Reactive species from aromatics and oxa-di-π-methane rearrangement: a stereoselective synthesis of (±)-hirsutene from salicyl alcohol

• Published in: Tetrahedron Vol. 60; no. 37; pp. 8161 - 8169
• Main Authors: Singh, Vishwakarma, Vedantham, Punitha, Sahu, Pramod K.
• Format: Journal Article
• Language: English
• Published: OXFORD Elsevier Ltd 06.09.2004; Elsevier
• Subjects: Chemistry; Chemistry, Organic; Cycloaddition; Oxa-di-π-methane rearrangement; Physical Sciences; Science & Technology; Spiroepoxycyclohexa-2,4-dienone; Oxa-di-π-methane rearrangement; Spiroepoxycyclohexa-2,4-dienone; Cycloaddition; EFFICIENT TOTAL-SYNTHESIS; cycloaddition; REAGENTS; oxa-di-pi-methane rearrangement; NATURAL-PRODUCTS; (PLUS-OR-MINUS)-HIRSUTENE; 1ST TOTAL-SYNTHESIS; spiroepoxycyclohexa-2,4-dienone; CYCLOPROPANES; EQUIVALENT
• ISSN: 0040-4020; 1464-5416
• DOI: 10.1016/j.tet.2004.06.096

A total synthesis of hirsutene, a triquinane sesquiterpene, from salicyl alcohol is reported. Oxidation of salicyl alcohol in the presence of cyclopentadiene gave 9-spiroepoxy- endo-tricyclo[5.2.2.0 2,6]undeca-4,10-dien-8-one which was elaborated to the 3-hydroxy-2-methyl- endo-tricyclo[5.2.2.0 2,6]undeca-10-en-8-one containing major structural and functional features of hirsutene. Photochemical sigmatropic 1,2-acyl shift in 3-hydroxy-2-methyl- endo-tricyclo[5.2.2.0 2,6]undeca-10-en-8-one followed by radical induced cleavage of peripheral cyclopropane bond, olefination and Simmon–Smith reaction furnished 11-hydroxy-1-methyl-4-spirocyclopropanetricyclo[6.3.0.0 2,6]undecane that upon treatment with hydrogen on PtO 2 and PCC oxidation gave 1,4,4-trimethyltricyclo[6.3.0.0 2,6]undecan-11-one, a known precursor. Wittig methylenation on this precursor gave hirsutene. Graphical Abstract