidative Biaryl CouplingAtropisomers, 484–485, 562, 614–615Complex Substrates, 562Enantiofacial Differentiation, 614–615In a Multistep Reaction, 484–485

Oxidative Coupling, of 2-Naphthol, 536–538Oxidative Cyclization, of Enynes, 215Oxindole, Via Heck Reaction, 98Oxygenation, Sulfides, Enantiotopic Group

Differentiation, 552, 609Oxypalladation, in a Multistep Reaction, 460–461

Pπ-Allylation, 116π–π Interactions, 70,76π-Allyl Complexes

Cationic, 100–103Via Hydrometallation, 103–104

π-Allyl Intermediates, 266–267, 288Heck Reaction, 318–319

π-Allylation, vii, 21–25C2-Symmetric Ligands, 116Decarboxylation, 24, 555Desymmetrization, 102Differentiation of Enantiotopic Termini, 100–102Double Diastereoselective, 571–572Dynamic Kinetic Asymmetric Transformation,

23–24, 101–102Enantiodiscrimination Mechanisms, 101–102Enantiotopic Facial Discrimination, 101–102From Styrenes, 103–104In a Multistep Reaction, 468–469Intramolecular, 102–103Kinetic Resolution, 21–23Large-Scale, 553–554Non-C2-Symmetric Ligands, 116Palladium Catalysts, 21–25, 100–103, 468–469,

553–554, 555, 561, 571–572, 616–617Selective Reaction of Enantiotopic Leaving Groups,

101–102Synthesis of Callipeltoside A Synthesis, 571–572Synthesis of Sphingofungin E Synthesis, 561Synthesis of Strychnine Synthesis, 555To Alkylidene Cyclohexanes, 616–617Via Hydrometallation, 103–104η2-Coordination, 100–103π–σ–π Interconversion, 116π-Activation, 100–103

π-Benzyl ComplexesCationic, 103–104Via Hydrometallation, 103–104

π-CoordinationActivation, 93–107Back Bonding, 93–94Double η2, 105–107Orbital Interactions, 93–94η2, 94–100η3, 100–104

662 Index

Organocatalysts (cont.)

18_index.qxp 6/30/08 12:02 PM Page 662

η4, 104–105η5, 104η6, 93–94, 104

π–π Interactions, 166P, Axial chirality, 587P, Helical chirality, 589P, Planar chirality, 590Palladium Catalysts, 123

Alcohol Oxidation, 26–27Anhydride Desymmetrization, 621–622Apparent DKR, 24BINAP Complex, 94–95, 103, 566–567, 616–617Binaphthyl Bisoxazoline Complex, 96BINAPO Complex, 555BOXAX Complex, 460–461Callipeltoside A Synthesis, 571–572Complex Substrates, 566–567Cross-Coupling, 92–93, 613–615, 619, 621–622

Desymmetrization, 320–321Cycloisomerization, 611Decarboxylative Allylation, 24, 555Desymmetrization, Oxabicyclic Alkenes, 307–308Desymmetrization, Via Allylation, 321–323DPPBA Complex, 21–24, 102–103, 553–554, 561,

571–572Dynamic Kinetic Asymmetric Transformation,

287–291, 292–293Ferrocenyl Phosphine Complex, 92–93, 613, 619,

621–622Heck Reaction, 97–98, 317–319, 566–567Hydrometallation, 103In a Multistep Reaction, 460–461JOSIPHOS Complex, 621–622Kinetic Resolution, 26–27Kumada Reaction, 613, 615Large-Scale Reaction, 553–554Nanoparticles, in Allylation, 515–516Oxidation, 26–27π-Allyl Intermediate, 24, 100–103π-Allylation, 21–24, 100–103, 553–554, 555, 561,

616–617Phosphinooxazoline Complex, 24, 97Psycholeine Synthesis, 319–320, 566–567Quadrigemine C Synthesis, 319–320, 566–567Segphos Complex, 611Sparteine Complex, 26–27, 628Sphingofungin E Synthesis, 561Spiro Bisoxazoline Complex, 97Strychnine Synthesis, 555Suzuki Reaction, 92–93, 614Wacker Reaction, 94–97, 460–461, 628Wagner–Meerwein Shift, 103

Bifunctional Catalysts, 401–403Dynamic Kinetic Asymmetric Transformation,

23–24, 102Kinetic Resolution, 21–23

Pancratistatin, Synthesis of, 101, 324–325Paracyclophane, 589–590Parallel Kinetic Resolution, 255–269, 449, 482,

489–490, 572–574

Acylation Catalyst, 260–262Chemodivergent, 256–262Concepts, 255–256Dual-Catalyst System, 260–262Enzymes, 268Ketone Reduction, 268Regiodivergent, 262–268Stereodivergent, 268–269Vs. Kinetic Resolution, 256

P-Chirogenic PhosphinesCAMP, DIPAMP, 582Dynamic Kinetic Asymmetric Transformation,

288–290P-Chirogenicity, 332Penam Antibiotics

Synthesis of, with Supported Catalysts, 542β-Lactams, 409

Penicillin, β-Lactams, 409Peptide, Copper Complex, Conjugate Addition, 467Peptide Catalysts

Alcohol Acylation, 612Alcohol Phosphorylation, 621–622Desymmetrization of Meso Diols, 309–310Hydrocyanation, 67, 367Morita–Baylis–Hillman Reaction, 407–409

Perlactone B, Synthesis of, Via Cross Aldol, 394–395

Perylenequinones, 562PHANEPHOS, 589–590Pharmacophores, β-Lactams, 409Phase Behavior, on Nonlinear Effects, 355–357Phase Isolation, in Parallel Kinetic Resolution,

259–260Phase-Transfer Catalysis (PTC), 77–79, 179–181,

184–187, 446–447, 581, 609–610, 613–614Binaphthalene, 78–79, 446–447, 581C2-Symmetric, 78–79, 446–447, 581Cinchona Alkaloids, 78, 581, 610, 613Conjugate Addition, 79Double Diastereoselection, 446–447DyKAT, 613–614Electrostatic Interactions, 184Enantioface Differentiation, 609–610Enolate Alkylation, 77–79, 446–447, 581, 609–610,

613van der Waals Forces, 184

Phelix, Rhodium Complex, Enamide Hydrogenation,589

Phenols, in Allylation Reactions, 322–323Phenylsilane, 126Phosphination, with Dynamic Kinetic Asymmetric

Transformation, 288–290Phosphine, Chirality, 129, 288– 290, 581Phosphine, Edge-Face Interactions, 130, 144Phosphine Arsine, Chirality, 581Phosphine Borane, Chirality, 581Phosphine Ligands

Enamide Hydrogenation, 11Temperature Effect, 11

Phosphine Metal Complex, Chirality, 581

Index 663

π-Coordination (cont.)

