Ferrocenyl-substituted tetrahydrothiophenes via formal [3 + 2]-cycloaddition reactions of ferrocenyl thioketones with donor-acceptor cyclopropanes.

Grzegorz Mlostoń,Mateusz Kowalczyk,Daniel B Werz,Peter G Jones,André U Augustin

doi:10.3762/bjoc.16.109

Abstract

Ferrocenyl thioketones reacted with donor–acceptor cyclopropanes in dichloromethane at room temperature in the presence of catalytic amounts of Sc(OTf)3 yielding tetrahydrothiophene derivatives, products of formal [3 + 2]-cycloaddition reactions, in moderate to high yields. In all studied cases, dimethyl 2-arylcyclopropane dicarboxylates reacted with the corresponding aryl ferrocenyl thioketones in a completely diastereoselective manner to form single products in which (C-2)-Ar and (C-5)-ferrocenyl groups were oriented in a cis-fashion. In contrast, the same cyclopropanes underwent reaction with alkyl ferrocenyl thioketones to form nearly equal amounts of both diastereoisomeric tetrahydrothiophenes. A low selectivity was also observed in the reaction of a 2-phthalimide-derived cyclopropane with ferrocenyl phenyl thioketone.

Highlights

Ferrocenyl thioketones reacted with donor–acceptor cyclopropanes in dichloromethane at room temperature in the presence of catalytic amounts of Sc(OTf)3 yielding tetrahydrothiophene derivatives, products of formal [3 + 2]-cycloaddition reactions, in moderate to high yields
Functionalized tetrahydrothiophenes constitute an important group of five-membered sulfur heterocycles; many of them, both chiral and achiral, with biotin as the best-known representative, form the key motif in numerous compounds of great practical importance [1,2]
The present study showed once more that ferrocenyl/aryl and ferrocenyl/alkyl thioketones 8 are versatile and useful building blocks for a simple and efficient preparation of ferrocenyl-functionalized five-membered sulfur heterocycles

Summary

Introduction

Functionalized tetrahydrothiophenes constitute an important group of five-membered sulfur heterocycles; many of them, both chiral and achiral, with biotin as the best-known representative, form the key motif in numerous compounds of great practical importance [1,2]. In the course of these studies, a non-orthodox stepwise mechanism of the 1,3-dipolar cycloaddition was established by experiments performed with the sterically crowded thiocarbonyl S-methanide 1, derived from 2,2,4,4-tetramethyl-3-thioxocyclobutanone and extremely electron-deficient ethylenes 2 such as (E)- and (Z)-dialkyl dicyanobutenoates (R = CO2Me) [6], tetracyanoethylene (R = CN) [7] or (E)- and (Z)-1,2-bis(trifluoromethyl)ethylene-1,2-dicarbonitrile (R = CF3) [8]. Both five-membered spirotetrahydrothiophenes 3 and seven-membered S,N-heterocycles (ketene imines) 4 were observed in the course of these reactions (Scheme 1).

Objectives

Results

Conclusion