Intermolecular [2π+2σ]-photocycloaddition enabled by triplet energy transfer

For more than one century, photochemical [2+2]-cycloadditions have been used by synthetic chemists to make cyclobutanes, four-membered carbon-based rings. In this reaction, typically two olefin subunits (two π -electrons per olefin) cyclize to form two new C–C σ -bonds. Although the development of photochemical [2+2]-cycloadditions has made enormous progress within the last century, research has been focused on such [2 π +2 π ]-systems, in which two π -bonds are converted into two new σ -bonds 1 , 2 . Here we report an intermolecular [2+2]-photocycloaddition that uses bicyclo[1.1.0]butanes as 2 σ -electron reactants 3 – 7 . This strain-release-driven [2 π +2 σ ]-photocycloaddition reaction was realized by visible-light-mediated triplet energy transfer 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—groups that convey similar biological properties to 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]-photocycloadditions to σ -bonds and provides previously inaccessible structural motifs. A strain-release approach, realized by visible-light-mediated triplet energy transfer catalysis, enabled an intermolecular [2 π +2 σ ]-photocycloaddition.