Indium-Mediated Debromination of gem-Bromonitroalkanes under Mild Conditions in Aqueous Medium

Abstract

gem-Bromonitroalkanes are efficiently reduced into the corresponding dehalogenated products in excellent yields with indium metal in the presence of a palladium(0) catalyst and indium(III) chloride in aqueous medium. The addition of bromonitromethane to carbohydrate-derived aldehydes or imines, followed by debromination of the intermediate bromonitro compounds represents an extremely efficient method for the stereoselective preparation of nitrosugars.

Nitroalkanes are important synthons for the preparation of more complex molecules. Under basic conditions, they readily form a nitronate anion that can undergo aldol reactions with aldehydes and ketones (Henry reaction),[1] or imines (aza-Henry reaction),[2] and additions to α,β-unsaturated carbonyl compounds (Michael reaction).[3] Moreover, a wide variety of other organic compounds can be accessed by transformations of the nitro group into other chemical functionalities, such as amines,[4] carbonyl groups,[5] hydroxylamines[6] and oximes or nitriles.[7]

gem-Bromonitroalkanes are useful analogues of nitroalkanes and have been employed in organic synthesis as precursors of aliphatic nitro derivatives, with the aim of improving diastereoselection and avoiding dimerization.[8] For example, the enantioselective conjugate addition of gem-bromonitroalkanes to α,β-unsaturated ketones followed by debromination of the resulting products, afforded the corresponding nitroalkanes with excellent enantioselectivity.[9] Similarly, debromination of the enantiopure products arising from the addition of bromonitromethane to aldehydes or imines gave the corresponding nitroalkanols[10] or nitroamines,[11] whilst preserving the absolute configuration at the β-position. Radical dehalogenation promoted by tri-n-butyltin hydride has been widely used to transform gem-halonitroalkanes into nitroalkanes.[12]

During our recent investigations on the use of bromonitromethane in organic synthesis,[13] we became interested in the use of gem-bromonitrosugars as precursors of the corresponding enantiopure nitrosugars. This, combined with our long-term interest in the use of indium in organic chemistry,[14] prompted us to initiate a search for an indium-promoted procedure for the reduction of gem-bromonitroalkanes that would avoid using highly toxic tri-n-butyltin hydride.

The very low first ionization energy of indium(0) makes it an ideal candidate to be used in single-electron transfer (SET) reactions.[15] This property, together with its stability toward oxygen and water, has prompted exhaustive studies focused on indium-mediated carbon–carbon bond-forming reactions[16] and reductions of functional groups.[17] Various reactions in which a carbon–halogen bond is reduced by indium have been reported.[18] However, to the best of our knowledge, the indium-promoted transformation of gem-halonitroalkanes into nitroalkanes has not been described to date.

Herein, we describe a novel dehalogenation reaction of 2-bromo-2-nitroalkan-1-ols and 2-bromo-2-nitroamines promoted by indium metal in the presence of tetrakis(triphenylphosphine)palladium(0) [Pd(PPh₃)₄] as the catalyst and indium(III) chloride (InCl₃) in aqueous medium.[19]

To determine the optimum reaction conditions, we first used a model substrate, 2-bromo-1-cyclohexyl-2-nitroethanol (1a), and various reagent systems (Scheme [1, ]Table [1]).

Thus, treatment of bromoalkanol 1a with indium powder (200 mol%) and indium(III) chloride (50 mol%) in the presence of tetrakis(triphenylphosphine)palladium(0) (2 mol%) in a 2:1 (v/v) mixture of tetrahydrofuran–water afforded the desired nitroalkane product 2a in 93% yield (Table [1], entry 1).[20] [21]

The reaction did not occur in the absence of either indium(III) chloride or indium (Table [1], entries 2 and 3). The indium/indium(III) chloride reagent system in the absence of Pd(PPh₃)₄ reduced the C–Br bond at a very low rate, resulting in a poor yield of 2a (Table [1], entry 4). Employing other solvent systems also led to poor results (Table [1], entries 5–7). When zinc metal was used instead of indium, the reaction did not proceed (Table [1], entry 8).

