Ceric Ammonium Nitrate Catalyzed aza-Michael Addition of Aliphatic Amines to α,β-Unsaturated Carbonyl Compounds and Nitriles in Water [1]

Abstract

Ceric ammonium nitrate (3 mol%) efficiently catalyzes the aza-Michael reaction of amines with α,β-unsaturated carbonyl compounds in water to produce the corresponding β-amino carbonyl compounds in good to excellent yields (55-99%) for most of the compounds under mild conditions. The reaction is procedurally simple and displays limited chemoselectivity, as aromatic amines were found to be unreactive.

ceric ammonium nitrate - aza-Michael reaction - aliphatic amines - α,β-unsaturated carbonyl compounds

References and Notes

1

IICT Communication number: 050617.

2a Perlmutter P. Conjugate Addition Reactions in Organic Synthesis   Pergamon Press; Oxford: 1992. 

2b Lee VJ. In Comprehensive Organic Synthesis   Vol. 4:  Trost BM. Fleming I. Pergamon Press; New York: 1991.  Chap. 1.2. p.69 

3a Cardillo G. Tomasini C. Chem. Soc. Rev.  1996,  25:  117 

3b Drury WJ. Ferraris D. Cox C. Young B. Lecka T. J. Am. Chem. Soc.  1998,  120:  11006 

3c Hagiwara E. Fujii A. Sodeoka M. J. Am. Chem. Soc.  1998,  120:  2474 

3d Fustero S. Pina B. Salavert E. Navarro A. Ramirez de Arellano MC. Fuentes AS. J. Org. Chem.  2002,  67:  4667 

3e Xu L.-W. Xia C.-G. Eur. J. Org. Chem.  2005,  633 

4a Arend M. Westermann B. Risch N. Angew. Chem. Int. Ed.  1998,  37:  1045 

4b Sibi MP. Shay JJ. Liu M. Jasperse CP. J. Am. Chem. Soc.  1998,  120:  6615 

5 Arend M. Westermann B. Risch N. Angew. Chem. Int. Ed.  1998,  37:  1044 

6a Vicario JL. Badia D. Carrillo L. Org. Lett.  2001,  3:  773 

6b Gellman S. Acc. Chem. Res.  1998,  31:  173 

7a Adrian JC. Snapper ML. J. Org. Chem.  2003,  68:  2143 

7b Ambhaikar NB. Snyder JP. Liotta DC. J. Am. Chem. Soc.  2003,  125:  3690 

8a Yb(OTf)₃: Jenner G. Tetrahedron Lett.  1995,  36:  233 

8b InCl₃: Loh T.-P. Wei L.-L. Synlett  1998,  975 

CeCl₃·7H₂O:

8c Bartoli G. Bosco M. Marcantoni E. Petrini M. Sanbri L. Torregiani E. J. Org. Chem.  2001,  66:  9052 

8d Bartoli G. Bartolacci M. Giuliani A. Marcantoni E. Torregiani E. J. Org. Chem.  2005,  70:  169 

8e Bi(NO₃)₃: Srivastava N. Banik BK. J. Org. Chem.  2003,  68:  2109 

8f Bi(OTf)₃: Varala R. Alam MM. Adapa SR. Synlett  2003,  720 

8g Cu(OTf)₂: Xu LW. Li JW. Xia CG. Zhou SL. Hu XX. Synlett  2003,  2425 

8h FeCl₃·7H₂O/Co(OAc)₂: Xu LW. Li L. Xia CG. Helv. Chim. Acta  2004,  87:  1522 

8i LiClO₄: Azizi N. Saidi MR. Tetrahedron  2004,  60:  383 

8j Heterogeneous solid acids: Shaikh NS. Despande VH. Bedekar AV. Tetrahedron  2001,  57:  9045 

8k Ionic liquids: Yadav JS. Reddy BVS. Basak AK. Narsaiah AV. Chem. Lett.  2003,  32:  988 

8l Quaternary ammonium salts in water: Xu LW. Li JW. Zhou SL. Xia CG. New J. Chem.  2004,  28:  183 

8m Cu(acac)₂ immobilized in ionic liquids: Kantam ML. Neeraja V. Kavita B. Haritha Y. Adv. Synth. Catal.  2005,  347:  763 

9a Narayan S. Muldoon J. Finn MG. Fokin VV. Kolb HC. Sharpless KB. Angew. Chem. Int. Ed.  2005,  44:  3275 

