Quaternary β2,2 -Amino Acids: Catalytic Asymmetric Synthesis and Incorporation into Peptides by Fmoc-Based Solid-Phase Peptide Synthesis.

β-Amino acid incorporation has emerged as a promising approach to enhance the stability of parent peptides and to improve their biological activity. Owing to the lack of reliable access to β2,2 -amino acids in a setting suitable for peptide synthesis, most contemporary research efforts focus on the use of β3 - and certain β2,3 -amino acids. Herein, we report the catalytic asymmetric synthesis of β2,2 -amino acids and their incorporation into peptides by Fmoc-based solid-phase peptide synthesis (Fmoc-SPPS). A quaternary carbon center was constructed by the palladium-catalyzed decarboxylative allylation of 4-substituted isoxazolidin-5-ones. The N-O bond in the products not only acts as a traceless protecting group for β-amino acids but also undergoes amide formation with α-ketoacids derived from Fmoc-protected α-amino acids, thus providing expeditious access to α-β2,2 -dipeptides ready for Fmoc-SPPS.