Publication Cover
Synthetic Communications
An International Journal for Rapid Communication of Synthetic Organic Chemistry
Volume 32, 2002 - Issue 19
112
Views
18
CrossRef citations to date
0
Altmetric
Original Articles

A SIMPLE AND EFFICIENT PREPARATION OF (ARYLPHOSPHINYL)-METHYLPHOSPHONATES

&
Pages 2951-2957 | Received 04 Oct 2001, Published online: 16 Aug 2006

REFERENCES

  • Trowbridge , D.B. and Kenyon , G.L. 1970 . Adenosine 5′-Bis(dihydroxyphosphinylmethyl)phosphinate, the α,β : β,γ-Bismethylene Analog of Adenosine 5′-Triphosphate . J. Am. Chem. Soc. , 92 ( 7 ) : 2181 – 2182 .
  • Shirokova , E.A. , Shipitsin , A.V. , Victorova , L.S. , Dyatkina , N.B. , Goryunova , L.E. , Beabealashvilli , R.Sh. , Hamilton , C.J. , Roberts , S.M. and Krayevsky , A.A. 1999 . Modified Nucleoside 5′-Triphosphonates as a New Type of Antiviral Agents . Nucleosides Nucleotides , 18 ( 4&5 ) : 1027 – 1028 .
  • Shipitsin , A.V. , Victorova , L.S. , Shirokova , E.A. , Dyatkina , N.B. , Goryunova , L.E. , Beabealashvilli , R.Sh. , Hamilton , C.J. , Roberts , S.M. and Krayevsky , A. 1999 . New Modified Nucleoside 5′-Triphosphates: Synthesis, Properties Towards DNA Polymerases, Stability in Blood Serum and Antiviral Activity . J. Chem. Soc. Perkin Trans. 1 , : 1039 – 1050 .
  • McClard , R.W. , Fujita , T.S. , Stremler , K.E. and Poulter , C.D. 1987 . Novel Phosphonylphosphinyl (P–C–P–C) Analogues of Biochemically Interesting Diphosphates. Syntheses and Properties of P–C–P–C-Analogues of Isopentenyl Diphosphate and Dimethylallyl Diphosphate . J. Am. Chem. Soc. , 109 ( 18 ) : 5544 – 5545 .
  • Biller , S.A. , Forster , C. , Gordon , E.M. , Harrity , T. , Scott , W.A. and Ciosek , C.P. Jr. 1988 . Isoprenoid (Phosphinylmethyl)phosphonates as Inhibitors of Squalene Synthetase . J. Med. Chem. , 31 ( 10 ) : 1869 – 1871 .
  • Flohr , A. , Aemissegger , A. and Hilvert , D. 1999 . α-Functionalized Phosphonylphosphinates: Synthesis and Evaluation as Transcarbamoylase Inhibitors . J. Med. Chem. , 42 ( 14 ) : 2633 – 2640 .
  • McKenna , C.E. , Pham , P.-T.T. , Rassier , M.E. and Dousa , T.P. 1992 . α-Halo[(Phenylphosphinyl)methyl]phosphonates as Specific Inhibitors of Na+-Gradient-Dependent Na+-Phosphate Cotransport Across Renal Brush Border Membrane . J. Med. Chem. , 35 ( 26 ) : 4885 – 4892 .
  • Bau , R. , Pham , P.-T.T. , Duncan , G.D. and McKenna , C.E. 1995 . Absolute Configuration of (+)-[Fluoro(hydroxyphenylphosphinyl)methyl]phosphonic Acid, a Specific Inhibitor of Na+-Gradient-Dependent Na+-Phosphate Cotransport Across Renal Brush Border Membrane, by X-ray Crystallographic Analysis of Its (−)-Quinine Salt . J. Med. Chem. , 38 ( 9 ) : 1575 – 1578 .
  • Ebetino , F.H. , Degenhardt , C.R. , Jamieson , L.A. and Burdsall , D.C. 1990 . Recent Work on the Synthesis of Phosphonate-Containing, Bone-Active Heterocycles . Heterocycles , 30 ( 2 ) : 855 – 862 .
  • McOsker , J.E. Methods for the Treatment of Osteoporosis . WO 92/14474 . September 3, 1992 .
