Transition-metal catalyzed C—C bond cleavage

2011.09.17

Chaoren Shen

Wanbin Group Literature Seminar

1.Decarboxylation(Cu Ag Pd Rh)

2. Decarbonylation(Ni Pd)

3. Deacylation(Pd Rh)

Jon A. Tunge（ University of Kansas, USA ）Lukas J. Goossen（ TU Kaiserslautern, Germany ）Seijiro Matsubara and Takuya Kurahashi （Kyoto University）Hideki Yorimitsu and Koichiro Oshima（Kyoto University）Andrew G. Myers (Harvard)Lei Liu（Tsinghua Univ.）

Decarboxylation1. Decarboxylative Suzuki cross-coupling2. Decarboxylative Heck reaction3. Decarboxylative allylation4. Decarboxylative Aldol and Mannich reaction5. Decarboxylative Clasien rearrangement6. Decarboxylative Michael addition

Advantages of carboxylic acid compound as starting material for cross-coupling:1.large scale industrial production2.Easy to preparation. (Molecular oxygen oxidation catalyzed by heterogeneous catalysis from side-chain aromatic compound. Water is side-product

1. High temperature2. Need stoichiometric Mecury, Sliver or Copper3. In system of protonic solvent, the decarboxylativeintermediate is usually transformed into alkane or arene

Nilsson M., Acta. Chem. Scand., 1966, 20, 423-426

COOH

NO2

ICuIQuinoline

>250 CNO2

less than 20%

Origin of Decarboxylative Suzuki cross-coupling

Lukas J. GoossenScience, 2006, 313,662-664JACS, 2007, 129, 4824-4833ACIE, 2008, 47, 7103-7106JACS, 2008, 130, 15248-15249

aryl-copper species copper-mediated Ullmann-type coupling

Bimetallic catalystcopper complex capable of mediating the strongly endothermic extrusion of CO2 from arenecarboxylates

COOH

NO2

Cl

Br

Cl

NO2

2 mol% Pd(acac)26 mol% iPrPPh2

1.5 eq. CuCO31.5 eq. KFNMP, 120 C,24h

ClCl

NO2

O2N

1.Addition of KF: the formation of ArC(O)OCuF seems tolower the decarboxylation barrier

2.Optimization of the steric and electronic propertiesof the phosphine ligand coordinated to Pd

3.azeotropic distillation/additon of molecular sieves: limitingthe competing protonation of the aryl copper intermediate,

4.the yields collapsed when most CuCO3 replaced byK2CO3, an outcome attributed to an irreversible reductionof Cu(II) to Cu(I).Clearly, an alternative protocol that is catalytic in bothmetals-as is required for industrial-scaleapplications-- would only be possible with morestable but less effective Cu(I) complexes, at theexpense of an increased reaction temperature.

Added halide ions (which would be released in the transmetallationstep) retarded this decarboxylation.

the halides are in competition with the carboxylates for coordination sites at the copper.

A key to achieving a general process catalytic in both metals is to induce a stronger preference of the copper for carboxylate over bromide ions by tuning its ligandenvironment.

Decrease the use of 3A MS: carboxylic acid mixed with base, then heated into salt and dehydration in prior of reaction

It was successfully scaled up to molar quantities at SaltigoGmbH, with 20% toluene added to adjust the solvent boiling point to 160℃ and allow azeotropic drying of the reaction mixture

L. J. Goossen, G. Deng, patent pending, filing number PCT-DE2006-001014 (2005).

0.3mol% CuI and 0. 06mol% Pd(acac)2

N

N

NO

NH

NN N

Tasosartan (an angiotensin IIreceptor antagonist)

N

NO

O

NNH

NN

OH

O

OO

Olmesartan

HO N

N

HNN N

N

Cl Losartan

N

NO

NHN N

N

N

N

O

HO NNH

NN

O

Candesartan

Irbesartan

CNOHO

N

N

N

N

Telmisartan((Boehringer Ingelheim))

洛沙坦

O

OHO

N

NNH

NN

Valsartan(Boehringer Ingelheim)

ACIE. 2010, 49, 1111 –1114

Chem. Eur. J. 2010, 16, 3906–3909

One-Pot Three-Component Decarboxylative Coupling

Adv. Synth. Catal. 2011, 353, 337 – 342

ACIE, 2008, 47, 3043—3045

JACS, 2009, 131, 5738–5739

a bulky, electron-rich ligandsimilar in structure to dppp

No addition of Cu

Decarboxylation is the rate-limiting step in the catalytic cycle.

