Solvent and Catalyst Free Three-component Coupling of Carbonyl Compounds, Amines and Triethylphosphite; a new Synthesis of α-Aminophosphonates

Abstract

The first solvent and catalyst free three-component coupling of carbonyl compounds, amines and triethylphosphite is achieved producing α-aminophosphonates at ambient temperature in very high yields.

Key words

three-component coupling - carbonyl compounds - amines - triethyl phosphite - α-aminophosphonates

References

• 1a Cave GWV. Raston CL. Scott JL. Chem. Commun.  2001,  2159 
• 1b Toda F. Tanaka K. Chem. Rev.  2000,  100:  1025 
• 1c Cave GWV. Raston CL. Chem. Commun.  2000,  2199 
• 1d Toda F. Acc. Chem. Res.  1995,  28:  480 
• 1e Toda F. Synlett  1993,  303 
• 2a Welton T. Chem. Rev.  1999,  99:  2071 
• 2b Wasserscheid P. Keim W. Angew. Chem. Int. Ed.  2000,  39:  3773 
• 2c Gordon CM. Wasserscheid P. Appl. Catal. A: General  2001,  222:  101 
• 2d Sheldon R. Chem. Commun.  2001,  2399 
• 3a Manabe K. Kobayashi S. Chem. Commun.  2000,  699 
• 3b Li CJ. Chang TH. Organic Reactions in Aqueous Media   Wiley; New York: 1997. 
• 3c Organic Synthesis in Water   Grieco PA. Blackie Academic and Professional; London: 1998. 
• 3d Li CJ. Chem. Rev.  1993,  2023 
• 3e Hermann WA. Kohlpainter CW. Angew. Chem., Int. Ed. Engl.  1993,  32:  1524 
• 4a Namboodiri VN. Varma RS. Green Chemistry  2001,  3:  146 
• 4b Santaniello E. Manzocchi A. Sozzani P. Tetrahedron. Lett.  1979,  47:  4581 
• 4c Badone D. Jommi G. Pagliarin R. Tabecchia P. Synthesis  1987,  920 
• 5a Ugi I. Pure Appl. Chem.  2001,  73:  187 
• 5b Ugi I. Lohberger S. Karl R. In Comprehensive Organic Chemistry, Selective Efficiency   Vol. 20:  B M. Heathcock CH. Pergamon; Oxford: 1991.  p.1083 
• 6 Kafarski P. Lejezak B. Phosphorus, Sulfur, Silicon Relat. Elem.  1991,  63:  1993 
• 7 Hirschmann R. Smith ABIII. Taylor CM. Benkovic PA. Taylor SD. Yager KM. Sprengler PA. Venkovic SJ. Science  1994,  265:  234 
• 8a Allen MC. Furher W. Tuck B. Wade R. Wood JM. J. Med. Chem.  1989,  32:  1652 
• 8b Gianousis PP. Bartlett PA. J. Med. Chem.  1987,  30:  603 
• 9 Heyderi A. Karimian A. Ipaktschi J. Tetrahedron Lett.  1998,  39:  6729 
• 10 Laschat S. Kunz H. Synthesis  1992,  90 
• 11 John J. Pol. J. Chem.  1981,  55:  643 
• 12a Quian C. Huang T. J. Org. Chem.  1998,  63:  4125 
• 12b Lee S. Park JH. Kang J. Lee JK. Chem. Commun.  2001,  1698 
• 13 Chandrasekhar S. Prakash SJ. Jagadeshwar V. Narsihmulu Ch. Tetrahedron Lett.  2001,  42:  5561 
• 14 Ranu BC. Hajra A. Jana U. Org. Lett.  1999,  1:  1141 
• 15a Yadav JS. Reddy BVS. Madan C. Synlett  2001,  1131 
• 15b Yadav JS. Reddy BVS. Raj KS. Reddy KB. Synthesis  2001,  2277 

16

Representative Procedure: Benzaldehyde (5 mmol), aniline (5 mmol) and triethyl phosphite (5 mmol) were added successively and the mixture was stirred for 15 min at r.t. After completion of the reaction (monitored by TLC), the reaction mixture was adsorbed on silicagel and eluted with petroleum ether-EtOAc (7:3) to give (phenyl-phenylamino-methyl)-phosphonic acid diethylester. ¹H NMR (200 MHz, CDCl₃): δ = 7.45 (d, J = 7.4 Hz, 2 H), 7.35-7.20 (m, 3 H), 7.04 (t, J = 8.2 Hz, 2 H), 6.68-6.50 (m, 3 H), 4.98 (d, J = 8.2 Hz, 2 H), 4.78 (d, J = 6.7 Hz, 2 H), 4.66 (d, J = 7.4 Hz, 2 H), 4.18-3.98 (m, 2 H), 3.92-3.82 (m, 1 H), 3.70-3.54 (m, 1 H), 1.26 (t, J = 7.4 Hz, 3 H), 1.08 (t, J = 6.7 Hz, 3 H). MS (FAB): m/z = 319 [M⁺], 210, 182, 119, 109, 91, 77, 55. FT-IR (KBr): 3310, 2924, 1452, 1239, 1029 cm^-1.