Asymmetric Electrophilic Fluorination of α-Cyanoalkylphosphonates ­Catalyzed by Chiral Palladium Complexes

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

References and Notes

• 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 

16

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).