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Synlett 2009(20): 3279-3282  
DOI: 10.1055/s-0029-1218374
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

A Chiral Bifunctional Sulfonamide as an Organocatalyst: Alcoholysis of σ-Symmetric Cyclic Dicarboxylic Anhydrides

Takashi Honjoa, Takeshi Tsumuraa, Shigeki Sano*a, Yoshimitsu Nagaoa, Kentaro Yamaguchib, Yoshihisa Seib
a Graduate School of Pharmaceutical Sciences, The University of Tokushima, Sho-machi, Tokushima 770-8505, Japan
Fax: +81(88)6339503; e-Mail: ssano@ph.tokushima-u.ac.jp;
b Faculty of Pharmaceutical Sciences at Kagawa Campus, Tokushima Bunri University, 1314-1 Shido, Sanuki, Kagawa 769-2193, Japan
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Publication History

Received 8 September 2009
Publication Date:
18 November 2009 (online)

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Abstract

Enantioselective alcoholysis of σ-symmetric cyclic dicarboxylic anhydrides with benzyl alcohol catalyzed by a chiral bifunctional sulfonamide was achieved in up to 98% ee at 5 mol% loading.

Key words

anhydrides - asymmetric synthesis - homogeneous catalysis - sulfonamides - alcoholysis

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General Experimental Procedure for Chiral Sulfonamide 1 Catalyzed Alcoholysis of Cyclic Dicarboxylic Anhydrides
To a solution of 3-phenylglutaric anhydride (2a, 190 mg, 1.0 mmol) and chiral sulfonamide 1 (25.8 mg, 0.05 mmol) in Et2O (10 mL) was added BnOH (125 µL, 1.2 mmol) at r.t. After stirring at r.t. for 20 h, the reaction mixture was treated with 10% HCl followed by extraction with CHCl3. The extract was dried over anhyd MgSO4, filtered, and concentrated in vacuo. To a solution of the residue in benzene-MeOH (7:2, 9 mL) was added a solution of TMSCHN2 (2.0 M in Et2O, 1 mL, 2.0 mmol). After being stirred at r.t. for 15 min, the reaction mixture was evaporated in vacuo. The oily residue was purified by silica gel column chromatography [EtOAc-n-hexane (1:4)] to afford methyl ester (S)-4a (286 mg, 92% yield, 87% ee) as a colorless oil. The ee (%) of (S)-4a was determined on a Chiralpak AD-H column [Daicel, eluent: n-hexane-2-PrOH (15:1), flow rate: 1 mL/min, detection: 254 nm]. The retention times were 12.5 min [minor isomer, (R)-4a] and 13.8 min [major isomer, (S)-4a], respectively. The absolute configuration of (S)-4a was explicitly determined by its chemical conversion to thioester (S)-5 (Scheme  [¹] ). [7]

Scheme1

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For details see Supporting Information.