Novel Helical Foldamers Based on the Conformational Properties of Aromatic Amides

Abstract

In this review, we focus on our recent work on the development of novel helical foldamers based on the cis conformational properties of aromatic amide bonds. First, we describe the conformational properties of N-alkylated pyrroleamides and their oligomers. The conformation of the amide bond on the pyrrole ring is altered by N-alkylation, and the ratio of the cis conformer is lower in N-methylated amides with an N-pyrrole ring compared with that in N-methylbenzanilide. Pyrrole-containing oligomers, in which benzene and pyrrole rings are linked alternately by amide bonds with chiral N-substituents, show significant CD signals that depend on the chain length, temperature, and solvent properties, indicating that the oligoamides take folded conformations in solvents. Second, we describe the design and synthesis of alternately N-alkylated aromatic oligoamides as novel helical oligoamides with larger cavities compared with those of poly(N-alkylated p-benzamides). Spectroscopic studies and calculated optimized structures indicate that these oligoamides adopt helical structures with a cavity of about 9 Å in diameter. Finally, we describe the synthesis of a series of strained aromatic oligoamide macrocycles based on the cis conformational preference of the aromatic N-alkylated amide bond, building on the work of Huc et al. on the construction of large macrocycles by cyclization of helical quinoline oligoamides. The crystal structures are also presented. Our findings demonstrate that N-alkylated amides with the cis conformation are useful building blocks for unique aromatic foldamers.