Mitchell, D,Coppert, DM,Moynihan, HA,Lorenz, KT,Kissane, M,McNamara, OA,Maguire, AR;

2011

January

Organic Process Research & Development

A Practical Synthesis of Biaryls via a Thermal Decarboxylative Pd-Catalyzed Cross-Coupling Reaction Operating at Moderate Temperature

Validated

()

ARENECARBOXYLIC ACIDS AROMATIC CARBOXYLATES ARYL HALIDES SALTS

15

981

985

The palladium-catalyzed decarboxylative cross-coupling of aminothiophene carboxylate and 1-bromo-4-chlorobenzene to produce 3-amino-2-(4-chlorophenyl)thiophene (2) is described. The cross-coupling proceeds under relatively mild conditions using catalytic Pd(0) and TBAB. Through use of a mixed-solvent system of DMF and NMP, it was possible to operate the cross-coupling system at 80 degrees C. An assessment of carbon dioxide liberation, which provides insight into the reaction operating parameters, is also discussed.

DOI 10.1021/op200030t