DDQ-Promoted Mild and Efficient Metal-Free Oxidative α-Cyanation of <i>N</i>-Acyl/Sulfonyl 1,2,3,4-Tetrahydroisoquinolines

Abstract

A mild and highly efficient metal-free oxidative α-cyanation of N-acyl/sulfonyl 1,2,3,4-tetrahydroisoquinolines (THIQs) has been accomplished at an ambient temperature via DDQ oxidation and subsequent trapping of N-acyl/sulfonyl iminium ions with (n-Bu)3SnCN. Employing readily removable N-acyl/sulfonyl groups as protecting groups rather than N-aryl ones enables a wide range of applications in natural product synthesis. The synthetic utility of the method was illustrated using a short and efficient formal total synthesis of (±)-calycotomine in three steps.

Keywords

• tetrahydroisoquinoline
• oxidation
• C(sp³)-H activation
• α-cyanation