Mechanically induced sequential one-pot Wittig olefination–Diels–Alder reaction: a solvent-free approach to complex bicyclic scaffolds

Abstract

Herein we present a mechanically induced, solvent-free protocol that sequentially combines the Wittig olefination and Diels–Alder cycloaddition in one-pot and enables the synthesis of structurally complex bicyclic compounds. This method proceeds entirely under ball milling conditions without the requirement of any solvent while eliminating the need for intermediate purification. Careful optimization of the milling parameters and reagent addition enables efficient conversion of various α,β-unsaturated aldehydes and ketones with electron-deficient dienophiles to the corresponding cycloadducts via diene intermediates, demonstrating high stereoselectivity and yielding exclusively endo Diels–Alder adducts. Furthermore, the extension of the sequence by a solvent-free one-pot oxidation is exemplified, achieving a three-step synthesis in a single milling vessel without intermediate workup and purification, which exhibits excellent green metrics in comparison with solution-based methods. This operationally simple and sustainable approach demonstrates the potential of mechanochemistry to streamline multistep organic synthesis, while reducing solvent use and energy demand.