A Short Synthesis of Natural (-)-Oblongolide via an Intramolecular or a Transannular Diels-Alder Reaction

Article abstract of DOI:10.1021/jo00123a011

The absolute configuration on naturally occurring oblongolide is confirmed as (3aS,5aR,7S,9aS,9bS)-3a,5a,6,7,8,9,9a,9b-octahydro-7,9b-dimethylnaphtho<1,2-c>furan-1(3H)-one (1) on the basis of a six-stage or an eight-stage synthesis from (-)-citronellol involving a steric-controlled, regioselective reduction and an intramolecular Diels-Alder (IMDA) reaction or a transannular Diels-Alder (TDA) reaction as the key steps. (-)-Citronellol (5) was converted into methyl (2E,4E,10E)-(S)-(+)-11-(tert-butoxycarbonyl)-7-methylundeca-2,4,10-trienoate (7) by sequential Lemiuex-Johnson oxidation, Wittig olefination, pyridinium dichromate oxidation, and Wadsworth-Emmons-Horner alkenation.A regioselective reduction of the methoxycarbonyl group in 7 afforded tert-butyl (2E,8E,10E)-(S)-(+)-2,6-dimethyl-12-hydroxydodeca-2,8,10-trienoate (8) from which oblongolide (1) was obtained via an IMDA reaction.The macrocyclic (2E,8E,10E)-(S)-(+)-2,6-dimethyldodeca-2,8,10-trieno-1,12-lactone derived from 8 underwent a highly stereoselective TDA reaction to give 1 at a lower reaction temperature, in a shorter reaction time and in a better yield than the analogous IMDA reaction.