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

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.