Stereodynamic Quinone–Hydroquinone Molecules That Enantiomerize at sp³-Carbon via Redox-Interconversion

Abstract

Since the discovery of molecular chirality, non-superimposable mirror-image organic molecules have been found to be essential across biological, chemical processes, and increasingly in materials science. Generally, carbon centers containing four different substituents are configurationally stable, unless bonds to the stereogenic carbon atom are broken and reformed. Herein, we describe sp3-stereogenic carbon-bearing molecules that dynamically isomerize, interconverting between enantiomers without cleavage of a constituent bond, nor through remote functional group migration. The stereodynamic molecules were designed to contain a pair of redox-active substituents, quinone and hydroquinone groups, which allow the enantiomerization to occur via redox-interconversion. In the presence of an enantiopure host, these molecules undergo a deracemization process that allows observation of enantiomerically enriched compounds. This work reveals a fundamentally distinct enantiomerization pathway available to chiral compounds, coupling redox-interconversion to chirality.

A Stereodynamic Redox‐Interconversion Network of Vicinal Tertiary and Quaternary Carbon Stereocenters in Hydroquinone–Quinone Hybrid Dihydrobenzofurans

“…[5] In molecules that contain both hydroquinone and quinone groups (Figure 1B, left and middle), [6–7] this dynamic redox behavior can result in facile enantiomerization in cases where both hydroquinone and quinone are substituents at the same stereogenic center (Figure 1B, right). [8] This phenomenon of dynamic stereochemistry, [9–13] when a function of redox chemistry, [14] has also been observed with helical chirality in copper complexes upon reversible change of oxidation state. [15] The stereodynamic nature of these molecules allows for potential application as chiral redox switches [16–17] or oxidation and reduction catalysts [18–19] in stereoselective transformations.…”

“…This seems to be consistent with the second mechanistic scenario, as dark and very colorful solutions were observed in our previous study on stereodynamic hydroquinone-quinone compounds due to the presence of significant quantities of quinhydrone-like structures (Figure 1A, right). [4, 8] Additionally, neither bis-hydroquinone, xanthene 1 , nor bis-quinone 2 were detected after completion of the interconversion experiment of u -4 (see SI). In order to further probe for any intermolecular redox processes, we attempted to reduce u -4 under the interconversion conditions (Figure 5C).…”

“…Along with our aim for phenomenological and mechanistic insights, dihydrobenzofuran model compounds also provide the opportunity to demonstrate epimerization of aq uaternary carbon stereocenter without achiral intermediates.T his question of whether or not stereodynamic systems could be achieved with quaternary stereogenic carbon atoms has not been addressed in any system, to our knowledge,and stands in contrast to our previous study of methine-based intramolecular quinhydrones. [8] Thus,i na ddition to reversible bondbreaking and hindered rotation, our study was designed to highlight intramolecular redox chemistry as afundamental interconversion pathway in organic molecules.…”

Racemization and Deracemization through Intermolecular Redox Behaviour

“…Kim et al. recently reported chiral compound 3 , which contains both a quinone and hydroquinone moiety in the same molecule . In this system, bisquinone 1 and bishydroquinone 2 , which are both achiral, react to form chiral compound 3 (Figure ).…”

“…Kim et al recently reported chiral compound 3,w hich contains both aq uinonea nd hydroquinone moiety in the same molecule. [15] In this system,b isquinone 1 and bishydroquinone 2,w hich are both achiral, react to form chiral compound 3 (Figure 3). The equilibrium of the reversible reaction between 1 and 2 lies towards compound 3.Although it has been unambiguously shown that compounds 1 and 2 can engage in a redox reaction to produce compound 3,t his specific intercon- Figure 4).…”