Furan recyclization reaction as a new approach to isochromenes

As part of our ongoing interest in the synthesis of benzannelated heterocycles from o-substituted benzylfurans, recyclization of [o-(hydroxymethyl)aryl] difuryl methanes was studied. It was shown that, under acidic conditions, the o-hydroxymethyl group in these compounds acts as a nucleophile and tetracyclic isochromene derivatives are formed via a recyclization-cyclization tandem sequence. Alternatively, these compounds can be synthesized by reduction of the corresponding isochromone derivatives with lithium aluminum hydride. The potent biologically active analogues of cannabinoids were also obtained by interaction of isochromone derivatives with excess of methylmagnesium iodide.