Isocyanide-Based Multicomponent Reaction: Cascade α-Acyloxylation/Carboxamidation and [3 + 1+1] Cyclization of I(III)/S(VI)-Ylides.

A metal-free cascade of α-acyloxylation/carboxamidation of I(III)/S(VI)-ylides, carboxylic acids, and isonitriles via a Passerini-like multicomponent reaction is reported. Unexpectedly, [3 + 1+1] cyclization involving I(III)/S(VI)-ylides and two molecules of ethyl isocyanoacetate was observed. The strategy allows for the synthesis of unsymmetrical α,α-disubstituted ketones and functionalized pyrroles with up to 99% yield and wide substrate compatibility. Notably, the procedure has been extended to the late-stage modification of drugs and natural products, offering an elegant complement to the classic Passerini reaction.