Helical Oligourea Foldamers as Powerful Hydrogen Bonding Catalysts for Enantioselective C–C Bond-Forming Reactions

Substantial
progress has been made toward the development of metal-free
catalysts of enantioselective transformations, yet the discovery of
organic catalysts effective at low catalyst loadings remains a major
challenge. Here we report a novel synergistic catalyst combination
system consisting of a peptide-inspired chiral helical (thio)­urea
oligomer and a simple tertiary amine that is able to promote the Michael
reaction between enolizable carbonyl compounds and nitroolefins with
excellent enantioselectivities at exceptionally low (1/10 000)
chiral catalyst/substrate molar ratios. In addition to high selectivity,
which correlates strongly with helix folding, the system we report
here is also highly amenable to optimization, as each of its components
can be fine-tuned separately to increase reaction rates and/or selectivities.
The predictability of the foldamer secondary structure coupled to
the high level of control over the primary sequence results in a system
with significant potential for future catalyst design.