Insights into Cu(I)-Catalyzed Decarboxylation of Propargylic Cyclic Carbonates with Amines: Origins of Regioselectivity and Enantioselectivity

Chiral α-functionalized α-amino ketones are sought-after compounds for drug development; however, their acyclic enantioselective synthesis with amines as nucleophiles remains challenging. The catalytic decarboxylation of propargylic cyclic carbonates through metal–allenylidene intermediates has proven to be an efficient route to chiral quaternary centers, but its enantioselective mechanisms require clarification. Herein, we computationally investigate the Cu(I)-catalyzed decarboxylation of propargyl cyclic carbonates with aniline [Guo, W. J. Am. Chem. Soc. 2021, 143, 7629–7763]. The calculation results elucidate the mechanistic details of the reaction and reveal that enantioselectivity stems from the distinct noncovalent interactions in the (R)- and (S)- transition states, while regioselectivity arises from the lower steric hindrance for aniline attack at C5 versus C1 atom in the zwitterionic metal–allenylidene intermediate. IGMH analysis further validates the enantiocontrol. The theoretical results offer insights into the mechanisms of Cu(I)-catalyzed decarboxylation of propargyl cyclic carbonates with amines as nucleophiles, advancing the understanding of propargylic amination and aiding the development of this research field.