Highly Functional Allyl-Bicyclo[1.1.1]pentane Synthesis by Radical-Initiated Three-Component Stereoselective Allylation

Abstract

Rapid access to highly functional allylated BCP synthons can be achieved with good selectivity and yield through a radical, three-component reaction (3CR) regime using various combinations of radical precursors and vinyl-appended heterocycles acting as versatile and modular precursors. This practical process combines mild operating conditions, a wide scope of reaction partners, and the ability to diversify the functionalized allylic scaffolds further using the allyl and other functional groups as synthetic branching points. The developed protocol allows structural alteration and increases the molecular complexity through late-stage drug modifications and drug conjugation approaches. Mechanistic probes demonstrate that the 3CR process is initiated by a selective, light-promoted radical addition to [1.1.1]-propellane, followed by coupling with the vinyl-substituted heterocycle, which represents a formal decarboxylative radical addition/double bond relay/protonation sequence.