Theoretical investigation on the Cu(i)-catalyzedN-carboxamidation of indoles with isocyanates to form indole-1-carboxamides: effects of solvents

摘要

The mechanisms of Cu(i)-catalyzedN-carboxamidation of indoles with isocyanates are studied in detail to explore the effects of DMSOvs.THFvs.acetone based on theoretical calculations. The calculated results are shown as follows: (a) the Cu(i) catalyst can activate the N1-C1 double bond ofim1to promote the intermolecular addition. (b) The solvents DMSO, THF and acetone can not only act as the hydrogen-bond acceptor to facilitate intermolecular addition between C1 and N2 by the hydrogen-bond N2-H1MIDLINE HORIZONTAL ELLIPSISO2 (O3 or O4), but also play the role of a proton-transfer shuttle in assisting the H1(+)-shift by the stepwise proton-transport process (the protonation of solvent and the deprotonation of solvent-H+). Due to the assistance of DMSO, THF and acetone, the rate-determining free energy barrier of the Cu(i)-catalyzed reaction is greatly reduced from 44.7 to 24.3, 25.6 and 28.6 kcal mol(-1), which explains the experimental phenomena well (95%vs.58%vs.24% in yields). More importantly, the electron-donating ability of solvents (DMSO, THF and acetone) is found to be the primary factor that critically affects the catalytic activity of solvents, and the stronger electron-donating properties of solvents (DMSO > THF > acetone) are favorable for the present Cu(i)-catalyzed reactions. (c) Substrate1acan also assist the reaction, but the catalytic capability of1ais weaker than that of solvents DMSO, THF and acetone (energy barrier: 40.0vs.24.3, 25.6 and 28.6 kcal mol(-1)). Briefly, the present study is expected to help one understand the influence of solvents on the transition metal-catalyzed reactions including the addition reaction and the proton-transfer process.