Enantioselective Fluorination Reactions Catalyzed by Chiral Palladium Complexes

Abstract

On the basis of our chiral palladium enolate chemistry, efficient catalytic enantioselective fluorination reactions have been developed. These reactions can be carried out in environmentally friendly alcoholic solvents without any precaution to exclude water and moisture. The reaction was found applicable to a wide range of active methine compounds including β-ketoesters, β-ketophosphonates, and other related compounds (up to 99% ee). Furthermore, we succeeded in developing efficient fluorination reactions of 3-substituted oxindoles, which are found among many natural products. Interestingly, sequential fluorination-solvolysis reaction of a 3-nonsubstituted oxindol allowed monofluorination of an active methylene compound, and an optically active α-fluoroarylacetate was obtained (93% ee). To confirm the utility of these reactions, ­stereoselective synthesis of chiral fluorinated analogues of fundamental building blocks and catalytic asymmetric synthesis of BMS204352, which is a promising agent for the treatment of stroke, were demonstrated.

1 Introduction

2 Chiral Palladium Enolates for Fluorination Reactions

3 Catalytic Enantioselective Fluorination Reactions of
β-Ketoesters

4 Reuse of the Pd Catalysts in the Fluorination Reactions ­Using Ionic Liquids as a Reaction Medium

5 Catalytic Enantioselective Fluorination of β-Ketophos­phonates and Related Compounds

5.1 Fluorination of β-Ketophosphonates

5.2 Fluorination of Other Active Methine Compounds

6 Catalytic Enantioselective Fluorination Reactions of ­Oxindole Derivatives

7 Summary

Key words

asymmetric catalysis - fluorine - palladium - medicinal chemistry - ionic liquids

