ortho‐Phenylene‐Based Macrocyclic Hydrocarbons Assembled Using Olefin Metathesis

Abstract

While many foldamer systems reliably fold into well‐defined secondary structures, higher order structure remains a challenge. A simple strategy for the organization of folded subunits in space is to link them together within a macrocycle. Previous work has shown that o‐phenylenes can be co‐assembled with rod‐shaped linkers into twisted macrocycles, showing an interesting synergy between folding and thermodynamically controlled macrocyclization. In these systems the foldamer units were largely decoupled from each other both conformationally and electronically. Here, we show that hydrocarbon macrocycles, with very short ethenylene linkers, can be assembled from o‐phenylenes using olefin metathesis. Characterization by NMR spectroscopy, X‐ray crystallography, and ab initio calculations shows that the products are approximately triangular trimer macrocycles with helical o‐phenylene corners in a heterochiral configuration. Their photophysics are dominated by the 4,4'‐diphenylstilbene moieties, the longest conjugated segments, with further conjugation broken by the twisting of the o‐phenylenes.

Folding-controlled assembly of ortho-phenylene-based macrocycles

“…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. 1a.…”

Chiral, sequence-definable foldamer-derived macrocycles

“…9 However, the field of foldamer-derived macrocycles -analogous to macrocyclic peptides -remains in its infancy. Extant foldamer-derived macrocycles typically display a large degree of symmetry, [18][19][20][21][22][23][24][25][26][27][28][29][30][31][32] probably due to synthetic convenience (a notable exception is in mixed peptide/foldamer [33][34][35][36][37] and peptoid 38,39 systems). However, Nature demonstrates that diversity (rather than uniformity) of structure is crucial in enabling the use of macrocycles across a range of functions.…”

Fluorine Labeling of ortho-Phenylenes to Facilitate Conformational Analysis

“…For example, macrocycles with multiple o-phenylene moieties, simple examples of higher-order structure, exhibit predictable misfolding because of structural restrictions. [25][26][27] Further, o-phenylenes have been functionalized with chiral groups to promote a preferred handedness to their folding, with a nuanced relationship between group orientation and the sense of chiral induction. 28 These systems give complex 1 H NMR spectra, with contributions from multiple inequivalent o-phenylene species, that ultimately yielded detailed information about conformational distributions.…”