Asymmetric Synthesis of 2-Thiocyanato-2-(1-aminoalkyl)-substituted 1-Tetralones and 1-Indanones with Tetrasubstituted Carbon Stereogenic Centers via Cooperative Cation-Binding Catalysis

摘要

In this study, the concept of cooperative cation-binding catalysis was applied for direct generation of two contiguous trisubstituted and tetrasubstituted stereogenic centers. Using the readily accessible chiral oligoethylene glycol (oligoEG) as a cation-binding catalyst, asymmetric Mannich reactions of alpha-thiocyanato cyclic ketones as Mannich donors were performed with alpha-amidosulfones as the bench-stable imine precursors in the presence of potassium fluoride as the base, affording 2-thiocyanato2-( 1-aminoalkyl)-substituted 1-tetralones and 1-indanones possessing fully substituted C-SCN centers. The salient features of this process include (i) a transition metal-free and operationally simple pro-cedure, (ii) direct use of a-amidosulfones as bench-stable precursors of sensitive imines, (iii) direct enolization of racemic cyclic alpha-thiocyanato ketones and (iv) excellent stereoselectivity with up to 99% ee and > 20:1 diastereoselectivity (anti:syn). This protocol is easily scalable and provides a new approach for the syntheses of some biologically relevant products possessing fully substituted C-SCN centers.