[3 + 2] Cycloadditions of alpha,beta-Unsaturated Sultams

Abstract

A highly efficient multigram synthesis of fused sultams (up to 97 g in a single run) via the regio- and diastereoselective [3 + 2] cycloaddition reaction of alpha,beta-unsaturated sultams was developed. The scope and limitations of the method were studied by evaluating common 1,3-dipolar compounds. The reactions with azomethine ylide (obtained from N-(methoxymethyl)-N-(trimethylsilylmethyl)benzylamine), nitrile oxides (generated from chloroximes), and nitrones worked well to give the fused heterocyclic building blocks in a regio- and diastereoselective manner. In turn, attempted reactions with allenes, azides, and several other 1,3-dipolar compounds were not fruitful. A series of functional group transformations were applied to obtain fused bicyclic sultam building blocks as promising derivatives for modern drug discovery. In addition to that, antiviral activity was discovered for some representatives of the synthesized bicyclic sultams.