Mechanisms and origins of stereoselectivity of NHC-catalyzed reaction of aldehyde and butadienoate

The first computational study on the mechanisms and stereoselectivities of the reaction between benzaldehyde and butadienoate generating E-4-oxo-2-butenoate catalyzed by N-heterocyclic carbene (NHC) has been carried out using density functional theory (DFT) calculations. We have located and compared several possible pathways, which allows us to determine the most preferred mechanism. We found that the most preferred mechanism consists six key steps, i.e. the addition of catalyst to the benzaldehyde (Step I), intramolecular 1,2-proton transfer affording the Breslow intermediate (Step II), carbon-carbon bond formation in which the Breslow intermediate adds to the butadienoate (Step III), the protonation of the gamma-carbon (Step IV), the deprotonation of the hydroxyl group (Step V) and elimination of the catalyst (Step VI). The solvent chloroform (CHCl3) plays a vital role in the 1,2-proton transfer, protonation and deprotonation. The carbon-carbon bond formation step determines the stereoselectivity of the reaction, and the E-isomer is the predominant product, which agrees well with the experimental results. In addition, we performed non-covalent interaction analysis, and found that the transition state that responsible for generating the major product E-4-oxo-2-butenoate was stabilized by a number of weak interactions such as C-H center dot center dot center dot pi, O-H center dot center dot center dot pi and pi center dot center dot center dot pi interactions. The mechanistic picture presented here would be useful in designing new NHC-catalyzed reactions in the future.