Entropy-Driven 1,2-Type Friedel-Crafts Reaction of Phenols with N-tert-Butoxycarbonyl Aldimines

Abstract

Differential activation entropy (ΔΔS(≠)) is revisited as an important parameter that governs catalytic stereodiscrimination processes by investigating temperature effects on the basis of the Eyring theory. However, correlating the ΔΔS(≠) effect and the molecular structure of the asymmetric catalyst is still an underdeveloped area. Efforts to identify factors (including catalyst structure, reactants, and reaction conditions) that contribute to the attainment of large ΔΔS(≠) values for enantioselective 1,2-type Friedel-Crafts reactions of phenols with N-tert-butoxycarbonyl aldimines catalyzed by conformationally flexible guanidine bisthioureas are described. First, we uncover an interesting property of the ΔΔS(≠)-driven stereodiscrimination process: maximum enantioselectivity is obtained at around room temperature. Second, a plausible transition-state model accounting for the characteristic ΔΔS(≠) effect and the structural dynamics of the conformationally flexible organocatalyst in the stereodiscrimination process is discussed.

Keywords: Friedel-Crafts reactions; entropy; organocatalysis; phenols; transition states.