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Synlett 2002(3): 0510-0512
DOI: 10.1055/s-2002-20481
LETTER
© Georg Thieme Verlag Stuttgart · New York

An Efficient Regioselective and Diastereoselective Synthesis of the Epoxy-quinol Functionality as Building Block for the Manumycin Antibiotics by the Sequence of Photooxygenation, Reduction and Weitz-Scheffer Epoxidation

Waldemar Adama, Hamdullah Kιliç*b, Chantu R. Saha-Möllera
a Institut für Organische Chemie, Universität Würzburg, Am Hubland, 97074 Würzburg, Germany
b Department of Chemistry, Atatürk University, 25240 Erzurum, Turkey
e-Mail: hkilic@atauni.edu.tr;
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Publication History

Received 5 November 2001
Publication Date:
05 February 2007 (online)

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Abstract

The photooxygenation of the acetanilide 2 affords the hydroperoxide 3, which by titanium-tetraisopropoxide-catalyzed reduction with dimethyl sulfide gives the corresponding quinol 4. Regioselective and diastereoselective Weitz-Scheffer epoxidation of the latter by tert-butyl hydroperoxide (TBHP) and DBU as base catalyst leads to the cis-epoxy quinol 1, the essential functionality in Manumycin antibiotics.

Key words

photooxygenation - quinol - Weitz-Scheffer epoxidation - diastereoselectivity - regioselectivity

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Procedure for the Preparation of N -(3-Hydroperoxy-3-methyl-6-oxocyclohexa-1,4-dienyl)-acetamide(3): A sample of the acetanilide 2 (1.0 g, 6.0 mmol) and meso-tetraphenylporphine (TPP, 50 mg) in acetone:methylene chloride (7:3; 80 mL) was irradiated for 2 d at -25 °C with a 400-W sodium lamp, while a gentle stream of dry oxygen gas was allowed to pass through the solution. After removal of the solvent (ca. 10 °C, 15 Torr), the mixture was chromatographed on silica gel (100 g) with EtOAc:petroleum ether (40-50 °C) (1:1) as eluent to remove TPP as the first fraction. Further elution gave the title compound (0.74 g, 62%) as a white solid. Recrystallization from EtOAc:CH2Cl2 gave colorless plates, mp 125-126 °C(dec); 1H NMR (250 MHz, CD3COCD3): δ = 11.05 (br s, 1 H), 8.45 (br s, 1 H), 7.67 (d, J = 3.0 Hz, 1 H), 7.08 (dd, J = 10.0, 3.0 Hz, 1 H), 6.27 (d, J = 10 Hz, 1 H), 2.16 (s, 3 H), 1.41 (s, 3 H); 13C NMR (63 MHz, CD3COCD3): δ = 180.2, 163.4, 153.3, 133.0, 128.8, 127.3, 78.9, 23.8, 23.3; IR (KBr): 3340, 3164, 2846, 1654, 1646, 1532, 1396, 1343, 1242, 1136, 1060 cm-1. Anal. Calcd for C9H11NO4 (197.1): C, 54.82; H, 5.62; N, 7.10. Found: C, 55.16; H, 5.77; N, 7.11.

