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

• Published in: Organic letters 2024-07, Vol.26 (29), p.6263
• Main Authors: Shen, Dan-Ting, Wu, Wen-Rong, Zou, Wen-Xuan, Hu, Qiong, Wei, Jiaohang, Bao, Mei-Zhu, Liu, Xiang, Zhang, Shang-Shi
• Format: Article
• Language: English
• ISSN: 1523-7052; 1523-7052
• DOI: 10.1021/acs.orglett.4c02255

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.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.