Chemoselective Double Annulation of Two Different Isocyanides: Rapid Access to Trifluoromethylated Indole-Fused Heterocycles

Abstract

An unprecedented chemoselective double annulation of α-trifluoromethylated isocyanides with o-acylaryl isocyanides has been developed. This new reaction provides a rapid, efficient, and complete atom-economic strategy for the synthesis of trifluoromethylated oxadiazino[3,2-a]indoles in a single operation from readily available starting materials. Isocyanide insertion into C═O double bonds is disclosed for the first time as indicated by the results of ¹⁸O-labeling experiment. A mechanism for this domino reaction is proposed involving chemoselective heterodimerization of two different isocyanides, followed by indole-2,3-epoxide formation and rearrangement.