Synlett, Table of Contents Synlett 2013; 24(15): 1949-1952DOI: 10.1055/s-0033-1339486 letter © Georg Thieme Verlag Stuttgart · New YorkOne-Pot Three-Component Barbier-Type Reaction for the Synthesis of β-Nitroamines Raquel G. Soengas* Department of Chemistry & QOPNA, University of Aveiro, 3810-193 Aveiro, Portugal Fax: +351(234)370084 Email: artur.silva@ua.pt Email: rsoengas@ua.pt , Artur M. S. Silva* Department of Chemistry & QOPNA, University of Aveiro, 3810-193 Aveiro, Portugal Fax: +351(234)370084 Email: artur.silva@ua.pt Email: rsoengas@ua.pt› Author AffiliationsRecommend Article Abstract Buy Article All articles of this category Abstract The combination of an aldehyde, bromonitromethane, and p-methoxyaniline in the presence of tin(II) chloride and titanium tetraethoxide allows a straightforward access to β-nitroamine derivatives. The use of solid paraformaldehyde results in the amino methylation of methylnitronate. On the other hand, chiral sugar-derived aldehydes furnished the corresponding nitrosugars in high yields and stereoselectivities. Key words Key wordsone-pot reaction - β-nitroamine - bromonitroalkane - aza-Henry reaction - aminomethylation Full Text References References and Notes 1a Baer HH, Urbas L In The Chemistry of the Nitro and Nitroso Groups, Part 2. Patai S. Wiley Interscience; New York: 1970: 117 1b Sasai H, Suzuki T, Arai S, Arai T, Shibasaki M. J. Am. Chem. Soc. 1992; 114: 4418 1c Arai T, Yamada Y, Yamamoto N, Sasai H, Shibasaki M. Chem. Eur. J. 1996; 2: 1368 1d Adams H, Anderson JC, Peace S, Pennell AM. K. J. Org. Chem. 1998; 63: 9932 1e Yamada K, Harwood SJ, Gröger H, Shibasaki M. Angew. Chem. Int. Ed. 1999; 38: 3504 1f Anderson JC, Paece S. Synlett 2000; 850 2a Lucet D, Le Gall T, Mioskowski C. Angew. Chem. 1998; 110: 2724 2b Westermann B. Angew. Chem. Int. Ed. 2003; 42: 151 3 Ballini R, Petrini M. Tetrahedron 2004; 60: 1017 4 García Ruano JL, López-Cantarero J, de Haro T, Alemán J, Cid MB. Tetrahedron 2006; 62: 12197 5 Czekelius C, Carreira EM. Angew. Chem. Int. Ed. 2005; 44: 612 6 Marqués-López E, Merino P, Tejero T, Herrera RP. Eur. J. Org. Chem. 2009; 2401 7a Soengas RG, Silva S, Estévez AM, Estévez JC, Estévez RJ, Rodríguez-Solla H. Eur. J. Org. Chem. 2012; 4339 7b Rodríguez-Solla H, Concellón C, Alvaredo N, Soengas RG. Tetrahedron 2012; 68: 1736 7c Soengas RG, Silva AM. S. Tetrahedron Lett. 2013; 54: 2156 8 Broadwater SJ, Roth SL, Price KE, Kobaslija M, McQuade DT. Org. Biomol. Chem. 2005; 3: 2899 9 Bruggink A, Schoevaart R, Kieboom T. Org. Proc. Res. Dev. 2003; 7: 622 10a Zhu J, Bienaymé H. Multicomponent Reactions. Wiley-VCH; Weinheim: 2005 10b For imine-based multicomponent reactions, see: Choudhury LH, Parvin T. Tetrahedron 2011; 67: 8213 11 Kouznetsov VV, Vargas Méndez LY. Synthesis 2008; 491 12a Soengas RG, Estévez AM. Eur. J. Org. Chem. 2010; 5190 12b Soengas RG, Estévez AM. Tetrahedron Lett. 2012; 53: 570 12c Rodríguez-Solla H, Soengas RG, Alvaredo N. Synlett 2012; 23: 2083 12d Soengas RG, Silva AM. S. Synlett 2012; 23: 873 12e Soengas RG, Silva AM. S. Tetrahedron 2013; 69: 3425 13 González-Gómez JC, Medjahdi M, Foubelo F, Yus M. J. Org. Chem. 2010; 75: 6308 14 Mahasneh AS, Qaraqe H. Z. Naturforsch., B 2005; 60b: 797 15 General Procedure for the Synthesis of β-Nitroamines 4: To a solution of the corresponding aldehyde (0.50 mmol) in anhyd THF (1 mL), Ti(OEt)4 (1.00 mmol) was added, followed by SnCl2 (1.00 mmol) and p-anisidine (0.45 mmol). After 1 h, bromonitromethane (0.50 mmol) was added and the reaction mixture was stirred at r.t. over a period of 4 h. The excess of Ti(OEt)4 was then decomposed by the slow addition of a solution of brine. The resulting suspension was filtered through a pad of Celite® and the pad washed with EtOAc. The organic layer was separated and washed with aq 1 M HCl, H2O, aq sat. solution of HNaCO3 and brine, dried over Na2SO4 and concentrated under vacuum. The residue was purified by flash column chromatography eluting with mixtures of EtOAc–hexane to yield β-nitroamines 4. 