Synthesis of chiral α-amino acids <i>via</i> Pd(ii)-catalyzed enantioselective C-H arylation of α-aminoisobutyric acid.

ABSTRACT: Non-natural chiral α,α-disubstituted α-amino acids (α,α-AAs) constitute an attractive α-aminoisobutyric acid (Aib) replacement for improving bioavailability of linear peptides as therapeutics due to the ability of these amino acids to induce the peptides to form helical structures. Enantioselective β-C(sp³)-H arylation of Aib could potentially provide a versatile one-step strategy for accessing diverse α,α-AAs, but the installation and removal of external directing groups was found in our previously reported work to reduce the efficiency of this approach. Herein we report a Pd(ii)-catalyzed enantioselective C-H arylation of N-phthalyl-protected Aib enabled by a N-2,6-difluorobenzoyl aminoethyl phenyl thioether (MPAThio) ligand, affording α,α-AAs with up to 72% yiel

SUBMITTER: Zhang ZY 

PROVIDER: S-EPMC11427991 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature