Direct Synthesis of 2-Substitued Bicyclo[1.1.1]pentanes by Sequential C=C, C–C Functionalization Reactions

2-Substitued bicyclo[1.1.1]pentanes have be synthesized using two sequential diazo carbene reactions. The dirhodium mediated cycliza-tion to form a bicyclo[1.1.0]butane proceeds in near quantitative yield, followed by a photoinduced triplet energy transfer catalyzed carbene formation which undergoes a radical addition into the strained C–C bond. A variety of novel 2-substitued bicy-clo[1.1.1]pentanes have been synthesized good to moderate yields, offering fast access to these valuable scaffolds. Additionally, a one-pot two-reaction sequence was developed in which the bicyclo[1.1.1]pentane was afforded starting from two distinct diazo compounds. Computational analysis supports thetriplet carbene intermediate addition into the bicyclo[1.1.0]butane C–C bond. Additionally, the analysis shows the importance of a phenyl substituent to stabilize the radical intermediate, ultimately affording the bicyclo[1.1.1]pentane product. This methodology will greatly enhance the synthetic utility of 2-substituted bicyclo[1.1.1]pentanes, allowing for easy access to a novel chemical space.