Carbon Isotope Labeling Strategy for β‑Amino Acid Derivatives via Carbonylation of Azanickellacycles

A series
of 4-membered azametallacycles have been prepared by the
oxidative addition of Ni(0) with aziridines. Stoichiometric 13C-labeled carbon monoxide could be efficiently incorporated via Ni–C
bond insertion to generate air stable and isolable cyclic Ni-acyl
complexes. Upon subjection to a range of C-, N-, O-, and S-nucleophiles, 13C-labeled β-amino acids and derivatives thereof, as
well as β-aminoketones, could be rapidly accessed. The methodology
proved highly adaptable for the synthesis of the antidiabetic drug,
sitagliptin, with a single carbon isotope label.