Cuprous chloride accelerated Stille reactions. A general and effective coupling system for sterically congested substrates and for enantioselective synthesis
Xj. Han et al., Cuprous chloride accelerated Stille reactions. A general and effective coupling system for sterically congested substrates and for enantioselective synthesis, J AM CHEM S, 121(33), 1999, pp. 7600-7605
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.