Organic compounds -- part of the class 532-570 series – Organic compounds – Phosphorus containing
Reexamination Certificate
2001-09-14
2004-04-27
Vollano, Jean F. (Department: 1621)
Organic compounds -- part of the class 532-570 series
Organic compounds
Phosphorus containing
C568S016000, C556S021000
Reexamination Certificate
active
06727390
ABSTRACT:
BACKGROUND OF THE INVENTION
The present invention relates to fluorous phosphine compounds and to methods of increasing the fluorous nature of chemical entities using such fluorous phosphine compounds, and, particularly, to branched fluorous phosphine compounds and to methods of increasing the fluorous nature of chemical entities using such branched fluorous phosphine compounds.
References set forth herein may facilitate understanding of the present invention or the background of the present invention. Inclusion of a reference herein, however, is not intended to and does not constitute an admission that the reference is available as prior art with respect to the present invention.
Fluorous techniques for the synthesis of small organic molecules are becoming increasingly useful as more and more fluorous compounds are synthesized and studied. These techniques are attractive for strategic separation of reaction mixtures since fluorous-tagged compounds can be quickly separated from non-tagged compounds in, for example, binary liquid-liquid and solid-liquid extractions. Fluorous tagging is discussed, for example, in U.S. Pat. Nos. 5,859,247, 5,777,121, and 6,156,896, and U.S. patent application Ser. No. 09/506,7796, all assigned to the assignee of the present invention, the disclosures of which are incorporated herein by reference. The fluorine content of a fluorous molecule is an important aspect to be balanced to obtain suitable performance during both the reaction and the separation. Opposing needs during reaction and separation can be thought of as dividing the fluorous field into two branches or techniques, which have recently been termed “heavy fluorous” and “light fluorous”. Those two techniques are actually ends of a continuum with a considerable gray area in between.
On the heavy fluorous end, fluorous techniques strive for very high partition coefficients in liquid-liquid separation, requiring fluorous reagents and catalysts with large numbers of fluorine atoms. Heavy fluorous techniques afford easy separation, but the large numbers of fluorines tend to render the fluorous compounds insoluble in typical organic reaction solvents. Fluorous cosolvents are thus used which have poor dissolving power for organic compounds, so the modification and optimization of reaction conditions is often required. However, once suitable conditions are found, the resulting heavy fluorous techniques are very powerful, especially when applied to catalytic reactions.
On the light fluorous end, the number of fluorine atoms are reduced to provide fluorous compounds that have properties more similar to their organic parents. While reduction of the fluorine content can allow the use of standard literature reaction conditions with little or no modification, the reduced fluorine content compromises the separation of fluorous from non-fluorous components by liquid-liquid extraction. However, the recently introduced technique of fluorous solid phase extraction is proving far superior to liquid-liquid extractions for separation of compounds with fewer fluorines. See, for example, a) Curran, D. P.; Hadida, S.; He, M.
J. Org. Chem
. 1997, 62, 6714. b) Curran, D. P.; Luo, Z. Y.
J. Am. Chem. Soc
. 1999, 121, 9069. c) Curran, D. P.; Hadida, S.; Kim, S. Y.; Luo, Z. Y.
J. Am. Chem. Soc
. 1999, 121, 6607. d) Curran, D. P.; Hadida, S.; Studer, A.; He, M.; Kim, S. -Y.; Luo, Z.; Larhed, M.; Hallberg, M.; Linclau, B. In
Combinatorial Chemistry: A Practical Approach
; H. Fenniri, Ed.; Oxford Univ Press: Oxford, in press; Vol. 2. Light fluorous techniques are especially useful for small scale and discovery oriented research, including parallel synthesis applications and so-called techniques of fluorous synthesis. See, for example, a) Curran, D. P.
Med. Res. Rev
. 1999, 19, 432; b) Studer, A.; Hadida, S.; Ferritto, R.; Kim, S. Y.; Jeger, P.; Wipf, P.; Curran, D. P.
Science
1997, 275, 823. c) Curran, D. P.
The Cancer Journal
1998, 4 Supp. 1, S73.
Fluorous biphasic catalysis (FBC) was the original fluorous technique introduced in 1994 by Horváth and Rábai, and that technique is finding increasing utility in the catalysis community. Horváth, I. T.; Rábai, J.
Science
1994, 266, 72. Most of the work in the area of fluorous biphasic catalysis involves the use of fluorous phosphines and phosphites. Mathivet, T.; Monflier, E.; Castanet, Y.; Mortreux, A.; Couturier, J. L.
Tetrahedron Lett
. 1999, 40, 3885. The original trialkylphosphine ligand [P(CH
2
CH
2
C
6
F
13
)
3
] introduced by Horváth and Rábai has proved useful in a number of reactions catalyzed by rhodium and iridium. See, for example, a) Guillevic, M. A.; Rocaboy, C.; Arif, A. M.; Horváth, I. T.; Gladysz, J. A.
