safety moment · 2015-07-02 · chemistry nobel prize 2010 •discovering and developing highly...
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Safety Moment:Distillation Station Information
Seechurn, C. C. C. J.; Kitching, M. O.; Coalacot, T. J.; Snieckus, V. Angew. Chem. Int. Ed. 2012, 51, 5062-5085.
Chiller Too Cold?• Dioxane (m.p. 12oC)
• Cyclohexane (m.p. 6.5oC)
• Benzene (m.p. 5.5oC)
• p-Xylene (m.p. 13oC)
• t-BuOH (m.p. 26oC)
• Cyclopentadiene dimer (m.p. 33oC)
_________________________
• Some chillers don’t temperature regulate
• Always check before going home
• Always set to an appropriate temperature
Never heat a closed system!!
Never heat a closed system!!
Buchwald-Hartwig Cross-Coupling: History and seminal developments
Tyler Lab Group Meeting : 2015/07/01
Alexander J. Kendall
Seechurn, C. C. C. J.; Kitching, M. O.; Coalacot, T. J.; Snieckus, V. Angew. Chem. Int. Ed. 2012, 51, 5062-5085.
Outline• I. A Brief History of Everything: Cross-Coupling for Dummies
• What is cross-coupling• Homocoupling• Cross-coupling• Early catalysis
• II. Early Catalytic Cross-Coupling• Heck, Negishi, and Suzuki• Catalytic transformations• Generalizations about cross-coupling reactions
• III. A Walk Across the Periodic Table: C-C to C-N Coupling Reactions
• Buchwald, Hartwig, and Fu• Phosphine ligands• Current state
• IV. State of the Union: C-N Bond Forming Catalysis
Disclaimer/Caveat • Lots of cross-
coupling reactions
• Focus on:• Seminal
discoveries
• Key players
• General conditions
• Mechanistic detail
Seechurn, C. C. C. J.; Kitching, M. O.; Coalacot, T. J.; Snieckus, V.
Angew. Chem. Int. Ed. 2012, 51, 5062-5085.
http://www.Wikipedia.org/crosscoupling
I. A Brief History of Everything:Cross-Coupling for Dummies
What is Cross-Coupling?• General formula:
• Combining two different organic fragments
• Metal mediated or catalyzed
• Catalytic work pioneered in the 1970’s
Why is Cross-Coupling Difficult?• Homocoupling
Wurtz, A. Ann. Chim. Phys. 1855, 44, 275-312.
Lampman, G. M; Aumiller, J. C. Org. Synth. 1971, 51, 55.
Why is Cross-Coupling Difficult?• Homocoupling
Wurtz, A. Ann. Chim. Phys. 1855, 44, 275-312.
Lampman, G. M; Aumiller, J. C. Org. Synth. 1971, 51, 55.
Why is Cross-Coupling Difficult?• Homocoupling
Glaser, C. Ber. Dtsch. Chem. Ges. 1869, 2, 422-424.Baeyer, A. Berichte Dtsch. Chem. Ges. 1882, 15 (1), 50–56.
Why is Cross-Coupling Difficult?• Homocoupling
Glaser, C. Ber. Dtsch. Chem. Ges. 1869, 2, 422-424.Baeyer, A. Berichte Dtsch. Chem. Ges. 1882, 15 (1), 50–56.
Why is Cross-Coupling Difficult?• Homocoupling
Baeyer, A. Berichte Dtsch. Chem. Ges. 1882, 15 (1), 50–56.
Why is Cross-Coupling Difficult?• Homocoupling
Baeyer, A. Berichte Dtsch. Chem. Ges. 1882, 15 (1), 50–56.
Why is Cross-Coupling Difficult?• Homocoupling
Ullmann, F.; Bielecki, J. Ber. Dtsch. Chem. Ges. 1901, 34, 2174-2185.
Goodbrand, H. B.; Hu, N.-X. J. Org. Chem. 1999, 64 (2), 670–674.
Why is Cross-Coupling Difficult?• Homocoupling
Ullmann, F.; Bielecki, J. Ber. Dtsch. Chem. Ges. 1901, 34, 2174-2185.
Goodbrand, H. B.; Hu, N.-X. J. Org. Chem. 1999, 64 (2), 670–674.
