Synthesis of β³-Amino Acid Derivatives via the Regioselective Carbozincation of Ynamides and Subsequent Asymmetric Hydrogenation

Abstract

β-Amino acids are key constituents of various bioactive molecules, pharmaceuticals, and natural products, thereby highlighting their importance in organic chemistry. A novel synthetic method was developed for β³-amino acid derivatives based on the use of ynamides bearing ester moieties. Initially, the Cu-catalyzed regioselective carbozincation of these ynamides afforded β-aminoacrylic acid esters bearing a substituent at the β-position. Subsequent asymmetric hydrogenation using a rhodium catalyst and the Walphos ligand yielded the corresponding β³-amino acid derivatives.

Keywords

Ynamide - Regioselective carbozincation - Asymmetric hydrogenation - Transition metal-catalyzed synthesis - β³-Amino acid derivative

Publication History

Received: 08 November 2025

Accepted after revision: 24 December 2025

Accepted Manuscript online:
24 December 2025

Article published online:
21 January 2026

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