Given this satisfactory result (Table [1], entry 1), the indium-mediated reductive elimination was applied to various gem-halonitro compounds (Scheme [2, ]Table [2]), the requisite starting materials being readily prepared by reactions of aldehydes or imines with bromonitromethane.[10] [11a] [22] After aqueous work-up, the intermediate bromonitro derivatives were submitted, without any further purification, to the debromination reaction.

As shown by the results compiled in Table [2], the Pd(PPh₃)₄/In/InCl₃ system was effective for the reductive dehalogenation of various 2-bromo-2-nitro intermediates in aqueous medium, affording the corresponding nitroalkanes 2a–f in good to excellent yields.[23] Accordingly, the combination of a sodium iodide catalyzed addition followed by dehalogenation was an effective procedure for the preparation of nitroalkanes from either aldehydes or imines.

The interest in this procedure lies in the better diastereoselection achieved on the addition of bromonitromethane to aldehydes and imines, rather than on the addition of simpler nitromethane. Thus, the addition of nitromethane to sugar aldehydes[13a] [b] [c] ^, [e] or imines[11a] [13d] [f] gave moderate to good diastereoselectivity, while the addition of bromonitromethane resulted in excellent anti-selectivity.[13d] [g] Accordingly, the sequence of bromonitromethane addition/debromination would be predicted to afford the anti-isomers with superior diastereoselection than the addition of nitromethane alone. In order to prove our hypothesis, we explored the sequence of bromonitromethane addition/debromination on several sugar-derived aldehydes and imines 3g–l. The corresponding nitrosugars 2g–l were obtained in good yields and with excellent diastereoselectivities (Scheme [3, ]Table [3]).[24] The absolute configurations were established by comparison with the literature data on nitrosugars 2g–l.

The observed stereochemistry of products 2 can be explained by assuming Felkin–Ahn-type addition of the bromonitronate anion. The stereochemistry at the β-nitro position is preserved during the dehalogenation reaction.

A mechanistic proposal for the debromination process is depicted in Scheme [4]. Thus, treatment of gem-bromonitroalkanes 1 with indium(I), generated in situ by the reaction of indium metal and indium(III) chloride, in the presence of a catalytic amount of palladium(0) would generate indium nitronate intermediates 4, hydrolysis of which would afford the corresponding nitroalkanes 2. Even though the role of palladium(0) is not clear, it is probably involved in some kind of palladium insertion into the C–Br bond, which would facilitate the metallation.

Table 3 Synthesis of Nitrosugars 2g–l

Entry	Substrate	Sugar	Y	Product	dr	Yielda
1	3g		O	2g	95:5	83%
2	3h		O	2h	>98:2	88%
3	3i		NPMPb	2i	>98:2	69%
4	3j		O	2j	>98:2	81%
5	3k		NPMPb	2k	>98:2	65%
6	3l		O	2l	95:5	81%

^a Yield of isolated product after column chromatography based on the starting aldehyde or imine 3.

^b NPMP = N-p-methoxyphenyl

In summary, we have developed an easy, efficient and general reductive debromination procedure for converting gem-bromonitroalkanes into the corresponding nitroalkanes using a palladium(0) catalyst, indium metal and indium(III) chloride. The reactions proceeded smoothly under mild conditions in neutral aqueous medium, preserving the stereochemistry of any existing stereogenic centers. In combination with the sodium iodide catalyzed addition of bromonitromethane to aldehydes or imines, the present method offers an efficient alternative for the stereoselective preparation of nitrosugars.

Acknowledgment

Thanks are due to the University of Aveiro, Fundação para a Ciência e a Tecnologia (FCT) and FEDER for funding the Organic Chemistry Research Unit (project PEst-C/QUI/UI0062/2013) and the Portuguese National NMR Network (RNRMN). R.S. thanks the FCT for an ‘Investigador Auxiliar’ position.

