Synthesis of non-peptidyl α,α-difluoromethylenephosphonic acids on a soluble polymer support

Journal of Combinatorial Chemistry

Volumn 2, Issue 3, 2000, Pages 234-242

  Hum, Gabriel ^a   Grzyb, Justyna ^a   Taylor, Scott D ^a  

^a UNIVERSITY OF WATERLOO   (Canada)

Author keywords

[No Author keywords available]

Indexed keywords

EID: 0001477715     PISSN: 15204766     EISSN: None     Source Type: Journal    
DOI: 10.1021/cc9900596     Document Type: Article

References (46)

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16. (j) Yokomatsu, T.; Murano, T.; Umesue, I.; Soeda, S.; Shimeno, H.; Shibuya, S. Synthesis and Biological Evaluation of α,α-Difluorobenzylphosphonic Acid Derivatives as Small Molecule Inhibitors of Protein Tyrosine Phosphatase 1B. Bioorg. Med. Chem. Lett. 1999, 9, 529-532.
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19. Recently, Ganesan and co-workers have constructed DFMP-bearing peptidomimetics using an Ugi four-component condensation reaction on Rink resin. See ref 2h.
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26. Yokomatsu, T.; Murano, T.; Suemune, K.; Shibuya, S. Facile Synthesis of Aryl(difluoromethyl)phosphonates through CuBr-Mediated Cross Coupling Reactions of [(Diethoxyphosphinyl)difluoromethyl]zinc Bromide with Aryl Iodides. Tetrahedron 1997, 53, 815-822.
27. (a) Taylor, S. D.; Kotoris, C. C.; Dinaut, A. N.; Chen, M.-J. Synthesis of Aryl(Difluoromethylenephosphonates) via Electrophilic Fluorination of α-Carbanions of Benzylic Phosphonates with N-fluorobenzenesulfonimide. Tetrahedron 1998, 54, 1691-1714.
28. (b) Taylor, S. D.; Dinaut, A. N.; Thadani, A. T.; Huang, Z. Synthesis of Benzylic Mono(α,α-Difluoromethylenephosphonates) and Benzylic Bis(α,α-Difluoromethylenephosphonates) via Electrophilic Fluorination. Tetrahedron Lett. 1996, 37, 8089-8092.
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32. The percentage of chloromethyl groups was determined by NMR using the method of Janda and co-workers. See ref 13b.
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35. (c) Campbell, D. A.; Bermak, J. C. Phosphonate Ester Synthesis Using a Modified Mitsunobu Condensation J. Org. Chem. 1994, 59, 658-660.
36. Campbell, D. A.; Bermak, J. C.; Burkoth, T. S.; Patel, D. A Transition State Analogue Inhibitor Combinatorial Library. J. Am. Chem. Soc. 1995 117, 5381-5382.
37. (a) Anderson, J. C.; Namli, H. Ambient Temperature Unsymmetrical Biaryl Synthesis Using Suzuki Methodology. Synlett 1995, 765-766.
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40. (d) Campi, E. M.; Jackson, W. R.; Marcuccio, S. M.; Naeslund, C. G. M. High yields of Unsymmetrical Biaryls via Cross Coupling of Arylboronic Acids with Haloarenes using a Modified Suzuki-Beletskaya Procedure. J. Chem. Soc., Chem. Commun. 1994, 2395.
41. 2, and 3 mol % of an electron-rich and statically encumbered phosphine ligand (not commercially available) in dioxane. See: Old, D. W.; Wolfe, J. P.; Buchwald, S. L. A Highly Effective Catalysts for Palladium-Catalyzed Cross-Coupling Reactions: Room Temperature Suzuki Couplings and Amination of Unactivated Aryl Chlorides. J. Am. Chem. Soc. 1998, 120, 9722-9723. Very recently, Buchwald has improved this methodology using a more readily available and effective phosphine ligand. See: Wolfe, J. P.; Buchwald, S. L. A Highly Active Catalyst for the Room-Temperature Amination and Suzuki Couplings of Aryl Chlorides Angew. Chem., Int. Ed. Engl. 1999, 38, 2413-2416.
42. 2, and 3 mol % of an electron-rich and statically encumbered phosphine ligand (not commercially available) in dioxane. See: Old, D. W.; Wolfe, J. P.; Buchwald, S. L. A Highly Effective Catalysts for Palladium-Catalyzed Cross-Coupling Reactions: Room Temperature Suzuki Couplings and Amination of Unactivated Aryl Chlorides. J. Am. Chem. Soc. 1998, 120, 9722-9723. Very recently, Buchwald has improved this methodology using a more readily available and effective phosphine ligand. See: Wolfe, J. P.; Buchwald, S. L. A Highly Active Catalyst for the Room-Temperature Amination and Suzuki Couplings of Aryl Chlorides Angew. Chem., Int. Ed. Engl. 1999, 38, 2413-2416.
43. 2. See ref 19.
44. 19F NMR chemical shift of polymers bearing the biaryl products (19 and 20) differed by about 1-2 ppm from that of starting polymers 16 and 17.
45. The results of the PTP inhibition studies with the compounds prepared in this report will be reported in due course.
46. 2. J. Am. Chem. Soc. 1975, 97, 865-873.