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DOI: 10.1055/s-2004-835656
2-Diethoxyphosphoryl-4-nitroalkanoates - Versatile Intermediates in the Synthesis of α-Alkylidene-γ-lactones and Lactams
Publication History
Publication Date:
08 November 2004 (online)
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Abstract
Michael addition of various nitroalkanes 7a-f to ethyl (2-diethoxyphosphoryl)acrylate (6) gave 2-diethoxyphosphoryl-4-nitroalkanoates 8a-f. Transformation of the nitro functionality into hydroxy or amino group and cyclization yielded 3-(diethoxyphosphoryl)tetrahydro-2-furanones 11a-e or 3-(diethoxyphosphoryl)pyrrolidin-2-ones 14a-e, respectively. These compounds were then used in Horner-Wadsworth-Emmons olefinations of aldehydes to give 3-alkylidenedihydrofuran-2-ones 12a-e or 17a-c and 3-methylidenepyrrolidin-2-ones 15a-e.
Key words
Michael addition - nitroalkanoates - Wittig type olefination - α-alkylidenelactones - α-methylidenelactams
- 1
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Basavaiah D.Rao PD.Hyma RS. Tetrahedron 1996, 52: 8001 - 6
Bauchet R.Le Rouille E.Foucaud A. Bull. Soc. Chim. Fr. 1991, 128: 267 - 7
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Janecki T.Błaszczyk E. Synthesis 2001, 403 -
10a
Prepared in 73% yield by modified literature procedure. [10b] A mixture of 36% formaline (28 mL, 0,30 mol), piperidine (1 mL) and MeOH (450 mL) was refluxed for 0.5 h. To this mixture was added triethyl phosphono-acetate (30.0 g 0.13 mol) in one portion at 25 °C and the mixture was heated at reflux for 70 h. After 20 h and 48 h additional portions of piperidine (0.5 mL) were added. Progress of the reaction was monitored by 31P NMR. The solution was cooled and concentrated by rotatory evaporation, the residue was extracted with CCl4 (3 × 100 mL), combined extracts were dried (MgSO4), evaporated and 85% H3PO4 (3 mL) was added to the residue which was distilled in high vacuum (85-87 °C/0.4 Torr) to give pure ethyl 2-(diethoxyphosphory)lacrylate (6, 22.4 g; 73%).
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10b
Semmelhack MF.Tomesh JC.Czarny M.Boettger S. J. Org. Chem. 1978, 43: 1259 - 12
Villieras J.Rambaud M. Synthesis 1984, 406 - 15
Macomber RSA. Complete Introduction to Modern NMR Spectroscopy John Wiley and Sons; New York: 1998. p.416
References
General Procedure for the Preparation of Ethyl 2-diethoxyphosphoryl-4-nitroalkanoates 8a-f. A solution of nitroalkane 7 (17.0 mmol) in THF (10 mL) was added to a stirred suspension of NaH (0.213 g; 8.9 mmol) in THF (40 mL) under argon atmosphere at 0-4 °C. The reaction mixture was stirred for 40 min at r.t., cooled to 0-4 °C, and a solution of ethyl 2-diethoxyphosphorylacrylate (6) (2.000 g; 8.5 mmol) in THF (10 mL) was added. The mixture was then stirred for 24 h at r.t., THF was evaporated off at r.t. and the residue was quenched with H2O (15 mL) and extracted with CH2Cl2 (4 × 20 mL). The organic extracts were dried (MgSO4) and evaporated at r.t., to give a crude product, which was purified by column chromatography (silica gel, eluent CHCl3-acetone = 90:10 for 8a-c, CHCl3-acetone = 95:5 for 8d,e and EtOAc-hexane = 95:5 for 8f). Spectroscopic data for ethyl 2-diethoxyphosphoryl-5-(3,4-dimethoxyphenyl)-4-nitropentanoate (8e); dr 65:35. IR (film): 1732, 1552, 1260 cm-1. 1H NMR (250 MHz, CDCl3): δ = 1.28 (t, 3 J HH = 7.0 Hz, 3 H, major + minor), 1.31 (t, 3 J HH = 7.0 Hz, 3 H, major), 1.32 (td, 3 J HH = 7.2 Hz, 4 J PH = 0.5 Hz, 3 H, minor), 1.33 (td, 3 J HH = 7.5 Hz, 4 J PH = 0.5 Hz, 3 H, major), 1.34 (td, 3 J HH = 7.0 Hz, 4 J PH = 0.5 Hz, 3 H, minor), 2.28-2.75 (m, 2 H, major + minor), 2.84 (m, 1 H, major + minor), 3.02 (dd, 2 J HH = 14.5 Hz, 3 J HH = 7.2 Hz, 1 H, minor), 3.03 (dd, 2 J HH = 14.5, 3 J HH = 5.5 Hz, 1 H, major), 3.22 (dd, 2 J HH = 14.5 Hz, 3 J HH = 8.8 Hz, 1 H, major), 3.23 (dd, 2 J HH = 14.5 Hz, 3 J HH = 7.5 Hz, 1 H, minor), 3.85 (s, 3 H, major + minor), 3.86 (s, 3 H, major + minor), 4.02-4.28 (m, 4 H, major + minor), 4.67-4.81 (m, 1 H, major), 4.90-5.03 (m, 1 H, minor), 6.62-6.82 (m, 3 H, major + minor). 13C NMR (62.9 MHz, CDCl3): δ = 13.82 (s), 16.07 (d, 3 J PC = 6.0 Hz), 30.04 (d, 2 J PC = 4.5 Hz), 30.26 (d, 2 J PC = 3.5 Hz), 39.46 (s), 39.60 (s), 41.77 (d, 1 J PC = 130.2 Hz), 42.06 (d, 1 J PC = 130.6 Hz), 55.67 (s), 55.70 (s), 61.76 (s), 61.82 (s), 62.99 (d, 2 J PC = 6.5 Hz), 87.39 (d, 3 J PC = 8.4 Hz), 87.67 (d, 3 J PC = 15.0 Hz), 111.26 (s), 111.73 (s), 111.81 (s), 120.88 (s), 121.02 (s), 127.10 (s), 148.28 (s), 148.93 (s), 167.58 (d, 2 J PC = 5.7 Hz), 167.73 (d, 2 J PC = 6.3 Hz). 31P NMR (101 MHz, CDCl3): δ = 20.46 (major), 21.12 (minor). Anal. Calcd for C19H30NO9P: C, 51.00; H, 6.76; N, 3.13; P, 6.92. Found: C, 51.12; H, 6.69; N, 3.20; P, 6.80.