• References

• 1a Henry L. Bull. Soc. Chim. Fr. 1895; 13: 999
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• 1b Luzzio FA. Tetrahedron 2001; 57: 915
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• 1c Palomo C, Oiarbide M, Laso A. Eur. J. Org. Chem. 2007; 2561
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• 2b Alcaide B, Almendros P, Rodríguez-Acebes R. J. Org. Chem. 2005; 70: 3198
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• 3a Knochel P, Seebach D. Synthesis 1982; 1017
  Thieme Connect
• 3b Lucet D, Sabelle S, Kostelitz O, Le Gall T, Mioskowski C. Eur. J. Org. Chem. 1999; 2583
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• 8a Soengas RG, Acurcio R, Silva AM. S. Eur. J. Org. Chem. 2014; in press
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• 12 Bowman WR, Crosby D, Westlake PJ. J. Chem. Soc., Perkin Trans 2 1991; 73
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  Thieme ConnectSearch in Google Scholar
• 13d Rodríguez-Solla H, Concellón C, Alvaredo N, Soengas RG. Tetrahedron 2012; 68: 1736
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• 13e Soengas RG, Silva AM. S. Tetrahedron 2013; 69: 3425
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• 13f Soengas RG, Silva AM. S. Tetrahedron Lett. 2013; 54: 2156
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• 13g Soengas RG, Rodríguez-Solla H, Silva AM. S, Llavona R, Paz FA. A. J. Org. Chem. 2013; 78: 12831
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• 14a Soengas RG. Tetrahedron Lett. 2010; 51: 105
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• 14c Soengas RG, Estévez AM. Synlett 2011; 2625
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• 14f Soengas RG. Ultrason. Sonochem. 2012; 19: 916
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For reviews on indium chemistry, see:
• 15a Cintas P. Synlett 1995; 1089
• 15b Li CJ. Tetrahedron 1996; 52: 5643
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• 15c Marshall JA. Chemtracts Org. Chem. 1997; 10: 481
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• 15d Li CJ In Green Chemistry, Frontiers in Benign Chemical Syntheses and Processes . Anastas P, Williamson TC. Oxford University Press; New York: 1998. Chap. 14
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• 15e Paquette LA In Green Chemistry, Frontiers in Benign Chemical Syntheses and Processes . Anastas P, Williamson TC. Oxford University Press; New York: 1998. Chap. 15
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• 15f Li C.-J, Chan T.-H. Tetrahedron 1999; 55: 11149
  CrossrefSearch in Google Scholar
• 15g Ranu BC. Eur. J. Org. Chem. 2000; 2347
• 15h Podlech J, Maier TC. Synthesis 2003; 63

Allylations:
• 16a Araki S, Kamei T, Hirashita T, Yamamura H, Kawai M. Org. Lett. 2000; 2: 847
  CrossrefSearch in Google Scholar
• 16b Tan K.-T, Chang S.-S, Cheng H.-S, Loh T.-P. J. Am. Chem. Soc. 2003; 125: 2958
  CrossrefPubMedSearch in Google Scholar
• 16c Propargylations: Isaac MB, Chan T.-H. J. Chem. Soc., Chem. Commun. 1995; 1003
• 16d Alkynylations: Augé J, Lubin-Germain N, Seghrouchni L. Tetrahedron Lett. 2002; 43: 5255
  CrossrefSearch in Google Scholar

