Synthesis of Sugar-Derived 2-Nitroalkanols via Henry Reaction Promoted by Samarium Diiodide or Indium

Abstract

We present herein an improved synthesis of nitro sugars, consisting of a Henry-type reaction of bromonitromethane and sugar aldehydes. The reaction can be promoted by either SmI₂ or indium metal, yielding in both cases high yields and good diastereoisomeric ratios. However, while the SmI₂-promoted reaction is very sensitive to steric factors and only gives satisfactory results with bromonitromethane, the indium-mediated reaction is not subjected to this limitation, giving excellent results with bromonitromethane as well as more hindered bromonitroalkanes.

Key words

carbohydrates - Henry reaction - 2-nitroalkanols - samarium - indium

• References

• 1 Baer HH. Advances in Carbohydrate Chemistry and Biochemistry . Vol. 24. Wolfrom MI, Tipson RS. Academic Press; New York: 1969: 67-138
• 2 Hauser FM, Ellemberg SR. Chem. Rev. 1986; 86: 35
• 3 Ganguty AK, Sarre OZ, Reimann H. J. Am. Chem. Soc. 1968; 90: 1721
• 4 Seebach D. Angew. Chem., Int. Ed. Engl. 1990; 29: 1320
• 5 Wade PW, Giuliano RM. Nitro Compounds Recent Advances in Synthesis and Chemistry . Feuer H, Nielsen AT. VCH; New York: 1990
• 6 Soengas RG, Estévez JC, Estevez AM, Fernández F, Estévez RJ. Carbohydr. Chem. 2009; 35: 1
• 7 Henry L. Bull. Soc. Chim. Fr. 1895; 13: 999
• 8 Baer HH, Urbas L. The Chemistry of the Nitro and Nitroso Groups . Part 2. Feuer H. Wiley; New York: 1970: 75-200
• 9 Ono N. The Nitro Group in Organic Synthesis . Wiley-VCH; Weinheim: 2001
• 10 Palomo C, Oiarbide M, Laso A. Eur. J. Org. Chem. 2007; 2561 ; and references cited therein
• 11 Seebach D, Lehr F. Angew. Chem., Int. Ed. Engl. 1976; 15: 505
• 12a Rosini G, Ballini R, Sorrenti P, Petrini M. Synthesis 1984; 607
• 12b Melot J.-M, Texier-Boullet F, Foucaud A. Tetrahedron Lett. 1986; 27: 493
• 12c Chen YJ, Lin WY. Tetrahedron 1993; 49: 10263
• 12d Kolter T, van Echten-Deckert G, Sandhoff K. Tetrahedron 1994; 50: 13425
• 12e Ballini R, Bosica G, Forconi P. Tetrahedron 1996; 52: 1677
• 12f Bulbule VJ, Deshpande VH, Velu S, Sudalai A, Sivasankar S, Sathe VT. Tetrahedron 1999; 55: 9325
• 12g Akutu K, Kabashima H, Seki T, Hattori H. Appl. Catal., A 2003; 247: 65
• 12h Ballini R, Fiorini D, Gil MV, Palmieri A. Tetrahedron 2004; 60: 2799
• 13a Crich D, Ranganathan K, Rumthao S, Shirai M. J. Org. Chem. 2003; 68: 2034
• 13b Luzzio FA, Ott JP, Duveau DY. J. Org. Chem. 2006; 71: 5027
• 13c Crich D, Shirai M, Brebion F, Rumthao S. Tetrahedron 2006; 62: 6501
• 14 Concellón JM, Rodríguez-Solla H, Concellón C. J. Org. Chem. 2006; 71: 7919

