Reagents for electrophilic

Scheme 4.3. Sulfur and Selenium Reagents for Electrophilic Addition Reactions...

Hydroxylation of arenes.1 Sodium perborate in combination with trifluoro-methanesulfonic acid is an attractive reagent for electrophilic oxidation of arenes to phenols. 

Fig. 1. Achiral neutral N-fluoro reagents for electrophilic fluorination.

These data imply that dioxane and acetonitrile suppress the electrophilic character of the reagent. The simplest interpretation of these results is that methyl metaphosphate itself is the reagent for electrophilic substitution, but since it will react readily with any unshared pair of electrons, it is deactivated by dioxane or acetonitrile to produce Compounds IV and V shown below. Since S03 reacts with dioxane to form a crystalline adduct, VI, a parallel reaction of metaphosphate appears reasonable. 

An equally serious problem is that the nitrogen lone pair is basic and a reasonably good nucleophile—this is the basis for its role as a nucleophilic catalyst in acylations. The normal reagents for electrophilic substitution reactions, such as nitration, are acidic. Treatment of pyridine with the usual mixture of HN03 and H2SO4 merely protonates the nitrogen atom. Pyridine itself is not very reactive towards electrophiles the pyridinium ion is totally unreactive. 

In a similar manner, easy-to-handle solvents/reagents for electrophilic iodochlorination and iodobromination have been demonstrated.[11]... 

In recent years a second generation of reagents for electrophilic fluori-nation has been developed. These reagents contain N—F bonds. They are more stable, easier to handle, and often more selective. These reagents could be useful in the synthesis of bioactive molecules where selectivity and mild reaction conditions are essential. 

Finally, two other reagents for electrophilic animations should be mentioned, a ni-trenoid25 and an oxaziridine7, which, so far, however, have not been used in stereoselective reactions of this type. 

Differding, E. and Ofner, H. (1991) N-Fluorobenzenesulfonimide a practical reagent for electrophilic fluorinations. Synlett, 7-189. 

As noted above (Sect. 2.2), Lewis acids are useful reagents for electrophilic activation of C-F bonds and have a long and continuing fascinating history in or-ganometallic chemistry. Continuing this trend, Green and coworkers [55] have discovered an unusual C-F bond activation reaction of tris(pentafluorophe-nyl)boron with transition metal alkyls as illustrated below. 

Acetyl hypofluorite (CH3CO2F) > has been used to fluorinate tetraisopropyl methylenediphosphonate in two steps. In the first step, the sodium salt of tetraisopropyl methylenediphosphonate is added to a solution of AcOF in CFCI3 at -78°C. After 5 min, the reaction is quenched, and tetraisopropyl fluoromethylenediphosphonate is isolated in 66% yield. This compound is metallated with NaH and submitted to a second electrophilic fluorination as above to obtain tetraisopropyl difluoromethylenediphosphonate in 40% yield. Even if acetyl hypofluorite seems to be a more selective reagent for electrophilic monofluorination than FCIO3, its relative instability and the special equipment required to manipulate moleculai fluorine greatly limit its use. 

The number of methods for the formation of carbon-nitrogen bonds500-505 is too large to permit a meaningful comparison. A few other methods were mentioned where appropriate in Scope and Limitations. The following is a brief discussion of the reagents for electrophilic animation that were excluded from the scope of this chapter. 

A mixture of trifluoroperoxyacetic acid and boron trifluoride has proved an excellent reagent for electrophilic hydroxylation of aromatic compounds e.g., its use leads to an 88% yield of mesitol from mesitylene below 70.311... 

Combination of CF3S03H with Me3SiN3 was used as a reagent for electrophilic amination of alkylbenzenes and halobenzenes45 (equation 22). 

O-Mesitylenesulfonyl)hydroxylamine (X) is used as a reagent for electrophilic NH2 transfer to the pyridine-like N of azoles and azines (cf p 273). The resulting N-aminated systems can be subjected to acylation, deprotonation (to give dipolar N-imides) and other transformations [76]. The following sequence of reactions may serve as an example ... 

Togni and coworkers have found that 1-trifluoromethylbenziodoxole 770 is a useful reagent for electrophilic trifluoromethylation of nucleophilic substrates. This reagent, in particular, reacts with (3-ketoesters 769 under mild conditions in the presence of potassium carbonate to give a-trifluoromethylated product 771 in good yield (Scheme 3.303) [1026, 1027]. Likewise, this mild electrophilic trifluoromethylating... 

As onium ions they can serve as excellent reagents for electrophilic substitution on the aromatic ring via the transition state shown. 

Ar-bromosucclnlmlde (NBS) A crystalline solid, C402NBr, used extensively as a reagent for electrophilic addition of bromine. It acts by producing a small constant supply of bromine in solution C402NBr + H+ + Br - C4O2NH + Bt2. 

Thallation of thiophens in the 2-position with thallium(m) trifluoro-acetate in trifluoroacetic acid is complete within a few minutes at room temperature. The thallium derivative reacts in situ with aqueous potassium iodide solution to give a convenient and high-yield synthesis of iodo-thiophens. A mixture of thallium(m) acetate has been shown to be a mild and efficient reagent for electrophilic aromatic bromination. Thiophen yields 2-bromothiophen in 82% yield and very little dibromothiophen. 3-Methylthiophen appears to be selectively brominated in the 2-position and 2-methylthiophen in the 5-position in 70—75% yield. The direct thiocyanation of thiophen and some alkylthiophens with thiocyanogen under various conditions using a variety of Friedel-Crafts catalysts has... 

Handling, Storage, and Precautions reagents for electrophilic aminations with f (f tdimethyl(dialkyl) functionality like (1) are much more stable than their NH2 analogs. Thus the pure compound (1) can be stored at —30°C for at least 1 year. Impure (1) (and related compounds), however, may decompose at rt, as also reported for fV,yV-diethyl-0-(mesitylsulfonyl)hydroxylamine. ... 

Eisenherger P (2007) The developmoit of new hyptavalent iodine reagents for electrophilic trifluoromethylation. Dissertation ETH no. 17371, ETH Zurich. doi 10.3929/ethz-a-005507897... 

Matousek V, Pietrasiak E, Schwenk R, Togni A (2013) One-pot synthesis of hypervalent iodine reagents for electrophilic tiifluonnnethylation. J Org Chem 78 6763-6768. doi 10. 

Niedermann K, Welch JM, Roller R, Cvengros J, Santschi N, Battaglia P, Togni A (2010) New hypervalent iodine reagents for electrophilic trifluoromethylation and their precursors synthesis, structure, and reactivity. Tetrahedron 66 5753-5761. doi 10.1016/j.tet.2010.04.125... 

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