9b Lindstrom UM. Chem. Rev.  2002,  102:  2751 

9c Wei C. Li C.-J. J. Am. Chem. Soc.  2003,  125:  9584 

10a Varala R. Ramu E. Alam MM. Adapa SR. Synlett  2004,  1747 

10b Varala R. Ramu E. Alam MM. Adapa SR. Chem. Lett.  2004,  33:  1614 

10c Varala R. Ramu E. Adapa SR. Bull. Chem. Soc. Jpn.  2006,  79:  140 

10d Alam MM. Varala R. Adapa SR. Tetrahedron Lett.  2003,  5115 

10e Varala R. Alam MM. Adapa SR. Synlett  2003,  67 

10f Varala R. Ramu E. Sreelatha N. Adapa SR. Tetrahedron Lett.  2006,  47:  877 

10g Alam MM. Varala R. Ramu E. Adapa SR. Lett. Org. Chem.  2006,  3:  187 

10h Varala R. Ramu E. Sreelatha N. Adapa SR. Synlett  2006,  1009 

11a Nair V. Balagopal L. Rajan R. Mathew J. Acc. Chem. Res.  2004,  37:  21 

11b Seiders JRII. Wang L. Floreancig PE. J. Am. Chem. Soc.  2003,  125:  2406 

11c Nair V. Suja TD. Mohanan K. Tetrahedron Lett.  2005,  46:  3217 

11d Bandgar BP. Makone SS. Synlett  2003,  262 

12

Representative Procedure.
A mixture of amine (1.2 mmol), α,β-unsaturated compound (1 mmol) and CAN (0.017 g, 3 mol%) in H₂O (2 mL) was stirred at r.t. for the time specified in Table [2] and Table [3] . After the reaction was over, the reaction mixture was filtered, and extracted with Et₂O (3 × 10 mL). The combined organic layers were dried over Na₂SO₄, concentrated in vacuo and purified by column chromatography on silica gel with EtOAc and n-hexane (1:4) as eluent to afford the corresponding β-amino product in pure form. The products were characterized by comparison of their NMR and mass spectra with those of authentic samples. All new compounds gave satisfactory spectral data in accordance to their proposed structures.
Spectral Data for Selected Compounds.
3-(4-Phenylpiperazin-1-yl) Propanenitrile (Table 2, Entry 2).
Yellow needles; mp 72-74 °C. ¹H NMR (300 MHz, CDCl₃): δ = 7.30-7.22 (m, 2 H), 6.96-6.83 (m, 3 H), 3.21 (t, J = 4.5 Hz, 4 H), 2.77 (t, J = 6.0 Hz, 2 H), 2.65 (t, J = 6.0 Hz, 4 H), 2.55 (t, J = 7.5 Hz, 2 H) ppm. MS: m/z = 216 [M + 1].
3-(4-Methylpiperazin-1-yl) Propanenitrile (Table 2, Entry 3).
Brown oil. ¹H NMR (300 MHz, CDCl₃): δ = 2.69 (t, J = 6.0 Hz, 2 H), 2.55-2.49 (m, 10 H), 2.30 (s, 3 H) ppm. MS: m/z = 154 [M + 1].
3-(4-Benzylpiperazin-1-yl) Propanenitrile (Table 2, Entry 4). Brown oil. ¹H NMR (300 MHz, CDCl₃): δ = 7.31-7.25 (m, 5 H), 3.63 (s, 2 H), 2.68 (t, J = 7.5 Hz, 2 H), 2.60-2.43 (m, 10 H) ppm. MS: m/z = 230 [M + 1].
3-[4-(2-Cyanoethyl)piperazin-1-yl] Propanenitrile (Table 2, Entry 6).
Light brown oil. ¹H NMR (300 MHz, CDCl₃): δ = 2.68 (t, J = 6.0 Hz, 4 H), 2.56-2.47 (m, 12 H) ppm. MS: m/z = 193 [M + 1].
Methyl 3-Tetrahydro-1 H -1-pyrrolylpropanoate (Table 3, Entry 2).
Oil. ¹H NMR (300 MHz, CDCl₃): δ = 3.67 (s, 3 H), 2.86 (t, J = 7.0 Hz, 2 H), 2.34 (m, 6 H), 1.17 (m, 4 H) ppm. MS: m/z = 158 [M + 1].
Methyl 3-Piperidinylpropionate (Table 3, Entry 4b).
Oil. ¹H NMR (300 MHz, CDCl₃): δ = 3.62 (s, 3 H), 2.61 (t, J = 8.0 Hz, 2 H), 2.47 (t, J = 7.9 Hz, 2 H), 2.34 (m, 4 H), 1.55-1.36 (m, 6 H) ppm. MS: m/z = 193 [M + 1].
Methyl 3-(Dibenzylamine) Propanoate (Table 3, Entry 8).
Solid. ¹H NMR (300 MHz, CDCl₃): δ = 7.42-7.26 (m, 10 H), 3.65 (s, 3 H), 3.60 (s, 4 H), 2.84 (t, J = 7.3 Hz, 2 H), 2.47 (t, J = 7.3 Hz, 2 H) ppm. MS: m/z = 283 [M⁺].