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

Abstract

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.

Diastereomeric Right‐ and Left‐Handed Helical Structures with Fourteen (R)‐Chiral Centers

“…[24] The chiral acetal moiety in the (R,R)-Ac 4 c 3BD was changeable and may also be used for low pH-triggerings tructural changes. [25] Therefore, precisely elucidated helical secondary structures may be invaluable for designing organo-catalysts, [26] cell-penetrating peptides, [27] and targetbinding peptides. [24] .…”

ortho‐Phenylene‐Based Macrocyclic Hydrocarbons Assembled Using Olefin Metathesis

“…The hierarchical structure of biomacromolecules has long inspired chemists to design abiotic foldamers, oligomers that adopt well-defined conformations because of noncovalent interactions. [1][2][3][4][5] Foldamers exhibiting molecular recognition, [6][7][8][9] catalysis, [10,11] interesting electronic properties, [12][13][14] self-assembly, [15] and biological activity [16][17][18] are now known. Ultimately, the goal is to complement biological systems, achieving analogous structural sophistication, and thus function, but using structural motifs with distinct properties.…”

Retention of strong intramolecular hydrogen bonds in high polarity solvents in binaphthalene–benzamide derivatives: extensive NMR studies

“…15 Nevertheless over the years the involvement of organic uorine in HB in large number of molecules including foldamers have been reported. [16][17][18][19][20][21][22] The studies report that the inter-or intra-molecular HB of the type X-H/F-C (X ¼ O, N) plays a signicant role in the dynamics as well as the functionalities of the drugs 23 viz., dipole-dipole interaction, HB and steric hinderance.…”