Acid-Catalysed Iterative Generation of o-Quinone Methides for the Synthesis of Dioxabicyclo[3.3.1]nonanes: Total Synthesis of Myristicyclins A-B

We report a practical and efficient method for the synthesis of bioactive flavanoids relying on the strategic use of o-quinine methide (o-QM) intermediates. This involves Bronsted acid-catalysed iterative generation of o-QMs/[4+2] cycloaddition/intermolecular Michael addition/cyclative acetalization in the cascade sequence for the synthesis of dioxabicyclo[3.3.1]nonanes. The ‘one-pot’, controlled cascade sequence successfully provided the shortest route amenable for gram scale synthesis of natural products (±)-myristicyclins A-B.