Nitromethylations:
• 16e Soengas RG, Estévez AM. Tetrahedron Lett. 2012; 53: 570
  CrossrefSearch in Google Scholar
• 16f Rodríguez-Solla H, Soengas RG, Alvaredo N. Synlett 2012; 23: 2083 ; and reference 10a
  Thieme ConnectSearch in Google Scholar
• 17 Augé J, Lubin-Germain N, Uziel J. Synthesis 2007; 1739
  Thieme Connect
• 18a Podlech J, Maier TC. Synthesis 2003; 633
• 18b Ranu BC, Dutta P, Sarkar A. J. Chem. Soc., Perkin Trans. 1 1999; 1139
• 19 A similar system was used for the reductive elimination of halohydrins, see: Cho S, Kang S, Keum G, Kang SB, Han S.-Y, Kim Y. J. Org. Chem. 2003; 68: 180
  CrossrefSearch in Google Scholar
• 20 Nitroalkanes 2; General Procedure NaI (0.12 mmol, 0.15 equiv) was added to a stirred solution of bromonitromethane (0.8 mmol, 1 equiv) and the corresponding aldehyde 3 (0.8 mmol, 1 equiv) in THF (10 mL), and the resulting mixture was stirred at r.t. for 5 h. After this period, the mixture was quenched with aq HCl (10 mL, 0.1 M) and extracted with Et₂O (1 × 20 mL). The combined extracts were washed with sat. aq Na₂S₂O₃ solution (1 × 20 mL), dried over Na₂SO₄, filtered and the solvent removed under reduced pressure to afford the crude 1-bromo-1-nitroalkan-2-ol. In metal (183 mg, 1.6 mmol), InCl₃ (88 mg, 0.4 mmol) and Pd(PPh₃)₄ (18 mg, 2 mol%) were added to a solution of the 1-bromo-1-nitroalkan-2-ol (0.8 mmol) in THF–H₂O (2:1, 6 mL). After stirring the mixture at r.t. for 12 h, it was quenched with HCl (3 mL, 1 M), diluted with H₂O (25 mL) and extracted with Et₂O (3 × 25 mL). The combined organic extracts were dried over Na₂SO₄, filtered and the solvent removed under reduced pressure to afford the nitroalkanes 2.
• 21 1-Cyclohexyl-2-nitroethanol (2a) Yellow oil; R_f  = 0.30 (hexane–EtOAc, 5:1). ¹H NMR (300 MHz, CDCl₃): δ = 4.45–4.33 (2 m, 3 H), 1.73–0.90 (m, 11 H). ¹³C NMR (75 MHz, CDCl₃): δ = 79.3, 72.8, 41.4, 27.9, 26.1, 25.9, 25.7, 22.8.
• 22 Concellón JM, Rodríguez-Solla H, Concellón C, García-Granda S, Díaz MR. Org. Lett. 2006; 8: 5979
  CrossrefSearch in Google Scholar
• 23 N-(1-Cyclohexyl-2-nitroethyl)-4-methoxybenzenamine (2e) Brown oil; R_f  = 0.22 (hexane–EtOAc, 3:1). ¹H NMR (300 MHz, CDCl₃): δ = 6.76 (d, J = 9.0 Hz, 2 H), 6.65 (d, J = 9.0 Hz, 2 H), 4.72 (dd, J = 12.3, 5.2 Hz, 1 H), 4.46 (dd, J = 12.3, 7.4 Hz, 1 H), 4.08–4.04 (m, 1 H), 3.73 (s, 3 H), 2.73 (s, 11 H). ¹³C NMR (75 MHz, CDCl₃): δ = 152.7 (C), 141.0 (C), 115.0 (2 × CH), 114.9 (2 × CH), 75.7 (CH₂), 60.9 (CH), 55.7 (CH₃), 43.0 (CH), 34.7 (2 × CH₂), 25.2 (CH₂), 21.6 (2 × CH₂). MS (ESI): m/z (%) = 279 (6) [M + H]⁺, 234 (19), 216 (100), 214 (28). HRMS (ESI): m/z [M + H]⁺ calcd for C₁₅H₂₃N₂O₃: 279.1709; found: 279.1703.
• 24 7-Deoxy-1,2:3,4-di-O-isopropylidene-7-nitro-d-glycero-β-d-galacto-heptopyranose (2g) Yellow oil; R_f  = 0.20 (hexane–EtOAc, 3:1); [α]_D ²⁰ –49.4 (c 0.6, CHCl₃). ¹H NMR (300 MHz, CDCl₃): δ = 5.49 (d, J = 5.0 Hz, 1 H), 4.78 (apparent 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, CH ₃), 1.46 (s, 3 H, CH ₃), 1.37 (s, 3 H, CH ₃), 1.32 (s, 3 H, CH ₃). ¹³C NMR (75 MHz, CDCl₃): δ = 109.6, 108.9, 96.2, 78.1, 70.6, 70.5, 70.1, 67.7, 67.4, 25.9, 24.8, 24.3. MS (ESI): m/z (%) = 342 (24) [M + Na]⁺, 337 (100) [M + NH₄]⁺, 320 (19) [M + H]⁺, 262 (48).

