Phthalides, absolute

To a hot solution of 20.6 g of sodium in 400 ml of absolute ethanol, there is added a solution of 110 g of phthalide and 110 g of p-methoxybenzaldehyde. A vigorous reaction ensues and one-helf of the alcohol is distilled off over a two hour period. Ice and water are added to the red solution end the diluted solution is ecidified with hydrochloric acid. The resulting gum solidifies end the aqueous phase is removed by decantation. The crude solid is recrystallized twice from two liters of ethenol yielding 2-(p-methoxyphenyl)-1,3-indandione as pale yellow crystals, MP155°-156°C. 

In the case of flexible molecules all chiral conformers contribute to the observed CD spectrum. This usually leads to substantial reduction of the magnitude of the exciton Cotton effect. Nevertheless, if the conformation of the main contributor is established independently (e.g.. by molecular mechanics or NMR spectroscopy), its absolute configuration can be deduced from the exciton Cotton effect. Thus, for 3-(l-naphthalenyl)phthalide 5, the preferred conformation is 5 a. The negative couplet is in accordance with the left-handed screw between the phthalide 1 Ld and the naphthalene lBb transition dipole moment vectors, when the absolute configuration is R121. 

Absolute asymmetric synthesis was observed in the solid-state photoreaction of benzoylbenzamide 59 to phthalide 60 however, the reaction mechanism was completely different from that of thioester 57. [35] Recrystallization of these amides 59a-c from the chloroform-hexane solution afforded colorless prisms in all cases. X-ray crystallographic analysis revealed that all prochiral amides 59a-c adopted orthorhombic chiral space group P2 2 2 and were frozen in chiral and helical conformation in the crystal lattice. 

Sakamoto, M. (1998) Solid-State Photochemistry of o-Aroylbenzothioates Absolute Asymmetric Phthalide Formation Involving 1,4-Aryl Migration, J. Am. Chem. Soc., 49, 12770-12776. 

Scheme 24 Absolute asymmetric phthalide synthesis via aryl migration.

Scheme 26 Absolute asymmetric phthalide formation via radical pair intermediate.

The enantioselective synthesis of phthalide 227 (the (3 )-isomer), and other substituted phthalides, and the determination of their absolute configuration has been reported <2005CH218>. In a different approach to the same compounds, 2-alkylbenzoic acids were fed to microorganisms known to affect asymmetric hydroxylation. Lactonization of the resulting alcohols yielded the phthalides, used as scents in cosmetics and soaps <1997JPP10243794>. There is sufficient interest in these optically pure compounds for a chiral gas chromatography (GC) stationary phase to have been developed to quantify stereoisomeric mixtures. A silylated /3-CD was employed... 

Hydrolysis of in acidic medium gave the phthalide 1. In order to assess the absolute configuration of the lactones, particularly those with a dialkyl substitution pattern, which are not known in the literature, an x-ray study was performed using the -bromophenyl acetophenone, (R = Me, R -Bromophenyl, configuration). Pure enantiomers of were obtained by MPLC-assisted resolutions of followed by hydrolysis with acid. 

Dendrobium pierardii Roxb. (D. aphyllum Roxb.) (Orchidaceae) (Vol. 1, p. 459) Pierardine (71) has now been synthesized and shown to possess the (S) configuration. Condensation of the lithium salt of phthalaldehydic acid with 3-dimethylaminopropylmagnesium chloride followed by lactonization with acid gave ( )-pierardine, which was resolved by recrystallization of its di-0-benzoyl-L-tartrate. The (— )-enantiomer was shown to be identical with an authentic sample of the alkaloid. The absolute configuration of pierardine as (3S)-(3-dimethylaminopropyl)phthalide (71) was determined by comparison of... 

Following the formation of phthalide 44, the absolute configuration at C-1" and C-3 was confirmed by formation of the corresponding Mosher esters, confirming that the Sharpless asymmetric dihydroxylation had indeed proceeded according to the mnemonic to generate the 3S,1"S diastereomer. ... 

Kosaka M, Sekiguchi S, Naito J, Uemura M, Kuwahara S, Watanabe M, Harada N, Hiroi K (2005) Synthesis of enantiopure phthalides including 3-butylphthalide, a fragrance component of celery oil, and determination of their absolute configurations. Chirality 17 218-232... 

Chiral thietane-fused (3-lactam from an achiral monothioimide using the chiral crystal environment. /. Am. Chem. Soc., Vol. 115, p. 818 (b) Takahashi, M. Sekine, N. Fujita, T. Watanabe, S. Yamaguchi, K. Sakamoto, M. (1998). Solid-state photochemistry of o-aroylbenzothioates Absolute asymmetric phthalide formation involving 1,4-aryl migration. /. Am. Chem. Soc., Vol. 49, pp. 12770-12776... 

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