13
General Procedure for the Preparation of 3-Methylidenedihydrofuran-2-ones 12a-e. A mixture of 3-(diethoxyphosphoryl)tetrahydrofuran-2-one 11 (1.0 mmol), K2CO3 (0.415 g; 3.0 mmol) and 36% formaline (0.54 mL; 7.0 mmol) was stirred at 0-4 °C for 15 min. The mixture was extracted with Et2O (4 × 15 mL), dried (MgSO4) and evaporated. Residue was purified by column chromato-graphy (silica gel, eluent CHCl3) to give 12. Spectroscopic data for 5-(3,4-dimethoxyphenylmethyl)-3-methylidene-dihydrofuran-2-one (12e). IR (film): 1772, 1664 cm-1.
1H NMR (250 MHz, CDCl3): δ = 2.59 (ddt, 2
J
HH = 17.0 Hz, 3
J
HH = 6.0 Hz, 4
J
HH = 2.8 Hz, 1 H), 2.81 (dd, 2
J
HH = 14.3 Hz, 3
J
HH = 6.0 Hz, 1 H), 2.89 (ddt, 2
J
HH = 17.0 Hz, 3
J
HH = 7.8 Hz, 4
J
HH = 2.8 Hz, 1 H), 2.95 (dd, 2
J
HH = 14.3 Hz, 3
J
HH = 6.0 Hz, 1 H), 3.79 (s, 3 H), 3.80 (s, 3 H), 4.69 (dq, 3
J
HH = 7.8 Hz, 3
J
HH = 6.0 Hz, 1 H), 5.49 (t, 4
J
HH = 2.8 Hz, 1 H), 6.10 (t, 4
J
HH = 2.8 Hz, 1 H), 6.65-6.78 (m, 3 H). 13C NMR (62.9 MHz, CDCl3): δ = 32.50 (s), 41.27 (s), 55.90 (s), 55.92 (s), 77.21 (s), 111.32 (s), 112.74 (s), 121.68 (s), 127.89 (s), 148.14 (s), 149.02 (s), 121.98 (s), 134.37 (s), 170.13 (s). Anal. Calcd for C14H16O4: C, 67.73; H, 6.50. Found: C, 67.88; H, 6.41.
General Procedure for the Preparation of 3-Methylidenepyrrolidin-2-ones 15a-e. A solution of 3-(diethoxyphosphoryl)pyrrolidin-2-one 14 (1.00 mmol) in THF (7.0 mL) was added to a suspension of NaH (0.025 g; 1.05 mmol) in THF (3 mL) and the reaction mixture was stirred at r.t. for 30 min. Next, paraformaldehyde (0.033 g, 1.10 mmol) was added in one portion, the mixture was refluxed for 1 h and cooled to 0-4 °C. Then H2O (3 mL) was added, THF was evaporated under reduced pressure and the residue was extracted with CH2Cl2 (3 × 15 mL). Combined organic extracts were washed with H2O (5 mL), dried (MgSO4) and evaporated to give crude 15, which were purified by column chromatography (silica gel, eluent CHCl3). Spectroscopic data for 5-(3,4-dimethoxyphenyl-methyl)-3-methylidenepyrrolidin-2-one (15e). IR (film): 3100, 1684, 1662 cm-1. 1H NMR (250 MHz, CDCl3): δ = 2.45 (ddt, 2 J HH = 17.0 Hz, 3 J HH = 4.0 Hz, 4 J HH = 2.2 Hz, 1 H), 2.73 (ddt, 2 J HH = 17.0 Hz, 3 J HH = 7.5 Hz, 4 J HH = 2.2 Hz, 1 H), 2.82 (dd, 2 J HH = 13.8 Hz, 3 J HH = 7.6 Hz, 1 H), 3.15 (dd, 2 J HH = 13.8 Hz, 3 J HH = 3.4 Hz, 1 H), 3.86 (s, 3 H), 3.87 (s, 3 H), 4.02-4.20 (m, 1 H), 5.18 (t, 4 J HH = 2.2 Hz, 1 H), 5.83 (t, 4 J HH = 2.2 Hz, 1 H), 6.53-6.57 (m, 3 H). 13C NMR (62.9 MHz, CDCl3): δ = 28.13 (s), 37.41 (s), 55.81 (s), 58.20 (s), 115.92 (s), 111.14 (s), 112.69 (s), 121.72 (s), 128.17 (s), 147.89 (s), 148.93 (s), 135.58 (s), 163.89 (s). Anal. Calcd for C13H15NO3: C, 66.94; H, 6.48; N, 6.00. Found: C, 67.09; H, 6.57, N, 5.83.