Reactions reductive fluorination

The fluorination reactions considered so far can be categorized as metathesis, oxidation or substitution, Occasionally reductive fluorination is the preferred route to a lower fluoride. Examples are ... 

In contrast to the cathodic reduction of organic tellurium compounds, few studies on their anodic oxidation have been performed. No paper has reported on the electrolytic reactions of fluorinated tellurides up to date, which is probably due to the difficulty of the preparation of the partially fluorinated tellurides as starting material. Quite recently, Fuchigami et al. have investigated the anodic behavior of 2,2,2-trifluoroethyl and difluoroethyl phenyl tellurides (8 and 9) [54]. The telluride 8 does not undergo an anodic a-substitution, which is totally different to the eases of the corresponding sulfide and selenide. Even in the presence of fluoride ions, the anodic methoxylation does not take place at all. Instead, a selective difluorination occurs at the tellurium atom effectively to provide the hypervalent tellurium derivative in good yield as shown in Scheme 6.12. 

Excellent quality metal, comparable to that from the halide reduction, can be prepared by this technique. A big advantage is that no neutrons are present from (a,ra) reactions on fluorine nuclei, in marked contrast to the case with actinide fluorides. 

Reductive coupling reaction of fluorinated vinyl iodides or bromides has been used as a route to fluorinated dienes [246, 247, 248, 249, 250]. Generally, the vinyl iodide is heated with copper metal in DMSO or DMF no i ntermediate perfluorovinyl-copper reagent is detected. Typical examples are shown in equations 163-165 [246, 247, 249], The X-ray crystal structure of perfluorotetracyclobutacyclooctatetraene, prepared via coupling of tetrafluoro-l,2-dnodocyclobutene with copper, is planar... 

Uranium tnfluonde can be prepared by reduction of UF4 with hydrogen at LOOCFC, Uranium hexafluoride. UFg, white and orthorhombic, is best obtained by direct fluorination of UF4, green and monoclinic, although any uranium compound will yield UFg by reaction with fluorine at elevated temperatures ... 

Fluorinated y -amino alcohols have been prepared in moderate yield, but high de and very high ee, using a proline-catalysed cross-Mannich reaction of fluorinated aldimines with aliphatic aldehydes, followed by NaBH4 reduction.35... 

Attempts at reductive fluorination or iodination of phenothiazine have failed. Reduction of the 5-oxide was the only reaction which took place with either HF or HI. ... 

Alkylations, A stepwise synthesis of amines via I-aminomethylbenzotriazoles involves reductive alkylation with Zn in DME. Stereoselective synthesis of 1,2-amino alcohols is attained by Zn-mediated allylation of a-amino aldehydes. Change of regioselectivity is observed in the reactions of fluorinated prenylzinc species with aldehydes (aliphatic vs. aromatic)."... 

Substituted 2-oxazolidones 165 are useful chiral auxiliaries for diastereoselective functionalization at the a-carbon of their amide carbonyl group. The a-fluoroaldehydes 166 were prepared by a series of reactions electrophilic fluorination of the corresponding oxazolidinone sodium enolates with AMluorobenzenesulfonimine reductive removal of the auxiliary with LiBH4 and Dess-Martin oxidation. The aldehydes are so unstable for isolation that they are converted with (R)-/ -toluenesulfinamide to /7-toluenesul(inimines 167, which are isol-able and satisfactorily enantio-enriched. Chiral sulfinimine-mediated diastereoselective Strecker cyanation with aluminum cyanide provided cyanides 168 in excellent diastereose-lectivity, which were finally derived to 3-fluoroamino acids 169 (see Scheme 9.37) [63]. 

The introduction of a polyfluorinated chain is not so easy as that of an alkyl chain. Transition metal catalyzed cross-coupling of Grignard reagents and organozinc compounds are inefficient in the synthesis of polyfluorinated 3-alkylthiophene. The copper-catalyzed perfluoroalkylation results in the formation of 2-and 3-substituted thiophenes, which are difficult to separate from each other. The reaction of fluorinated alkylmagnesium iodide with 3-formylthiophene, follwed by reduction with lithium aluminum hydride, gave (22) in an overall yield of 40% [27]. 

Through a similar reaction sequence, fluorinated tryptophan 187 was synthesized. Condensation of aldehyde 175 with A-benzoyl glycine afforded oxazolone 184, which was converted into unsaturated acid 185. Reduction of 185 by hydrogen and subsequent acid-catalyzed hydrolysis gave fluorinated tryptophan 187 in good total yield [54]. 

Aldehyde purity can be of critical importance some of the reactions of fluorinated aldehydes are adversely affected by the presence of small amounts of precursor acid chloride or aldehyde hydrate. For example, some of the catalysts used for polymerization (vide infraf are effectively deactivated by small amounts (0.1-0.5%) of aldehyde hydrate. We have not examined medium effects in the silane/acid chloride reaction, but the high reactivity of the fluorinated aldehydes can lead to unexpected results. For example, fluorinated aldehydes and acid chlorides condense rapidly in THF to afford esters of the form RfC(0)0CHCIR f. In contrast, this reaction is very slow in CHCI3. Fortunately, esters of this type are usually not significant products under our preferred reduction conditions. The aldehydes described here are quite reactive and can undergo spontaneous... 

Beyer synthesis, 2, 474 electrolytic oxidation, 2, 325 7r-electron density calculations, 2, 316 1-electron reduction, 2, 282, 283 electrophilic halogenation, 2, 49 electrophilic substitution, 2, 49 Emmert reaction, 2, 276 food preservative, 1,411 free radical acylation, 2, 298 free radical alkylation, 2, 45, 295 free radical amidation, 2, 299 free radical arylation, 2, 295 Friedel-Crafts reactions, 2, 208 Friedlander synthesis, 2, 70, 443 fluorination, 2, 199 halogenation, 2, 40 hydrogenation, 2, 45, 284-285, 327 hydrogen-deuterium exchange, 2, 196, 286 hydroxylation, 2, 325 iodination, 2, 202, 320 ionization constants, 2, 172 IR spectra, 2, 18 lithiation, 2, 267... 

These reactions differ from those of sulfur tetrafluoride with carbonyl compounds in that a formal oxidation-reduction of the sulfur atoms m the thiocarbonyl compound and sulfur tetrafluoride molecule occurs, resulting in the formation of free sulfur and the complete utilization of the fluorine atoms in sulfur tetrafluoride. 

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