From Hexafluoroacetone

At first, hexafluoroacetone is converted into an intermediate (generally, a 1,3-dipole), which then undergoes cycloaddition under the action of binucleophilic reagents. This approach opens up new synthetic possibilities and offers a new methodology for the syntheses of five-membered heterocyclic compounds. 

As described in the following sections, condensations of hexafluoroacetone with various amines frequently give hetero-1,3-dienes as intermediates, used in the syntheses of heterocycles. 

Cyanoformamidines, exhibiting nucleophilic and electrophilic properties in the 1,3-positions, react with hexafluoroacetone forming five-membered heterocycles (86CB2127). This ability to form five-membered heterocycles is the major characteristic of hexafluoroacetone, which is also inherent in some perfluorinated and partially fluorinated ketones, aldehydes, and imines in their reactions with a-functional derivatives of carboxylic acids, as well as w-amino, a-N-alkylamino, 

The first stage of the reaction is a [4+1] cycloaddition of SnCl2 at room temperature, forming hetero-1,3-diene 6 in a quantitative yield. In solution, 

Elimination of Triethyl Phosphate Occurs on Heating or Photolysis 

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The alcohol was obtained from PCR, Incorporated, or was prepared from hexafluoroacetone (E. I. du Pont de Nemours and Company), benzene, and aluminum chloride by the published procedure. 

A7-Acylhexafluoroacetone imines are prepared from hexafluoroacetone and carboxylic amides m the presence of p-toluenesulfonic acid (TsOH) [100] (equation 86)... 

The reaction of tnfluoromethyl-substituted A -acyl umnes toward nucleophiles in many aspects parallels that of the parent polyfluoro ketones Heteronucleophiles and carbon nucleophiles, such as enarmnes [37, 38], enol ethers [38, 39, 40], hydrogen cyanide [34], tnmethylsilylcarbomlnle [2,47], alkynes [42], electron-nch heterocycles [43], 1,3-dicarbonyl compounds [44], organolithium compounds [45, 46, 47, 48], and Gngnard compounds [49,50], readily undergo hydroxyalkylation with hexafluoroace-tone and amidoalkylation with acyl imines denved from hexafluoroacetone... 

Novel fluonnated 2,2-bis(trifluoromethyl)dioxolanes containing alkyne groups [97] have been synthesized from hexafluoroacetone and either 1,4-dibro-mo-2-butene-orpropargylic alcohol [92]. 

An unusual 1,4-migration of a trifluoromethyl group was observed when azomethine imines were synthesized from hexafluoroacetone azine and alkoxy-acetylenes The rearrangement, which occurs at temperatures as low as 0 "C, results in the formation of A-(perfluoro-ferf-butyl)pyrazoles [207] (equation 46)... 

Little l-//-pentafluoropropylene is produced anymore, because its existence IS no longer justified as a less stable alternative to HFP m VDF-based elastomers, given the expiration of patents covenng the basic VDF/HFP/(TFE) compositions Perfluoro-1,1-dimethyl dioxole is prepared from hexafluoroacetone and ethylene oxide in four propnetary steps [5] (equation 4)... 

Horner and Jurgens39 reported that benzoyl peroxides 21 in the presence of sulphides decompose to give sulphoxides and a-acyloxysulphides 22 (equation 8). The latter compounds are undoubtedly formed as a result of the Pummerer reaction. The oxidation reaction leading to sulphoxides has been shown to be an ionic process40. However, till now it has not found wider synthetic applications. Ganem and coworkers41 showed that 2-hydroperoxyhexafluoro-2-propanol 23 formed in situ from hexafluoroacetone and... 

Simple criss-cross cycloadditions described so far are in fact limited to aromatic aldazines and cyclic or fluorinated ketazines. Other examples are rather rare, including the products of intramolecular criss-cross cycloaddition. The criss-cross cycloadditions of hexafluoroacetone azine are probably the best studied reaction of this type. It has been observed that with azomethine imides 291 derived from hexafluoroacetone azine 290 and C(5)-C(7) cycloalkenes < 1975J(P 1)1902, 1979T389>, a rearrangement to 177-3-pyrazolines 292 competes with the criss-cross adduct 293 formation (Scheme 39). 

The 10-57-5-hydridosiliconate ion 62 is known in association with lithium,323 tetrabutylammonium,101 and bis(phosphoranyl)iminium93 cations. It is synthesized by hydride addition to the 8-.S7-4-silane 63, which is derived from hexafluoroacetone.101 Benzaldehyde and related aryl aldehydes are reduced by solutions of 62 in dichloromethane at room temperature101 or in tetrahydrofuran at 0°96 within two hours. The alkyl aldehyde, 1-nonanal, is also reduced by 62 in tetrahydrofuran at O0.96 Good to excellent yields of the respective alcohols are obtained following hydrolytic workup. The reactions are not accelerated by addition of excess lithium chloride,96 but neutral 63 catalyzes the reaction, apparently through complexation of its silicon center with the carbonyl oxygen prior to delivery of hydride from 62.101... 

Research on fluorine-containing condensation polymers is rather limited compared to that on fluorine-containing addition polymers. This fact is attributed to the difficulty in synthesis and the high cost of fluorine-containing condensation monomers. Recently, 2,2-bis(4-hydroxyhpenyl)-1,1,1,3,3,3-hexafluoropropane (Bisphenol AF) with a hexafluoroisopropylidene unit, HOC6H4C(CF3)2-C6H4OH, was produced commercially from hexafluoroacetone and phenol, and now Bisphenol AF and its derivatives are available as condensation monomers. 

