Removable Silyl Group as a "Masked Proton" in Oxy-2-oxonia(azonia)-Cope Rearrangement: Applications in Stereoselective Total Synthesis of Natural Macrolides

In the presence of a Lewis acid, trimethylsilyl‐substituted β,γ‐unsaturated ketones and aldehydes (imines) undergo nucleophilic addition to produce zwitterionic intermediates, followed by oxy‐2‐oxonia(azonia)‐Cope rearrangements to give homoallylic esters (amides). In the case of TMS‐containing 2‐vinylcycloalkanones, the process results in ring‐enlargement, providing 10‐ to 16‐membered lactones. This protocol was applied to the total synthesis of (R)‐phoracantholide I. In the presence of a Lewis acid, trimethylsilyl‐substituted β,γ‐unsaturated ketones and aldehydes (imines) undergo nucleophilic addition to produce zwitterionic intermediates, followed by oxy‐2‐oxonia(azonia)‐Cope rearrangements to give homoallylic esters (amides). This protocol was applied to the total synthesis of (R)‐phoracantholide I.