A One‐Pot Asymmetric Sequential Amination‐Alkylation of Aldehydes: Expedient Synthesis of Aliphatic Chiral Amines

A one‐pot asymmetric sequential amination‐alkylation method has been developed for the synthesis of alkyl‐alkyl′ α‐chiral primary amines (aliphatic primary amines with a chiral center adjacent to the nitrogen atom) from aldehydes. In situ aldimine formation from non‐branched, α‐branched, and β‐branched aliphatic aldehydes with ( R )‐ or ( S )‐α‐(methylbenzyl)amine [catalyzed by 5 mol‐% Ti(O i Pr) 4 ] followed by reaction with a methyl, ethyl, or n ‐butyl cuprate complex in the presence of boron trifluoride or an allyl Grignard reagent provides good yield (77–88 %) and diastereomeric excess (77–92 %) for amines 2 or 5 . To further demonstrate the usefulness of this method, several of the secondary amine products ( 2d , 2e , and 5 ) were hydrogenolyzed, providing the corresponding enantioenriched alkyl‐alkyl′ α‐chiral primary amines 3d , 3e , and 6 (86–96 % yield).(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)