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DOI: 10.1055/s-2006-939704
1-Trifluoromethyl-1-diethoxyphosphoryl Carbene: A New Synthon for the Preparation of CF3-Containing α-Hydroxy and α-Amino Phosphonic Acid Derivatives
Publication History
Publication Date:
26 April 2006 (online)
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Abstract
The first synthesis of diethyl 1-diazo-2,2,2-trifluoroethylphosphonate has been developed starting from readily available compounds. The synthetic utility of this compound is demonstrated via its Rh-catalyzed insertion into O-H and N-H bonds to produce CF3-substituted α-hydroxy phosphonic and α-amino phosphonic acid derivatives
Key words
diazo compounds - fluorine - aminophosphonates - hydroxyphoshonate - insertion reactions
-
1a
Field SC. Tetrahedron 1999, 55: 12237 -
1b
Heaney F. In Comprehensive Organic Functional Group Transformations Vol. 4:Katritzky AR.Meth-Kohn O.Rees CW. Elsevier Science; Oxford UK: 1995. Chap. 4. p.10 -
2a
Atherton FR.Hassall CH.Lambert RW. J. Med. Chem. 1986, 29: 29 ; and references cited therein -
2b
Kafarski P.Lejcazk B. Phosphorus, Sulfur Silicon Relat. Elem. 1991, 63: 193 -
2c
Bird J.De Mello RC.Harper HP.Hunter DJ.Karran EH.Markwell ER.Miles-Williams AJ.Rahman SS.Ward RW. J. Med. Chem. 1994, 37: 158 -
2d
McLeod DA.Brinkworth RI.Ashley JA.Janda KD.Wirsching P. Bioorg. Med. Chem. Lett. 1991, 1: 653 -
2e
Hirschmann R.Smith AB.Taylor CM.Benkovic PA.Taylor SD.Yager KM.Sprengeler PA.Benkovic SJ. Science (Washington, D.C.) 1994, 265: 234 -
2f
Grembecka J.Mucha A.Cierpicki T.Kafarski P. J. Med. Chem. 2003, 46: 2641 -
3a
Filler R.Kobayashi Y.Yagupolski LM. In Organofluorine Compounds in Medicinal Chemistry and Biomedicinal Applications Elsevier Science; Amsterdam: 1993. -
3b
Ojima I.McCarthy J.Welch JT. Biomedicinal Frontiers of Fluorine Chemistry, ACS Symposium Series 639 ACS; Washington, D.C.: 1996. - 4
Banks RE.Tatlow JC.Smart BE. In Organofluorine Chemistry: Principles and Commercial Applications Plenum Press; New York: 1994. -
5a
Osipov SN.Kolomiets AF.Fokin AV. Russ. Chem. Rev. 1992, 61: 798 ; and references cited therein -
5b
Osipov SN.Golubev AG.Sewald N.Kolomiets AF.Fokin AV.Burger K. Synlett 1995, 1269 -
5c
Osipov SN.Golubev AS.Sewald N.Michel T.Kolomiets AF.Fokin AV.Burger K. J. Org. Chem. 1996, 61: 7521 -
5d
Osipov SN.Artyushin OI.Kolomiets AF. Mendeleev Commun. 2000, 5: 192 -
5e
Kobel’kova NM.Osipov SN.Kolomiets AF. Russ. Chem. Bull. 2002, 7: 1298 -
6a
Shi G.Xu Y. Chem. Commun. 1989, 607 -
6b
Shi G.Xu Y. J. Org. Chem. 1990, 55: 3383 -
6c
Shi G.Xu Y.Xu M. Tetrahedron 1991, 47: 1629 -
6d
Shi G.Xu Y.Xu M. J. Fluorine Chem. 1991, 52: 149 -
6e
Shi G.Cao Z.Cai W. Tetrahedron 1995, 51: 5011 -
6f
Paulini K.Reissig H.-U. J. Prakt. Chem./Chem.-Ztg. 1995, 337: 55 -
6g
Osipov SN.Sewald N.Burger K.Kolomiets AF.Fokin AV. Tetrahedron Lett. 1996, 37: 615 -
