Frustrated Helicity: Joining the Diverging Ends of a Stable Aromatic Amide Helix to Form a Fluxional Macrocycle

Abstract

Macrocyclization of a stable two-turn helical aromatic pentamide, that is, an object with diverging ends that are not prone to cyclization, was made possible by the transient introduction of disruptors of helicity in the form of acid-labile dimethoxybenzyl tertiary amide substituents. After removal of the helicity disruptors, NMR, X-ray crystallography, and computational studies show that the macrocycle possesses a strained structure that tries to gain as high a helical content as possible despite being cyclic. Two points of disruption of helicity remain, in particular a cis amide bond. This point of disruption of helicity can propagate along the cycle in a fluxional manner according to defined trajectories to produce ten degenerate conformations.

Macrocycles of higher ortho-phenylenes: assembly and folding

“…Combining foldamer subunits within a macrocycle represents a simple strategy toward higher-order structure, placing multiple secondary structures into well-dened spatial relationships (note that this approach is distinct from macrocycles that themselves fold [13][14][15][16][17][18] or with a single folded unit 19,20 ).…”

Folding-controlled assembly of ortho-phenylene-based macrocycles

“…This intersection of foldamer and macrocycle chemistry has been reasonably well-explored; for example, macrocycles have been reported that are themselves folded, [17][18][19][20][21][22][23] as have macrocycles comprising a single foldamer moiety with its ends connected via unfolded segments. 24,25 It is less common to construct rings from multiple discrete foldamer subunits, but there are examples: Huc has demonstrated homochiral selfsorting of folded segments within macrocycles, 26 as has Jiang, 27 and structurally intricate, foldamer-based coordination complexes have been reported by Sawada and Fujita. 28,29 Recent work from our group [30][31][32] has focused on the selfassembly of foldamer monomers into macrocycles via dynamic covalent chemistry, 33,34 as shown in Fig.…”

ortho‐Phenylene‐Based Macrocyclic Hydrocarbons Assembled Using Olefin Metathesis

“…questions about how the two concepts together can yield products with emergent structural complexity. For helical foldamers, the products will be twisted macrocycles that combine the features of globally folded macrocycles [25][26][27][28][29][30][31] with those with conformationally rigid axially chiral subunits. [32][33][34][35][36][37][38][39] Our work has focused on the ortho-phenylenes, a simple class of aromatic foldamers.…”

“…To synthesize these targets, folding can be combined with thermodynamically controlled self‐assembly, raising questions about how the two concepts together can yield products with emergent structural complexity. For helical foldamers, the products will be twisted macrocycles that combine the features of globally folded macrocycles with those with conformationally rigid axially chiral subunits …”