Regioselective Activation of Benzocyclobutenones and Dienamides Lead to Anti-Bredt Bridged-Ring Systems by a [4+4] Cycloaddition.

To the best of our knowledge, bridgehead carbon benzofused-bridged ring systems have previously not been accessible to the synthetic community. Here, we describe a formal type-II [4+4] cycloaddition approach that provides fully sp(2)-carbon embedded anti-Bredt bicyclo[5.3.1] skeletons through the Rh-catalyzed C-1-C-8 activation of benzocyclobutenones (BCBs) and their coupling with pedant dienamides. Variously substituted dienamides have been coupled with BCBs to provide a range of complex bicyclo[5.3.1] scaffolds (>20 examples, up to 89% yield). The bridged rings were further converted to polyfused hydroquinoline-containing tetracycles via a serendipitously discovered transannular 1,5-hydride shift/Prins-like cyclization/Schmidt rearrangement cascade. Bridgehead carbon benzofused-bridged ring systems have previously not been accessible via synthetic approaches. Here, the authors report a formal type-II [4+4] annulation approach that provides fully sp(2)-carbon embedded anti-Bredt bicyclo[5.3.1] skeletons through the Rh-catalyzed C1-C8 activation of benzocyclobutenones and their coupling with pedant dienamides.