Copper-catalyzed cross-coupling of amides and potassium alkenyltrifluoroborate salts: a general approach to the synthesis of enamides

Potassium alkenyltrifluoroborate salts undergo coupling with amides to give enamides using a catalytic amount of Cu(OAc)(2) under mild oxidative conditions. The air and water stable alkenyltrifluoroborate salts offer a practical alternative to the use of alkenyl halides and alkenylboronic acids as cross-coupling partners. A range of amides participate in the cross-coupling, including heterocyclic amides, imides, carbamates, benzamides, and acetamides. Optimization studies established two sets of conditions, best suited to either high pK(a) or low pK(a) amide substrates. Lower pK(a) amide substrates worked best using a dichloromethane solvent system in the presence of 4 angstrom molecular sieves, 10 mol % Cu(OAc)(2), and 20 mol % N-methylimidazole. Higher pK(a) amide substrates worked best using a 'ligandless' protocol using a 1:1 dichloromethane/DMSO solvent system in the presence of 4 angstrom molecular sieves and 10 mol % Cu(OAc)(2). The cross-coupling reactions occur stereospecifically with retention of alkene configuration from the alkenyltrifluoroborate salt. The mild reaction conditions employed are tolerant of various functionalities, including nitro, acetals, alkyl and aryl halides, and alpha,beta-unsaturated carbonyls. Finally, the importance of copper sources and the presence of minor impurities were investigated. (C) 2010 Elsevier Ltd. All rights reserved.