Selectfluor fluorinating reagent

Electrophilic fluorinating reagents such as Selectfluor and related compounds can be used for the ring fluorination of phenols. The reaction of phenol with l,3-bis(4-fluoro-l,4-diazoniabicyclo[2.2.2]oct-l-yl)propane tetratriflate in methanol gives moderate yields... 

A major drawback so far for all NF-reagents is their relatively high molecular weight and their low content of active fluorine. For example, for Selectfluor the ratio of active fluorine to the molecular weight is only 5.4%, for NFTh it is 8.0%, and for NFPy 6.0%. This issue was addressed by synthesis of more compact fluorination reagents [191]. One approach towards this goal was to link two or more pyridinium units to a single molecule (4, commercialized as Synfluor). 

Newer approaches make use of derivatives of quinuclidinc alkaloids, such as quinine. The quinine derivative is first converted into the fluorination reagent by Selectfluor, in one-pot procedure, and in a second step reacted with the desired substrate (Scheme 2.93). The enantiomeric excesses achieved with this type of reagent are higher than for the N-fluoroimides but still below those of other enantioselec-tive reactions. 

Scheme 2.93 Enantioselective electrophilic fluorination of silyl enol ethers by N-fluorodihydro-quinine 4-chlorobenzoate. The enantioselective fluorination reagent is generated in situ from F-TEDA-BF4 (Selectfluor) and dihydroquinine 4-chlorobenzoate [206].

Shreeve and coworkers reported a convenient procedure for preparing (difluoroiodo)arenes by direct fluorination of the respective iodoarenes with the commercially available fluorinating reagent Selectfluor in acetonitrile solution. This procedure has been further improved by using the corresponding arene, elemental iodine and Selectfluor in a one-pot oxidative iodination/fluorination procedure [33]. 

Chloromethyl)-4-flnoro-1,4-diazobicyclo[2.2.2]octane tetrafluoroborate (Selectfluor ) can also serve as selective fluorinating reagent. Thus 3-acetamidothiophene 9 was fluorinated in the 2-position exclusively on treatment with Selectfluor, bnt the yield of 11 was 5 % [13]. Fluorination of the isomeric 2-acetamidothiophene 10 gave the 3-fluorinated prodnct 12 in low yield. 

Incorporation of a fluorine at C-3 can be achieved by treatment of a preformed 3H)-indazole with electrophilic fluorinating reagents. In the context of a medicinal chemistry programme, scientists at GSK carried out the fluorination of 4-nitro-6-bromo-(7//)-mdazole (120) with Selectfluor in a mixture of acetonitrile and acetic acid (Scheme 39). Best yields (64 %) were observed when the reaction mixture was submitted to microwave irradiation [65]. The scope of this synthetic transformation is somewhat limited, since the regioselectivity is controlled by the presence of two electron withdrawing groups on the phenyl ring. 

The fluorination of alkenylmetal reagents using electrophilic fluorination reagents such as Selectfluor M [17, 18], Xep2 [19-21], and W-fluoro-W-alkylsulfonamide [22] has been well studied for the stereoselective synthesis of fluoroalkene. 

The use of a C-8 BINOL derivative (142) as a chiral anionic phase-transfer catalyst in a nonpolar solvent allowed the enantioselective fluorination of enamides (139) using Selectfluor (140) as the fluorinating reagent (Scheme 48). The authors demonstrated that a wide range of stable and synthetically versatile a-(fluoro)benzoylimines (141) could be readily accessed with high enantioselectivity (82-99% ee). ... 

G.S. Lai, Site-selective fluorination of organic compounds using 1-alkyl-4-fluoro-1, 4-diazabicyclo[2.2.2]octane salts (selectfluor reagents), J. Org. Chem. 58 (1993) 2791-2796. 

Partially proton-exchanged Na faujasite X, in turn, is the best catalyst for selective monochlorination with tert-butyl hypochlorite.258 NaX, NaY, and NaKL zeolites used in the chlorination of toluene with sulfuryl chloride undergo rapid deactivation because of the accumulation of polychlorinated toluenes in the pores of the catalysts and dealumination.259, 260 Direct electrophilic fluorination of aromatics can be effected by using Selectfluor in the presence of triflic acid.261 Electrophilic fluorination may also be carried out by R2NF and R3N+FA reagents.262 Elemental fluorine may also act as a powerful electrophile in acidic media (sulfuric acid, trifluoroacetic acid, or formic acid), but monosubstituted aromatics give isomeric mixtures.263-265... 

A proposed reaction mechanism for the formation of fluorinated l,3-dihydro-2/7-indol-2-ones is shown in Scheme 72 <20000L639>. Reaction of 3-substituted indole with Selectfluor 310 gave 3-fluoro-37/-indole 312 as an unstable intermediate that underwent loss of HF due to addition of water. A subsequent [l,5]-prototropic shift gave the indol-2-ol 313. Fluorination of intermediate 313 with additional reagent resulted in indol-2-one 311 as the final product. Formation of nonfiuorinated indol-2-one 314 as a minor side product was explained by the tautomerism... 

Substitution reactions that generally display poor atom economy are omitted from this discussion. For example, guanidine-catalysed asymmetric fluorination or trifluoromethylation are important reactions, but fluorination and trifluorination reagents typically have high negative contributions to atom economy e.g. fluorine constitutes just 5.4% of Selectfluor s molecular weight). 

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