Asymmetric Au-catalyzed cycloisomerization of 1,6-enynes: An entry to bicyclo[4.1.0]heptene

Alexandre Pradal,Véronique Michelet,Chung-Meng Chao,Patrick Y Toullec

doi:10.3762/bjoc.7.116

Abstract

A comprehensive study on the asymmetric gold-catalyzed cycloisomerization reaction of heteroatom tethered 1,6-enynes is described. The cycloisomerization reactions were conducted in the presence of the chiral cationic Au(I) catalyst consisting of (R)-4-MeO-3,5-(t-Bu)2-MeOBIPHEP-(AuCl)2 complex and silver salts (AgOTf or AgNTf2) in toluene under mild conditions to afford functionalized bicyclo[4.1.0]heptene derivatives. The reaction conditions were found to be highly substrate-dependent, the best results being obtained in the case of oxygen-tethered enynes. The formation of bicyclic derivatives, including cyclopropyl pentasubstituted ones, was reported in moderate to good yields and in enantiomeric excesses up to 99%.

Highlights

Metal-catalyzed cycloisomerization reactions of 1,n-enynes have emerged as efficient processes that contribute to sustainable development and atom economy concepts [1,2,3,4,5,6,7,8]
Following our previous work with chiral gold catalysts [46], we report a comprehensive study on gold-catalyzed enantioselective synthesis of bicyclo[4.1.0]heptenes, focusing on the scope and limitations of such systems
We have contributed to the development of an asymmetric gold-catalyzed cycloisomerization reaction allowing the formation of oxa- and aza-bicyclo[4.1.0]heptene derivatives

Summary

Introduction

Metal-catalyzed cycloisomerization reactions of 1,n-enynes have emerged as efficient processes that contribute to sustainable development and atom economy concepts [1,2,3,4,5,6,7,8]. The reaction was conducted at 60 °C or 70 °C with good conversions and ee’s (Table 1, entries 6–8), the best results being obtained in toluene.

Results

Conclusion