• References

• 1a Henry L. Bull. Soc. Chim. Fr. 1895; 13: 999
  Search in Google Scholar
• 1b Luzzio FA. Tetrahedron 2001; 57: 915
  CrossrefSearch in Google Scholar
• 1c Palomo C, Oiarbide M, Laso A. Eur. J. Org. Chem. 2007; 2561
• 2a Alcaide B, Almendros P, Rodríguez-Acebes R. J. Org. Chem. 2005; 70: 2713
  CrossrefSearch in Google Scholar
• 2b Alcaide B, Almendros P, Rodríguez-Acebes R. J. Org. Chem. 2005; 70: 3198
  CrossrefSearch in Google Scholar
• 3a Knochel P, Seebach D. Synthesis 1982; 1017
  Thieme Connect
• 3b Lucet D, Sabelle S, Kostelitz O, Le Gall T, Mioskowski C. Eur. J. Org. Chem. 1999; 2583
• 4a Lucet D, Le Gall T, Mioskowski C. Angew. Chem. Int. Ed. 1998; 37: 2580
  CrossrefPubMedSearch in Google Scholar
• 4b Westermann B. Angew. Chem. Int. Ed. 2003; 42: 151
  CrossrefPubMedSearch in Google Scholar
• 5 Ballini R, Petrini M. Tetrahedron 2004; 60: 1017
  CrossrefSearch in Google Scholar
• 6 García-Ruano JL, López-Cantarero J, de Haro T, Alemán J, Cid MB. Tetrahedron 2006; 62: 12197
  CrossrefSearch in Google Scholar
• 7 Czekelius C, Carreira EM. Angew. Chem. Int. Ed. 2005; 44: 612
  CrossrefSearch in Google Scholar
• 8a Soengas RG, Acurcio R, Silva AM. S. Eur. J. Org. Chem. 2014; in press
• 8b Inokuma T, Takemoto Y. Bromonitromethane. e-EROS Encyclopedia of Reagents for Organic Synthesis. 2010
  CrossrefSearch in Google Scholar
• 9 Dong L.-T, Lu R.-J, Du Q.-S, Zhang J.-M, Liu S.-P, Xuan Y.-N, Yan M. Tetrahedron 2009; 65: 4124
  CrossrefSearch in Google Scholar
• 10 Blay G, Hernández-Olmos V, Pedro JR. Chem. Commun. 2008; 4840
• 11a Soengas RG, Silva S, Estévez AM, Estévez JC, Estévez RJ, Rodríguez-Solla H. Eur. J. Org. Chem. 2012; 4339
• 11b Dobish MC, Villalta F, Waterman MR, Lepesheva GI, Johnston JN. Org. Lett. 2012; 14: 6322
  CrossrefSearch in Google Scholar
• 12 Bowman WR, Crosby D, Westlake PJ. J. Chem. Soc., Perkin Trans 2 1991; 73
• 13a Soengas RG, Estévez AM. Eur. J. Org. Chem. 2010; 5190
• 13b Soengas RG, Estévez AM. Synlett 2011; 2625
• 13c Soengas RG, Silva AM. S. Synlett 2012; 23: 873
  Thieme ConnectSearch in Google Scholar
• 13d Rodríguez-Solla H, Concellón C, Alvaredo N, Soengas RG. Tetrahedron 2012; 68: 1736
  CrossrefSearch in Google Scholar
• 13e Soengas RG, Silva AM. S. Tetrahedron 2013; 69: 3425
  CrossrefSearch in Google Scholar
• 13f Soengas RG, Silva AM. S. Tetrahedron Lett. 2013; 54: 2156
  CrossrefSearch in Google Scholar
• 13g Soengas RG, Rodríguez-Solla H, Silva AM. S, Llavona R, Paz FA. A. J. Org. Chem. 2013; 78: 12831
  CrossrefSearch in Google Scholar
• 14a Soengas RG. Tetrahedron Lett. 2010; 51: 105
  CrossrefSearch in Google Scholar
• 14b Soengas RG. Tetrahedron: Asymmetry 2010; 21: 2249
  CrossrefSearch in Google Scholar
• 14c Soengas RG, Estévez AM. Synlett 2011; 2625
• 14d Soengas RG. Synlett 2011; 2549
• 14e Soengas RG, Segade Y, Jiménez C, Rodríguez J. Tetrahedron 2011; 67: 2617
  CrossrefSearch in Google Scholar
• 14f Soengas RG. Ultrason. Sonochem. 2012; 19: 916
  CrossrefSearch in Google Scholar

