Mechanism and Origins of Chemo-, Regio-, and Stereoselectivities in NHC-Catalyzed Reaction of 1-Cyclopropylcarbaldehydes with α-Alkynyl Enals: A Theoretical Study

In this paper, a density functional theory (DFT) study to characterize the reaction mechanism and the origin of stereoselectivity of the NHC-catalyzed reaction of 1-cyclopropylcarbaldehyde and α-alkynyl enal has been presented. Both the cyclopropylcarbaldehyde-first and α-alkynyl enal-first mechanisms were examined. The calculation results show that the cyclopropylcarbaldehyde-first mechanism is more favorable than the α-alkynyl enal-first mechanism. The nucleophilic addition to α-alkynyl enal is the stereochemistry-determining step that preferentially affords the RR-dihydropyranone. The calculated results correlate well with the experimental findings. The origins of regio- and enantioselectivities were investigated using Parr function, distortion-interaction, noncovalent interaction (NCI), and atoms in molecules (AIM) analyses. The observed stereoselectivity can be attributed to differential distortion and interactions in the nucleophilic addition transition states. The effects of substituents and solvents were also explored and discussed. This study will be helpful for understanding the reaction mechanism and guiding the future design of highly selective catalytic reactions.