Why is Cross-Coupling Difficult?• Homocoupling
• Isomerization
• Functional group intolerance
• Narrow substrate scope
• Stoichiometric metals
• Harsh reaction conditions
The First Cross-Coupling Catalysts• Job (1923)
• Studying Ni(II)Cl2, PhMgBr, and miscellaneous gasses• H2
• CO
• C2H4
• “Briefly, we believe that we have made progress by introducing catalysis into the field of organometallics.”
Job, A.; Reich, R. C. R. Hebd. Seances Acad. Sci. 1924, 179, 330-332.
The First Cross-Coupling Catalysts• Meerwein (1939)
• Homo and cross-coupling
• Non-selective
Meerwein, H.; Buchner, E.; van Emster, K. J. Prakt. Chem. 1939, 152, 237-266.
The First Cross-Coupling Catalysts• Kharasch (1941-1943)
• Homo and cross-coupling
• Non-selective Kharasch, M. S.; Fields, E. K. J. Am. Chem. Soc. 1941, 63, 2316-2320.
The First Selective Cross-Couplings• Cadiot-Chodkiewicz (1957)
• Castro-Stephens (1963)
Chodkiewicz, W.; Cadiot, P. Hebd. Seances Acad. Sci. 1955, 241, 1055-1057. : Chodkiewicz, W. Ann. Chim. Paris 1957, 2, 819-869. : Castro, C. E.; Stephens, R. D. J. Org. Chem. 1963, 28, 2163.
The First Selective Cross-Couplings• Cadiot-Chodkiewicz (1957)
• Castro-Stephens (1963)
Chodkiewicz, W.; Cadiot, P. Hebd. Seances Acad. Sci. 1955, 241, 1055-1057. : Chodkiewicz, W. Ann. Chim. Paris 1957, 2, 819-869. : Castro, C. E.; Stephens, R. D. J. Org. Chem. 1963, 28, 2163.
Palladium: A trash to treasure story• Discovered by Wollaston (1802)
• Considered a chemical novelty
• Upon his death in 1828, 97% of his Pd stock remained unsold
• Typically Ni and Pt preferred due to high activity
• Exceptions include:• Pd/C
• Lindlar’s catalyst
• Post WWII Europe Develops the Wacker Process (1959)
Wollaston, W. H. Philos. Trans. R. Soc. London 1805, 95, 316-330. : Smidt, J.; Hafner, W.; Jira, R.; Sedlmeier, J.; Sieber, R.; Kojer, H.; Ruttinger, R. Angew. Chem. 1959, 71, 176-182.
II. Early Catalytic Cross-Coupling
Chemistry Nobel Prize 2010• Discovering and developing highly practical
methodologies for C-C bond construction.
• Richard Heck• Developed Pd-catalyzed vinyl cross-coupling
• Worked on Wacker oxidation mechanism
• Ei-ichi Negishi• Developed Ni- and Pd-catalyzed organoaluminum and organozinc
cross-coupling
• Fleshed out transmetalation preferences in cross-coupling (including organoboron)
• Akira Suzuki• Developed Pd-catalyzed organoboron cross-coupling
• The most commonly used cross-coupling reaction
http://www.nobelprize.org/nobel_prizes/chemistry/laureates/2010/
Contributions from Heck• Henry (1966)
• Heck (1966)
Smidt, J.; Hafner, W.; Jira, R.; Sedlmeier, J.; Sieber, R.; Kojer, H.; Ruttinger, R.
Angew. Chem. 1959, 71, 176-182. : Heck, R. F. Synlett 2006, 2855-2860.
The Catalytic Heck Reaction
• Heck (1968)
• Mizoroki (1971)
• Heck (1972)
Heck, R. F. J. Am. Chem. Soc. 1968, 90, 5518-5526. : Mizoroki, T.; Mori, K.; Ozaki, A. Bull. Chem. Soc. Jpn. 1971, 44, 581. : Heck, R.
F.; Nolley, J. P. Jr. J. Org. Chem. 1972, 37, 2320-2322.
Heck Mechanism
Hartwig, J. Organotransition Metal Chemistry; University Science Books: Sausalito,
CA, 2010.
Contributions from Negishi
• Organoaluminum and organozinc coupling partners
• Negishi (1976)
• Negishi (1977)
Negishi, E.; Baba, S. J. Chem. Soc. Chem. Commun. 1976, 596b-597b. : Negishi, E.; King, A. O.; Okukado, N. J. Org. Chem. 1977,
42, 1821-1823. : King, A. O.; Okukado, N.; Negishi, E. J. Chem. Soc. Chem. Commun. 1977, 683-684.
