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 C-13-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, C-13-labeled beta-amino acids and derivatives thereof, as well as beta-aminoketones, could be rapidly accessed. The methodology proved highly adaptable for the synthesis of the antidiabetic drug, sitagliptin, with a single carbon isotope label.