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.
Department of Chemistry, University of Wisconsin, Oshkosh, Oshkosh, Wisconsin 54901, USA. kedrowsk@uwosh.edu
Brant L
BL
Kedrowski
Robert W
RW
Hoppe
D015394:Molecular Structure; D012717:Sesquiterpenes / Q000138:chemical synthesis*
D012717:Sesquiterpenes; C497192:cacalol