Stereoselective Synthesis of α-Arylalkylamines by Glycosylation-induced Asymmetric Addition of Organometallic Compounds to Imines

Arylalkylamines are of interest as building blocks for the synthesis of biologically active compounds and as chiral ligands or chiral auxiliaries in stereoselective syntheses [1]. Their stereoselective synthesis has been achieved by enantioselective reduction of ketimines using chiral reagents [2], as for example Corey’s oxaborolidines [3], or proline-derived triacyloxyborohydrides [4]. Particularly efficient asymmetric syntheses of chiral arylalkylamines have been accomplished by Noyori et al. [5] through enantioselective catalysis of hydrogen transfer reactions using a chiral 1,2-diphenyl-ethylenediamine ruthenium catalyst. Enantioselective transferhydrogenationshave also been achieved using a chiral titanocene catalyst [6] or sterically demanding BINOL phosphates [7]. Asymmetric hydrogenation of imines using transition metal catalysts has successfully been used to produce chiral branched amines [8, 9]. An alternative to these reductive procedures consists of the stereoselective addition of organometallic compounds to aldimines [10, 11]. We here report on a new asymmetric addition of organometallic reagents to imines, which is based on the principle of glycosylation-induced asymmetric synthesis [12].