Reactions of bromonitromethane and aldehydes to give 2-bromo-2-nitroalkan-1-ols have also been described:
• 15a Concellón JM, Rodríguez-Solla H, Concellón C, García-Granda S, Díaz MR. Org. Lett. 2006; 8: 5979
• 15b Blay G, Hernández-Olmos V, Pedro JR. Chem. Commun. 2008; 4840
• 16 Soengas RG, Estévez AM. Eur. J. Org. Chem. 2010; 5190
• 17 Representative Analytical Data 3-O-Benzyl-6-deoxy-6-nitro-1,2-O-isopropyliden-α-d-glucofuranose (3a) Yellow oil; [α]_D ²⁰ –26.8 (c 1.0 in CHCl₃). ¹H NMR (300 MHz, CDCl₃): δ = 7.49–7.30 (m, 5 H), 5.91 (d, J = 3.7 Hz, 1 H), 4.76–4.60 (m, 4 H), 4.56–4.42 (m, 2 H), 4.14–4.06 (m, 2 H), 2.58 (d, J = 4.9 Hz, 1 H), 1.47 (s, 3 H), 1.32 (s, 3 H) ppm. ¹³C NMR (75 MHz, CDCl₃): δ = 136.8 (C), 128.8 (2 × CH), 128.4 (CH), 127.9 (2 × CH), 112.1 (C), 105.1 (CH), 82.0 (CH), 80.9 (CH), 79.9 (CH), 78.5 (CH₂), 72.1 (CH₂), 66.3 (CH), 26.9 (CH₃), 26.1 (CH₃) ppm. MS (ESI⁺): m/z (%) = 362 (15) [M + Na]⁺, 357 (100) [M + NH₄]⁺, 316 (1), 288 (8), 282 (1). HRMS (ESI⁺): m/z calcd for [C₁₆H₂₁NO₇Na]⁺ [M + Na]⁺: 362.1216; found: 362.1210; R_f = 0.33 (hexane–EtOAc = 3:1). 7-Deoxy-1,2:3,4-di-O-isopropylidene-7-nitro-d -glycero-β-d-galacto-heptopyranose (3c) Yellow oil; [α]_D ²⁰ –49.4 (c 0.6 in CHCl₃). ¹H NMR (300 MHz, CDCl₃): δ = 5.49 (d, J =5.0 Hz, 1 H), 4.78 (app d, J = 11.2 Hz, 1 H), 4.65 (dd, J = 8.0, 2.5 Hz, 1 H), 4.51–4.47 (m, 2 H), 4.43 (dd, J = 8.0, 2.0 Hz, 1 H), 4.34 (dd, J = 4.9, 2.5 Hz, 1 H), 3.73 (dd, J = 8.2, 2.0 Hz, 1 H), 2.89 (d, J = 5.9 Hz, 1 H), 1.51 (s, 3 H), 1.46 (s, 3 H), 1.37 (s, 3 H), 1.32 (s, 3 H) ppm. ¹³C NMR (75 MHz, CDCl₃): δ = 109.6 (C), 108.9 (C), 96.2 (CH), 78.1 (CH₂), 70.6 (CH), 70.5 (CH), 70.1 (CH), 67.7 (CH), 67.4 (CH), 25.9 (2 × CH₃), 24.8 (CH₃), 24.3 (CH₃) ppm. MS (ESI⁺): m/z (%) = 342 (24) [M + Na]⁺, 337 (100) [M + NH₄]⁺, 320 (19) [M + H]⁺, 262 (48). HRMS (ESI⁺): m/z calcd for [C₁₃H₂₂NO₈]⁺ [M + H]⁺: 320.1340; found: 320.1339. R_f = 0.20 (hexane–EtOAc = 3:1).
• 18 General Procedure for the Samarium Diiodide Mediated Reaction of Bromonitromethane and Aldehydes SmI₂ (0.8 mmol, 0.1 M) in THF (8 mL) was added to a stirred solution of bromonitromethane (0.8 mmol) and the corresponding aldehyde (0.8 mmol) in THF (5 mL). After stirring the reaction mixture at r.t. for 5 h it was quenched with aq HCl (10 mL, 0.1 M) and extracted with CH₂Cl₂ (3 × 25 mL). The combined extracts were washed with an aq sat. solution of Na₂S₂O₃ (20 mL), then dried over MgSO₄, filtered, and the solvent was evaporated in vacuo. The residue was purified by flash column chromatography with mixtures of EtOAc–hexane.
• 19 General Procedure for the Indium-Mediated Reaction of Bromonitroalkanes and Aldehydes To a suspension of indium powder (0.5 mmol) in THF (1 mL) was added the bromonitroalkane (0.6 mmol), and the mixture was sonicated for 20 min. The corresponding aldehyde (0.5 mmol) was added, and sonication was continued for a further 4 h. The reaction mixture was neutralized with sat. aq NaHCO₃, diluted with H₂O (10 mL), and extracted with Et₂O (3 × 25 mL). The combined organic layers were dried over MgSO₄, filtered, and the solvent was evaporated in vacuo. The residue was purified by flash column chromatography with mixtures of EtOAc–hexane.

