ja309133z_si_001.pdf (6.59 MB)
Mechanism and Selectivity of Bioinspired Cinchona Alkaloid Derivatives Catalyzed Asymmetric Olefin Isomerization: A Computational Study
journal contribution
posted on 2013-05-22, 00:00 authored by Xiao-Song Xue, Xin Li, Ao Yu, Chen Yang, Chan Song, Jin-Pei ChengAsymmetric
olefin isomerization of β,γ- to α,β-unsaturated
butenolides catalyzed by novel cinchona alkaloid derivatives was investigated
in-depth using density functional theory (M05-2x and B2PLYP-D). Three
possible mechanistic scenarios, differing in the binding modes of
the substrate to the catalyst, have been evaluated. Computations revealed
that both the protonated quinuclidine and the 6′-OH of catalysts
may act as the proton donor in the stereocontrolling step. Variation
of the catalytic activity and enantioselectivity by tuning the electronic
effect of catalyst was well reproduced computationally. It suggested
that, for certain acid–base bifunctional chiral catalysts,
the acid–base active sites of catalysts may interconvert and
give new catalyst varieties of higher activity and selectivity. In
addition, the noncovalent interactions in the stereocontrolling transition-state
structures were identified, and their strength was quantitatively
estimated. The weak nonconventional C–H···O
hydrogen-bonding interactions were found to be crucial to inducing
the enantioselectivity of the cinchona alkaloid derivatives catalyzed
asymmetric olefin isomerization. The computational results provided
further theoretical evidence that the rate-limiting step of this bioinspired
organocatalytic olefin isomerization is inconsistent with that of
the enzyme catalyzed olefin isomerization.