1,1-Difluorides ketones

A mixture of an acid anhydride and a ketone is saturated with boron trifluoride this is followed by treatment with aqueous sodium acetate. The quantity of boron trifluoride absorbed usually amounts to 100 mol per cent, (based on total mola of ketone and anhydride). Catalytic amounts of the reagent do not give satisfactory results. This is in line with the observation that the p diketone is produced in the reaction mixture as the boron difluoride complex, some of which have been isolated. A reasonable mechanism of the reaction postulates the conversion of the anhydride into a carbonium ion, such as (I) the ketone into an enol type of complex, such as (II) followed by condensation of (I) and (II) to yield the boron difluoride complex of the p diketone (III) ... 

The preparation of e/n-difluoro compounds by the oxidative fluorodesul-furization ot 1,3-dithiolanes readily proceeds by treatment with a pyridinium polyhydrogen fluoride-Af-halo compound reagent the latter serves as a bromonium ion source [2], l,3-Dibromo-5,5-dimethylhydantoin is the most effective of several At-halo oxidants. It is believed that /V-halo compounds combine with hydrogen fluoride to generate in situ halogen fluorides, the oxidants. Formation of gem-difluorides from dithiolanes derived from ketones is efficient and rapid, even at -78 °C, whereas the reaction of dithiolanes derived from aldehydes requires higher temperature (0 °C) (equation 4). 

Recently, the pyrazole group containing bisphenols have been synthesized from activated aromatic dihalides and 3,5-bis (4-hydroxy phenyl)-4-phenyl pyrazole or 3,5-bis(4-hydroxy phenyl)-1,4-diphenyl pyrazole. A novel synthesis of imido aryl containing bisphenols has been reported [32]. N-substituted l,4-bis(4-hydroxy phenyl)-2,3-naphthalimides were prepared from phenolphthalein and copolymerized with aromatic sulfone or ketone difluorides to obtain the poly(imidoaryl ether) sulfones/ ketones. 

The nucleophilic aromatic substitution reaction for the synthesis of poly(arylene ether ketone)s is similar to that of polysulfone, involving aromatic dihalides and aromatic diphenolates. Since carbonyl is a weaker electron-withdrawing group titan sulfonyl, in most cases, difluorides need to be used to afford high-molecular-weight polymers. Typically potassium carbonate is used as a base to avoid the... 

Dialkylaminosulfur trifluorides are widely used as a safe substitute for SF4 in the replacement of oxygen by fluorine in many types of organic compounds, for example, converting alcohols to fluorides, or aldehydes and ketones to gem-difluorides. The most familiar of these reagents is DAST, while an increasingly popular one (considered safer to use than DAST) is bis(2-methoxyethyl)aminosulfur trifluoride (Deoxo-Fluor Reagent) (Scheme 7.15). 

Alkylated (R,RHetrahydroindcnyItitanium difluoride and phenylsilane serve to asymmetrically reduce a variety of ketones, especially aryl alkyl ketones, in excellent chemical yields and >96% ee.587 The use of the easier to handle and less expensive PMHS is also highly effective in these transformations. In a related study using the (W, W)-tctrahydroindcny I titanium l,T-binaphth-2,2/-diolate precursor to the active catalyst, similarly impressive results are obtained.588... 

Carbanions, generated by the reaction of benzylsilanes with tetra-n-butylammo-nium fluoride react with non-enolizable aldehydes to produce the alcohol [67], When a stoichiometric amount of the ammonium fluoride is used, the methylarene corresponding to the benzylsilane is frequently a by-product and arises from formation of the hydrogen difluoride salt during the reaction. When only catalytic amounts of the ammonium fluoride initiate the reaction, the formation of the methylarene is suppressed. In a similar type of reaction (although the mechanism is not known) between aldehydes and ketones, allyl bromide, and tin in the presence of trimethylsilyl chloride the yield of the but-l-en-4-ol is raised significantly by the addition of tetra-n-butylammonium bromide, particularly in the reactions with... 

Vinyltrimethylstannanes react with xenon difluoride in dichloromethane at room temperature in the presence of equimolar (or a 50 Vo excess) of silver trifluoromethanesulfonate and a catalytical (0.1 equiv) quantity of 2,6-di-/e/7-butyl-4-methylpyridine to form the corresponding vinyl fluorides in high to moderate yields.54 57 The substitution reaction is tolerant to various functional groups, such as ketones, esters, carbamates, ketals, ethers, phenol rings and tertiary alcohols. As byproducts corresponding alkenes have been detected due to pro-tiodestannylation. 

The stoichiometric equivalents of halofluorides have been recently applied to transform alkylene dithioacetals into gcm-difluorides.70-71 Dithioacetals such as 1,3-dithiolanes and 1,3-dithianes arc readily obtained from the corresponding carbonyl compounds by the reaction with ethane-1,2-dithiol or propane-1,3-dithiol in the presence of the complexes boron trifluoride-bis(acetic acid) or boron trifluoride-diethyl ether. Using a two-step procedure, a range of aldehydes and ketones can be converted into gem-difluorides under mild conditions. 

