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

Igor D. Titanyuk; Daria V. Vorob’eva; Sergej N. Osipov; Irina P. Beletskaya

doi:10.1055/s-2006-939704

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Synlett 2006(9): 1355-1358
DOI: 10.1055/s-2006-939704

LETTER

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

Igor D. Titanyuk^a, Daria V. Vorob’eva^b, Sergej N. Osipov*^b, Irina P. Beletskaya^a
^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;

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Publication History

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

Abstract
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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

References and Notes

1a Field SC. Tetrahedron 1999, 55: 12237

Crossref Google Scholar
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

Crossref Google Scholar
2a Atherton FR. Hassall CH. Lambert RW. J. Med. Chem. 1986, 29: 29 ; and references cited therein

Crossref PubMed Google Scholar
2b Kafarski P. Lejcazk B. Phosphorus, Sulfur Silicon Relat. Elem. 1991, 63: 193

Crossref PubMed Google Scholar
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

Crossref PubMed Google Scholar
2d McLeod DA. Brinkworth RI. Ashley JA. Janda KD. Wirsching P. Bioorg. Med. Chem. Lett. 1991, 1: 653

Crossref PubMed Google Scholar
2e Hirschmann R. Smith AB. Taylor CM. Benkovic PA. Taylor SD. Yager KM. Sprengeler PA. Benkovic SJ. Science (Washington, D.C.) 1994, 265: 234

Crossref PubMed Google Scholar
2f Grembecka J. Mucha A. Cierpicki T. Kafarski P. J. Med. Chem. 2003, 46: 2641

Crossref PubMed Google Scholar
3a Filler R. Kobayashi Y. Yagupolski LM. In Organofluorine Compounds in Medicinal Chemistry and Biomedicinal Applications Elsevier Science; Amsterdam: 1993.

Google Scholar
3b Ojima I. McCarthy J. Welch JT. Biomedicinal Frontiers of Fluorine Chemistry, ACS Symposium Series 639 ACS; Washington, D.C.: 1996.

Google Scholar
4 Banks RE. Tatlow JC. Smart BE. In Organofluorine Chemistry: Principles and Commercial Applications Plenum Press; New York: 1994.

Google Scholar
5a Osipov SN. Kolomiets AF. Fokin AV. Russ. Chem. Rev. 1992, 61: 798 ; and references cited therein

Google Scholar
5b Osipov SN. Golubev AG. Sewald N. Kolomiets AF. Fokin AV. Burger K. Synlett 1995, 1269

Google Scholar
5c Osipov SN. Golubev AS. Sewald N. Michel T. Kolomiets AF. Fokin AV. Burger K. J. Org. Chem. 1996, 61: 7521

Google Scholar
5d Osipov SN. Artyushin OI. Kolomiets AF. Mendeleev Commun. 2000, 5: 192

Google Scholar
5e Kobel’kova NM. Osipov SN. Kolomiets AF. Russ. Chem. Bull. 2002, 7: 1298

Google Scholar
6a Shi G. Xu Y. Chem. Commun. 1989, 607

Crossref Google Scholar
6b Shi G. Xu Y. J. Org. Chem. 1990, 55: 3383

Crossref Google Scholar
6c Shi G. Xu Y. Xu M. Tetrahedron 1991, 47: 1629

Crossref Google Scholar
6d Shi G. Xu Y. Xu M. J. Fluorine Chem. 1991, 52: 149

Crossref Google Scholar
6e Shi G. Cao Z. Cai W. Tetrahedron 1995, 51: 5011

Crossref Google Scholar
6f Paulini K. Reissig H.-U. J. Prakt. Chem./Chem.-Ztg. 1995, 337: 55

Crossref Google Scholar
6g Osipov SN. Sewald N. Burger K. Kolomiets AF. Fokin AV. Tetrahedron Lett. 1996, 37: 615

Crossref Google Scholar
6h Jiang B. Zhang Z. Luo Z. Org. Lett. 2002, 4: 2453

Crossref Google Scholar
6i Mueller P. Grass S. Shahi SP. Bernardinelli G. Tetrahedron 2004, 60: 4755

Crossref Google Scholar
6j Vorob’eva DV. Titanyuk ID. Beletskaya IP. Osipov SN. Mendeleev Commun. 2005, 6: 222

Crossref Google Scholar
6k Zhu S. Xing C. Zhu S. Tetrahedron 2006, 62: 829

Crossref Google Scholar
7a Sinitsa AD. Onisko PP. Kim TV. Kiseleva EI. Pirozhenko VV. J. Gen. Chem. USSR 1986, 52: 2372

Google Scholar
7b Flynn AG. Beight DW. Bohme EHW. Metcalf BW. Tetrahedron Lett. 1985, 26: 285

Google Scholar
7c Vaubaillon D. Giraud V. Rabiller C. Gruss U. Haas A. Haegele G. Phosphorus, Sulfur Silicon Relat. Elem. 1997, 126: 177

Google Scholar
8a Ingrassia L. Mulliez M. Synthesis 1999, 1731

Crossref Google Scholar
8b De Medina P. Ingrassia LS. Mulliez ME. J. Org. Chem. 2003, 68: 8424

Crossref Google Scholar
9a Yates P. J. Am. Chem. Soc. 1952, 74: 5376

Crossref Google Scholar
9b Ye T. McKervey A. Chem. Rev. 1994, 94: 1091 ; and references cited therein

Crossref Google Scholar
9c Aller E. Buck RT. Drysdale MJ. Ferris L. Haigh D. Moody CJ. J. Chem. Soc., Perkin Trans. 1 1996, 2879

Crossref Google Scholar
9d Ferris L. Haigh D. Moody CJ. J. Chem. Soc., Perkin Trans. 1 1996, 2885

Crossref Google Scholar
9e Moody CJ. Ferris L. Haigh D. Swann E. Chem. Commun. 1997, 2391

Crossref Google Scholar

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.