Synlett 2005(17): 2607-2610  
DOI: 10.1055/s-2005-917083
LETTER
© Georg Thieme Verlag Stuttgart · New York

Control of Diastereoselectivity in C=O/C=N Reductive Cyclizations Using an Intramolecularly Tethered Hydrazone

Jose Luis Chiara*, Ángela García
Instituto de Química Orgánica General, CSIC, Juan de la Cierva 3, 28006 Madrid, Spain
Fax: +34915644853; e-Mail: jl.chiara@iqog.csic.es;
Further Information

Publication History

Received 5 July 2005
Publication Date:
05 October 2005 (online)

Abstract

Cyclic hydrazones are efficient ketyl radical acceptors in reductive coupling cyclizations mediated by samarium diiodide, ­affording cyclic amino alcohols with controlled stereochemistry at the new aminated stereocenter. This approach has been successfully applied to the stereoselective synthesis of a fully functionalized trehazolin cyclitol starting from d-glucose, where the required cyclic hydrazone was directly obtained by partial hydrazynolysis of a 1,2-cyclic carbonate.

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Preparation of Compound 5.
To a solution of 4 (1.0 g, 2.22 mmol) in anhyd CH2Cl2 (30 mL) under argon was added carbonyldiimidazole (0.767 g, 4.73 mmol) and Et3N (0.9 ml, 2.8 mmol) and the mixture was stirred at r.t. for 5 h. The reaction was concentrated under reduced pressure, diluted with CH2Cl2 (10 mL) and washed with aq HCl 2% (3 × 10 mL). The organic phase was dried over Na2SO4, filtered and concentrated at reduced pressure. The crude was purified by flash chromatography (silica gel, hexane-EtOAc 5:1) to give 5 (799 mg, 86%) as a white solid. Mp 60-61 °C; [α]D 20 +4.9 (c 4.8, CHCl3). IR (KBr): 3435, 2862, 1813, 1453, 1367,1355, 1156,1050, 746, 696 cm-1. 1H NMR (300 MHz, CDCl3): δ = 7.39-7.28 (m, 13 H), 7.26-7.17 (m, 2 H), 6.06 (d, 1 H, J = 6.3 Hz, H-1), 4.70-4.42 (m, 7 H, H-2, 3 OCH2Ph), 3.93 (t, 1 H, J = 4.2 Hz), 3.84-3.81 (m, 2 H), 3.69-3.65 (m, 2 H). 13C NMR (75 MHz, CDCl3): δ = 152.4, 137.5, 137.3, 136.7, 128.5, 128.4, 128.2, 128.0, 127.9, 127.8, 127.8, 97.3, 77.2, 75.8, 73.4, 73.2, 73.1, 72.6, 71.6, 68.3. MS (ES+): m/z = 477.1 [M + H2O]+, 499.1 [M + Na]+. Anal. Calcd for C28H28O7: C, 70.57; H, 5.92. Found: C, 69.97; H, 6.12.

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Preparation of Compound 6.
To a solution of 5 (200 mg, 0.42 mmol) in EtOH (2 mL) was added i-Pr2NEt (161 µL, 0.92 mmol) and hydrazine hydrochloride (32 mg, 0.46 mmol) and the mixture was heated at 80 °C for 4 d. The reaction was concentrated at reduced pressure and the crude was purified by flash chromatography (silica gel, hexane-EtOAc 3:1) to give 6 (140 mg, 68%) as a yellowish oil. [α]D 20 -0.9 (c 1.7, CHCl3). IR (KBr): 3306, 292, 1748, 1722, 1454, 1360, 1260, 1212, 1072, 1026, 751, 698 cm-1. 1H NMR (300 MHz, CDCl3): δ = 7.91 (br s, 1 H, NH), 7.49-7.27 (m, 13 H), 7.26-7.17 (m, 2 H), 7.02 (d, 1 H, J = 2.4 Hz, H-1), 4.91 (dd, 1 H, J = 1.8, 5.4 Hz, H-2), 4.75 (d, 1 H, J = 11.7 Hz, OCH2Ph), 4.64 (d, 1 H, J = 11.4 Hz, OCH2Ph), 4.54-4.48 (m, 4 H, 2 OCH2Ph), 4.11 (dd, 1 H, J = 4.2, 5.1 Hz), 4.01 (q, 1 H, H-5), 3.80 (dd, 1 H, J = 3.9, 7.5 Hz), 3.71-3.62 (m, 2 H), 2.56 (d, 1 H, J = 6.6 Hz, OH). 13C NMR (75 MHz, CDCl3): δ = 149.0, 140.8, 137.4, 137.2, 137.1, 128.5, 128.4, 128.3, 128.1, 128.0, 127.9, 76.9, 74.8, 74.3, 73.8, 73.5, 70.4, 70.1. MS (ES+): m/z = 491.1 [M + H]+, 508.3 [M + Na]+.