  • Geddes , A.D. and Boyce , R.W. Methods for the Treatment of Osteoporosis Using Bisphosphonates and Parathyroid Hormone . WO 93/11786 . June 24, 1993 .
  • Gilmore , W.F. and Park , J.S. 1981 . “ Base-Catalyzed Reactions of Phosphonomethylphosphinates, Bis(phosphonomethyl)phosphinates, and Bis(phosphonomethyl)phosphinic Amides with Aldehydes ” . In Phosphorus Chemistry pp 611 – 614 . Washington, DC : ACS Symposium Series 171; American Chemical Society .
  • Prashad , M. 1993 . Phosphonate vs. Phosphinate Elimination During Olefination of Aldehydes . Tetrahedron Lett. , 34 ( 10 ) : 1585 – 1588 . and references cited therein
  • Gloyna , D. , Lachman , U. and Henning , H.G. 1975 . Preparation of Methylene-P(O) Compounds With Different Phosphorous Substituents . J. Prakt. Chem. , 317 ( 5 ) : 840 – 852 .
  • Gobel , R. , Richter , F. and Weichmann , H. 1992 . Synthesis and Reactivity of Methylene Bridged Diphosphonyl Compounds . Phosphorus, Sulfur Silicon Relat. Elem. , 73 ( 1–4 ) : 67 – 80 .
  • Vu , C.B. Unpublished results
  • Hirao , T. , Masunaga , T. , Ohshiro , Y. and Agawa , T. 1981 . A Novel Synthesis of Dialkyl Arenephosphonates . Synthesis , : 1981 – 56 .
  • Petrakis , K.S. and Nagabhushan , T.L. 1987 . Palladium-Catalyzed Substitutions of Triflates Derived from Tyrosine-Containing Peptides and Simpler Hydroxyarenes Forming 4-(Diethoxyphosphinyl)phenylalanines and Diethyl Arylphosphonates . J. Am. Chem. Soc. , 109 ( 9 ) : 2831 – 2833 .
  • Xu , Y. and Zhang , J. 1984 . Palladium-Catalyzed Synthesis of Functionalised Alkyl Alkylarylphosphinates . Synthesis , : 1984 – 778 .
  • Baxter , A.D. , Taylor , R.J. and Collingwood , S.P. Intermediates for Dinucleotide and Oligonucleotide Analogues . US Patent 5,952,478 . September 14, 1999 . Diethyl (ethoxyphosphinyl)methylphosphonate (2) can readily be prepared in multi-ten-gram quantities in three steps from commercially available materials
  • Baillie , A.C. , Wright , B.J. and Wright , K. Pesticidally Active Salts and Compositions Containing Them and Processes for Their Manufacture and Use . EP0009348 . April 2, 1980 .
  • A representative experimental is given for 3d: A mixture of methyl 4-iodobenzoate (1d) (160 mg, 0.607 mmol), diethyl (ethoxyphosphinyl)methylphosphonate (2) (163 mg, 0.668 mmol), NMM (0.20 mL, 1.82 mmol) and Pd(PPh3)4 (34 mg) in acetonitrile (2 mL) were stirred at 90°C in a sealed tube under an atmosphere of Ar for 3 h. The reaction mixture was then concentrated, and the residue partitioned between 0.5 N aq HCl and CH2Cl2. The layers were separated, and the aqueous layer was reextracted three times with CH2Cl2. The combined extracts were washed with saturated aq NaCl, dried over MgSO4, and concentrated. The crude product