DFT study on the reaction mechanisms and stereoselectivities of NHC-catalyzed [2 + 2] cycloaddition between arylalkylketenes and electron-deficient benzaldehydes.

In this paper, two possible mechanisms (mechanisms A and B) on the stereoselective [2 + 2] cycloaddition of aryl(alkyl) ketenes and electron-deficient benzaldehydes catalyzed by N-heterocyclic carbenes (NHCs) have been investigated using density functional theory (DFT). Our calculated results indicate that the favorable mechanism (mechanism A) includes three processes: the first step is the nucleophilic attack on the arylalkylketene by the NHC catalyst to form an intermediate, the second step is the [2 + 2] cycloaddition of the intermediate and benzaldehyde for the formation of a beta-lactone, and the last step is the dissociation of the NHC catalyst and the beta-lactone. Notably, the [2 + 2] cycloaddition, in which two chiral centers associated with four configurations (SS, RR, SR and RS) are formed, is demonstrated to be both the rate-and stereoselectivity-determining step. Moreover, the reaction pathway associated with the SR configuration is the most favorable pathway and leads to the main product, which is in good agreement with the experimental results. Furthermore, the analysis of global and local reactivity indexes has been performed to explain the role of the NHC catalyst in the [2 + 2] cycloaddition reaction. Therefore, this study will be of great use for the rational design of more efficient catalysts for this kind of cycloaddition.