title: Stereoselective synthesis of 2,3,7-trimethylcyclooctanone and related compounds and determination of their relative and absolute configurations by the MalphaNP acid method.
abstract: The copper/chiral phosphoramidite (L(1))-catalyzed conjugate addition of dimethylzinc to cycloocta-2,7-dienone 4, followed by the methylation of the intermediate enolate, yielded a single isomer of 7,8-dimethylcyclooct-2-enone (+)-5. Compound (+)-5 was subjected to the second conjugate addition with ent-L(1) giving only one stereoisomer of 2,3,7-trimethylcyclooctanone (+)-6, which was converted to 2,3,7-trimethylcyclooctanol 7. To determine the relative and absolute configurations of these compounds, the (1)H NMR anisotropy method using (S)-(+)-2-methoxy-2-(1-naphthyl)propionic acid {(S)-(+)-MalphaNP acid} 1 was applied. Racemic alcohol (+/-)-7 was esterified with (S)-(+)-MalphaNP acid 1 yielding diastereomeric esters, which were efficiently separated by HPLC on silica gel affording the first-eluted MalphaNP ester (-)-10a and the second-eluted one (-)-10b. The relative and absolute configurations of ester (-)-10a were determined to be (S;1R,2S,3R,7S) by analyzing the (1)H and (13)C NMR spectra of (-)-10a and (-)-10b, especially their HSQC-TOCSY and NOESY spectra, and by applying the MalphaNP anisotropy method. The alcohol 7 formed from (+)-6 was similarly esterified with (S)-(+)-MalphaNP acid 1 yielding an MalphaNP ester, which was identical with (-)-10a, and the relative and absolute configurations of 2,3,7-trimethylcyclooctanone (+)-6 were determined to be (2S,3R,7S).
authors.affiliation: Institute of Multidisciplinary Research for Advanced Materials, Tohoku University, Sendai, Japan.
authors.forename: Junpei
authors.initials: J
authors.lastname: Naito
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Kuwahara
authors.forename: Masataka
authors.initials: M
authors.lastname: Watanabe
authors.forename: John
authors.initials: J
authors.lastname: Decatur
authors.forename: Pieter H
authors.initials: PH
authors.lastname: Bos
authors.forename: Ruben P
authors.initials: RP
authors.lastname: Van Summeren
authors.forename: Bjorn
authors.initials: B
authors.lastname: Ter Horst
authors.forename: Ben L
authors.initials: BL
authors.lastname: Feringa
authors.forename: Adriaan J
authors.initials: AJ
authors.lastname: Minnaard
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Harada