Nickel-Catalyzed Remote Asymmetric Hydroalkylation of Alkenyl Ethers to Access Ethers of Chiral Dialkyl Carbinols

Jia-Wang Wang; Zhen Li; Deguang Liu; Jun-Yang Zhang; Xi Lu; Yao Fu

doi:10.1021/jacs.3c02950

Nickel-Catalyzed Remote Asymmetric Hydroalkylation of Alkenyl Ethers to Access Ethers of Chiral Dialkyl Carbinols

J Am Chem Soc. 2023 May 10;145(18):10411-10421. doi: 10.1021/jacs.3c02950. Epub 2023 Apr 26.

Authors

Jia-Wang Wang^{1

2}, Zhen Li¹, Deguang Liu¹, Jun-Yang Zhang¹, Xi Lu³, Yao Fu¹

Affiliations

¹ Hefei National Research Center for Physical Sciences at the Microscale, iChEM, CAS Key Laboratory of Urban Pollutant Conversion, Anhui Province Key Laboratory of Biomass Clean Energy, University of Science and Technology of China, 230026 Hefei, China.
² School of Plant Protection, Anhui Agricultural University, Hefei, Anhui 230036, China.
³ Key Laboratory of Precision and Intelligent Chemistry, School of Chemistry and Materials Science, University of Science and Technology of China, Hefei, Anhui 230026, China.

PMID: 37127544
DOI: 10.1021/jacs.3c02950

Abstract

Site- and enantio-selective alkyl-alkyl bond formation is privileged in the retrosynthetic analysis due to the universality of sp³-hybridized carbon atoms in organic molecules. Herein, we report a nickel-catalyzed remote asymmetric hydroalkylation of alkenyl ethers via synchronous implementation of alkene isomerization and enantioselective C(sp³)-C(sp³) bond formation. Regression analysis of catalyst structure-activity relationships accelerates the rational ligand modification through modular regulation. This reaction has several advantages for synthesizing chiral dialkyl carbinols and their ether derivatives, including the broad substrate scope, good functional group tolerance, excellent regioselectivity (>20:1 regioisomeric ratio), and high enantioselectivity (up to 95% enantiomeric excess).