18_index.qxp 6/30/08 12:02 PM Page 663

Phosphine OxideAs Achiral Additive, Aldehyde Hydrocyanation,

387–388Chirality, 581

Phosphine Sulfide, Chirality, 581Phosphinic Amides, Homochiral vs. Heterochiral

Association, Via Hydrogen Bonds, 332Phosphinooxazoline

Decarboxylative Allylation, 24Heck Reaction, 97–98Hydrogenation, 551Palladium Complex, 24, 97–98Platinum Complex, 551

Phosphite CatalystBrook Rearrangement, 60–61Umpolung Activation, 60–61

Phosphonium Salt, Chirality, 581Phosphoramidates, Lewis Base Catalysts, 352–355Phosphoramide Catalysts

Mukaiyama Aldol Reaction, 47–50Mukaiyama Aldol Reaction, Linked, 49Silicon Activation, 47–50

PhosphoramiditeAllylic Substitution, 459–460Conjugate Addition, 464–465, 468Copper Catalyst, 459–460, 464–465

Phosphorous, Centrochirality, 582Phosphorylation

Alcohol, 621–622Alcohol, Desymmetrization, 621–622Alcohol, Enantiotopic Group Differentiation,

621–622Phox; see PhosphinooxazolinePinacol Coupling, Enantioface Differentiation,

Chromium Catalyst, 624pKa, Values, 67,76–77Planar Chiral Catalysts, 589–590

Alcohol Acylation, 56–57Desymmetrization, 309–310DMAP Derivatives, 4, 56–57, 72Kinetic Resolution, 56–57, 234–237

Planar Chirality, 179–183, 589–590Generation of, 618–619Via Asymmetric Complexation, 618Via Asymmetric Substitution, 618–619

Platinum CatalystsCinchonidine Modified, 522–524, 551Diels–Alder Reaction, 215Heterogeneous Hydrogenation Catalysts,

522–524Hydroformylation, Mechanism Shift, 13–14Hydrogenation, α-Ketoester, 551Large-Scale Reaction, 551

PMHS; see PolymethylhydrosiloxanePolycyclization, 71–72, 567–568Polyester Support, Hydrogenation Catalysts, 513–515Polymer-Supported Catalysts, 498–508

Catalyst Construction in Pores, 499Coordination Polymers, 498Parallel Kinetic Resolution, 260–262

Via Charge–Charge Interactions, 499Via Polymer Derivatization, 498Via Tethering, 499

Polymethylhydrosiloxane (PMHS), 126Polyprenoid, Via Polycyclization, 71–72, 567–568Polystyrene

Modified, Argogels, 500Modified, Tentagel, 500Salen-Supported, Epoxide-Opening, 501Supports, 500–501With Supported Catalysts, 510–511

Pore Size, in Silica, Impact on Enantioselectivity,533–535

Positive Nonlinear Effect; see Nonlinear EffectpR, 590Pressure Effects, 16–17

Benzyl Alcohol Oxidation, 26Prilosec, Synthesis of, 582Privileged Structures, Salen, 237Pro-(R), Definition, 596, 598Pro-(S), Definition, 596, 598Prochiral, Definition, 593–598Prochiral Compounds, Transformation to Chiral

Compounds, 609–611, 619–625Product Catalyst Interactions, 360–361Product Inhibition, 17Proline, 207–208

Aldol Reaction, 8–9, 52, 67, 392–398, 627α-Amination of Aldehydes, 395–396Crystallization, 355–357Diastereomeric Dual Catalysts, 408Dual Catalyst, 407–409Dynamic Kinetic Resolution, 398Hajos–Parrish–Eder–Sauer–Weichert Reaction,

52, 67, 392–393Hydrogen Bonds, with Chloroform, 355–357In a Multistep Reaction, 472–474Mannich Reaction, 395–396, 472–474, 607–608Morita–Baylis–Hillman Reaction, 407–409Nonlinear Effects, 355–357Organocatalysis, 8–9, 52, 67, 392–398, 472–474,

607–608, 627α-Oxyamination of Aldehydes, 395–396pKa, 67Tandem Reactions, 397

Proline Methyl Ester, pKa, 67Propargylic Alcohol

Acylation, 56–57Ketone Reduction, 445Kinetic Resolution, 56–57Via Ene Reaction, 306

ProphosEnamide Hydrogenation, Temperature Effect, 11Rhodium Complex, 11

ProstaglandinSynthesis of, 463–4460–46165Synthesis of, Via Desymmetrization, 563

Proton Sponge, 54–55, 485–486Protonation, Asymmetric, 70–73, 567–568

Conjugate Addition, 558–559

664 Index

18_index.qxp 6/30/08 12:02 PM Page 664

Diamine, 70–71Heterobimetallic Catalyst, 558–559Lewis Acid Assisted Brønsted Acid, 72–73Lithium Enolate, 50, 70–71Polycyclization, 72–73Triamine, 50

pS, 590Pseudoenantiomers, 592, 628–629

Quinine vs. Quinidine, 628–629Psycholeine, Synthesis of, 319–320, 566–567Pybox; see Pyridine BisoxazolinePyranone, Via Hetero-Diels–Alder Reaction, 68–69,

447–448, 480, 557–558Pyrazoline, Via Conjugate Addition, 468–469Pyrethroid Insecticide, Synthesis of, Via

Hydrocyanation, 367Pyridine Bisoxazoline

Copper Catalyst, 18, 35–38, 442–444, 601, 624–625,631

Diels–Alder Reaction, 18, 44–45Friedel–Crafts Reaction, 45Gadolinium Complex, 44–45Mukaiyama Aldol Reaction, 35–38, 442–444, 601,

606, 624–625, 631Scandium Complex, 45Tin Complex, 606, 631

Pyrimidinyl Alcohols, Generation of, 357–360Pyrrolidine Catalyst

Conjugation Addition, 53Hetero-Diels–Alder Reaction, 54

PyrrolidinesVia C–H Insertion, 441–442, 449–450, 564–565,

620–621Via Cycloisomerization, 80–81

PyrroloindolineVia Friedel–Crafts/Aminal Formation Sequence,

472–473Via Heck Reaction, 566–567

Quadrant Diagrams, 117C–H Insertion, 305Copper Bisoxazoline Catalyst, 606Ferrocene-Based Catalyst, 234Hydroacylation, 133Hydrogenation, 146

Quadrigemine C, 319–320, 566–567QUINAP

Diboration, 460–461Rhodium Complex, 460–461

Quinidine; see Cinchona AlkaloidsQuinine; see Cinchona AlkaloidsQuininium, pKa, 67

RR; see Cahn–Ingold–Prelog ConventionRacemate, Definition, 590–591Racemates, Physical Properties, 331–335Racemic Compounds, Transformation to

Enantiopure Compounds, 612–614, 625–627Racemization

Definition, 591

Dynamic Kinetic Resolution, 272Aldol Reaction, 282Grignard Reagents, 284–286Nucleophilic Substitution, 284Of Allylic Acetates, 283Of Carboxyanhydrides, 280Of Organometallics, 320–321Of Secondary Phosphines, 288–290Organozinc Reagents, 284–286