The oxidation of sulfides to sulfoxides (1 eq. of oxidant) and sulfones (2 eq. of oxidant) is possible in the absence of a catalyst by employing the perhydrate prepared from hexafluoroacetone or 2-hydroperoxy-l,l,l-trifluoropropan-2-ol as reported by Ganeshpure and Adam (Scheme 99 f°. The reaction is highly chemoselective and sulfoxidation occurs in the presence of double bonds and amine functions, which were not oxidized. With one equivalent of the a-hydroxyhydroperoxide, diphenyl sulfide was selectively transformed to the sulfoxide in quantitative yield and with two equivalents of oxidant the corresponding sulfone was quantitatively obtained. 2-Hydroperoxy-l,l,l-fluoropropan-2-ol as an electrophilic oxidant oxidizes thianthrene-5-oxide almost exclusively to the corresponding cw-disulfoxide, although low conversions were observed (15%) (Scheme 99). Deprotonation of this oxidant with sodium carbonate in methanol leads to a peroxo anion, which is a nucleophilic oxidant and oxidizes thianthrene-5-oxide preferentially to the sulfone. 

Another powerful approach to prepare a-amino acids bearing an aromatic or unsaturated side chain in /I (but also many other compounds) is based on the reactivity of 5-fluoro-4-trifluoromethyloxazole, a starting material easily accessible from hexafluoroacetone. The fluorine atom in the 5 position is easily displaced by an allylic or benzylic alcohol. Then, the obtained ethers spontaneously undergo a Claisen rearrangement to afford, after acidic hydrolysis, an a-trifluoromethyl amino acid... 

Rearrangements arc common in reactions of sulfur tetrafluoride with acetylenic and allylic alcohols. Highly acidic acetylenic alcohols derived from hexafluoroacetone and other haloacetones react readily at ambient temperature to give fluorinated allenes 10 as the sole... 

Other difunctional compounds were prepared mainly from hexafluoroacetone for example ... 

Bis(trifluoromethyl)-4,5-difluoro-l,3-dioxole represents the monomer of a new family of amorphous fluoropoiymers (Teflon AF, DuPont) with unusual properties [89JFC(45)100]. Novel fluorinated 2,2-bis(triflu-oromethyl)dioxolanes containing alkyne groups have been synthesized from hexafluoroacetone and propargylic alcohol, bromomethyloxirane, or 1,2-bis(bromomethyl)oxirane [90MI1 91JFC(52)I59] (Scheme 95). 

Organic peroxides such as cyclohexyl or r-butyl hydroperoxide and benzoyl peroxides can oxidize various sulfides to the corresponding sulfoxides where oxidation with TBHP in alcohols or benzene appears to be synthetically useful. 2-Hydroperoxyhexafluoro-2-propanol [(Cp3)2C(OH)OOH], formed in situ from hexafluoroacetone and H2O2, is also a very effective and convenient reagent for this puipose. 4a-Hydroperoxylumifiavin (14) oxidizes sulfides to sulfoxides in organic solvents such as Bu OH or dioxane at 30 C much more effectively than The reactivi of the flavins was... 

Because of the ready reaction of fluorinated ketones with nucleophiles there is a considerable literature on this subject, although it is dominated by that of hexafluoroacetone. Burger and co-workers have prepared a variety of heterodienes, 8.11A (Figure 8.11), from hexafluoroacetone and developed an extensive chemistry of these derivatives, especially the formation of heterocycles [95, 96]. 

Perfluorinated ketones form stable hydrates, (Rp)2C(OH)2, and these diols are very acidic. Hexafluoroacetone hydrate is known to be a very good solvent and is particularly useful for certain polymers [112, 152]. Perfluoropinacol may be obtained from hexafluoroacetone by photolytic reduction (Figure 8.44), whilst classical reduction with magnesium amalgam gives only low yields [112]. The same pinacol is also obtained by heating 8.44A, which is produced as shown in Figure 8.44 [153]. 

In contrast to the limited chemistry of fluorinated amines, a large number of aza-alkenes and -dienes have been synthesised and these have an extensive chemistry. Some routes to aza-alkenes and -dienes [96] are illustrated in Table 8.5 some were included earlier (Section IB) in the variety of heterodienes that are obtained from hexafluoroacetone. 

In the case of diazirines, both difluorodiaztrine and bis(trifluoromethyl)diazirine have been obtained. Difluorodiazirine was originally prepared by reductive defluorination of bis(difluoroamino)difluoromethane [320, 321], but it can also be obtained by an interesting fluoride-ion-induced rearrangement of difluorocyanamide [322] (Figure 8.125). Bis(trifluoromethyl)diazirine [318, 323] is best obtained by the oxidation of 2,2-diaminohexafluoropropane, prepared from hexafluoroacetone, with sodium hypochlorite (Figure 8.126). 

The cyclic phosphinate (96) has been isolated from the reaction of dichloro(methyl)phosphine with the ethoxycarbonylimine derived from hexafluoroacetone. Treatment of trichloro(organo)phosphonium-hexafluorophosphate salts with dichloro(diethylamino)phosphine results in the halophosphonium salts (97). Some reactions of dichloro(-)menthylphosphine have been reported.As usual, nucleophilic displacement reactions of halogenophosphines have received attention as routes to new systems of interest as ligands.Of particular interest in this connection is a report of the synthesis of the phosphorus-functionalised calixarenes (98). Only one chlorine atom of dichloro(phenyl)-phosphine is replaced on treatment with an excess of dicyclohexylamine, enabling the stepwise synthesis of the chiral aminophosphines (99), described as air-stable solids. 

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