Gold(I)-Catalyzed Synthesis of 3-Sulfenyl Pyrroles and Indoles by a Regioselective Annulation of Alkynyl Thioethers.

Peter E Simm,Paul W Davies,Jeffery Richardson,Prakash Sekar

doi:10.1021/acscatal.1c01457

Abstract

The combination of nucleophilic nitrenoids and π-acid catalysis has emerged as a powerful tool in heterocycle synthesis. Accessing more varied heterocycle-substitution patterns by maintaining the same reaction pathways across different alkynes remains a challenge. Here we show that Au(I) catalysis of isoxazole-based nitrenoids with alkynyl thioethers provides controlled access to (3 + 2) annulation by a regioselective addition β to the sulfenyl group. The reaction with isoxazole-containing nitrenoids delivers sulfenylated pyrroles and indoles as single regioisomers bearing useful functional groups and structural variety.

Highlights

The combination of nucleophilic nitrenoids and πacid catalysis has emerged as a powerful tool in heterocycle synthesis
N -nucleophilic nitrenoids have proved to be versatile surrogates for nitrene-containing 1,3-dipoles, providing modular and expedient access to a variety of densely functionalized N-heterocycles by a formal (3 + 2) cycloaddition to gold-activated alkynes.[1]. Most of these annulations were first realized with ynamides,[2] and to date there are only a few specific instances where those same transformations have been achieved with other types of alkynes.2j,3 As the alkyne substitution pattern is directly translated into the product, retaining the same transformation across different alkyne types would greatly expand the potential of these convergent annulation methods for complex molecule synthesis
The prospective utility of sulfenylated pyrrole and indole products combined with the diversity of reaction pathways that can be accessed fromisoxazoles identified them as ideal systems for probing the wider utility of alkynyl thioethers in nitrenoid-based annulations

Summary

Introduction

The combination of nucleophilic nitrenoids and πacid catalysis has emerged as a powerful tool in heterocycle synthesis. Sulfursubstituted heterocycles are desirable, not least in medicinal chemistry.[6,7] The increasing number of C−S functionalization methods renders them potentially useful substrates for further elaboration.[8] The prospective utility of sulfenylated pyrrole and indole products combined with the diversity of reaction pathways that can be accessed from (benz)isoxazoles identified them as ideal systems for probing the wider utility of alkynyl thioethers in nitrenoid-based annulations.

Results

Conclusion