Via Oxidation–Reduction, 488–489Radical Decay, in C–H Hydroxylations, 301–302Radical Intermediates, in C–H Hydroxylations, 301Rate-Determining Step, (rds); see Turnover-

Limiting StepRe, Definition, 598Reaction Coordinate Diagrams

Catalyzed Background Reaction, 18Double Diastereoselection, 438Dynamic Kinetic Asymmetric Transformation, 22Dynamic Kinetic Resolution, 22Kinetic Resolution, 21Ligand-Deccelerated Catalysis, 17, 18Multiple-Pathway Reactions, 7Simple Asymmetric Induction, 3

Recycling, of Supported Hydrogenation Catalysts,513–515

ReductionCopper Catalyst, 51Denopamine Synthesis, 560–561Fostriecin Synthesis, 572–573Ketones, 51, 170–171, 273–278, 445, 480–481, 488,

551, 556–557, 560–561, 568–569, 572–573,626–627

Bifunctional Catalysts, 382–386Diastereoselection, 428–4291,7-Diastereoselection, 434Oxazaborolidines, 379–381Via Dynamic Kinetic Resolution, 276With Self-Supported Catalysts, 520–521

Large-Scale, 551Ruthenium Catalyst, 445, 480–481, 488, 551,

556–557, 560–561, 626–627Taurospongin A Synthesis, 568–569

Reductive Cyclization, of Enynes, 215Regiocontrol

α-Amination, 605Asymmetric Catalysts, 448–450C–H Insertion, 449–450Epoxide Opening, 448–449α-Hydroxylation, 605Mukaiyama Aldol Reaction, 605Substrate Directed, 432–433, 605

Regioselection, Definition, 604–608Relative Rates

Aldehyde Alkylation, 218–219Diastereomeric Catalysts, 201–202

Remote Stereocontrol, 434–436Reservoir Effect

Nonlinear Effects, (ML)2, 343–347Nonlinear Effects, ML2, 340–343

Index 665

Protonation, Asymmetric (cont.)

18_index.qxp 6/30/08 12:02 PM Page 665

Rhodium Catalysts, 26, 250–252Asymmetric Amplification, 564–565BINAP Complex, 105, 433, 465–466, 480–481,

489–490, 552BINAPHOS Complex, 99–100, 553BIPHEPHOS Compex, 459Bisphosphine, 215C–H Insertion, 89–90, 303–306, 441–442, 449–450,

564–565, 619–621Chiraphos Complex, 25–26, 98–99Conjugate Addition, 465–466, 489–490, 616–617[4+1] Cycloaddition, 104[5+2] Cycloaddition, 105Diboration, 460–461DIPAMP Complex, vii1,3-Dipolar Cycloaddition, 168DOSP Complex, 89–90, 441–442, 449–450, 564–565,

619–621DuPHOS Complex, 104, 435–436, 457–459, 551, 602,

623Enamide, Hydrogenation, vii, 10–13, 25–26, 98–99,

435–436, 444–445, 457–459, 480–481, 551, 586,602, 623

Eniphos Complex, 551Hydroformylation, 99–100, 553Hydrogenation

Alkene, 551, 589Enamide, vii, 10–13, 25–26, 98–99, 435–436,

444–445, 457–459, 480–481, 551, 586, 602, 623

Of Ketoesters, 533–535With Ion-Exchanged Catalysts, 525With Supported Catalysts, 532–533

Hydrosilylation, 314–316, 616–618In a Multistep Reaction, 457–459, 465–466, 460–461,

489–490Isomerization, 433, 552JOSIPHOS Complex, 444–445MACIM Complex, 619–620Parallel Kinetic Resolution, 256–257, 262–264,

489–490Phelix Complex, 589Phosphine Ligand Complexes, Enamide

Hydrogenation, 10–13QUINAP Complex, 460–461Segphos Complex, 616–617SILOP Complex, 616–618Spirane Formation, 616–618Supported Hydrogenation Catalyst, 503–504,

506–508Ring Opening of Oxabicyclic Alkenes,

Desymmetrization, 306–307Ring Expansion, 468Robinson Annulation, 52ROMP, Generation of Supported Catalysts, 512–513Rotation–Reflection Axes, 578Ruthenium Catalysts, 131

Alcohol Oxidation, 610Alcohol Racemization, 488Alkene Hydrogenation, 551, 568–569, 605

α-Amino Ketone Reduction, 560–561Bifunctional Catalysts, Ketone Reduction, 382–386BINAP Complex, 480–481, 551, 560–561, 568–569,

605, 626–627Combined with Enzymes, in DKR, 281Complex Substrate, 560–561Cyclopentylhydroxy, Dynamic Kinetic Resolution,

281DAIPEN Complex, 560–561Denopamine Synthesis, 560–561Desymmetrization, 610Dolichols Synthesis, 605Double Diastereoselection, 445, 568–569, 572–573DuPHOS Complex, 551Enantiotopic Group Differentiation, 610Fostriecin Synthesis, 572–573FR901464 Synthesis, 556–557α-Hydroxy Ketone Reduction, 551In a Multistep Reaction, 480–481, 488β-Ketoester Reduction, 480–481, 551, 626–627Ketone Reduction, 201, 210–216, 273–278, 445,

480–481, 488, 551, 556–557, 560–561, 568–569,572–573, 626–627

Large-Scale Reaction, 551Metathesis, 90–91, 240–241

Sequential Reaction, 459–460, 467–468N-Tosyl Diamide Complex, 445, 556–557, 568–569,

572–573, 610Oxidation, 610Racemization, 488Regioselective, 605Sequential Reaction, Metathesis, 459–460, 467–468Supported Hydrogenation Catalyst, 513–515,

517–519Taurospongin A Synthesis, 568–569TMBTP Complex, 551Transfer Hydrogenation, 170–174, 445, 480–481,

488, 556–557, 560–561, 572–573, 610Trimethyldodecanol Synthesis, 568–569

Sσ-Plane, 596S, Cahn–Ingold–Prelog Conventions (Selectivity Factor), 232Salen Catalysts

Alkylation, of α-Ketoesters, 607Bifunctional Catalyst, 607Bifunctional Ni,Cs Catalyst, 9–10Chromium Complex, 448–449, 557–558Cobalt Complex, 552, 557–558Cyclopropanation, 223Epoxidation, 84, 86–87, 552, 569–571Epoxide Opening

Azide, 448–449Water, 552, 557–558

Hetero-Diels–Alder Reaction, 557–558Manganese Catalyst, 84, 86–87, 552, 569–571Michael Reaction, 9–10Supported, 501Titanium Complex, 607

666 Index

18_index.qxp 6/30/08 12:02 PM Page 666

Sanfetrinem, Intermediate in the Synthesis of, 277S Axes, 578Scalemic, Definition, 591Scandium Catalysts

