Final Report Summary - CATFOLD (Cooperatively enhanced asymmetric hydrogen bonding catalysis)
Objectives: Taking a lead from nature, the aim of this project was to exploit the notion of cooperativity – namely that a hydrogen bond donor is made stronger if it is also involved as an acceptor – to increase catalytic efficiency and facilitate challenging asymmetric transformations. This will require the development and investigation of a series of folded materials, the probing of a series of non-covalent interactions and application of this information to the development of new folded catalysts. The work programme comprises three main interrelated elements.
(i) Development of new folded structures: we have demonstrated that a reverse-turn comprising an amino acid derived alcohol conjoined with an aromatic amine can promote parallel sheet structure in a γ-peptide sequence designed to fold with the aid of C-H…O hydrogen-bonds. In designing this parallel-turn motif, we reasoned that incorporating an ortho-amino phenol derivative would restrict the ψ(i+2) torsion to angles consistent with natural β-turns. An N-aryl amide proton would also possess a greater hydrogenbond donor ability than a conventional amide, and the presence of the aryl trifluoromethyl group may offer further conformational control through acidification of the ortho-proton, facilitating its participation in a hydrogen-bond with the adjacent carbonyl group (scheme 1). We have made a series of simple turn structures and then extended this to larger, more complex structures with repeat their hydrogen bonding patterns along a chain. As such we have generated materials with repeating turn stuctures stabilized by urea and amide hydrogen bonds, and have also synthesized larger materials containing two isolated turn structures.