Carbon nucleophiles perfluoroalkylation

Perfluoroalkylation of carbon nucleophiles using perfluoroalkyl phenyliodonium... 

The reactivities of the substrate and the nucleophilic reagent change vyhen fluorine atoms are introduced into their structures This perturbation becomes more impor tant when the number of atoms of this element increases A striking example is the reactivity of alkyl halides S l and mechanisms operate when few fluorine atoms are incorporated in the aliphatic chain, but perfluoroalkyl halides are usually resistant to these classical processes However, formal substitution at carbon can arise from other mecharasms For example nucleophilic attack at chlorine, bromine, or iodine (halogenophilic reaction, occurring either by a direct electron-pair transfer or by two successive one-electron transfers) gives carbanions These intermediates can then decompose to carbenes or olefins, which react further (see equations 15 and 47) Single-electron transfer (SET) from the nucleophile to the halide can produce intermediate radicals that react by an SrnI process (see equation 57) When these chain mechanisms can occur, they allow reactions that were previously unknown Perfluoroalkylation, which used to be very rare, can now be accomplished by new methods (see for example equations 48-56, 65-70, 79, 107-108, 110, 113-135, 138-141, and 145-146)... 

Oxiranes with a single perfluoroalkyl chain are regioselectively opened by nucleophilic reagents at the more accessible carbon [d4] (equation 30). 

Our early work examined the reaction of PCTFE with sulfur, selenium and phosphorous nucleophiles 9 to achieve high levels of functionalization through a well-precedented (in the case of perfluoroalkyl iodides)20"24 one electron transfer, radical anion chain process. While such a reaction demonstrated the feasibility of using one-electron processes for the functionalization of PCTFE, the carbon-sulfur linkage remained susceptable to oxidation. 

Apart from the above two major general reaction pathways, there are some further possibilities for instance, [bis(trifluoroacetoxy)iodo]benzene reacts as an ambident electrophile and is attacked by hard nucleophiles at its carbonyl carbon, whereas iodylarenes may react similarly from carbon rather than iodine. Alkynyl iodonium salts are actually tetraphilic electrophiles, whereas iodosylbenzene reacts also as a nucleophile from oxygen. Diaryl iodonium salts serve as arylating reagents, mostly homolytically other iodonium salts transfer groups such as perfluoroalkyl, vinyl, alkynyl or cyano to several nucleophiles in various ways. 

Thus the synthesis of heterocyclic compounds with one or more heteroatoms along with perfluoroalkyl groups is possible if the fluorinated molecule has a multiple bond and if an anionic center may be generated at the heteroatom or carbon atom of the functional group in intramolecular nucleophilic cyclization reactions. These new approaches point to the specific effect of fluorine atoms and to the important role of the electronic effects in... 

Another variation of the classic Darzens reaction is a one-pot synthesis of dietliyl 1-perfluoro-alkyl-1,2-epoxyalkylphosphonates using the nucleophilic attack of lithium diethyl phosphite on the carbonyl carbon of perfluorinated P-oxophosphonium salts (Scheme 4.8). The resulting intermediate can eliminate in two directions. When the oxygen anion in the least sterically hindered position (R = R = Me) attacks the neighboring carbon atom, diethyl 1-perfluoroalkyl-1,2-epoxyalkylphosphonates aie obtained in moderate yields (42-51%) after elimination of PhjP (anti fashion). The formation of a-(perfluoroalkyl)vinylphosphonates by attack at phosphorus (syn fashion) can be a competing reaction. The results indicate that the selectivity can be controlled to produce exclusively either epoxyphosphonates or vinylphosphonates. ... 

The silver-carbon bond in compounds containing a perfluoroalkyl group is considerably more stable than in non-fluorinated compounds. The synthesis can be accomplished by the nucleophilic addition of silver fluoride to fluoro-olefines. A typical example of this reaction is given in equation 9. The complexes are soluble in organic solvents and have been isolated as the 1 1 complexes with acetonitrile [RAg(CH3CN)]23. 

We generally think of electrophilic and nucleophilic additions as being heterolytic processes, but there can be electrophilic and nucleophilic character to radical additions also. Alkyl or aryl substituents on a carbonmethyl radical, while electron-withdrawing substituents make it more electrophilic. For a discussion, see Zipse, H. He, J. Houk, K. N. Giese, B. /. Am. Chem. Soc. 1991,113,4324. Perfluoroalkyl radicals are strongly electrophilic see, for example, Avila, D. V. Ingold, K. U. Lusztyk, J. Dolbier, W. R. Pan, H.-Q. /. Am. Chem. Soc. 1993,115,1577. 

Aldehydes, ketones and esters of general formula 708 reacted with amidines to give pyrimidine derivatives (Table 40, Entries 1-4). Analogous methods were developed for (per)fluorinated vinyl halides 709 (Entry 5) and 710 (Entries 6, 7). Analogous reaction was successful with enol phosphate 814, obtained from ketone 813 and sodium diethyl phosphite (Scheme 162) [120], In aU these cases, nucleophilic substitution of two fluorine atoms at a-carbon of the perfluoroalkyl group occurred. 

NBS and then pyridine, undergo dehydrobromination to 2//-l,4-oxazin-2-ones (331). Hexafluoro-1,2-epoxypropane (332) is highly susceptible to nucleophilic attack at the /3-carbon centre, and this property has been utilized for the synthesis of a variety of perfluoroalkylated heterocycles. Representative examples are given in Scheme 78. 

The reaction produces a mixture of teloniers differing in the length of their carbon chain. The perfluoroalkyl iodides do not react with nucleophiles (e.g., OH , NH3) and cannot be converted directly to common intermediates of fluorocarbon repellents. Therefore, the perfluoroalkyl iodides are reacted with ethylene ... 

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