Friedel–Crafts Reaction, 45Pyridine Bisoxazoline Complex, 45

Schiff BaseChromium Complex, 34–35, 41, 447–448, 556–557Conjugate Addition, 467–468Copper Complex, vii, 467–468Cyclopropanation, viiDiels–Alder Reaction, 41Hetero-Diels–Alder Reaction, 34–35, 556–557

S-Chirogenicity, 316, 582–583Second Coordination Sphere, in Ketone

Hydrogenation Catalysts, 386Second-Order Catalyst

Deactivation, 503–504Dual Catalysts, 403Mukaiyama Aldol, 47–50Phosphoramidate, Allylation of Aldehydes, 353With Supported Catalysts, 502–503

Secondary Interactions, 41–42, 166, 168SEGPHOS

Conjugate Addition, 616–617Cycloisomerization, 611Formation of Axial Chiral Allenes, 616–617Hydrometallation, 103Palladium Complex, 103, 611Rhodium Complex, 616–617

Selectivity Factor; see krel

Self-AssemblyBifunctional Catalysts, 378–382Heterobimetallic Catalysts, 413Metal–Organic Coordination Networks, 516–521

Self-Supported Catalysts, 520–521Semicorrin, 118Sequential Processes, 90, 457–461, 464–465, 467–471,

473–483, 485–486, 488–489Definition; see Multistep Asymmetric Catalysis,

456Reaction Atmosphere, 458–459

Sequential Reactions, with Supported Catalysts,541–543

Shape Exclusion, 107Sharpless Asymmetric Dihydroxylation (AD);

see DihydroxylationSharpless, K. Barry, vs. Sharpless–Katsuki

Asymmetric Epoxidation; see Epoxidation

Ship in a Bottle, 529Si, Definition, 598Siam, S-Chirogenicity, 582–583Si-Chirogenicity, 580–581Si–H Insertion, 316Silanols, pka, 501Silica

Catalyst Loadings, 503–504Control of Catalyst Density, 502–503Continuous Flow Systems, with HKR, 502–503

Mesoporous, 505–506Support for Salens, in HKR, 501–506

Silicon, Centrochirality, 580–581Silicon Catalysts

Hypervalent Activation, 46Mukaiyama Aldol Reaction, 47–50

Silicon Tetrachloride, 49–50SILOP, Rhodium Complex, Hydrosilylation,

616–618Silver Catalysts

Aldehyde Allylation, 572–573BINAP Complex, 572–573Fostriecin Synthesis, 572–573

Silyl Transfer, 36–37Simmons–Smith; see CyclopropanationSimple Diastereoselection; see Diastereoselection,

SimpleSingle-Electron Transfer, 55–56Site Isolation, in Supported Catalysts, 502–503, 504SN1 Reaction, 603SN2 Reaction, 603SN2’ Displacement

Copper Catalysts, 459–460In a Multistep Reaction, 459–460

Sn axis, 596Soai Reaction, 357–360Sol-Gel, Encapsulation of Catalysts with, 532–533Solubility

Nonlinear Effects, 355–357Racemate vs. Enantioenriched, Nonlinear Effects,

331, 355–357Soluble Polymeric Supports, with Hydrogenation

Catalysts, 513–515Solution Spectra, Racemate vs. Enantioenriched,

332–333Solvent Effects, 15–16Solvent-Free Reactions, 16Solvent Viscosity, in Radical Reactions, 300–301SOMO, Catalysis, 55–56Sorbose-Derived Catalysts, Epoxidation, 87Sparteine

Alkyl Lithium Adduct, 17, 75–76Alkylation of Aldehydes, 17Deprotonation, 75–76Grignard Adduct, 17Kinetic Resolution, 26–27Oxidation of Alcohols, 26–27Palladium Complex, 26–27, 628Wacker Reaction, 628

Specific-Acid Catalysis, 66Sphingofungin E, Synthesis of, 561Spiranes

Axial chirality, 586–588Generation of, 616–618Via Desymmetrization, 316

Spiro Bisoxazoline; see BisoxazolineSpirocycles, 316Squalene, 565–566

Regioselective Dihydroxylation, 605Staudinger Reaction, 542

Index 667

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StereocentersAxial, 586–588Central, 580–585Helical, 588–589Planar, 589–590Types, 578–590

Stereoconvergent, 602Stereodivergent, 623Stereogenic Metals, 149Stereogenic Unit, Definition, 578–581Stereoinduction

Aldehyde Alkylation, 345Aldehyde Alkylation, Zinc Catalysts, 3, 8Aldol Reaction, Proline, 9Allylation, 116, 123Allylation, with Azlactones, 293Ansa-Metallocenes, 247C-Acylation, 4C–H Activation/Cope Rearrangement, 259C–H Insertion, 304–305Cross-Coupling, with DKR, 284–286Curtin–Hammett, 25–26Cyclopropanation, 259Desymmetrization of Divinyl Carbinols, 313Diels–Alder Reaction

(TADDOLate)Ti Catalyst, 137–140Boron Catalyst, 125Copper Catalyst, 120

Enamide Hydrogenation, 25–26Epoxide Desymmetrization, Zirconium Catalyst,

299Epoxide Elimination, 74–75Hajos–Parrish–Eder–Sauer–Weichert Reaction, 52,

67Heck Reaction, 318Hetero-Diels–Alder Reaction, Copper Catalyst,

625–626Hydrogenation, 25–26Hydrosilylation, 316Hydrosilylation of Imines, 128β-Ketoester Hydrogenation, 275Mukaiyama Aldol Reaction, 341

Copper Catalyst, 36–38, 443–444, 624–625Titanium Catalyst, 36–38

Planar Chiral DMAP Analog, 4Stereoisomers, Number Possible, 592Stereoselective

Definition, 601–603Dynamic Kinetic Resolution, 603Kinetic Resolution, 603

StereospecificDefinition, 601–603Kinetic Resolution, 603

Stetter Reaction, 59Strecker Reaction, 388–389Strychnine, Synthesis of, 555Sublimation Rates, Racemate vs. Enantioenriched,

331–332Substituent Effects, Transfer Hydrogenation, 174Substitution

Asymmetric, 618–619SN1 Reaction, 603SN2 Reaction, 603

Substrate1-Acetoxy-1,3-Butadiene, Diels–Alder Reaction,

347–3481,4-Bisacyloxy-2-Ene, 3231,5-Dicarbonyl,

Hajos–Parrish–Eder–Sauer–WeichertReaction, 52, 67, 392–393

1,2-Diketone, Mukaiyama Aldol Reaction, 606, 6312-Naphthol, Oxidative Coupling, 536–538Acid Chlorides

