The Synthesis of Cubebol from (−)-Carvone by Introducing the Electrochemical Acetoxylation Reaction

Abstract

Abstract The synthesis of cubebol and the related compounds from (−)-carvone is described. In the preparation of the key intermediate, 7,10-trans-2,6-epi-2-acetoxy-7-isopropyl-10-methyltricyclo[4.4.0.01,5]decan-4-one (10) the electrochemical acetoxylation reaction could be used as an effective method for introducing the acetoxy group at C-2 carbon atom instead of the carboxy function of 7,10-trans-2,6-epi-4-oxo-7-isopropenyl-10-methyltricyclo-[4.4.0.01,5]decan-2-carboxylic acid (6a). The condensation of (+)-p-menth-8-en-2-one (2a) prepared from (−)-carvone with dimethyl succinate afforded Stobbe half-ester 3, which provided the diazoketone 4 smoothly. Thermal decomposition of 4 in benzene gave intramolecular adducts 5a and 5b (4 : 1). Hydrolysis of 5a afforded 6a in ca. 40% yield. Electrolysis of 6a in AcOH-t-BuOH-Et3N (2 : 1 : 0.1) using platinum electrodes gave 10 in 72% yield. Elimination of acetic acid gave two isomers 11a and 11b (3 : 1) in 87% yield and subsequent methylation of 11a afforded 7-isopropyl-4,10-dimethyltricyclo[4.4.0.01,5]deca-2-en-4-ol (12) in 82% yield, which on hydrogenation gave the desired product 1a (36.5%) along with the epimer 1b (36.5%).