A General Route to Bicyclo[1.1.1]pentanes through Photoredox Catalysis

Citations Over TimeTop 10% of 2019 papers

Abstract

Photoredox catalysis has transformed the landscape of radical-based synthetic chemistry. Additions of radicals generated through photoredox catalysis to carbon–carbon π-bonds 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 sp2 carbon–halogen bonds to access (hetero)arylated BCPs, as well as the functionalization of nonstabilized 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 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.

Related Papers

• → In-depth insight into metal–alkene bonding interactions(2006)19 cited
• → A study of alkene disulfonoxylation(2024)6 cited
• → Drastic ring transformation reactions of fused bicyclic rings to bridged bicyclic rings(1992)11 cited
• → Novel head-to-tail alkyl-alkene or alkene-alkene coupling via zirconium-catalyzed reaction of alkylmagnesium derivatives with monosubstituted alkenes(1992)46 cited
• → Influence of alkene structure on the formation constants of alkene–ICl molecular complexes(1986)5 cited