Cannabis. Part 29. Synthesis of four benzofuro[6,7-c][2]benzopyrans related to cannabinol

Abstract

Four cannabinoids, the furan (6), the 2-methylfuran (7a), the 2-ethylfuran (7b), and the 2,3-dimethylfuran (11), related to cannabinol have been totally synthesized for the first time. The structures of two of three benzofuro[3,2-b][1]benzopyrans, the furan (6) and the 2-methylfuran (7a), recently isolated from cannabis resin smoke, were thereby confirmed. The earlier proposed structure of the third furan, as being the 2,3-dimethylfuran (11), was shown to be incorrect. The structure of 2-ethylfuran (7b) is now proposed for this cannabinoid. The key step in the syntheses of the furan (6) and the 2,3-dimethylfuran (11) was an internal site-specific base-catalysed cyclization of the intermediate aryloxyacetaldehyde (3) and 3-aryloxybutan-2-one (8), respectively. The 2-alkylated furans (7a) and (7b) have been synthesized in good yield by a highly selective lithiation of the furan (6) followed by treatment with an alkyl iodide.