An efficient diastereoselective reduction of alpha-alkyl-beta-keto carbonitriles with TiCl4/BH3 or LiBH4/CeCl3 to syn- or anti-alpha-alkyl-beta-hydroxy carbonitriles

alpha -Alkyl-beta -keto carbonitriles can be reduced stereoselectively to s yn- and anti-alpha -alkyl-beta -hydroxy carbonitriles. The stereoselectivit y can be explained in terms of properties of the Lewis acid employed. TiCl4 in noncoordinating solvents such as dichloromethane, followed by reduction with the borane/pyridine complex, predominantly led to the syrz-alpha -alk yl-beta -hydroxy carbonitriles, according to a chelate transition state, wh ereas CeCl3 in coordinating solvents such as THF, followed by reduction wit h LiBH4, predominantly led to the anti-isomers, in agreement with an open-c hain transition state. The reduction to syn-alpha -alkyl-beta -hydroxy carb onitriles is the first general preparation of these compounds.