Contributions from Negishi
• Negishi (1977)
• Explored coupling partners (not just unsaturated hydrocarbons)
Suzuki
Hiyama
Stille
Kumada
Negishi
Negishi
Negishi, E. Aspects of Mechanism and Organometallic
Chemistry; Plenum: New York, NY, 1978.
By Any Other Name Would be as Simple
• General mechanism for most* Pd-catalyzed cross-couplings
• Named reactions:
• M = MgX, Kumada (1972)
• M = Zn, Negishi (1977)
• M = SnR3, Stille (1978)
• M = B(OR)2, Suzuki (1979)
• M = SiR3, Hiyama (1988)
*Notable exceptions are: Heck (olefins), Buchwald-Hartwig (amines), and phosphorus cross-coupling
Contributions by Suzuki• Cross-coupling for the common chemist
• Worked for H. C. Brown as post-doc in 1977-1978
• Based on a stoichiometric organoboron study by Heck (1975)
• Persue Negishi’s “hit” of organoboron cross-coupling (1977)• easily handled: air and water stability
• mild reaction conditions
• virtually non-toxic byproducts
• Suzuki & Miyaura (1979)
Miyaura, N.; Suzuki, A. J. Chem. Soc. Chem. Commun. 1979, 866-867.
Suzuki’s Legacy• Dependent on base used for reactivity
Uenishi, J.-I.; Beau, J.-M.; Armstrong, R. W.; Kishi, Y. J. Am. Chem. Soc. 1987, 109, 4756-4758.
Hartwig, J. Organotransition Metal Chemistry; University Science Books: Sausalito, CA, 2010.
Suzuki’s Legacy• Dependent on base used for reactivity
Kishi (1987)
Uenishi, J.-I.; Beau, J.-M.; Armstrong, R. W.; Kishi, Y. J. Am. Chem. Soc. 1987, 109, 4756-4758.
Hartwig, J. Organotransition Metal Chemistry; University Science Books: Sausalito, CA, 2010.
Suzuki’s Legacy• Dependent on base used for reactivity
Kishi (1987)
Palytoxin, 1994
Y. Kishi, Harvard U.
Suh, E. M.; Kishi, Y. J. Am. Chem. Soc. 1994, 116, 11205-11206.
Suzuki’s Legacy• Dependent on base used for reactivity
Kishi (1987)
Palytoxin, 1994
Y. Kishi, Harvard U.
Suh, E. M.; Kishi, Y. J. Am. Chem. Soc. 1994, 116, 11205-11206.
Palythoa toxica
Some Generalizations
• M must be more electropositive than Pd for T/M step
• R can’t have β-hydrogens (tertiary, vinyl, aryl, etc.)
• Aryl:• electron rich Aryls undergo O/A slower and R/E faster
• electron poor Aryls undergo O/A faster and R/E slower
• X: I > OTf > OTs > Br >> Cl
• L:• electron rich L = O/A faster and R/E slower
• electron poor L = O/A slower and R/E faster
• Sterically large L = O/A slower and R/E faster
• Base needs appropriate pKa, can coordinate
Hartwig, J. Organotransition Metal Chemistry; University Science Books: Sausalito, CA, 2010.
Some Generalizations Hartwig, J. Organotransition Metal Chemistry;
University Science Books: Sausalito, CA, 2010.
III. A Walk Across the Periodic Table:C-C to C-N Coupling Reactions
I II III
Seechurn, C. C. C. J.; Kitching,
M. O.; Coalacot, T. J.; Snieckus,
V. Angew. Chem. Int. Ed. 2012,
51, 5062-5085.
Nitrogen Throws its Hat in the Ring• Seminal report by Migita (1983)
Kosugi, M.; Kameyama, M.; Migita, T. Chem. Lett. 1983, 927-928.
Buchwald and Hartwig Take Note• Buchwald (1994)
• Hartwig (1995)
• Buchwald (1995)
Guram, A. S.; Rennels, R. A.; Buchwald,
S. L. Angew. Chem. 1995, 107, 1456-
1459.
Louie, J.; Hartwig, J. F.
Tetrahedron Lett. 1995, 36, 3609-
3612.
Guram, A. S.; Buchwald, S. L. J.
Am. Chem. Soc. 1994, 116,
7901-7902.
