A concise synthesis of (+/-)-cacalol.
A simple synthesis of the natural product cacalol has been developed that proceeds in seven steps and 21-25% overall yield. Ortho-lithiation of 4-methylanisole and alkylation with 5-iodo-1-pentene, followed by intramolecular Friedel-Crafts alkylation, gave 5-methoxy-1,8-dimethyltetralin. This compound was then formylated in the 6-position. Baeyer-Villiger oxidation and hydrolysis of the resulting formate gave 6-hydroxy-5-methoxy-1,8-dimethyltetralin. Alkylation of the phenolic hydroxyl group with chloroacetone followed by cyclodehydration gave cacalol methyl ether. Deprotection of this aryl methyl ether yielded cacalol.
Kedrowski
Brant L
BL
Department of Chemistry, University of Wisconsin, Oshkosh, Oshkosh, Wisconsin 54901, USA. kedrowsk@uwosh.edu
Hoppe
Robert W
RW
D015394:Molecular Structure; D012717:Sesquiterpenes / Q000138:chemical synthesis*
D012717:Sesquiterpenes; C497192:cacalol