Rearrangement Approaches to Cyclic Skeletons. XIII. Total Synthesis of Triquinane Sesquiterpenes, (±)-Modhephene, and (±)-Isocomene, on the Basis of Formal Substitution at Both Bridgeheads of a Bicyclo[2.2.2]oct-5-en-2-one

• Published in: Bulletin of the Chemical Society of Japan Vol. 71; no. 1; pp. 231 - 242
• Main Authors: Uyehara, Tadao, Murayama, Tomohiro, Sakai, Katsunori, Onda, Kayoko, Ueno, Masako, Sato, Toshio
• Format: Journal Article
• Language: English
• Published: TOKYO The Chemical Society of Japan 01.01.1998; Chemical Soc Japan; Chemical Society of Japan
• Subjects: Chemistry; Chemistry, Multidisciplinary; Physical Sciences; Science & Technology; 1,3 ACYL MIGRATION; RING ENLARGEMENT; (+/-)-EPIMODHEPHENE; ISOCOMENE; MODHEPHENE; ENE-REACTION; (+1-)-ISOCOMENE; ADDITIONS; DERIVATIVES; STEREOCONTROLLED SYNTHESIS
• ISSN: 0009-2673; 1348-0634
• DOI: 10.1246/bcsj.71.231

A reaction of 1,4-dimethoxybicyclo[2.2.2]oct-5-en-2-one and R1MgX, followed by treatment with p-toluenesulfonic acid in benzene, gave the 5-methoxybicyclo[3.2.1]oct-6-en-2-one having a substituent (R1) at the C-1 bridgehead. This ketone was converted into the 5-methoxybicyclo[3.2.1]oct-3-en-2-one. By treatment with Li[CuR2], a second bridgehead substituent (R) was introduced at the C-4 position of the conjugated ketone. The product was converted into the corresponding α,β-unsaturated ketone, and then treated with R2Li or DIBAL-H (R2 = H). Acid treatment of the resulting allyl alcohols gave the bicyclo[2.2.2]oct-5-en-2-one having substituents R, R1, and R2 at the C-1, 4, and 5 positions, respectively. This procedure was successfully applied to a formal total synthesis of (±)-modhephene, a propellane-type triquinane sesquiterpene, and that of (±)-isocomene, an angular triquinane sesquiterpene, on the basis of an oxa-di-π methane rearrangement of the bicyclo[2.2.2]oct-5-en-2-ones.