A Convenient Enantiospecific Route towards Bioactive Merosesquiterpenes by Cationic‐Resin‐Promoted Friedel–Crafts Alkylation with α,β‐Enones

• Published in: European Journal of Organic Chemistry 2009-03, Vol.2009 (8), p.1139-1143
• Main Authors: Alvarez‐Manzaneda, Enrique, Chahboun, Rachid, Cabrera, Eduardo, Alvarez, Esteban, Haidour, Ali, Ramos, Jose Miguel, Alvarez‐Manzaneda, Ramón, Tapia, Rubén, Es‐Samti, Hakima, Fernández, Antonio, Barranco, Inmaculada
• Format: Article
• Language: English
• Subjects: Alicyclic compounds, terpenoids, prostaglandins, steroids; Arenes; Aromatic substitution; Biological activity; Chemistry; Cyclization; Exact sciences and technology; Heterocyclic compounds; Heterocyclic compounds with o, s, se, te hetero atom and condensed derivatives; Organic chemistry; Preparations and properties; Terpenoids
• ISSN: 1434-193X; 1099-0690
• DOI: 10.1002/ejoc.200801174

An enantiospecific route towards bioactive merosesquiterpenes, based on the cationic‐resin‐promoted Friedel–Crafts alkylation of alkoxyarenes with an α,β‐unsaturated ketone, is reported. Reaction of ketone 11 with 3,4‐methylenedioxyphenol afforded the corresponding chromene. Treatment of 11 with protected phenol 20 gave aryl nordrimane ketone 21, a suitable intermediate in the synthesis of bioactive merosesquiterpenes and their 8‐epi derivatives. By utilizing this methodology, a formal synthesis of (+)‐puupehenone and other related metabolites, via triflate 25, is described. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009) A new methodology for synthesizing bioactive merosesquiterpenes, such as the marine (+)‐puupehenone and related metabolites, is reported. The sequence involves a cationic‐resin‐promoted Friedel–Crafts alkylation of an aryl ether with a norsesquiterpene α,β‐enone and further C–O coupling catalyzed by palladium.