A DFT Study on the Binuclear Copper(I)-Catalyzed Synthesis Mechanism of 1,2,3-Triazolo[1,5-c]Pyrimidines via Interrupted Click and Ketenimine Rearrangement

Chemphyschem. 2021 Nov 20. doi: 10.1002/cphc.202100751. Online ahead of print.ABSTRACTIn this paper, the mechanism of the full catalytic cycle for binuclear Cu(I)-catalyzed sulfonyl azide-alkyne cycloaddition reaction for the synthesis of triazolopyrimidines was rationalized by density functional theoretical (DFT) calculations. The computed reaction route consists of (a) formation of dicopper intermediates, including C-H activation of terminal alkyne, 3+2 ring cycloaddition and ring-reducing reaction and transmetalation, (b) interrupted CuAAC reaction, including di-copper catalyzed ring-opening of 2H-azirines and C-C bond formation to generate the copper-triazoles and ketenimines, (c) two step C-N cross-coupling and following (d) multi-step hydrogen transfer by the hydrogen bonding chain of water to promote the C-N formation and another C-N cleavage through the removal of p-tolyl sulfonamides. Our DFT results indicate that the multi-step hydrogen transfer process is the rate-determining step along potential energy surface profile. The explicit water model was used for systematic determination of barrier for C-C cross-coupling, C-N bond formation and cleavage, and p-tolylsulfonamide removal. A critical insight in the interrupted CuAAC reaction was proposed. Further prediction interprets H 2 O hydrogen bond chain plays an important role in C-N bond formation and cleavage, and the removal of p-tolylsulfonamide. This may have fundamental guidance on the design of 1, 5-herterocycl...

Source: Chemphyschem - November 20, 2021 Category: Chemistry Authors: Zhaoman Zhou Qianqian Yue Yanying Zhao Source Type: research