Organic compounds -- part of the class 532-570 series – Organic compounds – Silicon containing
Reexamination Certificate
2002-11-27
2004-10-12
Barts, Samuel (Department: 1621)
Organic compounds -- part of the class 532-570 series
Organic compounds
Silicon containing
C556S476000, C556S488000
Reexamination Certificate
active
06803477
ABSTRACT:
TECHNICAL FIELD
This invention relates to a process of preparation of fluorinated alkyl silanes such as trifluoromethyl- and difluoromethylsilanes, as well as to the reactants used in this process. The invention more particularly relates to a technique for tri- and difluoromethylation typically carried out with tri- and difluoromethyl organosulfur compounds and a reducing metal such as magnesium.
BACKGROUND ART
The introduction of the trifluoromethyl (CF
3
) and the difluoromethyl (CF
2
H) groups into organic molecules has gained increasing attention due to the potential use of trifluoromethylated and difluoromethylated compounds in materials science, medicinal and agrochemistry. Although there are few approaches to achieve this goal, the fluoride induced trifluoromethylation or difluoromethylation with organosilicon reagents (R
f
SiR
3
, R
f
=CF
3
, CF
2
H) has been considered a straightforward and reliable method. (Trifluoromethyl)trimethylsilane (TMS-CF
3
), first developed by Prakash, G. K. S.; Krishnamuti, R.; Olah, G. A. in 1989 (
J. Am. Chem. Soc.
1989, 111, 393), as a nucleophilic trifluoromethylating reagent of choice under mild conditions, is widely used and also works with enolizable carbonyl compounds. Although several other types of nucleophilic trifluoromethylation methods have been appeared in literature thereafter, such as (1) direct introduction of trifluoromethyl group by electroreduction of bromotrifluoromethane into carbonyl-containing molecules: Sibille, S.; Mcharek, S.; Perichon, J.
Tetrahedron
1989, 45, 1423; (2) using CF
3
I as a trifluoromethylating reagent: Ait-Mohand, S.; Takechi, N.; Medebielle, M.; Dolbier, W. Jr.
Org. Lett.
2001, 3, 4271; (3) using trifluoromethylacetophenone-N,N-dimethyltrimethylsilylamine adduct as a trifluoromethylating agent: Motherwell, W. B.; Storey, L.
Synlett
2002, 646; (4) using trifluoromethane as a trifluoromethylating precursor: (a) Shono, T.; Ishifume, M.; Okada, T.; Kashimura, S.
J. Org. Chem.
1991, 56, 2. (b) Barhdadi, R.; Troupel, M.; Perichon,
J. Chem. Comm.
1998, 1251. (c) Folleas, B.; Marek, I.; Normant, J.-F.; Saint-Jalmes, L.
Tetrahedron Lett.
1998, 39, 2973. (d) Folleas, B.; Marek, I.; Normant, J.-F.; Saint-Jalmes, L.
Tetrahedron
2000, 56, 275. (e) Russell, J.; Roques, N.
Tetrahedron
1998, 54, 13771. (f) Large, S.; Roques, N.; Langlois, B. R.
J. Org. Chem.
2000, 65, 8848. (g) Roques, N.; Russell, J.; Langlois, B.; Saint-Jalmes, L.; Large, S
PCT Int. Appl.
1998, WO 9822435. (h) Roques, N.; Mispelaere,
Tetrahedron Lett.
1999, 6411; (5) using CF
3
−
/N-formylmorpholine adduct as a trifluoromethylating agent: Billard, T. B.; Langlois, B. R.
Org. Lett.
2000, 2, 2101; (6) using piperazino hemiaminal of trifluoroacetaldehyde as a trifluoromethylating agent: (a) Billard, T.; Langlois, B. R.; Blond, G.
Eur. J. Org. Chem.
2001, 1467. (b) Billard, T.; Langlois, B. R.
J. Org. Chem.
2002, 67, 997. However, all these recently developed methods are inefficient in the case of enolizable systems.
TMS-CF
3
was first prepared by Ruppert et al. and published in
Tetrahedron Lett.
1984, 25, 2195. Since then several other procedures have been developed via both chemical and electrochemical methods during last two decades: (a) In 1989 Pawelke reported a preparative route to TMS-CF
3
using chlorotrimethylsilane (TMSCl), trifluoromethyl iodide and tetrakis(dimethylamino)ethylene: Pawelke, G.
J. Fluorine Chem.
1989, 42, 429. (b) In 1991 Prakash et al. published a modified Ruppert procedure to prepare TMS-CF
3
: Krishnamurti, R.; Bellew D. R.; Prakash G. K. S.
J. Org. Chem.
1991, 56, 984; Ramaiah, P.; Krishnamurti, R.; Prakash, G. K. S.
Org. Syn.
1995, 72, 232. (c) In 1994 Prakash et al. developed a new and efficient electrochemical trimethylsilylation of bromotrifluoromethane to produce TMS-CF
3
: Prakash, G. K. S.; Deffieux, D.; Yudin, A. K.; Olah, G. A.