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Procedure for the Preparation of N -(3-Hydroxy-3-methyl-6-oxocyclohexa-1,4-dienyl)-acetamide(4): To a magnetically stirred solution of the hydroperoxide 3 (0.50 g, 2.53 mmol) and 4 Å molecular sieves (2 g) in methylene chloride (75 mL) at 10 °C were added dimethyl sulfide (0.19 g, 3.0 mmol) and titanium tetraisopropoxide (36.0 mg, 0.12 mmol). After 1 h of stirring, the reaction was stopped by the addition of water (50 µL), and the solids were removed by filtration. The solvent was evaporated (ca. 15 °C, 15 Torr), the residue was loaded on a short silica gel column (30 g), and eluted with a 4:1 mixture of EtOAc:petroleum ether (40-50 °C) to afford the title compound (0.38 g, 83%) as a colorless oil. Crystallization from a mixture of EtOAc:petroleum ether gave colorless needles, mp 104-105 °C; 1H NMR (250 MHz, CD3COCD3): δ = 8.58 (br s, 1 H,), 7.95 (d, J = 3.0 Hz, 1 H), 7.27 (dd, J = 10.0, 3.0 Hz, 1 H), 6.33 (d, J = 10 Hz, 1 H), 4.87 (br s, 1 H), 2.36 (s, 3 H), 1.68 (s, 3 H); 13C NMR (63 MHz, CD3COCD3): δ = 180.2, 169.3, 155.7, 132.1, 130.5, 124.3, 67.5, 27.9, 23.8; IR (KBr): 3277, 2966, 1655, 1611, 1533, 1383, 1234, 1092, 1054 cm-1. Anal. Calcd for C9H11NO3 (181.1): C, 59.66; H, 6.12; N, 7.73. Found: C, 59.25; H, 6.14; N, 7.67. Selected data for 4a: 1H NMR (250 MHz, CDCl3): δ = 8.00 (br s, 1 H), 7.68 (d, J = 3.0 Hz, 1 H), 6.95 (dd, J = 10.0, 3.0 Hz, 1 H), 6.26 (d, J = 10 Hz, 1 H), 2.10 (s, 3 H), 2.00 (s, 3 H), 1.54 (s, 3 H); 13C NMR (63 MHz, CDCl3): δ = 179.6, 169.5, 169.1, 152.1, 131.2, 128.2, 125.3, 74.7, 26.9, 24.6, 21.3; IR (KBr): 3352, 2980, 1734, 1695, 1657, 1516, 1400, 1368, 1341, 1240, 1099 cm-1. Anal. Calcd for C11H13NO4 (223.1): C, 59.19; H, 5.87; N, 6.27. Found: C, 59.14; H, 5.78; N, 6.16.

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Procedure for the Preparation of cis- N -(5-Hydroxy-5-methyl-2-oxo-7-oxabicyclo[4.1.0]hept-3-en-3-yl)-acetamide (cis-1): To a magnetically stirred solution of the quinol 4 (0.34 g, 1.87 mmol) in CH2Cl2 (30 mL) at r.t. (ca. 20 °C) were added anhyd tert-butylhydroperoxide (TBHP) (2.24 mmol; 0.56 mL, ca. 4.0 M in dichloroethane) and one drop of DBU. The resulting mixture was stirred at r.t. (ca. 20 °C) for 3 d, the solvent was removed (10 °C, 10 Torr), and the mixture was chromatographed on silica gel (40 g), by eluting with a 4:1 mixture of EtOAc:petroleum ether (40-50 °C). The first fraction consisted of unreacted TBHP; further elution gave the quinol epoxide cis -1 (0.29 g, 78%) as a white solid. On recrystallization from CH2Cl2:EtOAc (1:1) colorless needless were obtained, mp 185-186 °C. 1H NMR (250 MHz, CD3COCD3): δ = 8.19 (br s, 1 H), 7.38 (d, J = 2.7 Hz, 1 H), 4.71 (br s, 1 H), 3.68 (dd, J = 4.0, 2.7 Hz, 1 H), 3.53 (d, J = 4.0 Hz, 1 H), 2.09 (s, 3 H), 1.46 (s, 3 H); 13C NMR (63 MHz, CD3COCD3): δ = 189.5, 169.5, 130.7, 128.0, 68.2, 58.6, 53.0, 27.4, 23.7; IR (KBr): 3361, 3268, 3002, 1698, 1650, 1542, 1373, 1260, 1125, 1097, 1032, 931 cm-1. Anal. Calcd for C9H11NO4 (197.1): C, 54.82; H, 5.62; N, 7.10. Found: C, 54.73; H, 5.55; N, 7.03.