In IN4, the Pd center is coordinatively saturated, bidentatephosphine ligands are favored forpreventing decarbonylationto form an inactive Pd-CO complex

a value whose magnitude is consistent with the experimentaltemperature required for the reaction (ca 150 C).

A possible explanation for the outstanding performanceof diglyme is that diglyme can coordinate to K+, therebyfacilitating the complexation between CuI and C6F5CO2-

ACIE. 2009, 48, 9350 –9354

copper-only system

Diarylated by-products are observed

Decarboxylative reaction occur before oxdative addition of Cu(I) or at the stage of Cu(III) ?

strong steric repulsionin the hexacoordinated speciesOxidative addition constitutes the rate-limiting step in

pathway I

Decarboxylation is the rate-limiting step in pathway II

SheppardJACS1968, 90, 2186JACS 1970, 92,5419

potassium salts of 2-(3-pyridyl)-, 2-(4-pyridyl)-, and 2-phenyl acetic acids could not undergo this coupling reaction

breaking the C(sp3)-COOH bond: chelation-assisted activation of C(sp2)-C(sp3) bond

Inspired by the recent fascinating work of Oshima et al. onchelation-assisted activation of Csp3-Csp3 bond

OL, 2011,13, 4240–4243

Y-M Liang, C-J Li, ACIE, 2009,48, 792—795

TMEDA as ligand, TBHP as oxidant

Intermolecular decarboxylative and CDC

F. Glourius, JACS, 2009, 131, 4194—4195Decarboxylation/C-H Activation

5 mol% DMSO

Carboxylic Acids as Traceless Directing Groups for C-H activation

Igor Larrosa, ACIE, 2011, Early View DOI: 10.1002/anie.201103720

first meta-selective direct C-H arylation

3-methoxyphenylboronic acid costs ca. ￡2,310 per mol, compared to ￡24 for the equivalent 2-methoxybenzoic acid (Aldrich) used to synthesize compound 4l

Suzuki coupling: the only other straightforward approach to this important class of compounds using the corresponding meta-substituted aryl boronic acids.

However, the synthesis of these starting materials generally involves several steps, which is reflected in their higher cost (ca. 500–1000 times more expensive than the equivalent benzoic acid)

Hypothesis: decarboxylation of the more-hindered 3 is much faster than that of 1.

Which metal is responsible for decarboxylation? Pd or Ag?

Ag is not responsible for thedecarboxylation step in this process

Chem. Commun., 2009, 7176-7178

“Pd(II) salts have only been reported to mediate the protodecarboxylation of highly electron-rich benzoic acids, whereas our system seems to be independent of the electronic nature of the initial ortho substituent.”

Ya-Ming Li, Chunying Duan, Synlett 2011, 12, 1713–1716

Decarboxylative Heck reaction

JACS，2002，124, 11250—11251OL, 2004, 6, 433—436JACS, 2005, 127, 10323—10333

Andrew G. Myers(Harvard)

5% DMSO-DMF: DMSO-Pd complex

The evolutionof CO2 (precipitate formed in lime water) The disappearance of resonances associated with 1aPeaks for a new intermediate with arene resonances upfield of those of 1a, Qunched by styrene with simultaneous precipitation of a solid presumed to bePd(0)

decarboxylative or ortho-palladation reaction

Jin-Heng Li, OL, 2009,1139—1142

Decarboxylative Michael additionPinjing Zhao (NCSU)Angew. Chem. 2009, 121, 6854 –6858

M. Shibasaki JACS, 2009,131, 9610—9611

Decarboxylative Aldol and Mannich reactionM. Shair (Harvard), JACS, 2003, 125, 2852—2853

Craig( Imperial College London )OL, 2005，5: 463—465ACIE, 2005, 44, 618—621Chem. Commun., 2008, 3408-3410

Decarboxylative Clasien rearrangement

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Transition-metal catalyzed C—C bond cleavage