Highly enantioselective borane reduction of heteroaryl and heterocyclic ketoxime ethers catalyzed by novel spiroborate ester derived from diphenylvalinol:: Application to the synthesis of nicotine analogues

An asymmetric synthesis for the preparation of nonracemic amines bearing heterocyclic and heteroaromatic rings is described. A variety of important enantiopure thionyl and arylalkyl primary amines were afforded by the borane-mediated enantioselective reduction of O-benzyl ketoximes using 10% of catalyst 10 derived from (S)-diphenylvalinol and ethylene glycol with excellent enantioselectivity, in up to 99% ce. The optimal condition for the first asymmetric reduction of 3- and 4-pyridyl-derived O-benzyl ketoxime ethers was achieved using 30% of catalytic loading in dioxane at 10 degrees C. (S)-N-ethylnornicotine (3) was also successfully synthesized from the TIPS-protected (S)-2-arnino-2-pyridylethanol in 97% ee.