Total regioselective control of the carbonylative coupling of 1-heptyne with aniline and N-methyl aniline catalyzed by palladium(II) and phosphine ligand

The carbonylative coupling of 1-heptyne (1a) with aniline (2a) has been successfully achieved in the presence of Pd(OAc)(2) and a suitable bidentate phosphine ligand and solvent. The gem-alpha,beta-unsaturated amide (3aa) was formed as a predominant product in the presence of the catalytic system Pd(OAc)(2)/1,3-bis(diphenylphosphino)propane (dppp)/p-toluenesulfonic acid (p-TsOH)/CO in THF as a solvent. While the use Pd(OAc)(2) and 1,4-bis(diphenylphosphino)butane (dppb), under syngas (CO/H-2) conditions and in CH2Cl2 as a solvent, affords the trans-alpha,beta-unsaturated amide (4aa) as the major product. A minor cyclic product (5aa) was formed via the double carbonylation reaction. The regioselective carbonylative coupling reaction was also successfully applied to AT-methyl aniline (2b) with 1-heptyne (1a) producing excellent yields of tertiary unsaturated amides. (C) 2002 Elsevier Science B.V. All rights reserved.