Substituent Effects on Reactivity, Regioselectivity and Stereochemistry

It is significant that if an electron-poor diene is utilized, the preference is reversed and electron-rich alkenes, such as vinyl ethers and enamines, are the best dienophiles. Such reactions are called inverse electron demand Diels-Alder reactions, and the reactivity relationships are readily understood in terms of frontier orbital theory. Electron-rich dienes have high-energy HOMOs that interact strongly with the LUMOs of electron-poor dienophiles. When the substituent pattern is reversed and the diene is electron poor, the strongest interaction is between the dienophile HOMO and the diene LUMO. The FMO approach correctly predicts both the relative reactivity and regioselectivity of the D-A reaction for a wide range of diene-dienophile combinations. 

The question of regioseleclivity arises when both the diene and alkene are unsym-metrically substituted. Generally, there is a preference for the ortho and para orientations, respectively, as in the examples shown.  

Diene Substituents Dienophile Tetracyanoethene Maleic anhydride 

Normal electron demand diene HOMO and dienophile LUMO interactions are dominant 

Inverse electron demand diene LUMO and dienophile HOMO are dominant 

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