References and Notes

• 1a Kirsch P. Modern Fluoroorganic Chemistry: Synthesis, Reactivity, Applications   Wiley-VCH; Weinheim: 2004. 
• 1b Hiyama T. Kanie K. Kusumoto T. Morizawa Y. Shimizu M. Organofluorine Compounds: Chemistry and Applications   Springer; Berlin: 2000. 
• 1c Biomedical Frontiers of Fluorine Chemistry   Ojima I. McCarthy JR. Welch JT. ACS Symposium Series 639, American Chemical Society; Washington, DC: 1996. 
• For reviews:
• 1d O’Hagan D. Rzepa HS. Chem. Commun.  1997,  645 
• 1e Smart BE. J. Fluorine Chem.  2001,  109:  3 
• 1f Ismail FMD. J. Fluorine Chem.  2002,  118:  27 
• 1g Nyffeler PT. Durón SG. Burkart MD. Vincent SP. Wong C.-H. Angew. Chem. Int. Ed.  2005,  44:  192 
• 1h Shimizu M. Hiyama T. Angew. Chem. Int. Ed.  2005,  44:  214 
• 2a Asymmetric Fluoroorganic Chemistry: Synthesis, Application, and Future Directions   Ramachandran PV. ACS Symposium Series 746, American Chemical Society; Washington, DC: 2000. 
• 2b Enantiocontrolled Synthesis of Fluoro-Organic Compounds: Stereochemical Challenge and Biomedicinal Targets   Soloshonok VA. Wiley; New York: 1999. 
• 3a Mikami K. Itoh Y. Yamanaka M. Chem. Rev.  2004,  104:  1 
• 3b Iseki K. Tetrahedron  1998,  54:  13887 
• For representative examples of diastereoselective reactions, see:
• 4a Iwaoka T. Murohashi T. Sato M. Kaneko C. Tetrahedron: Asymmetry  1992,  3:  1025 
• 4b Davis FA. Kasu PVN. Tetrahedron Lett.  1998,  39:  6135 
• 4c Enders D. Faure S. Potthoff M. Runsink J. Synthesis  2001,  15:  2307 
• Reviews of enantioselective fluorination reactions:
• 5a Ibrahim H. Togni A. Chem. Commun.  2004,  1147 
• 5b Ma J.-A. Cahard D. Chem. Rev.  2004,  104:  6119 
• 5c Pihko PM. Angew. Chem. Int. Ed.  2006,  45:  544 
• For catalytic asymmetric α-halogenation reactions, see:
• 5d France S. Weatherwax A. Lectka T. Eur. J. Org. Chem.  2005,  475 
• 5e Oestreich M. Angew. Chem. Int. Ed.  2005,  44:  2324 
• 5f Bartoli G. Bosco M. Carlone A. Locatelli M. Melchiorre P. Sambri L. Angew. Chem. Int. Ed.  2005,  44:  6219 
• 5g Bertelsen S. Halland N. Bachmann S. Marigo M. Braunton A. Jørgensen KA. Chem. Commun.  2005,  4821 ; and references cited therein
• 6 For compound 1, see: Fried F. Sabo EF. J. Am. Chem. Soc.  1954,  76:  1455 
• 7 For compound 2, see: Paulsen H. Antons S. Brandes A. Lögers M. Müller SN. Naab P. Schmeck C. Schneider S. Stoltefuß J. Angew. Chem. Int. Ed.  1999,  38:  3373 
• 8 For compound 3, see: Hewawasam P. Gribkoff VK. Pendri Y. Dworetzky SI. Meanwell NA. Martinez E. Boissard CG. Post-Munson DJ. Trojnacki JT. Yeleswaram K. Pajor LM. Knipe J. Gao Q. Perrone R. Starrett JE. Bioorg. Med. Chem. Lett.  2002,  12:  1023 ; and references cited therein
• 9 For compound 4, see: Inagaki H. Miyauchi S. Miyauchi RN. Kawato HC. Ohki H. Matsuhashi N. Kawakami K. Takahashi H. Takemura M. J. Med. Chem.  2003,  46:  1005 
• For selected examples, see:
• 10a Shibata N. Suzuki E. Asahi T. Shiro M. J. Am. Chem. Soc.  2001,  123:  7001 
• 10b Mohar B. Baudoux J. Plaquevent J.-C. Cahard D. Angew. Chem. Int. Ed.  2001,  40:  4214 
• 10c Greedy B. Paris J.-M. Vidal T. Gouverneur V. Angew. Chem. Int. Ed.  2003,  42:  3291 
