Diastereo- and Enantioselective Synthesis of Hexasubstituted Cyclohexanes via a Metal-Organocatalytic Quadruple Cascade Sequence

A quadruple cascade reaction, comprising iminium, enamine-copper, iminium, and enamine catalysis, was investigated. This reaction afforded highly optically active hexasubstituted cyclohexanes from alpha, beta-unsaturated aldehydes, nitromethane, and 2,2,6,6-tetramethylpiperidin-1-yloxy (TEMPO). To enhance the stereoselectivity of the organocatalytic cyclization, TEMPO was incorporated into the cyclohexane skeleton using copper catalysts.