Synthesis of enantiopure phthalides including 3-butylphthalide, a fragrance component of celery oil, and determination of their absolute configurations

✍ Scribed by Masashi Kosaka; Satoshi Sekiguchi; Junpei Naito; Makoto Uemura; Shunsuke Kuwahara; Masataka Watanabe; Nobuyuki Harada; Kunio Hiroi

• Publisher: John Wiley and Sons
• Year: 2005
• Tongue: English
• Weight: 462 KB
• Volume: 17
• Category: Article
• ISSN: 0899-0042
• DOI: 10.1002/chir.20156

✦ Synopsis

Abstract

Enantiopure phthalides 2 and 5–8 were synthesized via enantioresolution of the corresponding alcohols with a chiral auxiliary of camphorsultam dichlorophthalic acid, (1__S__,2__R__,4__R__)‐(−)‐CSDP acid 3, followed by solvolysis with KOH in MeOH and the catalytic oxidation of chiral glycols with iridium complex 28. The absolute configurations of phthalides 2 and 5–8 were determined by applying the ^1^H‐NMR anisotropy method of MαNP acid (4), 2‐methoxy‐2‐(1‐naphthyl)propionic acid, to the chiral synthetic precursory alcohols. In the case of 3‐phenylphthalide (R)‐(−)‐7, the absolute configuration determined by the ^1^H‐NMR anisotropy method using MαNP acid 4 agreed with that by the X‐ray crystallographic method. By applying these methods, 3‐butylphthalide (S)‐(−)‐2, a fragrance component of essential oil of celery, has been synthesized in an enantiopure form, and its absolute configuration was unambiguously determined. Chirality 17:218–232, 2005. © 2005 Wiley‐Liss, Inc.