Subscribe to RSS
DOI: 10.1055/s-2007-977436
Asymmetric Electrophilic Fluorination of α-Cyanoalkylphosphonates Catalyzed by Chiral Palladium Complexes
Publication History
Publication Date:
13 April 2007 (online)
![](https://www.thieme-connect.de/media/synlett/200707/lookinside/thumbnails/10.1055-s-2007-977436-1.jpg)
Abstract
The catalytic enantioselective fluorination of α-cyanoalkylphosphonates catalyzed by chiral palladium complexes was examined. Treatment of α-cyanoalkylphosphonates with N-fluorobenzenesulfonimide as the electrophilic fluorinating reagent under mild reaction conditions afforded the corresponding α-fluorinated α-cyanoalkylphosphonates in excellent yields with high enantiomeric excesses (80-91%).
Key words
electrophilic fluorination - asymmetric catalysis - chiral palladium catalysts - α-cyanoalkylphosphonates - α-fluoroalkylphosphonates
-
1a
Chambers RD. Fluorine in Organic Chemistry Blackwell; Oxford: 2004. -
1b
Kirsch P. Modern Fluoroorganic Chemistry: Synthesis, Reactivity, Applications Wiley-VCH; Weinheim: 2004. -
1c
Hiyama T.Kanie K.Kusumoto T.Morizawa Y.Shimizu M. Organofluorine Compounds: Chemistry and Applications Springer-Verlag; Berlin: 2000. -
1d
Biomedical Frontiers of Fluorine Chemistry
Ojima I.McCarthy JR.Welch JT. ACS Symposium Series 639, American Chemical Society; Washington DC: 1996. - For reviews, see:
-
1e
Kirk KL. J. Fluorine Chem. 2006, 127: 1013 -
1f
Isanbor C.O’Hagan D. J. Fluorine Chem. 2006, 127: 303 -
2a
Bohm H.-J.Banmer D.Bendels S.Kansy M.Kuhn B.Muller K.Obst-Sander U.Stahl M. ChemBioChem 2004, 5: 637 -
2b
Smart BE. J. Fluorine Chem. 2001, 109: 3 -
2c
Ismail FMD. J. Fluorine Chem. 2002, 118: 27 -
3a
Ramachandran PV. Asymmetric Fluoroorganic Chemistry: Synthesis, Application, and Future Directions ACS Symposium Series 746, American Chemical Society; Washington DC: 2000. -
3b
Enantiocontrolled Synthesis of Fluoroorganic Compounds
Soloshonok VA. John Wiley & Sons; Chichester: 1999. -
3c For review, see:
Bravo P.Resnati G. Tetrahedron: Asymmetry 1990, 1: 661 - For reviews, see:
-
4a
Lal GS.Pez GP.Syvret RG. Chem. Rev. 1996, 96: 1737 -
4b
Taylor SD.Kotoris CC.Hum G. Tetrahedron 1999, 55: 12431 - For reviews, see:
-
5a
Mikami K.Itoh Y.Yamanaka M. Chem. Rev. 2004, 104: 1 -
5b
Ibrahim H.Togni A. Chem. Commun. 2004, 1147 -
5c
Ma J.-A.Cahard D. Chem. Rev. 2004, 104: 6119 -
5d
France S.Weatherwax A.Lectka T. Eur. J. Org. Chem. 2005, 475 -
5e
Prakash GKS.Bier P. Angew. Chem. Int. Ed. 2006, 45: 2172 - 6
Hintermann L.Togni A. Angew. Chem. Int. Ed. 2000, 39: 4359 - For β-keto esters, see:
-
7a
Hamashima Y.Yagi K.Takano H.Tamás L.Sodeoka M. J. Am. Chem. Soc. 2002, 124: 14530 -
7b
Hamashima Y.Takano H.Hotta D.Sodeoka M. Org. Lett. 2003, 5: 3225 -
7c
Ma J.-A.Cahard D. Tetrahedron: Asymmetry 2004, 15: 1007 -
7d
Shibata N.Ishimaru T.Nagai T.Kohno J.Toru T. Synlett 2004, 1703 -
7e
Shibata N.Kohno J.Takai K.Ishimaru T.Nakamura S.Toru T.Kanemasa S. Angew. Chem. Int. Ed. 2005, 44: 4204 - For α-cyano acetates, see:
-
8a
Kim HR.Kim DY. Tetrahedron Lett. 2005, 46: 3115 -
8b
Park EJ.Kim HR.Joung CW.Kim DY. Bull. Korean Chem. Soc. 2004, 25: 1451 - For β-keto phosphonates, see:
-
9a
Bernardi L.Jørgensen KA. Chem. Commun. 2005, 1324 -
9b
Hamashima Y.Suzuki T.Shimura Y.Shimizu T.Umebayashi N.Tamura T.Sasamoto N.Sodeoka M. Tetrahedron Lett. 2005, 46: 1447 -
