Direct Synthesis of Bicyclo[1.1.1]pentanes by Sequential C═C, C–C Functionalization Reactions

2-Substituted bicyclo[1.1.1]pentane carboxylates have been synthesized using two sequential carbene reactions. A dirhodium-catalyzed intramolecular cyclopropanation to form a bicyclo[1.1.0]butane is followed by a photoinduced formation of a triplet carbene, which undergoes a diradical addition into the strained C-C bond of the bicyclo[1.1.0]butane. A variety of novel 2-substituted bicyclo[1.1.1]pentanes have been synthesized in good to moderate yields, offering rapid access to these valuable scaffolds. Additionally, a one-pot, two-reaction sequence was developed in which the bicyclo[1.1.1]pentanes were afforded starting from two distinct diazo compounds. Computational analysis supports the triplet carbene intermediate addition into the bicyclo[1.1.0]butane C-C bond. Additionally, computational analysis shows the importance of an aryl substituent to stabilize the diradical intermediate, which is required for the productive formation of the bicyclo[1.1.1]pentanes.