High Acylation Rates and Enantioselectivity with Cyclodextrin Complexes of Rigid Substrates

Article abstract of DOI:10.1021/ja00391a028

Previous work in these laboratories has shown that the acylation of β-cyclodextrin by p-nitrophenyl-3-trans-ferrocenylpropenoate is an excellent model for the first step in the serine protease catalyzed hydrolysis of esters.Saturation kinetics were observed, and rate acceleration on the order of 10⁶ were attained.We report herein that improvement in the rate acceleration can be realized by freezing out residual rotational degrees of freedom in the acylation transition state.Partial immobolization of the acylate side chain has been accomplished by bridging to the ferrocene nucleus, resulting in a nearly 10-fold increase in the rate acceleration.Furthermore, a high enantioselectivity in the acylation of β-cyclodextrin by this bridged substrate has been observed with a 20-fold rate difference for the two enantiomers.The absence of a differential solvent deuterium isotope effect is offered as evidence that the enantioselectivity is not due to differential hydrogen bonding in the transition state (general-acid catalysis).The determination of the absolute configuration of the fast enantiomer together with the known configuration of β-cyclodextrin has allowed the postulation of geometric basis for the observed enantioselectivity.