Aminomutase-Inspired Methylene Insertion for α-to-β Homologative Transposition of Amino Acids
Year: 2026
Type: preprint
Abstract: A versatile method for the preparation of synthetically valuable β2-homologated amino acid esters from simple α-amino acid esters is described. Inspired by pyridoxal 5′-phosphate-dependent aminomutase enzymes, the described strategy exploits a straightforward protocol for substrate activation, alkylation, and migration leveraging a bio-inspired 3-exo-trig radical cascade. This approach enables a novel homologative strategy towards β-amino acids via methylene insertion into the Cα–N bond of α-amino acids. A broad substrate scope is demonstrated, and key activator electronic factors are elucidated through experimental and computational mechanistic studies. By engaging α-amino acids directly, the method provides unique access to β2-homologated amino acids.
Source: ChemRxiv
Institution: Stony Brook University
Language: English
Subfield: Organic Chemistry
Field: Chemistry
Domain: Physical Sciences
Open Access status: green
OpenAlex ID: W7214240234