Synlett 2002(8): 1344-1346
DOI: 10.1055/s-2002-32988
LETTER
© Georg Thieme Verlag Stuttgart · New York

TBAT-Mediated Nitrone Formation of ω-Mesyloxy-O-tert-butyldiphenylsilyl-oximes: Facile Synthesis of Cyclic Nitrones from Hemiacetals

Osamu Tamura*, Atsushi Toyao, Hiroyuki Ishibashi*
Faculty of Pharmaceutical Sciences, Kanazawa University, Takara-machi, Kanazawa, Ishikawa 920-0934, Japan
e-Mail: tamura@mail.p.kanazawa-u.ac.jp;
Further Information

Publication History

Received 22 May 2002
Publication Date:
25 July 2002 (online)

Abstract

Chiral and cyclic nitrones were synthesized by TBAT-mediated desilylative cyclization of ω-mesyloxy-O-tert-butyldiphenylsilyloximes, readily prepared from sugar derivatives by a consecutive treatment with O-tert-butyldiphenylsilylhydroxyl­amine and with mesyl chloride. The method was applied to sequential nitrone formation and intramolecular cycloaddition.

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When H2NOTMS or H2NOTBDMS was used, a mixture of the corresponding ω-hydroxy-O-silylated oxime and the desilylated oxime was obtained. Use of azeotropic removal of water instead of MgSO4, again gave a similar mixture.

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In contrast, treatment of desilylated congener of 2a with mesyl chloride (1 equiv) and Et3N (2 equiv) gave an inseparable complex mixture.

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The reaction required a prolonged reaction time without MS 4Å.

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Typical procedure. Preparation of 4a from 1a: A mixture of 1a (500 mg, 3.12 mmol) and MgSO4 (1.5 g) in toluene (5 mL) was heated at reflux for 5 min. To this mixture were added successively H2NOTBDPS (2.54 g, 9.36 mmol) and PPTS (39.0 mg, 0.156 mmol) at the same temperature. After further heating for 15 min, MgSO4 was filtered off, and the filtrate was washed successively with an aqueous saturated solution of NaHCO3 and brine, dried (MgSO4), and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel with n-hexane-EtOAc (2:1) to give 2a. Compound 2a was dissolved in CH2Cl2 (8 mL). Mesyl chloride (0.73 mL, 9.26 mmol) and Et3N (0.60 mL, 9.27 mmol) were added to the stirred solution at 0 °C. After stirring for 15 min, water was added to the mixture, and the whole was extracted with CHCl3. The organic phase was washed with brine, dried (MgSO4), and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel with n-hexane-EtOAc (3:1) to afford a 65:35 mixture of (E)-3a and (Z)-3a (1.51 g, 98% from 1a). (E)-3a: 1H NMR (500 MHz, CDCl3) δ 1.09 (9 H, s), 1.36 (3 H, s), 1.53 (3 H, s), 2.97 (3 H, s), 4.16 (1 H, dd, J = 6.8, 11.2 Hz), 4.20 (1 H, dd, J = 4.5, 11.2 Hz), 4.46 (1 H, br dt, J = 4.5, 6.8 Hz), 4.79 (1 H, br t, J = 7.3 Hz), 7.39-7.41 (5 H, m), 7.64-7.69 (6 H, m). (Z)-3a: 1.11 (9 H, s), 1.31 (3 H, s), 1.49 (3 H, s), 2.86 (3 H, s), 4.08 (1 H, dd, J = 5.5, 11.0 Hz), 4.27 (1 H, dd, J = 2.8, 11.0 Hz), 4.76 (1 H, br dt, J = 2.8, 7.3 Hz), 5.44 (1 H, br dd, J = 3.7, 7.3 Hz), 7.19 (1 H, d, J = 3.7 Hz), 7.36-7.43 (5 H, m), 7.61-7.68 (5 H, m). To a boiling suspension of 3a obtained above (603 mg, 1.23 mmol) and MS 4A (powder, 2.5 g) in THF (50 mL) was added a solution of TBAT (682 mg, 1.23 mmol) in THF (3 mL), and the mixture was further heated at the same temperature for 7 min. After cooling, MS 4A was filtered off and the filtrate was concentrated under reduced pressure. The residue was purified by column chromatography on silica gel with EtOAc-MeOH (1:0 to 8:1) to give 4a (135 mg, 70%), mp 110-112 °C (diisopropyl ether), [α]D 26 -26.3 (c 0.50, CH2Cl2) [lit. [4] mp 110-111 °C, [α]D 20 -28.0 (c 0.46, CH2Cl2)]. 1H NMR (500 MHz, CDCl3) δ 1.38 (3 H, s), 1.47 (3 H, s), 4.05 (1 H, br d, J = 15.1 Hz), 4.14 (1 H, br dd, J = 4.4, 15.1 Hz), 4.92 (1 H, br t, J = 6.4 Hz), 5.31 (1 H, br d, J = 5.9 Hz), 6.89 (1 H, br s); 13C NMR (125 MHz, CDCl3) δ 25.6, 27.1, 67.9, 73.5, 79.8, 112.1, 132.5. The 1H NMR spectral data are identical with those previously reported. [4]