Organometallics
1998, 17, 707. b) Horváth, I. T.; Kiss, G.; Cook, R. A.; Bond, J. E.; Stevens, P. A.; Rabai, J.; Mozeleski, E. J.
J. Am. Chem. Soc
. 1998, 120, 3133. c) Juliette, J. J. J.; Rutherford, D.; Horváth, I. T.; Gladysz, J. A.
J. Am. Chem. Soc
. 1999, 121, 2696. d) Li, C. B.; Nolan, S. P.; Horváth, I. T.
Organometallics
1998, 17, 452. e) Smith, D. C.; Stevens, E. D.; Nolan, S. P.
Inorg. Chem
. 1999, 38, 5277.
More recently, a number of fluorous analogs of triphenylphosphine have appeared, and several of these are shown in FIG.
1
. Phosphine
1
a
was introduced by Leitner for reactions in supercritical carbon dioxide and has also found use in an FBC variant of the popular palladium catalyzed allylic substitution (Tsuji/Trost) reaction. Kainz, S.; Koch, D.; Baumann, W.; Leitner, W.
Angew. Chem., Int. Ed. Engl
. 1997, 36, 1628; Kling, R.; Sinou, D.; Pozzi, G.; Choplin, A.; Quignard, F.; Busch, S.; Kainz, S.; Koch, D.; Leitner, W.
Tetrahedron Lett
. 1998, 39, 9439. Related phosphine
2
a
, lacking the ethylene spacer, has been used by Knochel as a ligand for palladium catalyzed Negishi couplings and Heck reactions. Betzemeier, B.; Knochel, P.
Angew. Chem., Int. Ed. Engl
. 1997, 36, 2623. Hope and coworkers have prepared families of phosphines bearing one, two, and three fluorous chains in both the para (
2
a-c
) and meta (
3
a-c
) series and studied the properties of several organometallic complexes of these ligands. See, a) Fawcett, J.; Hope, E. G.; Kemmitt, R. D. W.; Paige, D. R.; Russell, D. R.; Stuart, A. M.; ColeHamilton, D. J.; Payne, M. J.
Chem. Commun
. 1997, 1127. b) Bhattacharyya, P.; Gudmunsen, D.; Hope, E. G.; Kemmitt, R. D. W.; Paige, D. R.; Stuart, A. M.
J. Chem. Soc., Perkin Trans
. 1 1997, 3609. c) Fawcett, J.; Hope, E. G.; Kemmitt, R. D. W.; Paige, D. R.; Russell, D. R.; Stuart, A. M.
J. Chem. Soc. Dalton Trans
. 1998, 3751. d) Hope, E. G.; Kemmitt, R. D. W.; Stuart, A. M.
J. Chem. Soc. Dalton Trans
. 1998, 3765. e) Sinou, D.; Pozzi, G.; Hope, E. G.; Stuart, A. M.
Tetrahedron Lett
. 1999, 40, 849. f) Hope, E. G.; Kemmitt, R. D. W.; Paige, D. R.; Stuart, A. M.; Wood, D. R. W.
Polyhedron
1999,18, 2913. g) Hope, E. G.; Kemmitt, R. D. W.; Paige, D. R.; Stuart, A. M.
J. Fluorine Chem.
1999, 99, 197. Ligands with a silyl spacer (see
4
a
) have been synthesized and studied by van Koten and coworkers. See, for example, a) Richter, B.; Deelman, B. J.; van Koten, G.
J. Mol. Catal. A Chem
. 1999, 145, 317. b) Richter, B.; Spek, A. L.; vanKoten, G.; Deelman, B. J.
J. Am. Chem. Soc
. 2000, 122, 3945. c) Richter, B.; deWolf, E.; vanKoten, G.; Deelman, B. J.
J. Org. Chem
. 2000, 65, 3885. d) deWolf, E.; Richter, B.; vanKoten, G.; Deelman, B. J.
J. Org. Chem
. 2000, 65, 5424.
Given the utility of recently developed fluorous techniques, it is highly desirable to develop additional fluorous compounds that can be used in such techniques.
SUMMARY OF THE INVENTION
In one aspect, the present invention provides a method of increasing the fluorous nature of a compound. The method includes the step of reacting the compound with or tagging the compound with at least one of a second compound having the formula:
wherein R is an alkyl group or an aryl group, n is 1, 2 or 3 and Rs is a spacer group and Rf is a branched fluorous group.
In another aspect, the present invention provides a chemical compound having the gene
Curran Dennis P.
Zhang Qisheng
Bartony & Hare, LLP
University of Pittsburgh
Vollano Jean F.
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