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

Differential activation entropy (Delta Delta S-not equal) 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 Delta Delta S-not equal 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 Delta Delta S-not equal 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 Delta Delta S-not equal-driven stereodiscrimination process: maximum enantioselectivity is obtained at around room temperature. Second, a plausible transition-state model accounting for the characteristic Delta Delta S-not equal effect and the structural dynamics of the conformationally flexible organocatalyst in the stereodiscrimination process is discussed.