The reactivity of ortho-quinone methides (o-QMs) has been exploited in natural product synthesis, total synthesis, medicinal chemistry and biochemistry. The high reactivity of this structural intermediate makes it attractive, in particular for multi-component reactions (MCR). Quinone methides have been hardly ever isolated, due to reactions favored by rearomatization into phenol, acting as the driving force. Recently, our laboratory reported an effective procedure for C-3 reductive alkylation of 4- hydroxycoumarin by a dehydrogenative oxidation of benzylic alcohols in the presence of tris(triphenylphosphine)ruthenium(II) dichloride (5 mol%), KOH (0.2 eq) in tertamyl alcohol under microwave irradiation at 140°C in 2 hours. Supposed mechanism is described as a first step of activation of the alcoholic substrate by metallo-catalyzed dehydrogenative oxidation, followed by a Knoevenagel condensation / reduction sequence (restitution of hydride or H2 by the metal depending on its nature). All these steps proceed under one pot conditions with a single catalytic species. The Knoevenagel adduct (3-methylene-2,4-chromandione) displaying similar structural analogy with more classical o-quinone methide, is a versatile substrate for MCR. The approach developed in the laboratory is to trap the 3-methylene-2,4-chromandione highly reactive intermediate in a solid-state stable Mannich adduct. In solution, the equilibrium is more favourable for the o-QM adduct which upon treatment with various nucleophilic species can react in excellent yields. This communication aims to describe our recent efforts developed for trapping this intermediate by different nucleophiles (including simple reduction methods).

3-Methylene-2,4-chromandione in situ trapping

253rd National Meeting (2017)

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