Download PDF
Synlett 2006(9): 1355-1358  
DOI: 10.1055/s-2006-939704
LETTER
© Georg Thieme Verlag Stuttgart · New York

1-Trifluoromethyl-1-diethoxyphosphoryl Carbene: A New Synthon for the Preparation of CF3-Containing α-Hydroxy and α-Amino Phosphonic Acid Derivatives

Igor D. Titanyuka, Daria V. Vorob’evab, Sergej N. Osipov*b, Irina P. Beletskayaa
a Department of Chemistry, Moscow State University, 119992 Moscow, Leninskie gory 1, Bd.3, Russia
b A. N. Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences, 119991 Moscow, Vavilov str. 28, Russia
e-Mail: osipov@ineos.ac.ru;
Further Information

Publication History

Received 7 March 2006
Publication Date:
26 April 2006 (online)

    Permissions and Reprints All articles of this category

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

10

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.