A catalytic asymmetric Strecker-type reaction promoted by Lewis acid-Lewisbase bifunctional catalyst

A general asymmetric Strecker-type reaction is reported, catalyzed by the L ewis acid-Lewis base bifunctional catalyst 1. The reaction of trimethylsily l cyanide (TMSCN) with various fluorenyl imines, including n-aldimines and alpha,beta-unsaturated imines. proceeds with good to excellent enantioselec tivities in the presence of a catalytic amount of phenol as additive (20 mo l%) (catalytic system 1), The products were successfully converted to the c orresponding amino acid derivatives in high yields without loss of enantiom eric purity, Furthermore, hydrogenation or dihydroxylation of the products from alpha,beta-unsaturated imines afforded saturated or functionalized ami nonitriles also without loss of enantiomeric purity. The absolute configura tion of the products and a control experiment using catalyst 2 supported th e proposed dual activation of the imine and TMSCN by the Lewis acrid (Al) a nd the Le,vis base moiety (phosphine oxide) of 1. From the mechanistic stud ies including kinetic and NMR experiments of the catalytic species, the rol e of PhOH seems to he a proton source to protonate the anionic nitrogen of the intermediate, Specifically, we have found that TMSCN is more reactive t han HCN in this catalytic sl stem, probably due to the activation ability o f the phosphine oxide moiety of I toward TMSCN. This fact prompted us to de velop the novel catalytic system 2, consisting of 1 (9 mol%), TMSCN (20 mol %) and HCN (1.2 mol eq), This new system afforded comparable results with o btained by system 1 (1 (9 mol%)-TMSCN (2 mol eq)-PhOH (20 mol%)).