Theoretical Investigation on Regioselectivities of Diels‐Alder Reactions by Conjugated Effect

Summary of main observation and conclusion The regioselectivities of 76 Diels‐Alder reactions between unsymmetrical dienes and dienophiles were investigated by local softness and generalized local softness at atomic and chemical bond view, respectively, where the reactivity descriptors were calculated by finite difference approximation and ABEEMσπ model. Based on local HSAB principle and matching criterion of local softness, reasonable explanation and prediction on regioselectivities of all reactions through ABEEMσπ model have been obtained, which are in agreement with the experimental results. Especially, at π‐bond level, while the 1‐substituents of dienes were NH2, NMe2, and NEt2, because of the p‐π conjugated effect between the lone pairs of N atom and the conjugated π‐bond of the four double‐bonded carbon atoms in diene, it made the dienophile not easy to approach diene by Manner A, hence, Manner B can forecast the ortho regioisomer as main product well, and Manner A cannot. As to the other reactions, both Manner A and Manner B can predict their regioselectivities. It can be seen that the ABEEMσπ model can take the effect of the chemical environment on the reaction reactivity into account richly, especially the system includes π‐bond and lone pairs. However, the results through the finite difference approximation are not reasonable. The excellent predictions for the regioselectivity of Diels‐Alder reaction were obtained by using the conjugated interaction at ABEEMσπ model.