[2+2] Cycloaddition, 54–55, 485–486Ketene Generation, 409–413

Acyl Silanes, Brook Rearrangement, 60–61Alcohol

Acylation, 57, 612Dynamic Kinetic Resolution, 280–284, 488–489Kinetic Resolution, 26–27, 57, 234, 612Oxidation, 26–27, 610Parallel Kinetic Resolution, 260–262Phosphorylation, 621–622

AldehydeAldol Reaction, 8–9, 73–74, 179, 364–366, 393–394,

419, 428–429, 450–451, 463–466, 475–477,572–574, 627

Alkyl Lithium, 17Alkylation, 2–4, 7–8, 15, 17, 335–336, 343–347,

352–355, 381–382, 469–470, 480, 586, 589, 600

Allylation, 572–573α-Allylation, 56α-Amination, 53α-Chiral Additions, 429–430α-Chlorination, 53–54Conjugate Addition, 53, 59[2+2] Cycloaddition, 552Diorganozinc Addition, 2–4, 7–8, 15, 480, 586,

589–590, 600Ene Reaction, 34α-Fluorination, 53, 482–483Grignard, 17Hetero-Diels–Alder Reaction, 54, 68–69, 196,

447–448, 480, 556–557, 557–558Hydrocyanation, 67, 367, 387–388, 479,

558–559α-Hydroxylation, 53, 474α-Hydroxylation in a Multistep Reaction, 474α-Ketoesters, 53Mannich Reaction, 608Morita–Baylis–Hillman Reaction, 69, 399Mukaiyama Aldol Reaction, 35–38, 48–49,

442–444, 601, 624–625Nitroaldol, 416–417Nozaki–Hiyama–Kishi Coupling, 450–452Pinacol Coupling, 624α-Sulfenylation, 53Umpolung Activation, 59

Aldehyde with Ketones, Aldol Reaction, 8–9, 74

668 Index

18_index.qxp 6/30/08 12:02 PM Page 668

AlkeneCyclopropanation, vii, 82, 87, 258–259, 467–468,

470–471, 481–482Diboration, 460–461Dihydroxylation, 19–20,83, 445–446, 475–477,

481–482, 552, 559–560, 565–566, 605, 616,628–629

Dihydroxylation with Supported Osmium,526–527

Ene Reaction, 34, 306, 552Epoxidation, 83–88, 505–506, 552, 569–571Heck Reaction, 97–98,566–567Hydroformylation, 12–14, 99–100, 553Hydrogenation, 551, 586, 589, 623Hydrosilylation, 616–618Kinetic Resolution of Atropisomeric Amides,

247–248Wacker Reaction, 94–97, 460–461, 628

β-Alkoxy AldehydeAlkylation, 431Diastereocontrol, 431

α-Alkoxy KetoneDiastereocontrol, 429–430Grignard Addition, 429Reduction, 430

Alkyl Halide, Nozaki–Hiyama–Kishi Coupling,450–452

AlkynalKinetic Resolution, 262Parallel Kinetic Resolution, 262–264

Alkyne, [2+2+2] Cycloaddition, 105–106Allene

[4+1] Cycloaddition, 104Chiral Counterion Catalyst, 80–81Cycloisomerization, 80–81Hydroalkoxylation, 80–81Hydroamination, 80–81

Allyl AcetateRacemization, 283–283π-Allylation, 21–23, 102, 291–293, 402, 515–516,

553, 561, 616–617Allyl Alcohol

Hydrogenation, 551, 605Kinetic Resolution, 242–246Parallel Kinetic Resolution, 268–269Sharpless–Katsuki Epoxidation, vii, 84–85, 433,

552, 562–564, 569–571, 599–600, 625–626Chiral

Cyclopropanation, 432Diastereoselection, 432Epoxidation, 432

Allyl Amine, Isomerization, 433, 552Allyl Carbamate, π-Allylation, 554Allyl Carbonate

Decarboxylative Allylation, 24–25, 554, 555π-Allylation, 102–103, 571–572

Allyl Diester, π-Allylation, 323–325Allyl Epoxide

π-Allylation, 554Parallel Kinetic Resolution, 266–267

Allyl EtherChiral

Diastereoselection, 431Dihydroxylation, 431

Allyl HalideAllylic Substitution, 459–460Nozaki–Hiyama–Kishi Coupling, 450–452SN2’ Reaction, 459–460

Allyl Vinyl Ether, Claisen Rearrangement, 38–39

AllylsilaneAldehyde Addition, 352–355, 572–573α-Allylation, 56Chiral

Aldehyde Addition, 435Diastereoselection, 435

Amide, Axially ChiralDiastereoselection, 435Directed Deprotonation, 435Imine Addition, 435

AmineConjugate Additions, 420–421Kinetic Resolution, 236–237Mannich Reaction, 608

Amino Diene, Metathesis, 240–241β-Amino Ketone, Reduction, 560–561Anhydride

Acylation, 57Alcoholysis, 76Cross-Coupling, 621–622Kinetic Resolution, 76Parallel Kinetic Resolution, 264–266Silyl Ketene Acetal C-Ayclation, 4

Aryl Boronic AcidConjugate Addition, 465–466Suzuki Coupling, 92–93, 614, 618–619

Aryl Halide, Suzuki Coupling, 614, 619Aryl Triflate, Kumada Coupling, 615Atropisomers, 247–248Azalactone

Kinetic Resolution of Amines, 236π-Allylation, 292–293

Azide, Epoxide Opening, 448–449Benzyl Alcohol, π-Allylation, 554α-Benzyloxyacetaldehyde

In Hexose Formation, 397Mukaiyama Aldol Reaction, 36–38, 442–444

Bis(Allylic Alcohols), Via Epoxidation, 313Bis(Triflates), Desymmetrization, 320–321Bishomoallylic Alcohol, Chiral

Diastereoselection, 435Epoxidation, 435

Butenolides, in Dynamic Kinetic AsymmetricTransformation, 287–288

Carbon Monoxide[4+1] Cycloaddition, 104Hydroformylation, 12–14, 99–10

Centrosymmetric, Desymmetrization of, 298Centrosymmetric Bisepoxide, Ring Opening,

311–312

Index 669

Substrate (cont.)