16 As examples of the obtained β-nitroamines, we present the analytical data: 4-Methoxy-N-(2-nitro-1-phenylethyl)benzenamine (4a): brown oil; Rf 0.23 (hexane–EtOAc, 3:1). 1H NMR (300 MHz, CDCl3): δ = 7.24–7.61 (m, 5 H), 6.73 (d, J = 9.0 Hz, 2 H), 6.58 (d, J = 9.0 Hz, 2 H), 6.23 (d, J = 7.4 Hz, 1 H), 5.09 (t, J = 6.7 Hz, 1 H), 4.69 (d, J = 6.7 Hz, 2 H), 3.71 (s, 3 H). 13C NMR (75 MHz, CDCl3): δ = 153.1 (C), 139.6 (C), 137.9 (C), 129.2 (2 × CH), 128.5 (CH), 126.4 (2 × CH), 115.6 (2 × CH), 114.8 (2 × CH), 80.0 (CH2), 57.7 (CH), 55.6 (Me). MS (ESI+): m/z (%) = 273 (4) [M + H]+, 213 (7), 212 (100), 124 (7). HRMS (ESI+): m/z [M + H]+ calcd for [C15H17N2O3]+: 273.1239; found: 273.1233. IR (neat): 3375, 1554, 1511, 1378, 1243 cm–1. N-(1-Cyclohexyl-2-nitroethyl)-4-methoxybenzenamine (4c): brown oil; Rf 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), 4.04–4.08 (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 (Me), 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. IR (neat): 3389, 1553, 1513, 1384, 1243 cm–1.4-Methoxy-N-(2-nitroethyl)aniline (4i): orange oil; Rf 0.48 (hexane–EtOAc, 3:1). 1H NMR (300 MHz, CDCl3): δ = 6.81 (d, J = 8.9 Hz, 2 H, Ar), 6.61 (d, J = 7.2 Hz, 2 H, Ar), 4.32–4.59 (m, 2 H), 3.76–3.86 (m, 5 H). 13C NMR (75 MHz, CDCl3): δ = 153.0 (C), 140.0 (C), 115.0 (2 × CH), 114.8 (2 × CH), 74.3 (CH2), 55.7 (OMe), 42.3 (CH2). MS (ESI+): m/z (%) = 197 (100) [M + H]+, 180 (21), 90 (12). IR (neat): 3400, 1558, 1375 cm–1. 17a Otero JM, Soengas RG, Estévez JC, Estévez RJ, Watkin DJ, Evinson EL, Nash RJ, Fleet GW. J. Org. Lett. 2007; 9: 623 17b Soengas RG, Estévez AM. Synlett 2010; 2625 18 Senkus M. J. Am. Chem. Soc. 1946; 68: 10 19a Geue RJ, Hambley TW, Harrowfield JM, Sargeson AM, Snow MR. J. Am. Chem. Soc. 1984; 106: 5478 19b Supriya S, Raghavan A, Vijayaraghavan VR, Subramanian J. Polyhedron 2007; 26: 3388 20 Heath RL, Rose JD. J. Chem. Soc. 1947; 1486 21 Analytical Data of 3-O-Benzyl-5,6-dideoxy-1,2-O-isopropylidene-5-p-methoxyphenylamino-6-nitro-α-d-glucofuranose (4k): yellow oil; Rf 0.28 (hexane–EtOAc, 3:1); [α]D 27 –9.2º (c = 0.6 in CHCl3). 1H NMR (500 MHz, CDCl3): δ = 7.12–7.34 (m, 5 H), 6.54 (d, J = 9.0 Hz, 2 H), 6.34 (d, J = 9.0 Hz, 2 H), 5.83 (d, J = 3.6 Hz, 1 H), 4.67 (dd, J = 13.1, 3.9 Hz, 1 H), 4.44–4.59 (m, 3 H), 4.38–4.42 (m, 1 H), 4.17–4.24 (m, 3 H), 4.02 (d, J = 3.1 Hz, 1 H), 3.73 (s, 3 H), 1.47 (s, 3 H), 1.31 (s, 3 H). 13C NMR (125 MHz, CDCl3): δ = 153.3 (C), 139.3 (C), 136.9 (C), 128.4 (2 × CH), 128.0 (CH), 127.9 (2 × CH), 116.3 (2 × CH), 114.9 (2 × CH), 112.1 (C), 104.9 (CH), 81.9 (CH), 81.2 (CH), 79.9 (CH), 75.8 (CH2), 72.1 (CH2), 55.6 (Me), 51.9 (CH), 26.7 (Me), 26.2 (Me). MS (ESI+): m/z (%) = 445 (100) [M + H]+, 444 (1), 316 (5), 289 (1), 288 (21). HRMS (ESI+): m/z [M + H]+ calcd for [C23H29N2O7]+: 445.1975; found: 445.1969. IR (neat): 3380, 1556, 1513, 1377, 1241 cm–1. 22 It is known that the stereochemical outcome of the indium-mediated allylation of N-tert-butanesulfinyl imines can be highly dependent on the presence of Lewis acids or bases. See: Lin G.-Q, Xu M.-H, Zhong YW, Sun X.-W. Acc. Chem. Res. 2008; 41: 831 23a Felkin H, Prudent N. Tetrahedron Lett. 1968; 2199 23b Anh NT, Eisenstein O, Lefour J.-M, Dau M.-E. J. Am. Chem. Soc. 1973; 95: 6146 23c Anh NT, Eisenstein O. Nouv. J. Chim. 1977; 1: 61 Supplementary Material Supplementary Material Supporting Information
