Synthesis of α-Quaternary Bicyclo[1.1.1]pentanes through Synergistic Organophotoredox and Hydrogen Atom Transfer Catalysis

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 alpha-quaternary BCPs using organophotoredox and hydrogen atom transfer catalysis in which alpha-keto radicals, generated through oxidation of beta-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 alpha-quaternary stereocenters.

Automated summary

Bicyclo[1.1.1]pentanes (BCPs) are synthesized efficiently using organophotoredox and hydrogen atom transfer catalysis, allowing for the preparation of alpha-quaternary BCPs. The products can be further transformed into a variety of useful derivatives, including enantioenriched BCPs.