Nickel-Catalyzed Cross-Coupling of Amino-Acid-Derived Alkylzinc Reagents with Alkyl Bromides/Chlorides: Access to Diverse Unnatural Amino Acids

Fei-Hu Gou; Ming-Jian Ma; An-Jun Wang; Liang Zhao; Haoyang Wang; Jie Tong; Ze Wang; Zhen Wang; Chun-Yang He

doi:10.1021/acs.orglett.1c03884

Nickel-Catalyzed Cross-Coupling of Amino-Acid-Derived Alkylzinc Reagents with Alkyl Bromides/Chlorides: Access to Diverse Unnatural Amino Acids

Org Lett. 2022 Jan 14;24(1):240-244. doi: 10.1021/acs.orglett.1c03884. Epub 2021 Dec 27.

Authors

Fei-Hu Gou¹, Ming-Jian Ma¹, An-Jun Wang¹, Liang Zhao¹, Haoyang Wang², Jie Tong³, Ze Wang¹, Zhen Wang⁴, Chun-Yang He¹

Affiliations

¹ Key Laboratory of Biocatalysis & Chiral Drug Synthesis of Guizhou Province, Generic Drug Research Center of Guizhou Province, Zunyi Medical University, Zunyi, Guizhou 563000, China.
² Laboratory of Mass Spectrometry Analysis, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 200032, China.
³ School of Medicine, Yale University, New Haven, Connecticut 06510, United States.
⁴ School of Pharmaceutical Science, University of South China, Hengyang 421001, China.

PMID: 34958223
DOI: 10.1021/acs.orglett.1c03884

Abstract

Unnatural α-amino acids are important synthetic targets in the field of peptide science. Herein we report an efficient, versatile, and straightforward strategy for the synthesis of homophenylalanine derivatives via the nickel-catalyzed Csp³-Csp³ cross-coupling of (fluoro)benzyl bromides/chlorides with natural α-amino-acid-derived alkylzinc reagents. The current protocol features the advantages of a low-cost nickel catalyst system, synthetic convenience, and the tolerance of rich functionality and stereochemistry.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Nickel*

Substances

Nickel