Origins of the Regioselectivities in the Diels-Alder Reactions of Vinylindenes with 1,4-Quinone Monoketal and Acrolein Dienophiles

Computations with density functional theory (B3LYP/6-31G(d)) have elucidated the origins of regioselectivities in the Diels-Alder reaction of vinylindene with a 1,4-quinone monoketal reaction that was employed as the key step in the synthesis of fluostatin C. Frontier Molecular Orbital theory and an electrostatic model are applied to the reactions of alkyl-substituted and vinylindene dienes with 1,4-quinone monoketal and acrolein dienophiles. Regiochemical results that deviate from expectation are explained by a progression from electronic to steric control upon the addition of a Lewis acid catalyst.