Reviews on indium chemistry:
• 20a Cintas P. Synlett 1995; 1089
• 20b Li CJ. Tetrahedron 1996; 52: 5643
• 20c Marshall JA. Chemtracts – Org. Chem. 1997; 10: 481
• 20d Li CJ In Green Chemistry: Frontiers in Benign Chemical Syntheses and Processes . Anastas P, Williamson TC. Oxford University Press; New York: 1998. Chap. 14
• 20e Paquette LA. Green Chemistry: Frontiers in Benign Chemical Syntheses and Processes . Anastas P, Williamson TC. Oxford University Press; New York: 1998. Chap. 15
• 20f Li CJ, Chan TK. Tetrahedron 1999; 55: 11149
• 21 Representative Analytical Data
  1-O-tert-Butyldimethylsilyl-2,3-di-O-isopropylidene-5(R)-(1-methyl-1-nitroethyl)-α-d-lyxofuranose (5c) Yellow oil; [α]_D ²³ –21.3 (c 0.4 in CHCl₃). ¹H NMR (300 MHz, CDCl₃): δ = 5.09 (s, 1 H, 1-H), 4.84 (dd, 1 H, J = 3.8, 5.8 Hz), 4.53–4.63 (m, 2 H), 3.80–4.48 (m, 2 H), 2.85 (d, 1 H, J = 5.6 Hz, OH), 1.61 (s, 6 H, 2 × CH₃), 1.31, 1.47 (2 × s, 6 H, 2 × CH₃), 0.86 (s, 9 H, 3 × CH₃), 0.10 (s, 3 H, CH₃), 0.11 (s, 3 H, CH₃) ppm. ¹³C NMR (75 MHz, CDCl₃): δ = 113.12 (C), 106.13 (CH), 91.1 (C), 84.3 (CH), 81.1 (CH), 79.3 (CH), 73.9 (CH), 69.6 (CH), 26.3 (CH₃), 25.0 (CH₃), 24.0 (CH₃), 21.0 (CH₃), 19.8 (C), 17.8 (3 × CH₃), –4.5 (CH₃), –5.5 (CH₃) ppm. ESI-MS: m/z (%) = 488 (10) [M + H]⁺. HRMS: m/z calcd for C₂₆H₃₈NO₆Si [M + H]⁺: 488.2462; found: 488.2471. R_f = 0.30 (hexane–EtOAc = 7:1). 4-O-tert-Butyldiphenylsilyl-2,3-di-O-isopropylidene-1(S)-(1-methyl-1-nitroethyl)-d-threitol (5e) Yellow oil. ¹H NMR (300 MHz, CDCl₃): δ = 7.66–7.73 (m, 4 H, 4 × HAr), 7.35–7.48 (m, 6 H, 6 × HAr), 4.10–4.23 (m, 2 H), 3.83–3.90 (m, 2 H), 3.66–3.74 (m, 1 H), 1.67, 1.69 (2 × s, 6 H, 2 × CH₃) ppm. ¹³C NMR (75 MHz, CDCl₃): δ = 135.7 (C), 135.6 (C), 128.1 (CH), 128.0 (CH), 127.8 (CH), 127.7 (CH), 127.6 (CH), 110.2 (C), 91.3 (C), 81.0 (CH), 79.6 (CH), 76.3 (CH), 65.2 (CH₂), 26.7 (CH₃), 26.6 (CH₃), 23.3 (CH₃), 21.6 (CH₃), 19.3 (CH₃) ppm. ESI-MS: m/z (%) = 505 (100) [M + Na]⁺: 488 (20) [M + H]⁺. HRMS: m/z calcd for C₂₆H₃₈NO₆Si [M + H]⁺: 488.2462; found: 488.2484. R_f = 0.29 (hexane–EtOAc = 4:1).
