Exploration of a proposed biomimetic synthetic route to plumarellide. Development of a facile transannular Diels–Alder reaction from a macrocyclic enedione leading to a new 5,6,7-tricyclic ring system

Abstract

A concise synthesis of the macrocyclic vinylbutenolide 19 is described, based on a facile RCM reaction of the substrates 16/ 18. Treatment of 19 with TFA containing water led to the 5,6,7-tricyclic compound 27, in a single step, in >90% yield, rather than to the alternative ring system 23 found in plumarellide ( 1). A rationale for the formation of 27 is presented, involving initial acid-catalysed hydrolysis of the furanmethanol intermediate 20 to the furanoxonium ion 21, which is next hydrolysed to the enol ether cyclic hemiketal 22. The intermediate 22 undergoes rapid tautomerisation and isomerisation producing enedione 24, which then takes part in a transannular Diels–Alder cyclisation to 26. Dehydration of 26 finally produces the tricyclic compound 27.