18_index.qxp 6/30/08 12:02 PM Page 669

α-Chiral AldehydeAlkylation, 430Diastereocontrol, 431Felkin Control, 430

α-Chiral DieneAllylic Strain, 431Diastereocontrol, 431Diels–Alder Reaction, 431

α-Chloroamine, [2+2] Cycloaddition, 485–486Cyclopropane, [5+2] Cycloaddition, 105Cyclopropanol

Wagner–Meerwein Shift, 103π-Allylation, 103

Danishefsky’s DieneHetero-Diels–Alder Reaction, 447–448, 480,

557–558Parallel Kinetic Resolution, 196

Diastereomeric Complexes, 156Diazo Compound, Cyclopropanation, viiDiazodicarboxylate, Conjugate Addition, 468–469Diazoester

C–H Insertion, 304, 441–442, 449–450, 564–565,619–621

Cyclopropanation, 256–257N-Boc Imine Addition, 70

Diene[5+2] Cycloaddition, 105Asymmetric Metal Complexation, 618Desymmetrization, 97Diels–Alder Reaction, 15–16, 18, 41, 43–44, 56–58,

68–69, 362–364, 439–441, 447–448, 480,556–557, 557–558, 629–630

Heck Reaction, 318, 319Hydroamination, 103Metathesis, 90–91, 240–242Wacker Reaction, 97

Diimide, 325Diol

Desymmetrization, 610DKR, 281

DiorganozincAldehyde Alkylation, 2–4, 7–8, 15, 469–471, 480,

586, 589, 600Conjugate Addition, 14, 464–465, 467–468Cross-Coupling, 621–622α-Ketoester Alkylation, 607

Divinyl Carbinol, Desymmetrization, 312–313Diyne, [2+2+2] Cycloaddition, 105–106Enal, Diels–Alder Reaction, 177Enamide, Hydrogenation, vii, 10–13, 25–26, 89–99,

435–436, 444–445, 457–459, 503–504, 551, 586,602

EnamineConjugate Addition, 53Mannich Reaction, 474–474

Enediol Ester, Desymmetrization of, 321–322Ene-Dibenzoate, π-Allylation, 324Ene-Dicarbamates, in Desymmetrization, 325Enol Ether

Ene Reaction, 478

Hetero-Diels–Alder Reaction, 34–35, 38–39,625–626

EnolateAlkylation, 78, 184–187, 446–447, 609–610, 613Asymmetric Protonation, 50PTC Catalysis, 78, 446–447, 609–610, 613

Enol-Ester Epoxide, Rearrangements, 249–250Enone

Aza-Morita–Baylis–Hillman Reaction, 400Conjugate Additions, 420–421, 506–508Diorganozinc, 14Michael Reaction, 9–10

Enyne, 250–252Epibromohydrin, 284Epoxide

Asymmetric Deprotonation, 74, 75Bifunctional Catalysts, 404Desymmetrization, Dynamic Kinetic Resolution,

284Epoxide Opening, 404Isomerization of Meso Epoxides, 349–352Kinetic Resolution, 237–240Nonlinear Effects, 338–339Opening with Azide, 448–449Opening with Water, 552, 557–558Rearrangement, 75, 249–250

Glycine Imine EnolateAlkylation, 78, 184–187, 446–447, 609–610PTC Catalysis, 78–79, 446–447, 609–610

Glyoxylate, Ene Reaction, 478Grignard, Kumada Coupling, 613, 615Homoallylic Alcohol, Chiral

Diastereoselection, 432Hydrogenation, 432

α-Hydroxy Esters, in DKR, 281β-Hydroxy Ketone, Hydrogenation, 551Imine

Aza-Morita–Baylis–Hillman Reaction, 399Hydrocyanation, 611Hydrosilylation, 246Kinetic Resolution, 246–247β-Lactam Synthesis, 409–413Strecker Reaction, 388–389

α-Iminoester[2+2] Cycloaddition, 54–55, 485–486β-Lactam Formation, 54–55Mannich Reaction, 472–474

π–π Interactions, 166Indole, Friedel–Crafts Reaction, 45, 472–473Induced Asymmetry, 156Isocyanide-Ester, Aldol, 386–387Isocyanoacetates, 179Ketenes

Alcoholysis, 72–73[2+2] Cycloaddition, 54–55, 485–486, 535–536, 552From Acid Chlorides, 409–413

β-Keto Oxime Ethers, 381α-Ketoacetal, Reduction on Platinum, 522–524α-Ketoacid, Reduction on Platinum, 522–524α-Ketoamide, Reduction on Platinum, 522–524

670 Index

Substrate (cont.)

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α-KetoesterDiorganozinc Addition, 607Ene Reaction, 552Hetero-Diels–Alder Reaction, 54, 462, 487Hydrogenation, 551Mukaiyama Aldol Reaction, 6Reduction on Platinum, 522–524With Bifunctional Catalysts, 390–392

β-Ketoester, 532–533Dynamic Kinetic Resolution, 273–274Hydrogenation, 194, 551, 626–627Kinetic Resolution, 273–274π-Allylation, 553

α-Ketoether, Reduction on Platinum, 522–524Ketolactone, Reduction, 170–171, 276, 517–519Ketone

Aldol Reaction, 393–394, 418α-Amination, 606–607CBS Reduction, 379–381Chiral

Diastereoselection, 434Reduction, 434

Dynamic Kinetic Resolution, 276Hydrocyanation, 388–389, 572–573α-Hydroxylation, 606–607Nanoparticle Supported Hydrogenations,

508–509Mannich Reaction, 608Parallel Kinetic Resolution, 268Reduction, 51, 445, 551, 556–557, 568–569,

572–573Soluble Polymeric Supports, 513–515With Aldehyde, Aldol Reaction, 8–9, 74, 572–574,

627α-Ketophosphonates

Friedel–Crafts Reaction, 45Hetero-Diels–Alder Reaction, 38–39, 625–626

Lithium Enolate, Asymmetric Protonation, 50, 70–71Malonate

Conjugate Addition, 468–469Michael Reaction, 9–10, 463–464, 471–472, 553π-Allylation, 553

Meso, Desymmetrization, 298Meso Diols, 309–310Meso Enediol Ester, Desymmetrization, 321–322Meso-Epoxide, Nonlinear Effects, 338–339Methacrolein, Diels–Alder Reaction, 18, 41, 68–69Methyl Acrylate, Diels–Alder Reaction, 362–364Methyl Crotonate, Diels–Alder Reaction, 41Naphthol, Oxidative Biaryl Coupling, 484–485, 562,

614–615N-Boc Imine

Addition of Diazoesters, 70Mannich-Type Reaction, 68

N-Boc PyrrolidineAsymmetric Lithiation, 75C–H Insertion, 441–442, 449–450, 564–565,

620–621N-Carboxyanhydrides, DKR, 278Nitromethane, Nitroaldol, 416–417, 479

Nitrones, in 1,3-Dipolar Cycloaddition, 168–171Nitrosobenzene

α-Amination, 606–607α-Hydroxylation, 474, 606–607

Oxabicyclic Alkenes, 307–308Oxime Ethers, CBS Reduction, 381Phenol, π-Allylation, 322–323, 554Phenylsulfonylnitromethane Anion, π-Allylation,

23–24Phosphine, in Dynamic Kinetic Asymmetric

Transformation, 288–290Phthalimide, π-Allylation, 554Polyene

Hydrogenation, 605Polycyclization, 71–72, 567–568

Propargylic AlcoholAcylation, 57Kinetic Resolution, 57

Pyrimidine Carboxaldehydes, AutocatalyticReaction, 357–360

Quinone, Diels–Alder Reaction, 41, 44Siloxydienes, 314–315Silyl Ketene Acetals

Addition to Imines, 68Addition to α-Benzyloxyacetaldehyde, 36–38,

442–444, 601, 624–625Addition to α-Ketoesters, 6C-Acylation, 4Conjugate Addition, 42Mannich-Type Reaction, 68Mukaiyama Aldol Reaction, 6, 36–38, 49,

