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

Unnatural alpha-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 Csp(3)-Csp(3) cross-coupling of (fluoro)benzyl bromides/chlorides with natural alpha-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.

Automated summary

The study presents an efficient, versatile, and straightforward strategy for the synthesis of homophenylalanine derivatives via nickel-catalyzed Csp(3)-Csp(3) cross-coupling. The method features a low-cost nickel catalyst system, synthetic convenience, and tolerance of rich functionality and stereochemistry.