Given that bicyclo[2. 1.1]hexane structures are seen as potential sp -rich isosteres for orthoand meta-substituted benzene, we next investigated the tolerance of natural product and approved pharmaceutical derived alkenes in the newly developed [2π+2σ] cycloaddition reaction. Promisingly, substrates derived from the anti-inflammatory drug ibuprofen (3u) and the β-lactamase inhibitor sulbactam (3v) could be tolerated. In addition, derivatives of the cholesterol lowering pharmaceutical fenofibrate (3w), the gout medication probenecid (3x) and a protected glucose analogue (3y) were all capable of accessing the desired BCH products. As complex alkene substrates could be deemed more precious than the BCB coupling partner, we also demonstrated that inverting the stoichiometry of this reaction to have the olefin as the limiting reagent, could also provide access to the desired products in comparable yields (see Supplementary Information for details).