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

Abstract

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. Background and Originality Content Diels-Alder (D-A) reaction is one of the most useful synthetic reactions, and its overwhelming importance is well known in organic synthesis of six-membered functionalized carbocyclic compounds. The usefulness of D-A reaction arises from its versatility and from its remarkable regio-and stereoselectivity. The reaction between unsymmetrical diene and dienophile can produce two isomeric adducts depending on the orientation of the substituents in the dienes, as shown in Figure 1.

Pd‐Catalyzed Dienylation of Propargylic Esters Enabling Highly Stereoselective Synthesis of Danishefsky‐Type Trisubstituted Dienes

“…[ 6‐7 ] Attractively, Danishefsky's dienes are characterized by their highly electron‐rich effect and predictable regio‐ and stereochemical outcomes due to the two well‐defined lone pair‐containing oxygen substituents, enabling paramount importance on efficient methods for their stereoselective preparation. [ 8‐13 ]…”