• 11a Hintermann L. Togni A. Angew. Chem. Int. Ed.  2000,  39:  4359 
• 11b Piana S. Devillers I. Togni A. Rothlisberger U. Angew. Chem. Int. Ed.  2002,  41:  979 
• 11c Frantz R. Hintermann L. Perseghini M. Broggini D. Togni A. Org. Lett.  2003,  5:  1709 
• 12 Kim D. Y., Park E. J.; Org. Lett.; 2002, 4: 545
• For recent examples, see:
• 13a Baba Y. Ogoshi Y. Hirai G. Yanagisawa T. Nagamatsu K. Mayumi S. Hashimoto Y. Sodeoka M. Bioorg. Med. Chem. Lett.  2004,  14:  2963 
• 13b Baba Y. Mayumi S. Hirai G. Kawasaki H. Ogoshi Y. Yanagisawa T. Hashimoto Y. Sodeoka M. Bioorg. Med. Chem. Lett.  2004,  14:  2969 
• 13c Baba Y. Hirukawa N. Tanohira N. Sodeoka M. J. Am. Chem. Soc.  2003,  125:  9740 
• For β-ketoesters, see:
• 14a Ma J.-A. Cahard D. Tetrahedron: Asymmetry  2004,  15:  1007 
• 14b Shibata N. Ishimaru T. Nagai T. Kohno J. Toru T. Synlett  2004,  1703 
• 14c Shibata N. Kohno J. Takai K. Ishimaru T. Nakamura S. Toru T. Kanemasa S. Angew. Chem. Int. Ed.  2005,  44:  4204 
• 14d For cyanoacetates, see: Kim HR. Kim DY. Tetrahedron Lett.  2005,  46:  3115 
• 14e For β-ketophosphonates, see: Bernardi L. Jørgensen KA. Chem. Commun.  2005,  1324 
• 14f Kim SM. Kim HR. Kim DY. Org. Lett.  2005,  7:  2309 
• 15a Enders D. Hüttl MRM. Synlett  2005,  991 
• 15b Marigo M. Fielenbach D. Braunton A. Kjærsgaard A. Jørgensen KA. Angew. Chem. Int. Ed.  2005,  44:  3703 
• 15c Steiner DD. Mase N. Barbas CF. Angew. Chem. Int. Ed.  2005,  44:  3706 
• 15d Beeson TD. MacMillan DWC. J. Am. Chem. Soc.  2005,  127:  8826 
• 15e Huang Y. Walji AM. Larsen CH. MacMillan DWC. J. Am. Chem. Soc.  2005,  127:  15051 
• 16a Sodeoka M. Ohrai K. Shibasaki M. J. Org. Chem.  1995,  60:  2648 
• 16b Sodeoka M. Tokunoh R. Miyazaki F. Hagiwara E. Shibasaki M. Synlett  1997,  463 
• 16c Sodeoka M. Shibasaki M. Pure Appl. Chem.  1998,  70:  411 
• 16d Hagiwara E. Fujii A. Sodeoka M. J. Am. Chem. Soc.  1998,  120:  2474 
• 16e Fujii A. Hagiwara E. Sodeoka M. J. Am. Chem. Soc.  1999,  121:  5450 
• 16f Fujii A. Hagiwara E. Sodeoka M. J. Synth. Org. Chem. Jpn.  2000,  58:  728 
• 17 Kumobayashi H. Miura T. Sayo N. Saito T. Zhang X. Synlett  2001,  1055 
• 18a Hamashima Y. Hotta D. Sodeoka M. J. Am. Chem. Soc.  2002,  124:  11240 
• 18b Hamashima Y. Hotta D. Umebayashi N. Tsuchiya Y. Suzuki T. Sodeoka M. Adv. Synth. Catal.  2005,  347:  1576 
• 18c Sodeoka M. Hamashima Y. Bull. Chem. Soc. Jpn.  2005,  78:  941 
• 19 Hamashima Y. Sasamoto N. Hotta D. Somei H. Umebayashi N. Sodeoka M. Angew. Chem. Int. Ed.  2005,  44:  1525 
• 22 Hamashima Y. Yagi K. Takano H. Tamás L. Sodeoka M. J. Am. Chem. Soc.  2002,  124:  14530 
• 23 Hamashima Y. Suzuki T. Takano H. Shimura Y. Tsuchiya Y. Moriya K. Goto T. Sodeoka M. Tetrahedron  2006, in press
• 24 For the use of α-substituted α-fluoro-β-ketoester in a drug design: Denis A. Bretin F. Fromentin C. Bonnet A. Piltan G. Bonnefoy A. Agouridas C. Bioorg. Med. Chem. Lett.  2000,  10:  2019 
• For stereoselective reduction of ketones, see:
• 25a Fujita M. Hiyama T. J. Am. Chem. Soc.  1985,  107:  8294 
• 25b Kitazume T. Kobayashi T. Yamamoto T. Yamazaki T. J. Org. Chem.  1987,  52:  3218 
