Cyclodextrin-catalysed hydrolysis of oxazol-5(4H)-ones. Enantioselectivity of the acid–base and ring-opening reactions

Abstract

The kinetics of hydrolysis of three oxazol-5(4H)-ones bearing hydrophobic substituents on the positions 2 and 4 have been determined in the presence of α-, β-, and γ-cyclodextrin. The macrocycles catalyse both the deprotonation–reprotonation equilibrium on the asymmetric carbon and the ring opening. For this second reaction, both a nucleophilic mechanism with formation of an acylcyclodextrin and general base catalysis by the macrocycle appear to be operative. β-Cyclodextrin is a better catalyst than the other two, the effect of the macro-ring size on the reactivity being more important with the 2-phenyloxazolones. The enantioselectivity is low for the binding and for the catalysis of the acid–base reaction but larger for the ring opening. With the 2-phenyloxazolones, the L-isomer reacts faster in the ring-cleavage reaction with all three cyclodextrins. On the other hand, with the 4-benzyl-2-methyloxazolone, β- and γ-cyclodextrins favour the D-isomer; there is no stereoselectivity with α-cyclodextrin. The absence of solvent isotope effect on the enantioselectivity indicates that hydrogen bonding or proton transfer are not involved in chiral recognition. The effect of the cyclodextrins on the reactivity and stereoselectivity is interpreted with the help of molecular models, assuming reasonable binding modes.