Cannabis. Part 28. A new route to the synthesis of cannabifuran

Abstract

The total synthesis of the naturally occurring dibenzofuran cannabifuran (9-isopropyl-6-methyl-3-pentyl-dibenzofuran-1-ol)(25) is presented. In the key step, starting from 2,3-dimethoxy-p-toluic acid and 2-bromo-1,3-dimethoxy-5-pentylbenzene, the aryl–aryl bond was formed via a methoxy displacement in the aryldihydro-oxazole (17). The final furan ring closure in the trimethoxybiphenyl (23) to cannabifuran was accomplished by use of HI–Ac₂O. Investigations of other approaches resulted in an improved synthesis of 2,6-dimethoxybiphenyl using modifications of nickel-catalysed Grignard cross-coupling syntheses.