Catalytic enantioselective oxidative coupling of saturated ethers with carboxylic acid derivatives

Gang Wang,Xiaodong Xin,Yudao Ma,Lei Liu,Zehua Wang,Gang Lu

doi:10.1038/s41467-019-08473-x

Gang Wang, Xiaodong Xin + Show 4 more

Open Access

https://doi.org/10.1038/s41467-019-08473-x

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Journal: Nature Communications	Publication Date: Feb 4, 2019
Citations: 32	License type: open-access

Affiliation: Shandong University

Abstract

Catalytic enantioselective C–C bond forming process through cross-dehydrogenative coupling represents a promising synthetic strategy, but it remains a long-standing challenge in chemistry. Here, we report a formal catalytic enantioselective cross-dehydrogenative coupling of saturated ethers with diverse carboxylic acid derivatives involving an initial oxidative acetal formation, followed by nickel(II)-catalyzed asymmetric alkylation. The one-pot, general, and modular method exhibits wide compatibility of a broad range of saturated ethers not only including prevalent tetrahydrofuran and tetrahydropyran, but also including medium- and large-sized cyclic moieties and acyclic ones with excellent enantioselectivity and functional group tolerance. The application in the rapid preparation of biologically active molecules that are difficult to access with existing methods is also demonstrated.

Highlights

Catalytic enantioselective C–C bond forming process through cross-dehydrogenative coupling represents a promising synthetic strategy, but it remains a long-standing challenge in chemistry
Impressive progress has been made in enantioselective cross-dehydrogenative coupling (CDC) during the last decade, current studies predominantly focused on N-arylated amine[7,8,9,10,11,12,13,14,15,16,17,18,19] and xanthese substrates[20,21,22,23,24,25]
Two major challenges hamper the design of catalytic asymmetric oxidative coupling starting from saturated ethers

Summary

Introduction

Catalytic enantioselective C–C bond forming process through cross-dehydrogenative coupling represents a promising synthetic strategy, but it remains a long-standing challenge in chemistry. We report a formal catalytic enantioselective cross-dehydrogenative coupling of saturated ethers with diverse carboxylic acid derivatives involving an initial oxidative acetal formation, followed by nickel(II)-catalyzed asymmetric alkylation. Each catalytic asymmetric method is typically suitable for a single class of tetrahydrofuran (THF), tetrahydropyran (THP), or acyclic ether skeleton with a specific α-alkyl substitution pattern[31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46]. A general and modular catalytic enantioselective method to rapidly access saturated ethers with diverse skeletons and α-alkyl substituent patterns from readily available starting materials has remained elusive. The application in the rapid preparation of biologically active molecules that are difficult to access with existing methods has been demonstrated

Methods

Results

Conclusion