was purified by flash chromatography on silica gel. Gradient elution from 10% MeOH–CH2Cl2 to 25% MeOH–CH2Cl2 afforded 177 mg (77%) of 3d as a colorless oil. 1H NMR (300 MHz, CDCl3) δ 8.16–8.13 (m, 2H), 7.97–7.90 (m, 2H), 4.24–4.05, 4.04–3.97 (m, 6H), 3.95 (s, 3H), 2.73–2.59 (m, 2H), 1.33 (t, J = 7.1 Hz, 3H), 1.30 (t, J = 7.1 Hz, 3H), 1.18 (t, J = 7.1 Hz, 3H); 31P NMR (121 MHz, 1H-decoupled, CDCl3) δ 33.1 (d, J = 7 Hz), 19.1 (d, J = 7 Hz); Electrospray mass spectrum (50 : 50 acetonitrile : water + 0.1% NH4OH): m/z 379 [M + H]. Anal. Calcd. for C15H24O7P2: C, 47.62; H, 6.39. Found: C, 47.59; H, 6.32. Products 3a–c: 1H NMR (300 MHz, CDCl3) δ 7.89–7.82 (m, 2H), 7.59–7.46 (m, 3H), 4.21–3.95 (m, 6H), 2.69–2.56 (m, 2H), 1.35 (t, J = 7.1 Hz, 3H), 1.30 (t, J = 7.1 Hz, 3H), 1.18 (t, J = 7.1 Hz, 3H); 31P NMR (121 MHz, 1H-decoupled, CDCl3) δ 33.8 (d, J = 8 Hz), 19.6 (d, J = 8 Hz); Electrospray mass spectrum (50 : 50 acetonitrile: water + 0.1% NH4OH): m/z 321 [M + H]. Anal. Calcd. for C13H22O5P2: C, 48.75; H, 6.92. Found: C, 48.72; H, 6.90. Products 3e,f: 1H NMR (300 MHz, CDCl3) δ 8.33 (dd, J = 8.7, 2.6 Hz, 2H), 8.09 (dd, J = 11.7, 8.7 Hz, 2H); 4.27–3.96 (m, 6H), 2.73–2.60 (m, 2H), 1.36 (t, J = 7.1 Hz, 3H), 1.31 (t, J = 7.1 Hz, 3H), 1.22 (t, J = 7.1 Hz, 3H); 31P NMR (121 MHz, 1H-decoupled, CDCl3) δ 31.5, 18.6; Anal. Calcd. for C13H21NO7P2: C, 42.75; H, 5.80; N, 3.83. Found: C, 42.67; H, 5.70; N, 3.77. Product 3g: 1H NMR (300 MHz, CDCl3) δ 7.49–7.37 (m, 3H); 7.16–7.13 (m, 1H), 4.26–3.95 (m, 6H), 3.88 (s, 3H), 2.86–2.60 (m, 2H), 1.36 (t, J = 7.1 Hz, 3H), 1.34 (t, J = 7.1 Hz, 3H), 1.23 (t, J = 7.1 Hz, 3H); 31P NMR (121 MHz, 1H-decoupled, CDCl3) δ 35.2, 19.4; Electrospray mass spectrum (50 : 50 acetonitrile : water + 0.1% NH4OH): m/z 351 [M + H]. Anal. Calcd. for C14H24O6P2: C, 48.00; H, 6.91. Found: C, 47.84; H, 6.85. Product 3h: 1H NMR (300 MHz, CDCl3) δ 7.81 (dd, J = 12.0, 8.7 Hz, 2H), 7.02 (dd, J = 8.7, 2.9 Hz, 2H), 4.23–3.91 (m, 6H), 3.88 (s, 3H), 2.78–2.53 (m, 2H), 1.35 (t, J = 7.1 Hz, 3H), 1.33 (t, J = 7.1 Hz, 3H), 1.23 (t, J = 7.1 Hz, 3H); 31P NMR (121 MHz, 1H-decoupled, CDCl3) δ 34.8, 19.8; Electrospray mass spectrum (50 : 50 acetonitrile : water + 0.1% NH4OH): m/z 351 [M + H]. Anal. Calcd. for C14H24O6P2: C, 48.00; H, 6.91. Found: C, 47.95; H, 6.90. Product 3i: 1H NMR (300 MHz, CDCl3) δ 7.77–7.62 (m, 4H), 4.21–3.92 (m, 6H), 2.67–2.53 (m, 2H), 1.33 (t, J = 7.0 Hz, 3H), 1.31 (t, J = 7.0 Hz, 3H), 1.20 (t, J = 7.0 Hz, 3H); 31P NMR (121 MHz, 1H-decoupled, CDCl3) δ 33.0 (d, J = 7 Hz), 19.2 (d, J = 7 Hz); Anal. Calcd. for C31H21BrO5P2: C, 39.12; H, 5.30. Found: C, 39.00; H, 5.26.
  • The authors wish to thank Dr. Raji Sundaramoorthi for the preparation of 3i.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.