6h
Jiang B.Zhang Z.Luo Z. Org. Lett. 2002, 4: 2453 -
6i
Mueller P.Grass S.Shahi SP.Bernardinelli G. Tetrahedron 2004, 60: 4755 -
6j
Vorob’eva DV.Titanyuk ID.Beletskaya IP.Osipov SN. Mendeleev Commun. 2005, 6: 222 -
6k
Zhu S.Xing C.Zhu S. Tetrahedron 2006, 62: 829 -
7a
Sinitsa AD.Onisko PP.Kim TV.Kiseleva EI.Pirozhenko VV. J. Gen. Chem. USSR 1986, 52: 2372 -
7b
Flynn AG.Beight DW.Bohme EHW.Metcalf BW. Tetrahedron Lett. 1985, 26: 285 -
7c
Vaubaillon D.Giraud V.Rabiller C.Gruss U.Haas A.Haegele G. Phosphorus, Sulfur Silicon Relat. Elem. 1997, 126: 177 -
8a
Ingrassia L.Mulliez M. Synthesis 1999, 1731 -
8b
De Medina P.Ingrassia LS.Mulliez ME. J. Org. Chem. 2003, 68: 8424 -
9a
Yates P. J. Am. Chem. Soc. 1952, 74: 5376 -
9b
Ye T.McKervey A. Chem. Rev. 1994, 94: 1091 ; and references cited therein -
9c
Aller E.Buck RT.Drysdale MJ.Ferris L.Haigh D.Moody CJ. J. Chem. Soc., Perkin Trans. 1 1996, 2879 -
9d
Ferris L.Haigh D.Moody CJ. J. Chem. Soc., Perkin Trans. 1 1996, 2885 -
9e
Moody CJ.Ferris L.Haigh D.Swann E. Chem. Commun. 1997, 2391
References and Notes
Diethyl (1-Diazo-2,2,2-trifluoroethyl)phosphonate ( 4) The reaction was conducted in a 500 mL flask equipped with a condenser, a funnel, and magnetic stirrer. i-PrONO (9.5 g, 0.106 mol) was added to a vigorously stirred solution of aminophosphonate (19.6 g, 0.083 mol) in CHCl3 (300 mL). After the addition of approximately 1.0 g of i-PrONO an exothermic reaction began; the rest of the nitrite was added dropwise providing a mild refluxing reaction mixture for 20 min. After stirring for an additional 40 min (the temperature was reduced to r.t.) the solvent was removed under reduced pressure and the residue was distilled in vacuo to afford 13.7 g (67%) of diazo compound 4 as light yellow liquid. Bp 47-50 °C (1 Torr). IR (KBr): 2160, 1150 cm-1. 1H NMR (CDCl3): δ = 1.40 (t, 6 H, J = 7.1 Hz), 4.15-4.30 (m, 4 H). 13C NMR (CDCl3): δ = 15.9, 63.6, 118.6 (m), 124.1 (dq, J C-F = 271.0 Hz, J C-P = 12.1 Hz). 31P NMR (CDCl3): δ = 9.23. 19F NMR (CDCl3): δ = 23.0.
11
OH- and NH-Insertion; General Procedure A solution of diazo compound 4 (1.1 mmol) in anhydrous benzene (3 mL) was added to a solution of the hydroxy or amino compound (1.0 mmol) and dirhodium tetraacetate (2 mol%) in benzene (10 mL). The reaction mixture was stirred under reflux for 4 h. After evaporation of the solvent under reduced pressure the crude product was purified by column chromatography on silica gel (EtOAc-hexanes).
Diethyl (2,2,2-Trifluoro-1-methoxyethyl)phosphonate (
5a) Yield: 88%; oil. 1H NMR (CDCl3): δ = 1.38 (t, 6 H, J = 7.0 Hz), 3.65 (s, 3 H), 3.78-3.9 (m, 1 H), 4.20-4.30 (m, 4 H). 31P NMR (CDCl3): δ = 11.8 (app. q, J = 8.9 Hz). 19F NMR (CDCl3): δ = 6.7 (app. t, J = 8.5 Hz). Anal. Calcd for C7H14F3O4P: C, 33.61; H, 5.64. Found: C, 33.75; H, 5.75.
