Asymmetric Synthesis Of α-Thiocyanato-β-amines Via Cooperative Cation Binding Catalysis

Thiocyanates is a kind of natural product with unique biological activity,thiocyanato also has a wide application in organic chemistry.But because of its difficulty in synthesis,especially the literature on the synthesis of chiral thiocyanates is rarely reported,hindered the further study of its activity.In this paper,the concept of cooperative cation binding catalysis was elegantly applied for the direct generation of two contiguous tertiary and quaternary stereogenic centers.Using a highly accessible chiral oligoethylene glycol(oligoEG)as a cation-binding catalyst,asymmetric Mannich reaction of α-thiocyanato cyclic ketones as Mannich donors was performed with α-amido sulfones as bench-stable imine precursors in the presence of KF as a base,affording α-thiocyanato-β-amines possessing tetrasubstituted C-SCN centers.The salient features of this process include(a)a transition metal free and operationally simple procedure,(b)direct use of α-amido sulfones as bench-stable precursors of sensitive imines(c)direct enolization of racemic α-thiocyanato cyclic ketones and(d)excellent stereoselectivity up to 99% ee and >20:1 diastereoselectivity(anti:syn).Thus,this protocol can easily be scalable and provides a new approach for the syntheses of some biologically relevant products possessing tetrasubstituted C-SCN centers.