Total Synthesis of (±)-Merrilactone A

The total synthesis of racemic merrilactone A (a neurotrophic agent) is described, featuring simultaneous and stereospecific creation of the C4 and C5 stereocenters via a notable silyloxyfuran Nazarov cyclization. Full details of the successful synthetic strategy are given, as well as several examples of the interesting reactivity of intermediates that were prepared and studied during the execution of the total synthesis. A detailed investigation of the Lewis acid-catalyzed Nazarov cyclization of silyloxyfurans was conducted, including a systematic study of substrate scope and limitations. In addition, experiments were conducted that suggest the participation of Lewis acidic silicon species in the Nazarov cyclization.