Optimization of an Asymmetric Reaction in the Cavity of Chiral Aromatic Oligoamide Foldamers

Abstract

An asymmetric reaction can be implemented and refined in the helical cavity of aromatic oligoamide sequences. These sequences, which bear a chiral inducer, can fold into helical structures with absolute control of the helical sense, whereby a ketone substrate covalently linked in the cavity can be asymmetrically reduced to diastereomers. The diastereoselectivity of the reduction is highly dependent on the shielding efficiency of the helical cavity. Iterative modifications of the sequence, such as addition and replacement of monomers, can fine-tune the cavity to realize the asymmetric reaction, thereby progressively increasing the diastereomeric excess up to 90 %.