Trópos and Átropos Biindole Chiral Electroactive Monomers: A Voltammetry and HPLC Comparative Insight

Abstract

A series of 2,2’‐biindole‐based inherently chiral electroactive monomers are comparatively investigated with their 3,3’ analogues as an excellent study case of two equivalent redox centres interacting through a torsional barrier. The twin peak potential splitting observed in voltammetry for the first oxidation of the biheteroaromatic core accounts for the energy barrier height: the lower the barrier, the larger the peak potential splitting, with modulation by solvent and temperature. The height of the energy barrier is determining for the electrochemical and spectroscopic features of the monomers as well as for their configurational stability and applicability for enantioselection purposes. The 3,3’ monomers, featuring large twin peak splittings in CV, are “trópos” systems with a low torsional barrier, so they cannot exist as stable enantiomers at room temperature. Instead their 2,2’ isomers, with much smaller twin peak splittings, are “átropos” systems and can be separated by enantioselective HPLC into stable enantiomers, providing powerful “inherently chiral” selectors with outstanding enantioselection properties in chiral electroanalysis and electrochemistry as well as in chiroptical spectroscopy, with fascinating reciprocal correlations.

Cover Feature: Trópos and Átropos Biindole Chiral Electroactive Monomers: A Voltammetry and HPLC Comparative Insight (ChemElectroChem 6/2022)

“…Synthesis of 2,2'-and 3,3'-biindole derivatives The 2,2'-biindole based compounds 1a [5],1b and 2a,b [6] were synthesized following the Larock [35,36] protocol developed by Abbiati [37] in which the formation of the 2,2'-biindole core and its functionalization in 3 and 3'-positions take place in one step, although in modest yield. The key intermediate is the butadiine derivative 5 [38,39] that was made to react with the suitable haloderivative, namely the 5-iodo-2,2'-bithiophene and the 5-(4bromophenyl)-2,2'-bithiophene [40], in the presence of Pd(PPh3)4 as catalyst and K2CO3 as a base.…”

“…A winning strategy to achieve chiral electrode surfaces of huge and wide-scope enantiodiscrimination ability consists in the electrodeposition of "inherently chiral" oligomer films from electroactive monomers [1] of helical or axial stereogenicity, i.e. based either on a helical backbone [2] or on an atropisomeric one, that is, consisting of two, usually identical, moieties with reciprocal high sterical hindrance [3][4][5][6][7][8]. In such monomers, both chirality and key functional properties, like electrochemical and optical activity, originate from the whole main molecular backbone, featuring a tailored torsion associated with an energy barrier (enantiomerization barrier) too high to be overcome at room temperature.…”

“…Thus such molecules can exist as stable (R)-and (S)-enantiomers, that can be separated and stored; they also fully retain their configuration when electrooligomerizing, yielding (R)-or (S)enantiopure oligomer films. [3] Such electrode surfaces result in significant, often wide, potential differences for the enantiomers of a variety of chiral electroactive probes in voltammetry experiments [3][4][5][6][7][8][9][10], which can be ascribed to energetically different conditions for the probe enantiomers at the enantiopure surface, achieved through the many coordination elements available (heteroatoms and  conjugated systems) [11][12][13][14]. The axial stereogenicity approach, combining high three-dimensional character and oligomerization ability with convenient synthesis and wide structure modulability, has been so far more exploited than the helical one.…”

“…In particular, it has been so far implemented exploiting monomers based on four atropisomeric biheteroaromatic cores, i.e. 3,3'-bibenzothiophene [3,9,10], 3,3'-bithiophene [4], 2,2'-biindole [5][6][7] and 1,1'-binaphthyl [8] ones, in all cases combined with symmetrical oligothiophene-based terminals (some examples are reported in Figure 1). Besides their above highly successful application for chiral electroanalysis, such monomers are also attractive model systems in the frame of intramolecular charge communication studies.…”

“…As a convenient model case, to our knowledge a proof-of-concept one from the electrochemical perspective, the voltammetric features will be compared of two series of biindole-based atropisomeric monomers, 1a, 2a, 2b and 3, 4a, 4b, constituted by identical building blocks but (i) different connectivity between biindole core moieties, i.e. 2,2' [5,6] vs 3,3' (with wings conversely attached in 3,3' and in 2,2' positions respectively, Figure 2), a feature which we realized has a huge impact on the potential difference for the twin peak system; (ii) and without or with a phenyl spacer [6] between the biindole core and the (bi)thiophene terminals, a feature affecting the core/terminal conjugation. Monomers 1b and 4c, useful for sake of comparison, will also be considered.…”