Synlett
1994, 1057. (d) In 1994 Nedelec et al. reported an electrochemical reduction of CF
3
Br in N,N-dimethylformamide (DMF) in the presence of TMSCl and a sacrificial aluminum anode to produce TMS-CF
3
: Aymard, F.; Nedelec, J.-Y.; Perichon, J.
Tetrahedron Lett.
1994, 35, 8623. (e) In 1995, Grobe and Hegge reported trifluoromethylation of TMSCl with bromotrifluoromethane and aluminum metal in N-methylpyrrolidinone (NMP) to produce TMS-CF
3
: Grobe, J.; Hegge, J.
Synlett
1995, 641.
However, all of these methods have some drawbacks. First of all they all use bromotrifluoromethane (CF
3
Br) or iodotrifluoromethane (CF
3
I) as a source for the trifluoromethyl group. Trifluoromethyl halides, particularly CF
3
Br, in general are ozone depleting and recently their manufacture and use are regulated. Second, these procedures need special apparatus and well-controlled reaction conditions, and the product yields vary widely. Finally, none of the reported methods are amenable for the preparation of structurally diverse trifluoromethylsilanes. Compared with the trifluoromethylation, little is known on the nucleophilic difluoromethylation: Hagiwara, T.; Fuchikami, T.
Synlett
1995, 717. This is mainly due to the lack of general and efficient methods for the preparation of difluoromethylsilanes. There is an evident need for a new general, economic and efficient method for the preparation of structurally diverse trifluoromethyl- and difluoromethylsilanes.
Magnesium metal promoted reactions through electron transfer process have attracted increasing interest recently, such as C-F bond cleavage of trifluoromethyl ketones, trifluoroacetates, trifluoromethylimines, p-bis(trifluoromethyl)benzene and difluoromethyl ketones, O-silylation of tertiary alcohols, cross coupling of carbonyl compounds with TMSCl, and C-acylation of aromatic &agr;, &bgr;-unsaturated carbonyl compounds. (a) Uneyama, K.; Amii H.
J. Fluorine Chem.
2002, 114, 127. (b) Prakash, G. K. S.; Hu, J.; Olah, G. A.
J. Fluorine Chem.
2001, 112, 357-362. (c) Nishigachi, I.; Kita, Y.; Watanabe, M.; Ishino, Y.; Ohno, T.; Maekawa, H.
Synlett
2000, 1025. (d) Ishino, Y.; Maekawa, H.; Takenchi, H.; Sukata, K.; Nishiguchi, I.
Chem. Lett.
1995, 829. (e) Ohno, T.; Sakai, M.; Ishino, Y.; Shibata, T.; Maekawa, H.; Nishiguchi, I.
Org. Lett.
2001, 3, 3439. However, the magnesium metal mediated reductions of trifluoromethyl and difluoromethyl sulfones or sulfoxides are still not explored.
In the trifluoromethyl and difluoromethyl sulfones or sulfoxides, due to the strong electron withdrawing effect of CF
3
and CF
2
H groups, the bond between the pseudohalide and the sulfur atom is sufficiently polarized with the pseudohalide group bearing substantial negative charge. Thus, when the electrons are transferred from magnesium metal to the sulfones and sulfoxides, reductive cleavage of the C—S bond to generate anionic CF
3
−
or CF
2
H
−
species was anticipated over the C—F bond fission. These reactions are shown in
FIG. 1
as schemes I and II.
Moreover, phenyl trifluoromethyl sulfone (1) or phenyl trifluoromethyl sulfoxide (2) can also be conveniently prepared from environmentally benign precursors by the schemes illustrated in FIG.
2
. Precursors such as trifluoromethane (CF
3
H) or trifluoroacetate (see
FIG. 2
, scheme I), while difluoromethyl phenyl sulfone (4) can be obtained using known methods (see
FIG. 2
, scheme II). (a) Roques, N.; Russell, J.; Langlois B.; Saint-Jalmes, L.; Large S. U.S. Pat. No. 6,203,721 B1 (2001); PCT application: WO98/22435 (1998). (b) Gerard, F.; Jean-Mannel, M.; Laurent, S.-J. Eur. Pat. Appl. 1996, EP 733614. (c) Hine, J.; Porter, J.
J. Am. Chem. Soc.
1960, 82, 6178.
With these considerations in mind, a magnesium mediated reductive fluoroalkylation of chlorosilanes has been developed, thus providing a long sought after yet simple and efficient method for preparing various fluorinated alkyl silanes.
SUMMARY OF THE INVENTION
Accordingly, this invention provides a method for preparing fluorinated alkyl silanes by reacting a fluorinated alkyl sulfur containing compound, such as a fluorinated alkyl sulfone, a fluorinated alkyl sulfoxide or a fl
Hu Jinbo
Olah George A.
Prakash G. K. Surya
Barts Samuel
University of Southern California
Winston & Strawn LLP
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