Carbon isotope labeling strategy for β-amino acid derivatives via carbonylation of azanickellacycles

Anne K Ravn, Maria BT Vilstrup, Peter Noerby, Dennis U Nielsen, Kim Daasbjerg, Troels Skrydstrup

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.