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

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.

Key words

carbohydrates - electron transfer - hydrazones - ketones - samarium

References

• 1 Bergmeier SC. Tetrahedron  2000,  56:  2561 
• 2 Corey EJ. Pyne SG. Tetrahedron Lett.  1983,  24:  2821 
• For recent reviews, see:
• 3a Fallis AG. Brinza IM. Tetrahedron  1997,  53:  17543 
• 3b Naito T. Heterocycles  1999,  50:  505 
• 3c Friestad GK. Tetrahedron  2001,  57:  5461 
• For selected applications in natural products synthesis, see:
• 4a Miyabe H. Torieda M. Kiguchi T. Naito T. Synlett  1997,  580 
• 4b Miyabe H. Torieda M. Inoue K. Tajiri K. Kiguchi T. Naito T. J. Org. Chem.  1998,  63:  4397 
• 4c Boiron A. Zillig P. Faber D. Giese B. J. Org. Chem.  1998,  63:  5877 
• 4d Storch de Garcia I. Bobo S. Martin-Ortega MD. Chiara JL. Org. Lett.  1999,  1:  1705 
• 4e Miyabe H. Torieda M. Inoue K. Tajiri K. Kiguchi T. Naito T. J. Org. Chem.  1998,  63:  4397 
• 4f Riber D. Hazell R. Skrydstrup T. J. Org. Chem.  2000,  65:  5382 
• 4g Nicolaou KC. Snyder SA. Giuseppone N. Huang XH. Bella M. Reddy MV. Rao PB. Koumbis AE. Giannakakou P. O’Brate A. J. Am. Chem. Soc.  2004,  126:  10174 
• 5a Tsukinoki T. Nagashima S. Mitoma Y. Tashiro M. Green Chem.  2000,  2:  117 
• 5b Shimizu M. Iwata A. Makino H. Synlett  2002,  1538 
• 6a Shono T. Kise N. Fujimoto T. Tetrahedron Lett.  1991,  32:  525 
• 6b Shono T. Kise N. Kunimi N. Nomura R. Chem. Lett.  1991,  2191 
• 6c Shono T. Kise N. Fujimoto T. Yamanami A. Nomura R. J. Org. Chem.  1994,  59:  1730 
• 7a Hanamoto T. Inanaga J. Tetrahedron Lett.  1991,  32:  3555 
• 7b Sturino CF. Fallis AG. J. Am. Chem. Soc.  1994,  116:  7447 
• 7c Chiara JL. Marco-Contelles J. Khiar N. Gallego P. Destabel C. Bernabe M. J. Org. Chem.  1995,  60:  6010 
• 7d Marco-Contelles J. Gallego P. Rodriguez-Fernandez M. Khiar N. Destabel C. Bernabe M. Martinez-Grau A. Chiara JL. J. Org. Chem.  1997,  62:  7397 
• 7e Storch de Garcia I. Dietrich H. Bobo S. Chiara JL. J. Org. Chem.  1998,  63:  5883 
• 7f Chiara JL. In Carbohydrate Mimics: Concepts and Methods   Chapleur Y. Wiley-VCH; Weinheim: 1998.  Chap. 7. p.123-156  
• 7g Miyabe H. Kanehira S. Kume K. Kandori H. Naito T. Tetrahedron  1998,  54:  5883 
• 7h Machrouhi F. Namy J.-L. Tetrahedron Lett.  1999,  40:  1315 
• 7i Bobo S. Storch de Gracia I. Chiara JL. Synlett  1999,  1551 
• 7j Taniguchi N. Uemura M. J. Am. Chem. Soc.  2000,  122:  8301 
• 7k Ma Y. Zhang Y. Zhou L. J. Chem. Res., Synop.  2000,  250 
• 7l Masson G. Py S. Vallee Y. Angew. Chem. Int. Ed.  2002,  41:  1772 
• 7m Tanaka Y. Taniguchi N. Uemura M. Org. Lett.  2002,  4:  835 
• 7n Tanaka Y. Taniguchi N. Kimura T. Uemura M. J. Org. Chem.  2002,  67:  9227 
• 7o Kimura T. Shoda R. Taniguchi N. Kamikawa K. Uemura M. Inorg. Chim. Acta  2004,  357:  1829 
• 7p Chiara JL. de Gracia IS. Garcia A. Bastida A. Bobo S. Martin-Ortega MD. ChemBioChem  2005,  6:  186 
• 7q Masson G. Philouze C. Py S. Org. Biomol. Chem.  2005,  3:  2067 
• 8a Naito T. Tajiri K. Harimoto T. Ninomiya I. Kiguchi T. Tetrahedron Lett.  1994,  35:  2205 
• 8b Kiguchi T. Tajiri K. Ninomiya I. Naito T. Hiramatsu H. Tetrahedron Lett.  1995,  36:  253 
• 8c Tormo J. Hays DS. Fu GC. J. Org. Chem.  1998,  63:  201 
• 8d Egger A. Hunziker J. Rihs G. Leumann C. Helv. Chim. Acta  1998,  81:  734 
• 8e Naito T. Nakagawa K. Nakamura T. Kasei A. Ninomiya I. Kiguchi T. J. Org. Chem.  1999,  64:  2003 
• 8f Naito T. Nair JS. Nishiki A. Yamashita K. Kiguchi T. Heterocycles  2000,  53:  2611 
• 9a Storch de Gracia I. PhD Thesis   Universidad Autónoma de Madrid; Spain: 2002. 
• 9b

  See also ref. 4b (X = NOMe), 4c and 6h.

• 10a Lichtenthaler FW. Schneider-Adams T. J. Org. Chem.  1994,  59:  6728 
• 10b Fürstner A. Konetzki I. J. Org. Chem.  1998,  63:  3072 
• 16 Fernandez R. Ferrete A. Llera JM. Magriz A. Martin-Zamora E. Diez E. Lassaletta JM. Chem.-Eur. J.  2004,  10:  737 ; and references cited therein

11

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.

12

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]⁺.

13

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.

14

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).

15

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