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.

Vinyl azides are highly versatile synthons that provide access to numerous N-heterocycles and other functional groups.

Bicyclo[1.1.1]pentanes (BCPs) have become established as attractive bioisosteres for para-substituted benzene rings in drug design. Conferring various beneficial properties compared with their aromatic "parents," BCPs featuring a wide array of bridgehead substituents can now be accessed by an equivalent variety of methods. In this perspective, we discuss the evolution of this field and focus on the most enabling and general methods for BCPs synthesis, considering both scope and limitation. Recent breakthroughs on the synthesis of bridge-substituted BCPs are described, as well as methodologies for postsynthesis functionalization. We further explore new challenges and directions for the field, such as the emergence of other rigid small ring hydrocarbons and heterocycles possessing unique substituent exit vectors.

Photoredox catalysis has transformed the landscape of radical-based synthetic chemistry. Additions of radicals generated through photo-redox catalysis to carbon–carbon pi bonds have become well-established; however, this approach has yet to be applied to the functionalization of carbon–carbon sigma bonds. Here we report the first such use of photoredox catalysis to promote the addition of organic hal-ides to the cage 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 sp2 carbon–halogen bonds to access (hetero)arylated BCPs, as well as the functionalization of non-stabilized sp3 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 product- and drug-like 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.

A wide range of halogenated bicyclo[1.1.1]pentanes are accessed by functional group tolerant radical ring-opening of tricyclo[1.1.1.0^1,3]pentane, using triethylborane as initiator.