posted on 2016-07-09, 00:00authored byMatthew
N. Grayson, K. N. Houk
The cinchona alkaloid-derived
urea-catalyzed asymmetric conjugate
addition of aromatic thiols to cycloalkenones was studied using density
functional theory (DFT). Deprotonation of the thiol gives a protonated
amine that activates the electrophile by Brønsted acid catalysis,
while the urea group binds the nucleophilic thiolate by hydrogen bonding.
These results demonstrate the generality of the Brønsted acid−hydrogen
bonding transition state (TS) model for cinchona alkaloid catalysis
that we recently showed to be favored over Wynberg’s widely
accepted ion pair−hydrogen bonding model and represent the
first detailed mechanistic study of a cinchona urea-catalyzed reaction.
The conformation of the catalyst methoxy group has a strong effect
on the TS, an effect overlooked in previous mechanistic studies of
reactions catalyzed by cinchona alkaloids.