Synthesis of α-Quaternary Bicyclo[1.1.1]pentanes through Synergistic Organophotoredox and Hydrogen Atom Transfer Catalysis
Jeremy Nugent, Alistair J. Sterling, Nils Frank, James J. Mousseau, Edward A. Anderson
Abstract
Bicyclo[1.1.1]pentanes (BCPs) are important in drug design as sp 3 -rich bioisosteres of arenes and tert -butyl groups; however, the preparation of BCPs with adjacent quaternary carbons is barely known. We report a facile synthesis of α-quaternary BCPs using organophotoredox and hydrogen atom transfer catalysis in which α-keto radicals, generated through oxidation of β-ketocarbonyls, undergo efficient addition to [1.1.1]propellane. The BCP products can be transformed into a variety of useful derivatives, including enantioenriched BCPs featuring α-quaternary stereocenters.
Topics & Concepts
ChemistryStereocenterCatalysisBicyclic moleculeHydrogen atomCombinatorial chemistryOrganocatalysisOrganic chemistryEnantioselective synthesisAlkylRadical Photochemical ReactionsOxidative Organic Chemistry ReactionsCatalytic C–H Functionalization Methods