Dynamic Covalent Chemistry within Biphenyl Scaffolds: Reversible Covalent Bonding, Control of Selectivity, and Chirality Sensing with a Single System

Abstract

Axial chirality is ap revalent and important phenomenon in chemistry.H erein we report ac ombination of dynamic covalent chemistry and axial chirality for the development of av ersatile platform for the binding and chirality sensing of multiple classes of mononucleophiles.A ne quilibrium between an open aldehyde and its cyclic hemiaminal within biphenyl derivatives enabled the dynamic incorporation of ab road range of alcohols,t hiols,p rimary amines,a nd secondary amines with high efficiency.S electivity toward different classes of nucleophiles was also achieved by regulating the distinct reactivity of the system with external stimuli. Through induced helicity as aresult of central-to-axial chirality transfer,t he handedness and ee values of chiral monoalcohol and monoamine analytes were reported by circular dichroism. The strategies introduced herein should find application in many contexts,including assembly,sensing, and labeling.Axial chirality arises from the nonplanar arrangement of substituents about ac hiral axis, [1] such as the aryl-aryl bond within atropisomeric biaryl compounds, [2] which is of significant importance in the research areas of asymmetric catalysis, natural products,s upramolecular assemblies,a nd organic materials. [3] Despite the long history of exploring axial chirality,t here is continued interest in discovering novel strategies for communication between central and axial chirality. [1][2][3] Fore xample,l ight-or chemical-fuel-driven unidirectional molecular motors have been created through the control of rotamers. [4] Moreover,t he chirality of metalorganic or organic frameworks and cages has been modulated through the incorporation of atropisomeric motifs. [5] Atropisomeric receptors have also been used in av ariety of analytical applications, [6] such as chiroptical assays for enantiomeric composition, [7] which can be employed to rapidly analyze chiral samples for catalyst development. Them anipulation of axial chirality in af acile,d ynamic,a nd versatile fashion could find broad application.Reversible covalent bonding has had asignificant impact on the field of supramolecular chemistry, [8] in which the coupling and exchange of specific functional groups through dynamic covalent reactions (DCRs) can lead to systematic chemical diversity and complexity. [9] Monofunctionalities, such as monoamines and monoalcohols,a re among the most used building blocks and are among the most sought after targets in asymmetric catalysis.A sc ompared to imine formation with chiral primary amines, [10] dynamic covalent bonding and sensing systems for sterically hindered chiral secondary monoamines are nearly non-existent. [11] Furthermore,d ue to the poor nucleophilicity of alcohols,r eceptors that bind chiral mono-ols also remain scarce. [12] We have been seeking ag eneral strategy based on the use of ac ommon receptor capable of recognition, coupled with amechanism to optically report chirality,for multiple classes of monodentate organic functional groups.Building on the dynamic covalent c...

A Green and Wide‐Scope Approach for Chiroptical Sensing of Organic Molecules through Biomimetic Recognition in Water

“…[4][5][6] In addition, long reaction times and organic solvents are often needed for these sensors which cannot be easily recovered. [7] Host-guest chemistry is an alternative method to expand the substrate scope of CD-based chiroptical sensing.F or example,B iedermann and Nau [8] have reported that the complexes of cucurbit [8]uril with dicationic dyes can be applied in chiroptical sensing of av ariety of biological molecules and drug molecules in water. This strategy is general in terms of functional groups but limited to molecules with an aromatic group next to their chiral centers.A cyclic cucurbit[n]urils and molecular tweezers, [9] pillar[n]arenes, [10] calix[n]arene, [11] resorcinarene, [12] covalent cage molecules, [13] foldamers, [14] and helicates [15] with aromatic sidewalls have also been demonstrated as chirality sensors.But the guests are still limited to aromatic compounds,c harged organic compounds,o rr igid molecules.M olecular sensors with aw ide substrate scope still remain to be developed for optical chirality sensing.…”

Stereochemical analysis of chiral amines, diamines, and amino alcohols: Practical chiroptical sensing based on dynamic covalent chemistry

“…The exceptional potential of chiroptical sensing with circular dichroism (CD) probes was noticed early on by Berova and Nakanishi, who published several seminal papers with broadly useful zinc porphyrin tweezer hosts . Their outstanding work has spurred the development of a wide variety of CD sensor designs by Borhan, Canary, Anslyn, our group, and others …”

“…In addition, stereodynamic probes that undergo irreversible covalent bond formation with a chiral analyte to generate a CD signal that can be used for absolute configuration and ee determination have been developed by several groups . Nevertheless, reversible Schiff base formation with chiral amines has become a very popular and highly successful CD sensing strategy . We now wish to report a highly practical method that allows chiroptical ee analysis of a wide range of amines and amino alcohols using an inexpensive commercially available benzaldehyde derivative as probe.…”

“…12 The exceptional potential of chiroptical sensing with circular dichroism (CD) probes was noticed early on by Berova and Nakanishi, who published several seminal papers with broadly useful zinc porphyrin tweezer hosts. [13][14][15][16][17][18] Their outstanding work has spurred the development of a wide variety of CD sensor designs by Borhan, [19][20][21] Canary, 22,23 Anslyn, [24][25][26][27] our group, [28][29][30][31][32][33][34][35][36][37][38] and others. [39][40][41][42][43] The large majority of CD sensing assays introduced so far relies on the formation of supramolecular assemblies, metal coordination complexes, hydrogen bond adducts, or dynamic covalent chemistry (DCC).…”

“…[44][45][46][47][48][49][50][51][52] Nevertheless, reversible Schiff base formation with chiral amines has become a very popular and highly successful CD sensing strategy. 27,28,30,39,41,53,54 We now wish to report a highly practical method that allows chiroptical ee analysis of a wide range of amines and amino alcohols using an inexpensive commercially available benzaldehyde derivative as probe. The Schiff base formation is complete within 2.5 hours at room temperature and does not require operation under inert atmosphere, which greatly streamlines the workflow and would simplify automation of the assay and parallel handling of samples if desired.…”