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) has recently been extensively explored for the construction of both bicyclohexanes and bicycloheptanes. Adopting this approach for the synthesis of medium-sized bridged carbocycles has instead 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 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 easily accessed in good to very good yields. This convenient and scalable procedure was tolerant towards a range of both aromatic and aliphatic substituents on both the BCB substrates and the dienes. The obtained BCO products could be smoothly functionalized through reduction and cross-coupling reactions.