Single enantiomer free-radical chemistry - Lewis acid-mediated reductions of racemic halides using chiral non-racemic stannanes

Additions of one to two equivalents of Lewis acids that include magnesium salts to free-radical reduction reactions involving ester functionalized radicals and (1 R,2S,5R)-menthyldiphenyltin hydride 4, bis((1 R,2S,5R)-menthyl)phenyltin hydride 5, tris((1R.2S.SR)-menthyl)tin hydride 6. bis((1R,2S,5R)-menthyl)-[8-(N,N-dimethylamino)naphthyl]tin hydride 12, bis((1R,2S,5R)menthyl)-[1-((S)-N.N-dimethylaminoethyl)phenyl]tin hydride 13 or 3alpha-dimethylstannyl-5alpha-cholestane 14 result in remarkable enantioselectivities. Examples include (S)-naproxen ethyl ester 16, produced in 74% yield and greater than 99(V,) ee at -78degreesC from the bromide and 5 in the presence of MgBr2, and ethyl (R)-N-trifluoroacetyl-D-phenylglycinate 18, obtained in 78% yield and 99% ee under identical conditions. Kinetic and computational studies provide insight into the origins of these observations. (C) 2003 Elsevier Ltd. All rights reserved.