Ethylene dithioacetals of benzophenone and its 4-fluoro-, 4-bromo-, 4,4 -difluoro-, 4,4 -dichlo-ro-, and 3,5-dimethyl-substituted analogs react with sulfuryl chloride or sttlfuryl chloride fluoride in hydrogen fluoride/ pyridine at — 78 C to room temperature to give the corresponding geminal difluorides in 85-90% yield. The reaction is, however, not applicable to dialkyl or alkyl aryl ketones as they undergo chlorination under these conditions.73... 

When acetylenes react with oxygen difluoride at low temperature, a,a-difluoro ketones 20 and 21 are formed with a regioselectivity which is dependent on the structure of the acetylene.22... 

Carbonyl difluoride (2) has been used to convert the carbonyl group in ketones, aldehydes and amides to the corresponding difluoromethylene group. 

However, hexafluoroacetone is broken down almost completely87 over potassium tetrafluoro-cobaltate(III) at 250°C only traces of trifluoroacetyl fluoride are detected, the rest being carbon tetrafluoride and carbonyl difluoride. This shows that even if perfluoro ketones are formed in fluorination processes, they will break down, thus demonstrating that transition metal fluoride fluorination will not produce polyfluoro ketones. 

Dehydrocortisone, 87 8-Dehydroestradiol, 4 9(ll)-dehydroestradioI 3-methyl ether, 2 8(14)-DehydroestradioI 3-methyl ether, 3 Dehydrofluorination, 452 Dehydrofluorination of gem-difluorides, 446 Dehydrogenation, 306 Dehydrohalogenation of a-Halo ketones, 287 16-Dehydropregnenolone, 40 16-Dehydropregnenolone acetate, 48 16-Dehydropregnenolone tetrahydropyranyl ether, 40... 

The substitution of geminal difluoride groups with hydroxylamines or hydrazines leads to the corresponding oximes31 or hydrazones.3,32 Diamines, amino alcohols or amino thiols give rise to N,N, N,0- or /V.A-acetals, respectively.33 Yields are especially good when perfluoro-O-silyl enol ethers (e.g., 5) are used instead of the corresponding ketones.2,33... 

Tbngsten hexafluoride reacts in the presence of boron trifluoride with aliphatic aldehydes and ketones to form the corresponding difluorides albeit in low yields [202],... 

The acylating reagent may be an acid chloride or an acid anhydride. Symmetrical ketones (—CH2 R = R2) yield only a single regioisomer. Thus acetone or cyclohexanone may be acylated with acetic anhydride in the presence of boron trifluoride-etherate to pentane-2,4-dione and 2-acetylcyclohexanone respectively (Expt 5.102). Both diketones are present in the reaction mixture as boron difluoride complexes [(10) and (11) respectively], from which they may be released by treatment with sodium acetate. Pentane-2,4-dione is appreciably water soluble and is isolated by means of its characteristic copper complex (12). 

Trimethylsilyl ethers of several steroidal ketones were a-fluorinated by 4-(difluoroiodo)toluene, in moderate yield because of concomitant elimination, accompanied by the formation of other by-products from nucleophilic substitution to a phenyliodonium intermediate. The analogous reaction with xenon difluoride resulted in much better yields but different stereochemistry [50],... 

The saturated carbon atom can be functionalized by xenon difluoride in various ketones and diketones where, beside a-mono and a-difluoro ketones, the formation of rearranged products can also be observed however, the course of reaction depends strongly on the catalyst used22-24 (Scheme 5). 

Reaction of the r-butyldimethylsilyl enol ether of a protected dipeptide with xenon difluoride in a mixture of acetonitrile and 1,1,2-trichlorotrifluoroethane gave the fluoro ketone in 71 % yield as a 1 1 mixture of diasteroisomers, while further transformation to enol ether and fluorination affords the difluoro ketone81 (Scheme 23). 

Decarboxylative fluorination, presumably via intermediate acyl hypofluorites, has been achieved in low yield by passing a dilute stream of fluorine in nitrogen into aqueous solutions of sodium carboxy-lates. A somewhat more promising method, tolerant of aryl groups, ketones and ethers, involves reaction of a dichloromethane solution of the acid with xenon difluoride and hydrogen fluoride (equation 23). 7... 

X0 esters in the 2-position, but is not sufficiently reactive to fluorinate ketones. jl-Oxo esters are selectively fluorinated at the a-position by iodotoluene difluoride and a hydrogen fluoride pyridine complex. " ... 

The gaseous carbonyl difiuoridc (bp — 83 C) is used as a fluorinating agent for aldehydes and ketones. In a first reaction step, isolable fluoroformatcs are formed which are converted into the ew-difluorides 1 by loss of carbon dioxide. a-Dicarbonyl compounds yield cyclic 1,2-di-fluoroethene carbonates. ... 

Both hydrazones formed from ketones (Table 3, entries 1-6) and aldehydes (entry 7) react with bromine monofluoride, although the latter yield is low (28 %). Adamantanone azine (entry 8) reacts with bromine monofluoride afl ording the corresponding em-difluoride in high yield (77%). 

Acetylenes 1 react smoothly with oxygen difluoride to produce a,a-difluoro ketones 2. " The intermediates of this addition are a-fluorovinyl hypofluorites, which rearrange with a fluorine shift to the observed difluoro ketones. In all cases small amounts of acyl fluorides are formed as byproducts. 

---