Theoretical Study on Cooperation Catalysis of Chiral Guanidine/ Copper(I) in Asymmetric Azide-Alkyne Cycloaddition/[2+2] Cascade Reaction

Density functional theory (DFT) calculationswith BP86-D3(BJ) functionalswere employed to reveal the mechanism and stereoselectivity of chiralguanidine/copper(I) salt-catalyzed stereoselective three-componentreaction among N-sulfonyl azide, terminal alkyne,and isatin-imine for spiroazetidinimines that was first reported byFeng and Liu (Angew. Chem. Int. Ed. 2018, 57, 16852-16856). For the noncatalyticcascade reaction, the denitrogenation to generate ketenimine specieswas the rate-determining step, with an activation barrier of 25.8-34.8kcal mol(-1). Chiral guanidine-amide promoted thedeprotonation of phenylacetylene, generating guanidine-Cu(I) acetylidecomplexes as active species. In azide-alkyne cycloaddition,copper acetylene coordinated to the O atom of the amide moiety inguanidium, and TsN3 was activated by hydrogen bonding,affording the Cu(I)-ketenimine species with an energy barrier of 3.5 & SIM;9.4kcal mol(-1). The optically active spiroazetidinimineoxindole was constructed via a stepwise four-memberedring formation, followed by deprotonation of guanidium moieties forC-H bonding in a stereoselective way. The steric effect ofthe bulky CHPh2 group and chiral backbone in the guanidine,combined with the coordination between the Boc group in isatin-iminewith a copper center, played important roles in controlling the stereoselectivityof the reaction. The major spiroazetidinimine oxindole product withan SS configuration was formed in a kinetically more favored way,which was consistent with the experimental observation.