The synthesis of chiral amines is of great interest in the pharmaceutical and agrochemical industry and a large number of methods are available that produce enantio enriched amines. However most of these methods rely on classical resolution techniques or chiral auxiliary based approaches. Asymmetric hydrogenation of suitably protected imines or enamines has also been used to produce chiral amines with high enantioselectivity (up to 99%ee), but the current methodology has the disadvantage of low over-all atom economy due to the multi-step sequence. In this context direct methods for the preparation of enantio enriched amines from ketones is highly desired.<br/>Two new and practically useful methods for the highly enantioselective preparation of chiral primary amines based on asymmetric hydrogenation will be presented. The first method rely on highly enantioselective asymmetric hydrogenation of aryl-alkyl substituted ketoximes to provide a wide range of primary amines with good to excellent enantioselectivity (81-98% ee) and yield (83-97%). The second method rely on Direct Asymmetric Reductive Amination of aryl-alkyl ketones with an ammonia source under an hydrogen atmosphere providing chiral primary amines with 83-98% ee and 83-95% yield.<br/>Both methods show a broad substrate scope tolerating variation in steric and electronic properties of both the aryl and alkyl substituents.<br/>Method development, substrate scope and mechanistic investigations will be discussed.

Highly enantioselective preparation of chiral amines by direct asymmetric hydrogenation of ketoximes and by direct asymmetric reductive amination of ketones

249th National Meeting (2015)

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