Buchwald and Hartwig Take Note• Buchwald (1994)
• Hartwig (1995)
• Buchwald (1995)
Guram, A. S.; Rennels, R. A.; Buchwald,
S. L. Angew. Chem. 1995, 107, 1456-
1459.
Louie, J.; Hartwig, J. F.
Tetrahedron Lett. 1995, 36, 3609-
3612.
Guram, A. S.; Buchwald, S. L. J.
Am. Chem. Soc. 1994, 116,
7901-7902.
Buchwald-Hartwig Mechanism (simple)
Hartwig, J. Organotransition Metal Chemistry; University Science Books: Sausalito, CA, 2010.
A Ligand, a Ligand, My Kingdom for a Ligand!• Buchwald (1995)
• o-Biphenyl, dialkyl phosphine
• DavePhos (1995)
• S-Phos (2005)
• Hartwig (1996)• Bulky heteroleptic phosphines
• Adamantyl (1996)
• Q-Phos (2005)
• Fu (1998)• Bulky, e- rich phosphines
• Used for Ar-Cl cross-coupling
http://www.sigmaaldrich.com
S. Buchwald’s Contributions• Fine-tuned ligand effects
• Suzuki
• Buchwald-Hartwig
• C-O bond formation
• C-F bond formation
• “Ammonia” cross-coupling
• LiN(TMS)2
• LiNH2
Huang, X.; Buchwald, S. L. Org. Lett. 2001, 3, 3417-3419. : Martin, R.; Buchwald, S. L. Acc. Chem. Rev. 2008, 11, 1461-1473. : Surry, D. S.; Buchwald, S. L. Angew. Chem. Int. Ed. 2008, 47, 6338-6361.
S. Buchwald’s Contributions• Fine-tuned ligand effects
• Suzuki
• Buchwald-Hartwig
• C-O bond formation
• C-F bond formation
• “Ammonia” cross-coupling
• LiN(TMS)2
• LiNH2
Huang, X.; Buchwald, S. L. Org. Lett. 2001, 3, 3417-3419. : Martin, R.; Buchwald, S. L. Acc. Chem. Rev. 2008, 11, 1461-1473. : Surry, D. S.; Buchwald, S. L. Angew. Chem. Int. Ed. 2008, 47, 6338-6361.
J. Hartwig’s Contributions• Mechanistic details
• Cross-coupling kinetics
• Individual rate constants (k1, k2, etc.)
Alcazar-Roman, L. M.; Hartwig, J. F. J. Am. Chem. Soc. 2001, 123, 12905-12906.
J. Hartwig’s Contributions• Active species
• Pd(I) dimer
Stambuli, J. P.; Kuwano, R.; Hartwig, J. F. Angew. Chem. 2002, 114, 4940-4942.
G. Fu’s Contributions
• Ar-Cl Activation• Focused on bulky and e- rich phosphines
• Largely pragmatic solutions to synthesis
• Extreme Biaryl Coupling• Sterically demanding
• Exotic substrates
• Electronically demanding
• Typically Works on Suzuki Coupling• Many of his ligands are used for Buch.-Hart. amminations
Fu, G. C. Acc. Chem. Res. 2008, 41, 1555-1564.
IV. State of the Union: C-N Bond Forming Catalysis
Summary• Cross-coupling is a powerful tool for bond formation
• Typically Pd, Ni, or Pt mediated
• Used for aryl-R bond formation (R= alkyl, vinyl, aryl, BR2, NR2, OR, F)
• Very mild conditions can be used thanks to metals being chemoselective
Crabtree, R. H. Chem. Rev. 2015, 115, 127-150.
• Relies on organometallic mechanisms
• Understanding these steps leads to major advances
• Convoluted mechanisms often arise from simple models
• Subtle influences on TS’s have major effects
• Major advances currently being made in ligand design and influence
• The (cross-coupling) world is your oyster
Are You Not Entertained?!• Very e- rich aryl chlorides still difficult
• ex) grisofulvan
• O/A typically rate-limiting step• Better ligands mean faster catalysis• 1 vs 2 e- processes - Pd(I) vs Pd(II) - lend selectivity to
catalysis
• Kinetics not well explored for most systems• Namely Buchwald-type• Structure-function studies lacking
• β-hydride elimination and primary amines are still problematic
• Ligands determine reactivity in modern systems
__________________________
• It’s still voodoo in most cases
"GLADIATOR [Director's cut] (15)". British Board of Film Classification. 2005-08-05
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