Total synthesis of (+/-)-culmorin and (+/-)-longiborneol: an efficient construction of Tricyclo[6.3.0.0(3,9)]undecan-10-one by intramolecular double Michael addition.
The treatment of 4-[(5E)-6-methoxycarbonyl-5-hexenyl]-3, 4-dimethyl-2-cyclopenten-1-one (5) with LHMDS, TMSI-HMDS, Bu(2)OTf-HMDS, or TMSCl-NEt(3)-ZnCl(2) caused the intramolecular double Michael addition to afford tricyclo[6.3.0.0(3, 9)]undecan-10-one 12 in high yields with perfect stereoselectivity. The methodology was further elaborated to achieve efficient total syntheses of (+/-)-culmorin (1) and (+/-)-longiborneol (2). The common precursor 13 of them was obtained from 14 in 94% yield as a single isomer by the treatment with LHMDS. After the conversion of 13 into the corresponding acid 24 by hydrolysis, oxidative decarboxylation using S-(1-oxido-2-pyridinyl)-1,1,3, 3-tetramethylthiouronium hexafluorophosphate (HOTT, 27), followed by the Birch reduction, stereoselectively afforded (+/-)-culmorin (1). (+/-)-Longiborneol (2) was synthesized from 24 by the standard transformation. Additionally, the treatment of 24 with Pb(OAc)(4) led to 28 via uncommon migration. Its structure was determined by X-ray analysis after the transformation into the diketone 29.
Takasu
K
K
Department of Organic Chemistry, Graduate School of Pharmaceutical Sciences, Tohoku University, Aobayama, Sendai 980-8578, Japan.
Mizutani
S
S
Noguchi
M
M
Makita
K
K
Ihara
M
M
D003196:Computer Graphics; D005670:Fusarium / Q000378:metabolism; D007202:Indicators and Reagents; D008958:Models, Molecular; D008968:Molecular Conformation; D015394:Molecular Structure; D012717:Sesquiterpenes / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism
D007202:Indicators and Reagents; D012717:Sesquiterpenes; C013900:culmorin; C412581:longiborneol