Asymmetric radical carboesterification of dienes

Xiaotao Zhu,Daliang Li,Meirong Huang,Wujun Jian,Xinhao Zhang,Yajun Li,Hongli Bao

doi:10.1038/s41467-021-26843-2

Abstract

The straightforward strategy of building a chiral C-O bond directly on a general carbon radical center is challenging and stereocontrol of the reactions of open-chain hydrocarbon radicals remains a largely unsolved problem. Advance in this elementary step will spur the development of asymmetric radical C-O bond construction. Herein, we report a copper-catalyzed regioselective and enantioselective carboesterification of substituted dienes using alkyl diacyl peroxides as the source of both the carbon and oxygen substituents. The participation of external acids in this reaction substantially extends its applicability and leads to structurally diverse allylic ester products. This work represents the advance in the key elementary reaction of intermolecular enantioselective construction of C-O bond on open-chain hydrocarbon radicals and may lead to the discovery of other asymmetric radical reactions.

Highlights

H N diamorphineS Cys hydroxylation of alkanes d State-of-the-art of intermolecular C-O bond formation on [C] radicals
The straightforward strategy of building a chiral C-O bond directly on a general carbon radical center is challenging and stereocontrol of the reactions of open-chain hydrocarbon radicals remains a largely unsolved problem
The construction of a chiral C–O bond directly on a carbon radical center is a powerful elementary reaction. This elementary reaction is highly useful because it could deliver compounds containing chiral C–O bonds which are ubiquitous in natural products and bioactive molecules (Fig. 1b) but stereocontrol remains an important unsolved problem

Summary

H N diamorphine

S Cys hydroxylation of alkanes d State-of-the-art of intermolecular C-O bond formation on [C] radicals. In the category of radical asymmetric transformations, Buchwald et al developed a two-component asymmetric oxyfunctionalization of alkenes with intramolecular carboxylic acid groups[36,37,40], and Liu et al reported enantioselective oxyfunctionalization of alkenes with linked alcohols and oximes[39,41,44,45] These reports provide a solution to the long-standing unresolved problems concerning the stereocontrol of acyclic radicals, but with intramolecular oxygen functionalities. We report our work on asymmetric carboesterification of dienes (Fig. 1e) This type of reaction represents an advance on the elementary reaction, and on the stereocontrol of acyclic radicals with intermolecular oxygen functionalities. During the reviewing process of this paper, the Chen and Xiao group reported elegant photoinduced copper-catalyzed asymmetric carboesterifications of dienes with redox-active oxime esters[47,48,49]

Results

E Observed copper species and proposed catalytic cycle solution crystallization

Methods