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

Abstract

Reversible redox processes involving hydroquinones and quinones are ubiquitous in biological reaction networks, materials science, and catalysis. While extensively studied in intermolecular settings, less is known about intramolecular scenarios. Herein, we report hydroquinone-quinone hybrid molecules that form two-stereocenter dihydrobenzofurans via intramolecular cyclization under thermodynamic control. A π-methylhistidine peptide-catalyzed kinetic resolution allowed us to study the stereodynamic behavior of enantio- and diastereo-enriched dihydrofurans. In the course of this study, it was revealed that a reversible intramolecular redox-interconversion network connects all four possible stereoisomers via inversion of a quaternary carbon stereocenter without achiral intermediates. As a result, these findings on hydroquinone-quinone hybrid molecules provide insights into potential natural origin and synthetic access of the common dihydrobenzofuran motif.

Racemization and Deracemization through Intermolecular Redox Behaviour

“… Possible pathways resulting in the racemization of compound 3 as previously proposed by Kim et al. We find that the system follows route A , while intermolecular polar mechanisms could still operate …”

“…This indicates that while at low concentrations racemization is limited by the rare encounters between molecules, at higher concentrations the transition state of the actual racemization reaction becomes leading. Our racemization data thus support racemization mechanism A , although additional racemization through mechanism C cannot be excluded …”

“…The third proceeds through an addition–elimination mechanism, resulting in the interconversion of quinone and hydroquinone groups. For a related quinone–hydroquinone molecule, racemization proceeds through such a pathway . Although mechanism B could be quickly ruled out, Kim et al.…”

“…At low concentrations (< 1mgmL À1 ), the racemization rate increases drastically with increasing concentration, while at high concentrations We find that the system followsr oute A,while intermolecular polar mechanisms could still operate. [17] (> 1mgmL À1 ), this value levels off. This indicates that while at low concentrationsr acemizationi sl imited by the rare encounters between molecules, at higher concentrations the transition state of the actual racemizationr eaction becomes leading.…”

“…For ar elated quinone-hydroquinone molecule, racemization proceeds through such ap athway. [17] Althoughm echanism B could be quickly ruled out, Kim et al…”