5-Fluoro 5 -sulfoxides

Electron-withdrawing groups decrease the rate of the fluoro Pummerer reaction, which, in certain cases,7 allows a DAST-mediated deoxygenation to compete with the introduction of fluorine alpha to sulfur. The reaction is compatible with a number of functional groups and can readily be carried out with nucleosides. Robins and coworkers4 reported the synthesis of a 5 -fluoro-5 -S-phenyladenosine analog using antimony trichloride as catalyst at room temperature. It should be noted that a-fluoro sulfoxides provide a convenient entry to terminal fluoroalkenes.3 8 9 10... 

The same sequence of diastereoselective reduction of a /i-oxo-y-fluoro sulfoxide followed by Pummerer rearrangement and hydrolysis to the aldehyde has been used successfully in the synthesis of fluorine-containing carbohydrates.10... 

The reaction of a-phenylthio lactones 13 with two equivalents of difluoroiodotoluene results in fluorination-oxidation to give a-fluoro sulfoxides 14, which then undergo thermal syn elimination to produce vinyl fluorides 15 (Scheme 3.6) [25]. 

Treatment of ethyl 10-methylthio-9-fluoro-3-methyl-2,3-dihydro-7-oxo-7//-pyrido[l,2,3- 7e]-l,4-benzoxazine-6-carboxylate with oxone in aqueous MeOH at 0°C afforded 10-methylsulfonyl derivative (99H(51)1563). Methylthio group in a 7-(4-methylthiophenyl)-5-oxo-2,3-dihydro-5//-pyrido[l,2,3- 7e]-l,4-benzoxazine-3-carboxamide was oxidized to a sulfoxide and a sulfone group (OOMIPl). 

A. N-Trijluoroacetanilide. In a two-necked, round-bottomed flask fitted with a thermometer, a Drierite tube, and a magnetic stirring bar are placed 4.56 ml. (4.66 g., 0.050 mole) of aniline [Benzenamine] (Note 1) and 15 ml. of dimethyl sulfoxide (Note 2). The resulting solution is stirred and cooled in an ice water bath, and when the internal temperature has dropped to 10-15°, 21.5 g. (0.10 mole) of 1,1,1-tri-chloro -3,3,3 -trifiuoroacetone [2 -Propanone, 1,1,1 -trichloro-3,3,3-tri-fluoro-] (Note 3) is added in portions through the condenser. A mild exotherm results, and the addition is extended over ca. 5 minutes to... 

The syntheses of perhalogenated dithiethanes and their oxidation products (214-219) have been recently reported247. The method is based on the photochemical dimerization of thiophosgen or its fluoro- and bromo-analogues followed by partial oxidation with trifluoroperacetic acid to the desired sulfoxides (or sulfones)248 as shown in equation 84. 

Alkyl- and 5 -5-aryI-5 -deoxy-5 -fluoro-5 -thioadenosines were prepared by treatment of protected S -S -alkyl- and -aryl-thioadenosine sulfoxides with DAST-SbCl3, followed by deprotection. 

It should be noted that addition of the tributyltin radical to 1-fluoro-1-(phenylsulfonyl)ethene provides phenyl vinyl sulfone as the only isolated product. However, 2-trimethylsilyl-1-fluoro-1-(phenylsulfonyl)ethene reacts with tributyltin hydride in the presence of AIBN to provide (E)-2-trimethylsilyl-1-fluoro-1-tributylvinylstannane. The vinylstannane is an equivalent for the synthon "H2C=CF " providing a convenient route to 2-fluoro-1-alkenes.8 The trimethylsilyl group can be removed with potassium fluoride in dimethyl sulfoxide-water or oxalic acid-methanol at the end of the reaction sequence. 

Fluoro-substituted chiral vinyl sulfoxides such as 103 have been used in 1,3-dipolar cycloadditions with various benzonitrile oxides (Scheme 12.34) (158). The reaction proceeded slowly at room temperature, however, after 5-10 days the isoxazoline (104) was obtained with excellent de in good yield. In some cases, the product tends to eliminate the 5-methoxy substituent of the isoxazoline, thus, after loss of two chiral centers, an isoxazole is obtained (158,159). Other chiral suMnyl derivatives have also been used in 1,3-dipolar cycloadditions with nitrile oxides (160,161), and in one case a racemic vinyl phosphine was used in reactions with various nitrile oxides, but with moderate selectivities (151). 

Fluorine is used for the fluorination of sites x to sulfoxides with simultaneous oxidation of the sulfoxide moiety to a sulfone. The electrophilic fluorine attacks the electron lone pairs of the sulfur atom with a consequent loss of hydrogen fluoride forming an S-fluorosulfoxy alkene. A second molecule of fluorine adds across the newly formed double bond resulting, after hydrolysis, in an a-fluoro sulfone 12.88 This reaction is used for the construction of a fluorocy-clopropane derivative 13 which is essential in the synthesis of one of the most promising members of the quinolinecarboxylic acid antibiotics.89... 

It has been found that F-Teda BF4 (6) transforms chiral and optically pure ft-oxo sulfoxides into the corresponding a-fluoro-substituted compounds 30 without affecting the chiral sulfinyl group.106... 

Fluoro-6-iodopyridazine (6) required for palladium-catalyzed Heck coupling with hydroxy-protected prop-2-yn-l-ol has been prepared by simply heating the 3,6-diiodopyridazine (5) with potassium fluoride in dimethyl sulfoxide at 140°C for 18 hours.121... 

Tetrabutylammonium dihydrogen trifluoride also performs oxidative desulfurization fluorina-tion of 2-substituted l,l,l-txis(methylsulfanyl)ethanes in the presence of DBH leading to a new route to partially fluorinated alkenes. l,l,l-tris(methylsulfanyl)-5-phenylpentane (22) reacts with TBADTF in the presence of DBH to give the fluoro derivative 23, which is converted to the fluoroalkene 25 via the sulfoxide 24 followed by pyrolysis.217... 

In general, the chemistry of fluoro-l,3,5-triazines resembles that of the chloro derivatives, and therefore will not be discussed in detail. There is evidence that cyanuric fluoride is less reactive than cyanuric chloride in reaction with aniline (76CCC3378). Chambers et al. have reported the isolation of a stable anion cr- complex from the reaction of cyanuric fluoride and cesium fluoride (equation 32) (77JCS(Pl)l605). Such species are believed to be intermediates in the formation of (68) from cyanuric fluoride and perfluoropropene (equation 33). Olah et al. have shown that cyanuric fluoride deoxygenates sulfoxides efficiently (equation 34) (80S221). 

Nucleophilic attack of trimethylamine at 1-fluoro-4-nitrobenzene in dimethyl sulfoxide yields the aryltrimethylammonium fluoride, which loses fluoromethanc with formation of the 4-ni-troaniline derivative 10.201 Kinetic measurements have shown that trimethylamine reacts much faster thaii aniline or diisopropylamine. With pyridine, no nucleophilic substitution occurs. 

Chiral Sulfoxides in the Synthesis of Optically Pure Fluoro Substituted Compounds of Biological Interest ... 

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