For reviews on indium chemistry, see:
• 15a Cintas P. Synlett 1995; 1089
• 15b Li CJ. Tetrahedron 1996; 52: 5643
  CrossrefSearch in Google Scholar
• 15c Marshall JA. Chemtracts Org. Chem. 1997; 10: 481
  Search in Google Scholar
• 15d Li CJ In Green Chemistry, Frontiers in Benign Chemical Syntheses and Processes . Anastas P, Williamson TC. Oxford University Press; New York: 1998. Chap. 14
  Search in Google Scholar
• 15e Paquette LA In Green Chemistry, Frontiers in Benign Chemical Syntheses and Processes . Anastas P, Williamson TC. Oxford University Press; New York: 1998. Chap. 15
  Search in Google Scholar
• 15f Li C.-J, Chan T.-H. Tetrahedron 1999; 55: 11149
  CrossrefSearch in Google Scholar
• 15g Ranu BC. Eur. J. Org. Chem. 2000; 2347
• 15h Podlech J, Maier TC. Synthesis 2003; 63

Allylations:
• 16a Araki S, Kamei T, Hirashita T, Yamamura H, Kawai M. Org. Lett. 2000; 2: 847
  CrossrefSearch in Google Scholar
• 16b Tan K.-T, Chang S.-S, Cheng H.-S, Loh T.-P. J. Am. Chem. Soc. 2003; 125: 2958
  CrossrefPubMedSearch in Google Scholar
• 16c Propargylations: Isaac MB, Chan T.-H. J. Chem. Soc., Chem. Commun. 1995; 1003
• 16d Alkynylations: Augé J, Lubin-Germain N, Seghrouchni L. Tetrahedron Lett. 2002; 43: 5255
  CrossrefSearch in Google Scholar