• 22 Representative Analytical Data
  3-O-Benzyl-5(R)-(2,2-dimethyl-5-nitro-1,3-dioxan-5-yl)-1,2-O-isopropylidene-α-d-xylofuranose (7a) Yellow oil; [α]_D ²⁴ –39.7 (c 1.2 in CHCl₃). ¹H NMR (300 MHz, CDCl₃): δ = 7.36–7.24 (m, 5 H, 5 × HAr), 5.91 (d, 1 H, J _1,2 = 3.7 Hz, 1-H), 4.42–4.57 (m, 5 H), 4.05–4.34 (m, 5 H), 1.34, 1.39, 1.43, 1.45 (4 × s, 12 H, 4 × CH₃) ppm. ¹³C NMR (75 MHz, CDCl₃): δ = 136.8 (C), 129.2 (2 × CH), 128.9 (CH), 128.3 (2 × CH), 112.6 (C), 105.6 (C), 99.5 (CH), 90.2 (C), 82.5 (CH), 81.3 (CH), 78.7 (CH₂), 72.4 (CH), 70.4 (CH), 62.8 (CH₂), 61.1 (CH₂), 26.5 (CH₃), 25.6 (CH₃), 21.5 (CH₃), 20.6 (CH₃) ppm. ESI-MS: m/z (%) = 440 (21) [M + H]⁺, 462 (100) [M + Na]⁺. HRMS: m/z calcd for C₂₁H₃₀NO₉ [M + H]⁺: 440.1915; found: 440.1894. R_f = 0.31 (hexane–EtOAc = 3:1). 1,2:3,4-Di-O-isopropylidene-6(R)-(2,2-dimethyl-5-nitro-1,3-dioxan-5-yl)-β-d-galacto-heptopyranose (7b) Colorless oil; [α]_D ²⁵ +33.4 (c 0.9 in CHCl₃). ¹H NMR (300 MHz, CDCl₃): δ = 5.50 (d, 1 H, J = 5.1 Hz, H-1), 4.52–4.71 (m, 3 H), 4.03–4.37 (m, 5 H), 3.92 (dd, 1 H, J = 8.9, 1.9 Hz,), 3.16 (d, 1 H, J = 7.1 Hz, OH), 1.33, 1.35, 1.36, 1.45, 1.46, 1.59 (6 × s, 18 H) ppm. ¹³C NMR (75 MHz, CDCl₃): δ = 109.6 (C), 109.1 (C), 98.9 (C), 96.1 (CH), 89.9 (C), 70.8 (CH), 70.6 (CH), 70.5 (CH), 70.0 (CH), 66.6 (CH), 62.7 (CH₂), 61.1 (CH₂), 27.3 (CH₃), 25.8 (CH₃), 25.6 (CH₃), 24.3 (CH₃), 19.5 (CH₃) ppm. ESI-MS: m/z (%) = 420 (31) [M + H]⁺, 442 (9) [M + Na]⁺. HRMS: m/z calcd for C₁₈H₃₀NO₁₀ [M + H]⁺: 420.1870; found: 420.1863. R_f = 0.31 (hexane–EtOAc = 2:1).