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

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 

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.

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 

29

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

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 

34

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

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.

39

Hamashima, Y.; Moriya, K.; Sodeoka, M. unpublished results.