Transition-Metal-Free [4+3]-Cycloaddition of ortho-Quinone Methides and Isomunchnones: Catalytic and Diastereoselective Assembly of Oxa-bridged Oxazocine Scaffolds

Cycloadditions are powerful processes to synthesize complex polycyclic scaffolds. Herein, we disclose a [4+3]-cycloaddition between an insitu generated ortho-quinone methide and an isomunchnone to yield oxa-bridged oxazocine cores, generating N-2 and H2O as the sole by-products. Using only catalytic amounts of camphorsulfonic acid, it is possible to generate both reactive intermediates in one step, eliminating the need for rhodium catalysts generally employed for isomunchnone formation. Spectroscopic data and X-ray crystallography indicate the formation of the syn diastereomer, with the main side-product arising from a hydrate participating in a competing [4+2]-cycloaddition pathway.