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Preparation of Compound 7.
To a solution of 6 (50 mg, 0.101 mmol) in CH2Cl2 (1 mL) under argon was added a suspension of Dess-Martin periodinane (86.5 mg, 0.203 mmol) in CH2Cl2 (0.5 mL). After stirring at r.t. for 1 h, the mixture was diluted with CH2Cl2 (5 mL) and washed with aq sat. NaHCO3 (2 × 3 mL). The organic phase was washed with aq 10% Na2S2O3 (2 × 3 mL), dried over Na2SO4, filtered and concentrated at reduced pressure. The crude was purified by flash chromatography (silica gel, hexane-EtOAc 2:1) to give 7 (25 mg, 51%) as a colorless oil. [α]D 20 -6.6 (c 0.8, CHCl3). 1H NMR (300 MHz, CDCl3): δ = 7.89 (s, 1 H, NH), 7.36-7.20 (m, 15 H), 7.00-7.00 (d, 1 H, J = 2.1 Hz, H-1), 4.86 (dd, 1 H, J = 2.1, 5.4 Hz, H-2), 4.50 (s, 2 H OCH2Ph), 4.57 (d, 1 H, J = 11.4 Hz, H-6), 4.48 (s, 1 H), 4.39 (d, 1 H, J = 11.4 Hz, H-6′), 4.31 (d, 1 H, J = 3.9 Hz), 4.19 (m, 3 H). 13C NMR (75 MHz, CDCl3): δ = 206.8, 148.2, 140.0, 136.9, 136.3, 135.9, 129.0, 129.0, 129.0, 128.9, 128.8, 128.4, 128.4, 80.5, 76.9, 74.7, 74.3, 74.3, 73.5, 73.4.

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Reductive Cyclization of Compound 7.
A solution of 7 (90 mg, 0.184 mmol) in THF (5 mL) was added dropwise under argon to a 0.1 M THF solution of SmI2 (0.1 M, 5.5 mL, 0.552 mmol) and t-BuOH (88 µL, 0.92 mmol) at -30 °C. After stirring at -30 °C for 2 h, the flask was opened to air to oxidize excess SmI2 and the crude reaction mixture was filtered through Florisil®, rinsing with CH2Cl2-MeOH 10:1. The filtrate was evaporated at reduced pressure and the residue was purified by flash chromatography (silica gel, hexane-EtOAc 1:2) to give 8 as a 7:1 mixture of isomers (58 mg, 65%). IR (KBr): 3272, 2868, 1709, 1453, 1093, 1061, 924, 737, 697 cm-1. MS (ES+): m/z = 491.1 [M + H]+, 513.3 [M + Na]+.
Compound 8a: 1H NMR (400 MHz, CDCl3): δ = 7.37-7.12 (m, 15 H), 6.92 (s, 1 H, NH), 5.04 (dd, 1 H, J = 3.5, 5.4 Hz, H-2), 4.73 (d, 1 H, J = 12.0 Hz, OCH2Ph), 4.54 (d, 1 H, J = 12.0 Hz, OCH2Ph), 4.55 (d, 2 H, J = 12.0 Hz, OCH2Ph), 4.47 (dd, 1 H, J = 1.5, 12.6 Hz, NH), 4.42 (d, 1 H, J = 11.7 Hz, OCH2Ph), 4.35 (d, 1 H, J = 11.7 Hz, OCH2Ph), 4.19 (d, 1 H, J = 3 Hz, H-3), 3.75 (s, 1 H, H-4), 3.72 (d, 1 H, J = 9.6 Hz, H-6), 3.62 (d, 1 H, J = 9.6 Hz, H-6′), 3.51 (ddd, 1 H, J = 1.5, 5.4, 12.6 Hz, H-1), 3.31 (s, OH). 13C NMR (75 MHz, CDCl3): δ = 153.5 (C=O), 137.3, 137.0, 136.5, 128.4, 128.4, 128.3, 128.1, 128.0 127.9, 127.9, 127.8, 127.7, 88.2 (C-3), 87.9 (C-2), 86.6 (C-4), 80.7 (C-5), 73.7 (OCH2Ph), 72.0 (OCH2Ph), 71.6 (OCH2Ph), 68.3 (C-6), 62.4 (C-1)
Compound 8b (partial spectrum): 1H NMR (400 MHz, CDCl3): δ = 6.81 (s, 1 H, NH), 4.58 (dd, 1 H, J = 3.4, 8.3 Hz, H-2), 4.36 (m, 1 H, H-3), 3.93 (d, 1 H, J = 8.1 Hz), 3.75 (m, 1 H, H-1), 3.40 (d, 1 H, J = 9.2 Hz, H-6), 3.26 (d, 1 H, J = 9.2 Hz, H-6′), 3.10 (s, OH). 13C NMR (75 MHz, CDCl3): δ = 156.0 (C=O), 137.4, 87.2 (C-3), 83.2 (C-2), 80.1 (C-4), 73.4 (OCH2Ph), 73.3 (OCH2Ph), 72.6 (OCH2Ph), 69.4 (C-6), 55.3 (C-1).

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For clarity, the numbering of the carbons in the starting glucose derivative 4 has been kept for all the compounds.