442–444, 601, 606, 624–625, 631Vinylogous, 49–50

Silyl Nitronate, Conjugate Addition, 78–79Squalene, Dihydroxylation, 565–566Styrene, Hydroamination, 103Succinic Anhydrides, Ring Opening of, 264–266Sulfide, Oxygenation, 552, 609Tetrahydrofuran, in C–H Hydroxylations, 302–303Tetrahydropyran, in C–H Hydroxylations,

302–303Thiol, Conjugate Addition, 558–559Trichlorosilyl Enolate, Mukaiyama Aldol Reaction, 48Trienes, Metathesis, 90–91, 512–513, 553α,β-Unsaturated Acid, Hydrogenation, 551α,β-Unsaturated Aldehyde

Conjugate Addition, 78–79Cyclopropanation, 81–82Diels–Alder Reaction, 57–58Friedel–Crafts Reaction, 472–473Hetero-Diels–Alder Reaction, 34–35Hydrofluorination, 482–483Iminium Activation, 58Silyl Nitronate Addition, 78–79Transfer Hydrogenation, 80

α,β-Unsaturated AmideBrook Rearrangement, 60–61Conjugate Addition, 60–61

α,β-Unsaturated CarbonylConjugate Addition, 59, 558–559

Index 671

Substrate (cont.)

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Stetter Reaction, 59Umpolung Activation, 59

α,β-Unsaturated Ester, 166Diels–Alder Reaction, 41

α,β-Unsaturated Imide, Conjugate Addition ofCyanide, 405–407

α,β-Unsaturated KetoneConjugate Addition, 9–10, 42, 464–465, 467–468,

489–490, 616–617Hetero-Diels–Alder Reaction, 54, 462, 487Iminium Activation, 56–58Michael Reaction, 463–464, 471–472, 553Morita–Baylis–Hillman Reaction, 69

α,β-Unsaturated Nitro, Conjugate Addition, 53α,β-Unsaturated Oxazolidinone, Diels–Alder

Reaction, 15–16, 43–44, 43–44, 439–441,629–630

Urethane-Protected α-Amino Acid N-CarboxyAnhydrides, Alcoholysis, 76

Urethane-Protected π-Amino Acid N-CarboxyAnhydrides, Kinetic Resolution, 76

Vinyl Ether, Hetero-Diels–Alder Reaction, 34–35,38–39

Vinyl HalideKumada Coupling, 613Nozaki–Hiyama–Kishi Coupling, 450–452Suzuki Coupling, 619

Vinyl Triflate, 318Vinylogous Silyl Ketene Acetals, Mukaiyama Aldol

Reaction, 49With Chiral Relays, 157Ylide, Cyclopropanation, 81–82Ynal, Carbonyl-Ene, 306Ynone, in Direct Aldol, 364–366

Substrate Activation, 376Substrate Binding

C–H-π Interactions, 168α,β-Unsaturated Esters, 166

Substrate Dependency of Nonlinear Effects, 346–347

Substrate-Directed Reactions; see Diastereocontrol,Directed Reactions

Substrate Relay, 121Subtilisin, 283α-Sulfenylation, 53

Synthesis of, 418Synthesis of, with Proline, 393–394

Sulfide, OxygenationEnantiotopic Group Differentiation, 609Large-Scale, 552

Sulfonium Salts, 582Sulforaphane, 582–583Sulfoxides, 582

Formation, Enantiotopic Group Differentiation, 609Via Oxygenation, 552, 609

Sulfoximines, 582Sulfur, Centrochirality, 582–583Superparamagnetic Materials, as Solid Supports,

508–509Supported Catalysts, 481, 497–543

Chiral Catalysts as Part of Support, 509–521

Confinement Effects, 533–535Dual Catalysts, 540–541In Series, 542–543On Mesoporous Silica, 505–506On Silica, 501–506Organic, 497Organocatalysis, 535–536

Suzuki CouplingAtropisomer, 92–93, 614Axial Chirality, 92–93, 614Desymmetrization, 618–619Enantiotopic Group Differentiation, 618–619In a Multistep Reaction, 457–458, 460–461Palladium Catalyst, 92–93, 614, 619Planar Chirality, 618–619

Swainsonine, Synthesis of, Via Allylation, 324Synthesis

Asymmetric Catalysis with AdvancedIntermediates, 558–562

Convergent Assembly of Small Chiral Molecules,556–557

Diastereoselective, 553–555Double Diastereoselection, 568–574Multiple Stereocenters in More Than One Process,

563–568Multiple Stereocenters in One Process, 562–563Using Chiral Small Molecules, 550–553

TTADDOL, 135

α-Amination, 606–607Diels–Alder Reaction, 43, 68–69Hetero-Diels–Alder Reaction, 68–69Organocatalyst, 606–607pKa, 67Titanium Complex, 43

TADDOLate, (TADDOL dianion); see TADDOLTandem Reactions, Heck/Dihydroxylation, 540–541Tandem Reactions, Proline-Catalyzed, 397Taondiol, 567–568Tartrate, 592, 625–626

Sharpless–Katsuki Epoxidation, vii, 84–85, 433, 552, 562–564, 569–571, 599–600, 625–626

Sulfide Oxidation, 552, 609Titanium Complex, vii, 84–85, 433, 552, 562–564,

569–571, 599–600, 609, 625–626Taurospongin, Synthesis of, 568–569TBoxH, Chromium Catalyst, Pinacol Coupling, 624Temperature Effects, 10–13

Benzylic Alcohol Oxidation, 26Hydroformylation, 12Mechanism Shift, 11–13Multiple Pathway Reactions, 6–9Nonideal, 9–15

Conjugate Addition, 14Hydrogenation, 10–13Michael Reaction, 9–10

Simple, 5–6Teraryl Formation, [2+2+2] Cycloaddition, 105–106Termolecular Ring Opening, 278Tests for Homogeneous Catalysts, 515–516

672 Index

Substrate (cont.)

