Cuprous chloride accelerated Stille reactions. A general and effective coupling system for sterically congested substrates and for enantioselective synthesis

A major limitation of Stille coupling reactions arises from steric screenin g, especially in the vinylstannane component. For example, with 1-substitut ed vinylstannanes and aryl perfluoroalkanesulfonates or halides negligible or low yields are generally observed, due to very slow reaction rates and c ompeting cine substitution. This problem has been overcome in the present w ork through the discovery and application of cuprous chloride as an acceler ant for coupling. Thus, using a protocol for coupling that involves the sys tem Pd(PPh3)(4)/CuCl/LiCl under anaerobic conditions in dimethyl sulfoxide solution at 60 degrees C, a wide variety of Stille coupling reactions which otherwise fail can be effected in excellent yield (Table 1). The process h as been applied to the enantioselective synthesis of the chiral 1-(arylethy l)alkylcarbinol 26, a model for the natural product nicandrenone. The accel eration of Stille coupling by cuprous chloride can be explained by the inte rvention of a vinylstannane --> vinylcopper(I) transmetalation step and a s ubsequent accelerated coupling of ArPdX with the vinylcopper(I) intermediat e.