Stereoselective Synthesis of Cyclobutanes by Contraction of Pyrrolidines.

Chunngai Hui,Carsten Strohmann,Lukas Brieger,Andrey P Antonchick

doi:10.1021/jacs.1c10175

Abstract

Here we report a contractive synthesis of multisubstituted cyclobutanes containing multiple stereocenters from readily accessible pyrrolidines using iodonitrene chemistry. Mediated by a nitrogen extrusion process, the stereospecific synthesis of cyclobutanes involves a radical pathway. Unprecedented unsymmetrical spirocyclobutanes were prepared successfully, and a concise, formal synthesis of the cytotoxic natural product piperarborenine B is reported.

Highlights

We report a contractive synthesis of multisubstituted cyclobutanes containing multiple stereocenters from readily accessible pyrrolidines using iodonitrene chemistry
Lewis acid catalysis have been reported, in which heterocoupling of two different alkenes presents a very challenging task
The development of a new synthetic method for the direct stereocontrolled preparation of substituted cyclobutanes is of great importance

Summary

Introduction

We report a contractive synthesis of multisubstituted cyclobutanes containing multiple stereocenters from readily accessible pyrrolidines using iodonitrene chemistry. The stereospecific synthesis of cyclobutane from 1,1-diazene15−18 (isodiazene) derived from pyrrolidine was pioneered by Dervan’s group.19−23 The stereospecificity of the ring contraction is a result of the rapid C−C bond formation from the thermally generated singlet 1,4-biradical via nitrogen extrusion, affording the cyclobutanes stereoretentively.

Results

Conclusion