9c
Kim SM.Kim HR.Kim DY. Org. Lett. 2005, 7: 2309 -
9d
Kim SM.Kang YK.Lee K.Mang JY.Kim DY. Bull. Korean Chem. Soc. 2006, 27: 423 -
10a
Kim DY.Park EJ. Org. Lett. 2002, 4: 545 -
10b
Enders D.Hüttl MRM. Synlett 2005, 991 -
10c
Marigo M.Fielenbach D.Braunton A.Kjærsgaard A.Jørgensen KA. Angew. Chem. Int. Ed. 2005, 44: 3703 -
10d
Steiner DD.Mase N.Barbas CF. Angew. Chem. Int. Ed. 2005, 44: 3706 -
10e
Beeson TD.MacMillan DWC. J. Am. Chem. Soc. 2005, 127: 8826 -
10f
Huang Y.Walji AM.Larsen CH.MacMillan DWC. J. Am. Chem. Soc. 2005, 127: 15051 -
10g
Fukuzumi T.Shibata N.Sugiura M.Nakamura S.Toru T. J. Fluorine Chem. 2006, 127: 548 - 11
Berkowitz DB.Bose M. J. Fluorine Chem. 2001, 112: 13 -
12a
Blackburn GM. Chem. Ind. (London) 1981, 134 -
12b
McKenna CE.Shen P. J. Org. Chem. 1981, 46: 4573 -
12c
Nieschalk J.O’Hagan D. Chem. Commun. 1995, 719 -
12d
Nieschalk J.O’Hagan D. Chem. Commun. 1995, 719 -
12e
Jakeman DL.Ivory AJ.Willamson MP.Blackburn GM. J. Med. Chem. 1998, 41: 4493 -
12f
Jakeman DL.Ivory AJ.Willamson MP.Blackburn GM. J. Med. Chem. 1998, 41: 4493 -
12g
Berkowitz DB.Bose M.Pfannenstiel TJ.Doukov T. J. Org. Chem. 2000, 65: 4498 -
13a
Kang YK.Kim DY. Tetrahedron Lett. 2006, 47: 4265 -
13b
Park EJ.Kim MH.Kim DY. J. Org. Chem. 2004, 69: 6897 -
13c
Kim DY.Huh SC. Bull. Korean Chem. Soc. 2004, 25: 347 -
13d
Kim DY.Kim SM.Koh KO.Mang JY. Bull. Korean Chem. Soc. 2003, 24: 1425 -
13e
Kim DY.Choi YJ.Park HY.Joung CU.Koh KO.Mang JY.Jung K.-Y. Synth. Commun. 2003, 33: 435 -
13f
Kim DY.Huh SC.Kim SM. Tetrahedron Lett. 2001, 42: 6299 -
13g
Kim DY.Huh SC. Tetrahedron 2001, 57: 8933 -
14a
Li K.Hii KK. Chem. Commun. 2003, 1132 -
14b
Li K.Horton PN.Hursthouse MB.Hii KK. J. Organomet. Chem. 2003, 665: 250 -
14c For an aquapalladium complex, see:
Shimada T.Bajracharya GB.Yamamoto Y. Eur. J. Org. Chem. 2005, 59 ; and references cited therein -
14d
Vicente J.Arcas A. Coord. Chem. Rev. 2005, 249: 1135 -
14e For Pd(II) chemistry, see:
Tsuji J. Palladium Reagents and Catalysts: New Perspectives for 21st Century John Wiley & Sons; Chichester: 2004. - For the preparation of α-cyanoalkylphosphonates, see:
-
15a
Kim DY.Oh DY. Synth. Commun. 1987, 17: 953 -
15b
Kim DY.Oh DY. Bull. Korean Chem. Soc. 1997, 18: 994
References and Notes
Typical procedure: To a stirred solution of 1-phenyl-1-cyanomethylphosphonate (1a, 12.6 mg, 0.05 mmol), Pd catalyst 4g (3.0 mg, 0.0025 mmol) and 2,6-di-tert-butyl-4-methylpyridine (20.5 mg, 0.1 mmol) in EtOH (0.5 mL) at r.t. was added NFSI (2, 18.9 mg, 0.06 mmol). The reaction mixture was stirred for 12 h at r.t. The mixture was diluted with sat. NH4Cl solution (10 mL) and extracted into EtOAc (3 × 10 mL). The combined organic layers were dried over MgSO4, filtered, concentrated, and purified by flash column chromatography to afford diethyl 1-fluoro-1-phenyl-1-cyanomethylphosphonate 3a (12.2 mg, 90%): [α]D 17 -27.7 (c 0.6, CHCl3, 85% ee); 1H NMR (200 MHz, CDCl3): δ = 1.26-1.38 (m, 6 H), 4.03-4.32 (m, 4 H), 7.42-7.50 (m, 3 H), 7.55-7.67 (m, 2 H); 13C NMR (50 MHz, CDCl3): δ = 16.1, 65.7 (d, J = 7 Hz), 65.8 (d, J = 7 Hz), 87.6 (dd, J = 170, 195 Hz), 114.3 (d, J = 27 Hz), 125.8, 125.9, 128.7, 131.4; MS (EI): m/z = 271 [M+], 134, 109, 91, 81, 65, 43; HPLC (hexane-i-PrOH, 9:1, 220 nm, 1.0 mL/min, Chiralcel OJ column): t R = 11.1 min(minor), t R = 14.8 (major).