Copper(I)-catalyzed asymmetric 1,6-conjugate allylation

Chang-Yun Shi,Liang Yin,Zhi-Zhou Pan,Ping Tian

doi:10.1038/s41467-020-19293-9

Abstract

Catalytic asymmetric conjugate allylation of unsaturated carbonyl compounds is usually difficult to achieve, as 1,2-addition proceeds dominantly and high asymmetric induction is a challenging task. Herein, we disclose a copper(I)-NHC complex catalyzed asymmetric 1,6-conjugate allylation of 2,2-dimethyl-6-alkenyl-4H-1,3-dioxin-4-ones. The phenolic hydroxyl group in NHC ligands is found to be pivotal to obtain the desired products. Both aryl group and alkyl group at δ-position are well tolerated with the corresponding products generated in moderate to high yields and high enantioselectivity. Moreover, both 2-substituted and 3-substituted allylboronates serve as acceptable allylation reagents. At last, the synthetic utility of the products is demonstrated in several transformations by means of the versatile terminal olefin and dioxinone groups.

Highlights

Catalytic asymmetric conjugate allylation of unsaturated carbonyl compounds is usually difficult to achieve, as 1,2-addition proceeds dominantly and high asymmetric induction is a challenging task
Non-enantioselective methods based on different allyl metal species have been disclosed in the past several decades[4]
The catalytic asymmetric conjugate addition with allyl metal reagents is still in its infancy as such a reaction is not easy to achieve due to the competitive 1,2-addition and the difficulty in the asymmetric induction

Summary

Introduction

Catalytic asymmetric conjugate allylation of unsaturated carbonyl compounds is usually difficult to achieve, as 1,2-addition proceeds dominantly and high asymmetric induction is a challenging task. The phenolic hydroxyl group in NHC ligands is found to be pivotal to obtain the desired products Both aryl group and alkyl group at δ-position are well tolerated with the corresponding products generated in moderate to high yields and high enantioselectivity. Both 2-substituted and 3-substituted allylboronates serve as acceptable allylation reagents. The proposed six-membered ring transition state formed by the coordination of the allyl metal species to carbonyl group allows excellent asymmetric induction. Copper(I)-catalyzed asymmetric 1,6-addition with alkyl metal reagents (such as organozinc reagent and Grignard reagent) has been reported as a powerful tool to regioselectively construct carbon-carbon bonds[34,35,36,37,38,39,40,41,42,43,44,45,46]. In view of the bulky steric hindrance around the carbonyl group and the relative stability of the lactone moiety, it is envisioned that the highly nucleophilic allylcopper(I) species would not touch the carbonyl group in the dioxinone and would attack the less hindered conjugate carbon-carbon double bond to give the desired 1,6-allylation

Methods

Results

Conclusion