Acid-catalysed iterative generation of o-quinone methides for the synthesis of dioxabicyclo[3.3.1]nonanes: total synthesis of myristicyclins A–B

Abstract

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 Brønsted acid-catalysed iterative generation of o-QMs/[4+2] cycloaddition/intermolecular Michael addition/cyclative acetalization in a 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.