Nitromethylations:
• 16e Soengas RG, Estévez AM. Tetrahedron Lett. 2012; 53: 570
  CrossrefSearch in Google Scholar
• 16f Rodríguez-Solla H, Soengas RG, Alvaredo N. Synlett 2012; 23: 2083 ; and reference 10a
  Thieme ConnectSearch in Google Scholar
• 17 Augé J, Lubin-Germain N, Uziel J. Synthesis 2007; 1739
  Thieme Connect
• 18a Podlech J, Maier TC. Synthesis 2003; 633
• 18b Ranu BC, Dutta P, Sarkar A. J. Chem. Soc., Perkin Trans. 1 1999; 1139
• 19 A similar system was used for the reductive elimination of halohydrins, see: Cho S, Kang S, Keum G, Kang SB, Han S.-Y, Kim Y. J. Org. Chem. 2003; 68: 180
  CrossrefSearch in Google Scholar
• 20 Nitroalkanes 2; General Procedure NaI (0.12 mmol, 0.15 equiv) was added to a stirred solution of bromonitromethane (0.8 mmol, 1 equiv) and the corresponding aldehyde 3 (0.8 mmol, 1 equiv) in THF (10 mL), and the resulting mixture was stirred at r.t. for 5 h. After this period, the mixture was quenched with aq HCl (10 mL, 0.1 M) and extracted with Et₂O (1 × 20 mL). The combined extracts were washed with sat. aq Na₂S₂O₃ solution (1 × 20 mL), dried over Na₂SO₄, filtered and the solvent removed under reduced pressure to afford the crude 1-bromo-1-nitroalkan-2-ol. In metal (183 mg, 1.6 mmol), InCl₃ (88 mg, 0.4 mmol) and Pd(PPh₃)₄ (18 mg, 2 mol%) were added to a solution of the 1-bromo-1-nitroalkan-2-ol (0.8 mmol) in THF–H₂O (2:1, 6 mL). After stirring the mixture at r.t. for 12 h, it was quenched with HCl (3 mL, 1 M), diluted with H₂O (25 mL) and extracted with Et₂O (3 × 25 mL). The combined organic extracts were dried over Na₂SO₄, filtered and the solvent removed under reduced pressure to afford the nitroalkanes 2.
• 21 1-Cyclohexyl-2-nitroethanol (2a) Yellow oil; R_f  = 0.30 (hexane–EtOAc, 5:1). ¹H NMR (300 MHz, CDCl₃): δ = 4.45–4.33 (2 m, 3 H), 1.73–0.90 (m, 11 H). ¹³C NMR (75 MHz, CDCl₃): δ = 79.3, 72.8, 41.4, 27.9, 26.1, 25.9, 25.7, 22.8.
• 22 Concellón JM, Rodríguez-Solla H, Concellón C, García-Granda S, Díaz MR. Org. Lett. 2006; 8: 5979
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• 23 N-(1-Cyclohexyl-2-nitroethyl)-4-methoxybenzenamine (2e) Brown oil; R_f  = 0.22 (hexane–EtOAc, 3:1). ¹H NMR (300 MHz, CDCl₃): δ = 6.76 (d, J = 9.0 Hz, 2 H), 6.65 (d, J = 9.0 Hz, 2 H), 4.72 (dd, J = 12.3, 5.2 Hz, 1 H), 4.46 (dd, J = 12.3, 7.4 Hz, 1 H), 4.08–4.04 (m, 1 H), 3.73 (s, 3 H), 2.73 (s, 11 H). ¹³C NMR (75 MHz, CDCl₃): δ = 152.7 (C), 141.0 (C), 115.0 (2 × CH), 114.9 (2 × CH), 75.7 (CH₂), 60.9 (CH), 55.7 (CH₃), 43.0 (CH), 34.7 (2 × CH₂), 25.2 (CH₂), 21.6 (2 × CH₂). MS (ESI): m/z (%) = 279 (6) [M + H]⁺, 234 (19), 216 (100), 214 (28). HRMS (ESI): m/z [M + H]⁺ calcd for C₁₅H₂₃N₂O₃: 279.1709; found: 279.1703.
• 24 7-Deoxy-1,2:3,4-di-O-isopropylidene-7-nitro-d-glycero-β-d-galacto-heptopyranose (2g) Yellow oil; R_f  = 0.20 (hexane–EtOAc, 3:1); [α]_D ²⁰ –49.4 (c 0.6, CHCl₃). ¹H NMR (300 MHz, CDCl₃): δ = 5.49 (d, J = 5.0 Hz, 1 H), 4.78 (apparent 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, CH ₃), 1.46 (s, 3 H, CH ₃), 1.37 (s, 3 H, CH ₃), 1.32 (s, 3 H, CH ₃). ¹³C NMR (75 MHz, CDCl₃): δ = 109.6, 108.9, 96.2, 78.1, 70.6, 70.5, 70.1, 67.7, 67.4, 25.9, 24.8, 24.3. MS (ESI): m/z (%) = 342 (24) [M + Na]⁺, 337 (100) [M + NH₄]⁺, 320 (19) [M + H]⁺, 262 (48).

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