Lewis Acid Catalyzed (4π+2σ) Annulation of Bicyclobutanes with Dienol Ethers for the Synthesis of Bicyclo[4.1.1]octanes

Bicyclic carbocycles containing a high fraction of Csp3 have become highly attractive synthetic targets because of the multiple applications they have found in medicinal chemistry. The formal cycloaddition of bicyclobutanes (BCB) with two- or three- atom partners has recently been extensively explored for the construction of bicyclohexanes and bicycloheptanes, but applications to the synthesis of medium-sized bridged carbocycles remained more limited. We report herein the formal (4π+2σ) cycloaddition of BCB ketones with silyl dienol ethers. The reaction occurred in the presence of 5 mol% aluminium triflate as a Lewis acid catalyst. Upon acidic hydrolysis of the enol ether intermediates, rigid bicyclo[4.1.1]octanes (BCOs) diketones could be accessed in up to quantitative yields. This procedure tolerated a range of both aromatic and aliphatic substituents on both the BCB substrates and the dienes. The obtained BCO products could be functionalized through reduction and cross-coupling reactions.