Stereoselective synthesis of 2,3,7-trimethylcyclooctanone and related compounds and determination of their relative and absolute configurations by the MαNP acid method

✍ Scribed by Junpei Naito; Shunsuke Kuwahara; Masataka Watanabe; John Decatur; Pieter H. Bos; Ruben P. Van Summeren; Bjorn Ter Horst; Ben L. Feringa; Adriaan J. Minnaard; Nobuyuki Harada

• Publisher: John Wiley and Sons
• Year: 2008
• Tongue: English
• Weight: 303 KB
• Volume: 20
• Category: Article
• ISSN: 0899-0042
• DOI: 10.1002/chir.20637

✦ Synopsis

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)‐(+)‐MαNP acid} 1 was applied. Racemic alcohol (±)‐7 was esterified with (S)‐(+)‐MαNP acid 1 yielding diastereomeric esters, which were efficiently separated by HPLC on silica gel affording the first‐eluted MαNP ester (–)‐10a and the second‐eluted one (–)‐10b. The relative and absolute configurations of ester (–)‐10a were determined to be (S;1__R__,2__S__,3__R__,7__S__) 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 MαNP anisotropy method. The alcohol 7 formed from (+)‐6 was similarly esterified with (S)‐(+)‐MαNP acid 1 yielding an MαNP ester, which was identical with (–)‐10a, and the relative and absolute configurations of 2,3,7‐trimethylcyclooctanone (+)‐6 were determined to be (2__S__,3__R__,7__S__). Chirality, 2008. © 2008 Wiley‐Liss, Inc.