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Synlett 2007(4): 0579-0582  
DOI: 10.1055/s-2007-967964
LETTER
© Georg Thieme Verlag Stuttgart · New York

Catalytic Asymmetric Intramolecular Cyclopropanation of 2-Diazo-3-oxo-6-heptenoic Acid Esters

Hiroyuki Takeda, Masahiro Honma, Ryoji Ida, Takashi Sawada, Masahisa Nakada*
Department of Chemistry, Faculty of Science and Engineering, Waseda University, 3-4-1 Ohkubo, Shinjuku-ku, Tokyo 169-8555, Japan
Fax: +81(3)52863240; e-Mail: mnakada@waseda.jp;
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Publication History

Received 15 November 2006
Publication Date:
21 February 2007 (online)

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Abstract

This manuscript describes studies on the catalytic asymmetric intramolecular cyclopropanation (IMCP) of 2-diazo-3-oxo-6-heptenoic acid esters. The enantioselectivity depends on the bulkiness of the ester moiety, and the 2,6-di-tert-butyl-4-methylphenyl ester of 2-diazo-3-oxo-6-heptenoic acid provided the product with 78% ee, suggesting that the catalytic asymmetric IMCP of α-diazo-β-keto esters could be a key reaction for the enantioselective syn­thesis of natural products as well as artificial molecules.

Key words

asymmetric catalysis - cyclopropanation - α-diazo-β-keto ester - enantioselectivity - intramolecular reaction

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General Procedure.
A toluene azeotroped [CuOTf]2·toluene (7.7 mg, 0.0148 mmol, 10 mol% as CuOTf) was placed in a dried flask under Ar atmosphere. To this flask was added toluene (4 mL) and then a solution of toluene azeotroped ligand 3c (13.1 mg, 0.0445 mmol, 15 mol%) in toluene (2 × 0.5 mL) via a cannula. The mixture was stirred at r.t. for 0.5 h and then a solution of toluene azeotroped 2,6-di-tert-butyl-4-methyl-phenyl 2-diazo-3-oxo-6-heptenoate (10, 110.0 mg, 0.297 mmol) in toluene (2 × 0.5 mL) was added to the light blue solution via a cannula. The reaction mixture was stirred at 50 °C for 45.5 h, quenched with a mixture of sat. aq NH4Cl solution (1 mL) and NH4OH aq solution (3 mL), and extracted with Et2O (2 × 2 mL). The combined organic layer was washed with brine (2 mL), dried over Na2SO4, and eva-porated. The residue was purified by flash chromatography (hexane-EtOAc, 10:1) to afford 2-oxobicyclo[3.1.0]hexane-1-carboxylic acid 2,6-di-tert-butyl-4-methylphenyl ester (14, 57.0 mg, 56%, 78% ee) as a white solid. The absolute configuration was determined as described in the text. The ee was determined as described in ref. 9: [α]D 28 -23.0 (c 0.45, CHCl3, 78% ee). IR (KBr): νmax = 2984, 1761, 1727, 1324, 1264, 1189, 1139, 1076, 1033, 781, 714 cm-1. 1H NMR (400 MHz, CDCl3): δ = 7.09 (s, 1 H), 7.08 (8) (s, 1 H), 2.76 (ddd, J = 8.1, 5.4, 5.4 Hz, 1 H), 2.38-2.06 (m, 9 H including δ = 2.31, s, 3 H), 1.37 (s, 9 H), 1.30 (s, 9 H). 13C NMR (100 MHz, CDCl3): δ = 205.3, 169.2, 145.7, 142.1, 141.7, 134.5, 126.9, 38.2, 35.3, 35.1, 34.2, 34.0, 31.4 (4), 31.4, 23.3, 21.5, 20.8. HRMS-FAB: m/z calcd for C22H30O3 + H: 343.2273; found: 343.2285.

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Compound 12: DAICEL CHIRALCEL OD-H ∅ 0.46 cm × 25 cm; hexane-2-PrOH = 9:1; flow rate = 0.5 mL/min); t R = 15.0 min for ent-12, 18.2 min for 12.
Compound 13: DAICEL CHIRALPAK AS-H ∅ 0.46 cm × 25 cm; hexane-2-PrOH = 4:1; flow rate = 0.5 mL/min); t R = 25.8 min for ent-13, 28.8 min for 13.
Compound 14 was converted into its oxime, which was benzoylated and subjected to HPLC analysis: DAICEL CHIRALCEL OD-H ∅ 0.46 cm × 25 cm; hexane-2-PrOH = 14:1; flow rate = 0.2 mL/min); t R: 25.8 min for ent-14, 28.8 min for 14.