Intermolecular [2 pi+2 sigma]-photocycloaddition enabled by triplet energy transfer

For more than one century, photochemical [2+2]-cycloadditions have been used by synthetic chemiststo make cyclobutanes, four-membered carbon-based rings. In this reaction, typically two olefin subunits (two sigma-electrons per olefin) cyclize to form two new C-C sigma-bonds. Although the development of photochemical [2+2]-cycloadditions has made enormous progress within the last century, research has been focused on such [2 pi-2 pi]-systems, in which two pi-bonds are converted into two new sigma-bonds(1,2). Here we report an intermolecular [2+2]-photocycloaddition that uses bicyclo[1.1.0]butanes as 2 sigma-electron reactants(3,7). This strain-release-driven [2/T+20]-photocycloaddition reaction was realized by visible-light-mediated triplet energytransfer catalysis(8,9). A simple, modular and diastereoselective synthesis of bicyclo[2.1.1]hexanes from heterocyclic olefin coupling partners, namely coumarins, flavones and indoles, is disclosed. Given the increasing importance of bicyclo[2.1.1] hexanes as bioisosteres-groupsthat convey similar biological propertiesto those they replace-in pharmaceutical research and considering their limited access(10,11), there remains a need for new synthetic methodologies. Applying this strategy enabled us to extend the intermolecular [2+2]-photocycloadditionsto a-bonds and provides previously inaccessible structural motifs.