Photochemical Deracemization at sp³-Hybridized Carbon Centers via a Reversible Hydrogen Atom Transfer

Abstract

A photochemical deracemization of 5-substituted 3-phenylimidazolidine-2,4-diones (hydantoins) is reported (27 examples, 69%-quant., 80–99% ee). The reaction is catalyzed by a chiral diarylketone which displays a two-point hydrogen bonding site. Mechanistic evidence (DFT calculations, radical clock experiments, H/D labeling) suggests the reaction to occur by selective hydrogen atom transfer (HAT). Upon hydrogen binding, one substrate enantiomer displays the hydrogen atom at the stereogenic center to the photoexcited catalyst allowing for a HAT from the substrate and eventually for its conversion into the product enantiomer. The product enantiomer is not processed by the catalyst and is thus enriched in the photostationary state.

Stereochemical editing logic powered by the epimerization of unactivated tertiary stereocenters

“…The direct, catalytic interconversion of stereocenters featuring acidic C-H bonds (e.g., a-carbonyl) is well established, and recent efforts have identified innovative strategies to control isomer distributions (8,9). We and others have sought to expand the scope of stereoediting tools to allow for the revision of conventionally static stereocenters, leveraging radical reactions that selectively target homolytically weak C-H bonds adjacent to secondary alcohols (10)(11)(12)(13)(14) or other heteroatoms (15)(16)(17)(18) and transiently electronically activated positions (19,20). In spite of these substantial advances, the selective interconversion of stereocenters having strong, hydridic C-H bonds-such as unactivated tertiary methines-remains an unsolved problem.…”

Phase-Transfer-Catalyzed Alkylation of Hydantoins

“…After developing a robust alkylation protocol, we sought to develop an asymmetric version of our reaction (Figure D). Indeed, to date, there are only a hand full of asymmetric transformations that allow us to control the stereochemistry at the C5 position of a hydantoin; these include the enantioselective hydrogenation catalyzed by chiral rhodium complexes, the diastereoselective aldol using aldehydo sugars, the asymmetric Friedel-Craft alkylation catalyzed by chiral phosphoric acids, and the photochemical deracemization of C5-substituted hydantoins through a reversible hydrogen atom transfer . Besides the aforementioned methods that allow a direct functionalization of hydantoins, there are also several asymmetric syntheses of hydantoins reported in the literature, but they mainly rely on the preinstallation of the chirality prior to the formation of the ring. − Asymmetric phase-transfer catalysis has become a prominent part of organocatalysis with some fantastic examples reported by Maruoka, Denmark, Itsuno, Kitamura, Park, Andrus, Itoh, Arai, and others. , For our part, we sought to induce enantioselectivity by replacing TBAB with a chiral phase-transfer catalyst such as PTC-1 , which was initially developed by Maruoka and co-workers and proved successful in numerous asymmetric alkylation reactions.…”

Photoinduced Dynamic Radical Processes for Isomerizations, Deracemizations, and Dynamic Kinetic Resolutions

“…Bach developed a photochemical α-stereocenter deracemization of hydantoins using a chiral diarylketone catalyst (Figure 16). 44 From mechanistic studies, HAT occurs selectively with (S)-hydantoins, forming the achiral radical and protonated ketyl radical. Further deuterium scrambling experiments lends support for back HAT occurring intermolecularly after dissociation.…”