Organic compounds -- part of the class 532-570 series – Organic compounds – Oxygen containing
Reexamination Certificate
2003-03-13
2004-08-03
Price, Elvis O. (Department: 1621)
Organic compounds -- part of the class 532-570 series
Organic compounds
Oxygen containing
C568S840000, C568S841000, C570S140000, C570S162000
Reexamination Certificate
active
06770789
ABSTRACT:
BACKGROUND OF THE INVENTION
Compounds containing the trifluoromethyl group are of great interest in the pharmaceutical and agrochemical industry. Among the numerous methods for incorporation of the trifluoromethyl group into organic compounds (McClinton, M. A. et al.
Tetrahedron,
1992, 48:6555-6666), one of the most useful involves the use of reagents that effectively generate the unstable CF
3
−
anion as an in situ species for the purpose of nucleophilic trifluoromethylation of electrophilic substrates such as aldehydes and ketones. Because of the limited number of such reagents and because of specific limitations that pertain to each, there remains considerable interest in the development of new trifluoromethyl anion reagents that might offer an experimental or cost advantage.
Currently, there are two major trifluoromethyl anion methodologies that receive most of the attention from synthetic chemists around the world. Because of its diversity of applicability, deriving from extensive recent work by several research groups (Prakash, G. K. S. et al.
Chem. Rev.,
1997, 97:757-786; Singh, R. P. et al.
Tetrahedron,
2000, 56:7613-7632; Prakash, G. K. S. et al.
Chem. Rev.,
1997, 97:757-786; Singh, R. P. et al.
Tetrahedron,
2000, 56:7613-7632), (trifluoromethyl)-trimethylsilane (Me
3
SiCF
3
) is generally considered to be the most effective reagent of this type, but recent advances using trifluoroacetaldehyde hemiaminals and their derivatives as trifluoromethylating reagents in reactions with nonenolizable aldehydes and ketones have also sparked considerable interest (Large, S. et al.
J. Org. Chem.,
2000, 65:8848-8856, Billard, T. et al
Eur. J. Org. Chem.,
2001, pp. 1467-1471).
Trifluoromethyl iodide has previously been used for the purpose of nucleophilic trifluoromethylation of carbonyl compounds, via its derived organozinc reagent. However, the required use of ultrasound for these reactions seems to have limited their use by synthetic chemists (Kitazume, T. et al.
J. Am. Chem. Soc.,
1985, 107:5186-5191; Francese, C. et al.
J. Chem. Soc., Chem Commun.,
1987, pp. 642-643).
Beginning in 1998, it was demonstrated that tetrakis(dimethylamino)ethylene (TDAE) could be used as an effective reductant to generate synthetically competent nucleophilic heterocyclic difluoromethyl anions from chloro- and bromodifluoromethyl precursors (Burkholder, C. R. et al.
J. Org. Chem.,
1998, 63:5385-5394; Burkholder, C. R. et al.
J. Fluorine Chem.,
2001, 109:39-48). It was demonstrated that the combination of CF
3
I and TDAE could be used to prepare CF
3
TMS from TMSCl (Pawelke, G.
J. Fluorine Chem.,
1991, 52:229). A method for the nucleophilic trifluoromethylation of aldehydes and ketones, based on photo-induced reduction of trifluoromethyl iodide by TDAE has also recently been demonstrated (Ait-Mohand, S. et al.
Organic Letters,
2001, 3(26):4271-4273).
Despite their varying degrees of success with other organic compounds, none of the known trifluoromethyl anion methodologies have been utilized to achieve trifluoromethylation of sulfates.
BRIEF SUMMARY OF THE INVENTION
The subject invention provides materials and methods for the trifluoromethylation of sulfates. In a preferred embodiment, the processes of the subject invention comprise reacting a trifluoromethylating reagent with a sulfate to synthesize a trifluoromethylated carbinol.
Cyclic sulfates or acyclic sulfates can be trifluoromethylated according to the process of the subject invention. For example, cyclic sulfates, such as a 1,2-cyclic sulfate or 1,3-cyclic sulfate, can be utilized to synthesize a trifluoromethylated carbinol, such as 3,3,3-trifluoroethycarbinol or 4,4,4-trifluoropropylcarbinol, respectively.