1-(Diethoxyphosphoryl)-2,2,2-trifluoroethyl N
-(
tert
-Butoxycarbonyl)
-1-phenylalaninate (
5f) Yield: 62%; oil; dr 1:1. 1H NMR (CDCl3): δ = 1.35-1.45 (m, 6 H), 1.45 (s, 9 H), 3.10 (ddd, 1 H, J = 4.1, 6.4, 14.0 Hz), 3.28 (app. dt, 1 H, J = 5.5, 14.0 Hz), 4.20-4.37 (m, 4 H), 4.78 (m, 1 H), 4.98 (m, 1 H), 5.68-5.83 (m, 1 H), 7.20-7.30 (m, 2 H), 7.30-7.41 (m, 3 H). 31P NMR (CDCl3): δ = 8.7 (app. q, J = 7.4 Hz), 9.3 (app. q, J = 7.4 Hz). 19F NMR (CDCl3): δ = 7.63 (app. t, J = 7.3 Hz), 7.84 (app. t, J = 7.3 Hz). Anal. Calcd for C20H29F3NO7P: C, 49.70; H, 6.00; N 2.90. Found: C, 49.51; H, 6.21; N 2.75.
Diethyl (2,2,2-Trifluoro-1-phenoxyethyl)phosphonate (
5g) Yield: 78%; oil. 1H NMR (CDCl3): δ = 1.40 (t, 6 H, J = 7.1 Hz), 4.20-4.40 (m, 4 H), 4.88-5.00 (m, 1 H), 7.05-7.15 (m, 3 H), 7.40-7.50 (m, 2 H). 31P NMR (CDCl3): δ = 10.6 (app. q, J = 8.9 Hz). 19F NMR (CDCl3): δ = 7.10 (app. t, J = 8.2 Hz). Anal. Calcd for C12H16F3O4P: C, 46.16; H, 5.17. Found: C, 46.27; H, 5.21.
Diethyl {1-[(
tert
-Butoxycarbonyl)amino]-2,2,2-trifluoroethy}phosphonate (
6a) Yield: 59%; white crystals; mp 81.5-82.5 °C. 1H NMR (CDCl3): δ = 1.41 (t, 6 H, J = 8.1 Hz), 1.52 (s, 9 H), 4.20-4.30 (m, 4 H), 4.65-4.80 (m, 1 H), 5.20 (m, 1 H). 31P NMR (CDCl3): δ = 13.6 (app. q, J = 6 Hz). 19F NMR (CDCl3): δ = 8.05 (app. t, J = 7.5 Hz). Anal. Calcd for C11H21F3NO5P: C, 39.41; H, 6.31; N, 4.18. Found: C, 39.47; H, 6.31; N, 4.15.
Diethyl {1-[(Phenylsulfonyl)amino]-2,2,2-trifluoroethyl}phosphonate (
6c) Yield: 64%; white solid; mp 115-117 °C. 1H NMR (CDCl3): δ = 1.33 (t, 3 H, J = 7.1 Hz), 1.39 (t, 3 H, J = 7.1 Hz), 4.10-4.30 (m, 4 H), 4.35-4.57 (m, 1 H), 7.05-7.15 (m, 1 H), 7.30-7.65 (m, 3 H), 7.92-7.97 (m, 2 H). 31P NMR (CDCl3): δ = 12.3 (app. q, J = 7.4 Hz). 19F NMR (CDCl3): δ = 8.03 (app. t, J = 8.0 Hz). Anal. Calcd for C12H17F3NO5PS: C, 38.40; H, 4.57; N, 3.73. Found: C, 38.21; H, 4.44; N, 3.67.
Diethyl {1-[(Pentafluorophenyl)amino]-2,2,2-trifluoroethyl}phosphonate (
6d) Yield: 63%; white solid; mp 55-56 °C. 1H NMR (CDCl3): δ = 1.40 (dt, 6 H, J = 0.7, 7.1 Hz), 4.20-4.38 (m, 4 H), 4.38-4.50 (m, 1 H).
31P NMR (CDCl3): δ = 13.2 (app. q, J = 7.4 Hz). 19F NMR (CDCl3): δ = 8.06 (app. t, J = 7.8 Hz, 3 F), -78.0 (d, J = 21.8 Hz, 2 F), -85.2 (dt, J = 5.8, 21.8 Hz, 2 F), -88.9 (t, J = 21.8 Hz, 1 F). Anal. Calcd for C12H12F8NO3P: C, 35.93; H, 3.01; N, 3.49. Found: C, 36.25; H, 3.22; N, 3.47.