• 26 Review on the reuse of chiral catalysts: Fan Q.-H. Li Y.-M. Chan ASC. Chem. Rev.  2002,  102:  3385 
• 27a Dupont J. de Souza RF. Suarez PAZ. Chem. Rev.  2002,  102:  3667 
• 27b Sheldon R. Chem. Commun.  2001,  2399 
• 27c Wasserscheid P. Keim W. Angew. Chem. Int. Ed.  2000,  39:  3772 
• 27d Welton T. Chem. Rev.  1999,  99:  2071 
• 28 Hamashima Y. Takano H. Hotta D. Sodeoka M. Org. Lett.  2003,  5:  3225 
• 30 α-Fluorophosphonates have been used as mimics of a phosphate moiety. For a general review, see: Berkowitz DB. Bose M. J. Fluorine Chem.  2001,  112:  13 
• For example:
• 31a Nieschalk J. O’Hagan D. J. Chem. Soc., Chem. Commun.  1995,  719 
• 31b Li C. Wu L. Otaka A. Smyth MS. Roller PP. Burke TR. den Hertog J. Zhang Z.-Y. Biochem. Biophys. Res. Commun.  1995,  216:  976 
• 31c Yokoyama T. Yamagishi T. Matsumoto K. Shibuya S. Tetrahedron  1996,  52:  11725 
• 31d Berkowitz DB. Bose M. Pfannenstiel TJ. Doukov T. J. Org. Chem.  2000,  65:  4498 
• For selected examples, see:
• 32a Kotoris CC. Wen W. Lough A. Taylor SD. J. Chem. Soc., Perkin Trans. 1  2000,  8:  1271 
• 32b Ruiz M. Ojea V. Quintela JM. Guillín JJ. Chem. Commun.  2002,  1600 
• 33 Hamashima Y. Suzuki T. Shimura Y. Shimizu T. Umebayashi N. Tamura T. Sasamoto N. Sodeoka M. Tetrahedron Lett.  2005,  46:  1447 
• For Ru, see:
• 35a Murahashi S.-I. Naoto T. Taki H. Mizuno M. Takaya H. Komiya S. Mizuno Y. Oyasato N. Hiraoka M. Hirano M. Fukuoka A. J. Am. Chem. Soc.  1995,  117:  12436 
• For Rh, see:
• 35b Sawamura M. Hamashima H. Ito Y. J. Am. Chem. Soc.  1992,  114:  8295 
• 35c Kuwano R. Miyazaki H. Ito Y. J. Organomet. Chem.  2000,  603:  18 
• 35d For Pd, see: Takenaka K. Uozumi Y. Org. Lett.  2004,  6:  1833 ; and references therein
• 36 Hamashima Y. Suzuki T. Takano H. Shimura Y. Sodeoka M. J. Am. Chem. Soc.  2005,  127:  10164 
• For the synthesis of fluorous analogues of indole alkaloids, see:
• 37a Shibata N. Tarui T. Doi Y. Kirk KL. Angew. Chem. Int. Ed.  2001,  40:  4461 
• 37b

  For a stoichiometric enantioselective fluorination of oxindoles, see ref. 10a.

• For stoichiometric reactions, see:
• 38a Shibata N. Ishimaru T. Suzuki E. Kirk KL. J. Org. Chem.  2003,  68:  2494 
• 38b Zoute L. Audouard C. Plaquevent J.-C. Cahard D. Org. Biomol. Chem.  2003,  1:  1833 
• 38c

  Recently, Shibata and Toru et al. reported a highly enantioselective catalytic synthesis of 3 using a chiral Ni complex. See ref. 14c.

20

A space-filling model depicted in Scheme [3] was generated based on MM3 calculation method using CAChe 5.0. See also ref. 18b.

21

In the case of the Michael reaction, no reaction occurred with the Pd complexes 6. The addition of a strong protic acid, such as TfOH, which promotes the reaction cooperatively with the Pd enolate as an activator of the enone, was necessary.

29

Recently, Kim et al. also reported the reuse of the palladium complexes in their catalytic enantioselective fluorination. See ref. 14f.

34

Hamashima, Y.; Suzuki, T.; Goto, T.; Sodeoka, M. manuscript in preparation.

39

Hamashima, Y.; Moriya, K.; Sodeoka, M. unpublished results.