In view of the ready availability of chiral, optically-pure 1,2-diols, which are precursors of cyclic sulfates, the process of the subject invention advantageously permits ring-opening trifluoromethylation of cyclic sulfates, and efficient synthesis of chiral, optically-pure trifluoromethylated carbinols, such as 3,3,3-trifluoroethylcarbinols.
In specific embodiments, the trifluoromethylating reagent utilized to carry out the process of the subject invention can be selected from the group consisting of: (i) trifluoromethyl iodide (CF
3
I) and tetrakis(dimethylamino)ethylene (TDAE); (ii) HCF
3
/dimethylformamide (DMF) with N(SiMe
3
)
3
/Me
4
NF; (iii) a hemiaminal with a strong base, such as potassium tert-butoxide (tBuOK); and (iv) trifluoromethyltrimethyl silane (CF
3
Si(CH
3
)
3
).
The processes of the present invention allow a unique placement of the trifluoromethyl group relative to the alcohol function, and allows it to be done in a chiral manner.
The present invention also pertains to compounds, such as chiral compounds, produced using the processes of the subject invention. The compounds of the subject invention comprise trifluoromethylated carbinols.
REFERENCES:
patent: 5565689 (1996-10-01), Clavel et al.
A{haeck over (i)}c-Mohand, S. et al. “Nucleophilic Trifluoromethylation Using Trifluoromethyl Iodine. A New and Simple Alternative for the Trifluoromathylation of Aldehydes and Ketones”Organic Letters2001, vol. 3, No. 26, pp. 4271-4273.
Billard, T. et al. “New Stable Reagents for Nucleophilic Trifluoromethylation. 3. Trifluoromethylation of Nonenolizable Carbonyl Compounds with a Stable Piperazino Hemiaminal of Trifluoroacetaldehyde”Eur. J. Org. Chem.2001, pp. 1467-1471.
Burkholder, C.R. et al. “Tetrakis (dimethylamino) ethylene as a Useful Reductant of Some Bromodifluoromethyl Heterocycles. Application to the Synthesis of New gem-Diffuorinated Heteroarylated Comnpounds”J. Org. Chem.1998, vol. 63, pp. 5385-5394.
Burkholder, C.R. et al. “Systhesis and reactivity of halogeno-difluoromethyl aromatics and heterocycles Application to the synthesis of gem-difluorinated bioactive compounds”J. Fluorine Chem.2001, vol. 109, pp. 39-48.
Kitazume, T. et al., “Ultrasound-Promoted Selective Perfluoroalkylation on the Desired Position of Organic Molecules”J. Am. Chem. Soc.1995, vol. 107, pp. 5186-5191.
Krishnamurti, R. et al., “Preparation of Trifluoromethyl and Other Perfluoroalkyl Compounds with (Perfluoralkyl) trimethylsilanes”J. Org. Chem1991, vol. 56, pp. 984-989.
Large, S. et al. “Nucleophilic trifluoromethylation of carbonyl compounds and disulfides with trifluoromethane an silicon-containing bases”J. Org. Chem.2000, vol. 65, pp. 8848-8856.
Pawelke, G., “Tetrakis (dimethylamino) ethylene/trifluoro iodomethane, a Specific Novel Trifluoromethylating Agent”Journal of Fluorine Chemistry1989, vol. 42, No. 3, pp. 429-433.
Pawelke, G.J. “Reaction of Tetrakis (dimethylamino) Ethylene with CF2Br2in the presence of secondary amines, formation of N-Trifluoromethyl-Dialkylamines”Fluorine Chem.1991, vol. 52, p. 229.
Singh, R.P, et al. “Nucleophilic Trifluoromethylation Reactions of Organic Compounds with (Trifluoromethyl)trimethylsilane”Tetrahedron2000, vol. 56, pp. 7613-7632.
Takechi, N. et al. “Novel Nucleophilic Trifluoromethylation of Vicinal Diol Cyclic Sulfates”Organic Letters2002, vol. 4, No. 26, pp. 4671-4672.
Vanhessche, et al. “Catalytic Asymetric Synthesis of Halogenated Chiral Synthons”A European Journal1997, vol. 3, No. 4, pp. 517-522.
Prakash and Yudin, “Perfluoroalkylation with Organosilicon Reagents”Chem. Rev.1997, vol. 97, pp. 757-786.
Dolbier, Jr. William R.
Takechi Naoto
Price Elvis O.
Saliwanchik Lloyd & Saliwanchik
University of Florida Research Foundation
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