Litcius/Paper detail

Synthesis of Polysubstituted 2-Oxabicyclo[2.1.1]hexanes via Visible-Light-Induced Energy Transfer

Yujie Liang, Roman Kleinmans, Constantin G. Daniliuc, Frank Glorius

2022Journal of the American Chemical Society200 citationsDOI

Abstract

Synthesis of bicyclic scaffolds has attracted growing interest because they are of high importance in modern pharmaceutical development. Here we report a strategy to access polysubstituted 2-oxabicyclo[2.1.1]hexanes in a single operation from readily accessible benzoylformate esters and bicyclo[1.1.0]butanes via visible-light-induced triplet energy transfer catalysis. The process is proposed to involve a formal [2π + 2σ] photocycloaddition/backbone C–H abstraction/aryl group migration sequence. A diverse range of (hetero)aryl groups successfully underwent migration to the backbone (C2) position to provide previously inaccessible bicyclic molecules, and the ester group of the product can serve as a handle for downstream manipulation, thus offering opportunities to rapidly build up molecular complexity and access new sp3-rich chemical space.

Topics & Concepts

ChemistryBicyclic moleculeArylChemical spaceMoleculeStereochemistryCombinatorial chemistryDrug discoveryOrganic chemistryAlkylBiochemistryRadical Photochemical ReactionsCatalytic C–H Functionalization MethodsSulfur-Based Synthesis Techniques