TOTAL SYNTHESIS OF (+-)-BULNESOL AND RELATED STUDIES

A stereoselective route to 1,7-dimethylbicyclo[4.3.1]decan-10-ols 16e, 19e, and 79 and the subsequent rearrangement of their methanesulfonate derivatives to the corresponding hydroazulenes 22, 27, and 81 is described. The synthesis of the bicyclo[4.3.1]decane intermediates begins with 2-carbethoxycycloheptanones and proceeds via condensation with methyl vinyl ketone and cyclization of the resulting 2-carbethoxy-2-(3-oxobutyl)-cycloheptanones in sulfuric acid. Selective reduction of the derived bicycio[4.3.1]decenone carboxylic acids 34 and 69 thereby obtained yields the aforementioned hydroazulene precursors. The 7-methylol-substituted hydroazulene derivative 82 was converted to (±)-bulnesol (87) via oxidation to the corresponding acid 83, esterification with diazomethane and basic isomerization of the resulting ester 84 to the epimer 85. Treatment of ester 84 with methyllithium afforded 7-epibulnesol (86) whereas ester 85 yielded (±)-bulnesol (87). In the initial stages of this synthetic scheme p-chlorophenyl ether was employed as a protecting group for the methylol function which was ultimately converted to the C-7 isopropylol grouping of bulnesol. This protecting group was easily removed through reduction to an acid-labile enol ether with lithium in ammonia. © 1969.