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TethersImpact on Enantio- and Diastereoselectivity,

535–536Impact on Supported Catalysts, 535–536

Tethered Catalysts, 481–482Tetrahydrofurans, Via Cycloisomerization, 80–81Thienamycin, Synthesis of, 554–555Thiourea

Imine Addition, 68Mannich-Type Reaction, 68

Threonine Derivatives, Synthesis of, 275Tin Catalysts

Bisoxazoline Complex, 631Lewis Acid Assisted Brønsted Acids, 71–72,

567–568Mukaiyama Aldol Reaction, 606, 631Polycyclization, 71–72, 567–568Pyridine Bisoxazoline Complex, 606, 631

TINV; see Inversion TemperatureTitanium Catalysts, 126, 139

AlkylationOf Aldehydes, 220–221, 335–336Of α-Ketoesters, 607

Bifunctional Catalyst, 572–573, 607Bifunctional Salens, 390–392BINOL Complex, 34, 37–38, 306, 335–336, 478, 552Binuclear Compounds, 336Cryptophycin 52 Synthesis, 569–571Diels–Alder Reaction, 15–16, 43, 347–348Dimers, in Nonlinear Effects, 336EBTHI Complex, 15–16Ene Reaction, 34, 199–200, 306, 478, 552Epoxide Rearrangement, 249–250Fostriecin Synthesis, 572–573Hydrocyanation, of Ketones, 389–390In a Multistep Reaction, 478Metal–Organic Coordination Networks, 519–520Mukaiyama Aldol Reaction, 37–38Nonlinear Effects, Aldehyde Alkylation, 335–336Parallel Kinetic Resolution, Sharpless–Katsuki

Asymmetric Epoxidation, 268–269Salen Complex, 607Sharpless–Katsuki Epoxidation, vii, 85, 433,

242–246, 313, 552, 562–564, 569–571, 599–600,625–626

Silylcyanation, 572–573Solvent Effect, 15–16Sulfide Oxidation, 552, 609TADDOL Complex, 43, 136Tartrate Complex, vii, 85, 433, 552, 562–564,

569–571, 599–600, 609, 625–626Titanium Oxo, Possible Intermediate, Diels–Alder

Reaction, 347–348TMS-Azide, in Allylations, 325Tocopherol, Synthesis of, 568–569TOF; see Turnover FrequencyTON; see Turnover NumberTotal Synthesis; see SynthesisTrans Influence

Allylation, 116Hydrogenation, 145

Transetherification, in a Multistep Reaction, 462Transesterification, in a Multistep Reaction, 487Transfer Hydrogenation, 58, 80, 445, 482–483, 488,

556–557, 560–561, 572–573, 610Amino Alcohols, 170–175Charge-Transfer Interactions, 173C–H-π Interactions, 170Electronic Effects, 174

Transition StatesAldehyde Alkylation, Zinc Catalysts, 345Aldol Reaction, Proline, 9Hajos–Parrish–Eder–Sauer–Weichert Reaction, 52,

67Transmission of Asymmetry, 115

Bisoxazolines, 118–119C2- vs. Non-C2-Symmetric Catalysts, 116

Triamine, Enolate Protonation, 50Triazolidinylindene Carbene Catalyst, Stetter

Reaction, 59Trichlorosilyl Enolates, Lewis Base Catalysis, 47–49,

353α-(Trifluoromethyl)Lactic Acid, Sublimation of,

331–332Triketones, Hajos–Parrish–Eder–Sauer–Wiechert

Reaction, 52, 67, 392–393Trimethyldodecanol, Via Hydrogenation, 569Trimethylsilyl Azide, Epxoide Desymmetrization,

298–300Triple Diastereoselection; see Diastereoselection,

TripleTryptophan, 176–178Tsuji–Trost Asymmetric Allylic Alkylation Reaction;

see α-AllylationTunephos, in Asymmetric Hydrogenation, 275Tungsten Catalysts, Metathesis, 90Turnover Frequency, vi, 550–552Turnover Number, vi, 550–552Turnover-Limiting Step, 6, 16–17Two-Directional Synthesis, 477–478, 563Two-Point Binding, 170

Lewis Acid Catalysis, 35–39, 43–45Two-State Model, 5

UUmpolung, 58–61, 69–70γ,δ-Unsaturated Aldehyde, Via α-Allylation, of

Aldehydes, 56γ,δ-Unsaturated Carbonyl, Via Claisen

Rearrangement, 38–39Urea Catalysts

pKa, 67Strecker Reaction, 611

V

Valienamine, Toward the Synthesis of, 324van der Waals Forces, Phase-Transfer Catalysis,

184Vanadium Catalyst, 2-Naphthol Oxidation,

536–538Vapor Pressure, Racemate vs. Enantioenriched, 331

Index 673

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Vaulted BiarylAluminum Complex, 41Diels–Alder Reaction, 41

Vernolepin, Toward the Synthesis of, 319

W

Wacker Reactionη2-Coordination, 94–96Desymmetrization, 96–97In a Multistep Reaction, 460–461In Synthesis, 555Intermolecular, 94–95Intramolecular, 95–97, 460–461, 628Palladium Catalysts, 94–98, 460–461, 628

Wagner–Meerwein Shift, in π-Allylation, 103Wang Resin, 535Wieland-Miescher Ketone, Via Hajos–Parrish–Eder–

Sauer–Weichert Reaction, 52, 67, 392–393Chiral Relay Substrates, 158

XX-Ray Structure

(Arene)Os(Bisphosphine), 150(BINAP)M,(Binolate)Ti,(BIPHEN)Rucl2(Diamine),

213[(S,S)-t-Bu-Box)]Cu(OH2)2(SbF6), 119Chromium Schiff Base Catalyst, 35Cinchona Phase-Transfer Catalyst, 78Cp*Ir(Prophos)(Methacrolein)2+, 170[Cu(PhPyBox)(BnOCH2CHO)](SbF6)2, 36(Diamine)Zinc, 141Diamine(Me2Zn) Complex, 141Hetero- and Homochiral Dimers, 345Li3(THF)N(BINOLate)3Ln Derivatives, 415(Ph2-BINOLate)Zn(Diamine), 220Phase-Transfer Catalyst, 186Planar Chiral Catalyst, 336Planar Chiral DMAP Analog, 56–57

TADDOL, 68(TADDOLate)Ti, 136, 137Ti–TADDOL complex, 43

YYlide, Cyclopropanation, 81–82Ytterbium Catalysts, BINOL Complex, Diels–Alder

Reaction, 629–630

ZZaragozic Acid, Synthesis of, 559–560Zeolite EMT

Structure, 529Support, 529–531

Zeolite Supports, Positive Impact onEnantioselectivities, 506–508

Zeolites, Molecular Sieves, 506–508Zimmerman–Traxler-Like Transition State, with

Proline, 394–395Zinc Catalysts, 121, 148

Aldehyde Alkylation, 381–382β-Amino Alcohol Complexes, 2–4, 7–8, 469–471,

600BINOL/Bisimine Complex, 480DAIB Complex, 2–4, 7–8HELOL Complex, 589MIB Complex, 469–471

Aldol Reaction, 364–366Aldolase, 377–378Desymmetrization, Oxabicyclic Alkenes, 307–308Hetero-Diels–Alder Reaction, BINOL/Bisimine

Complex, 480In a Multistep Reaction, 469–471

BINOL/Bisimine Complex, 480Zirconium

Epoxidation, Desymmetrization, 314In Desymmetrizations, 298–300

Zoloft, Synthesis, Via Hydrosilylation of Imines, 247

674 Index

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