A wide range of halogenated bicyclo[1.1.1]pentanes are accessed by functional group tolerant radical ring-opening of tricyclo[1.1.1.01,3]pentane, using triethylborane as initiator.

Cascade (domino) reactions have an unparalleled ability to generate molecular complexity from relatively simple starting materials; these transformations are particularly appealing when multiple rings are forged during this process. In this tutorial review, we cover recent highlights in cascade polycyclizations as applied to natural product synthesis, including pericyclic, heteroatom-mediated, cationic, metal-catalyzed, organocatalytic, and radical sequences.

Photoredox catalysis has transformed the landscape of radical-based synthetic chemistry. Additions of radicals generated through photoredox catalysis to carbon−carbon πbonds are well-established; however, this approach has yet to be applied to the functionalization of carbon−carbon σ-bonds. Here, we report the first such use of photoredox catalysis to promote the addition of organic halides to the carbocycle [1.1.1]propellane; the product bicyclo[1.1.1]pentanes (BCPs) are motifs of high importance in the pharmaceutical industry and in materials chemistry. Showing broad substrate scope and functional group tolerance, this methodology results in the first examples of bicyclopentylation of sp 2 carbon−halogen bonds to access (hetero)arylated BCPs, as well as the functionalization of nonstabilized sp 3 radicals. Substrates containing alkene acceptors allow the single-step construction of polycyclic bicyclopentane products through unprecedented atom transfer radical cyclization cascades, while the potential to accelerate drug discovery is demonstrated through late-stage bicyclopentylations of natural productlike and druglike molecules. Mechanistic investigations demonstrate the importance of the photocatalyst in this chemistry and provide insight into the balance of radical stability and strain relief in the reaction cycle.