Arylation sulfone electrophiles

In principle, sulfonyl compounds bearing highly-electron-accepting substituents are able to transfer the sulfonyl group as an electrophile. Thus, the exchange of aryl substituents in methyl aryl sulfones under catalysis of trifluoromethanesulfonic acid takes place258 (equation 46). This reaction represents a further example for the reversibility of Friedel-Crafts reactions. 

The facility of arene reductive elimination underpins numerous C-C, C-O and C-N bond-forming reactions, which may be catalysed by late transition metals, in particular palladium (Figure 4.10). Although there are many variants, the general reaction scheme involves introduction of the aryl in electrophilic form via oxidative addition of an aryl halide (or sulfonate), substitution of the palladium halide by a nucleophile (which may also be carbon based) followed by reductive elimination. It is noteworthy that nucleophilic aromatic substitution in the absence of such catalysts can be difficult. 

Preparation of Arylamines. Many methods to prepare arylamines by electrophilic amination are available. Some have been mentioned previously (Eqs. 13, 15, 22, 24, 25, 26, 28, and 29) and some of the methods described for the preparation of alkylamines (Eqs. 33, 35-37) can also be used to synthesize arylamines. Additional methods are shown in Eqs. 62,73 63,82 64,101 65264 66,333,334 and 67.305 The recently developed direct catalytic amination of aryl halides and aryl sulfonates,362-373 and arylboronic acids,374 however, has the advantage over these methods of requiring one or more fewer steps. The approach that merits consideration will need to be decided based on each individual objective. 

The few examples indicate that sulfone-stabilized carbanions should react normally with electrophilic animating reagents (Eqs. 145158 and 146465) with the caveat that free a-amino sulfones are unstable.158,465 The (3,y-unsaturated sulfone 74 is animated at the y-position (Eq. 147),250 presumably by an ene reaction. The preparation of a-tosyl azides from nitronates was shown above in Eq. 144. The scope of this reaction does not seem to have been determined. Reaction of the anions of nitrobenzyl aryl sulfones with l-oxa-2-azaspiro[2.5]octane (13a) gives nitrobenzaldehydes by cleavage of the initially formed amination products.466 Similarly, reaction of the lithium salt of benzyl phenyl sulfone with phenyl azide gives benzilydeneaniline and phenyl sulfinate.467 No reports on animations of sulfoxide-stabilized carbanions were found. 

Arynes prepared from the aryl iodides 57 via 2-magnesiated aryl sulfonates 58 have been reported to undergo nucleophilic addition by magnesium thiolates [45], amides [45] or phenylselenide [46], giving rise to ortho-thio, amino, or seleno-substituted arylmagnesium species 59-61, respectively (Scheme 12.21). These arylmagnesium intermediates can be trapped in situ by various electrophiles, such... 

Various heterocyclic sulfones were investigated in this coupling, including pyridyl and pyrimidyl derivatives as well as electron-poor aryl sulfones. Due to lower electrophilicity of the carbon center linked to the sitifur atom, these are more stable th in BT-sulfones. For instance, the pyridylsulfone carbanion does not self-condense at room temperature over several minutes. These conpounds have been recently used in the preparation of ycosidic vinyl ethers 42 through the condensation of p-glycosidyl-substituted pyridylsulfones 41 with aldehydes (Scheme 19.161. ... 

Many oxidative additions of alkyl iodides other than methyl iodide and many oxidative additions of alkyl bromides to neutral transition metal complexes occur by radical pathways. The factors that lead to reaction by a radical pathway over an S 2 or concerted pathway are subtle and depend on the identity of the metal and the substrate. Broadly speaking, reactions of weaker and more-hindered electrophiles occur by radical pathways more often than reactions of stronger and less-hindered electrophiles, and reactions of aryl sulfonates almost always occur by non-radical pathways. Also, reactions of coordinatively saturated metal centers tend to occur by radical pathways more than reactions of coordinatively imsaturated metal centers. Coordinatively saturated complexes tend to react by outer-sphere processes because oxidative additions of organic halides by inner-sphere pathways require an open coordination site. Finally, metal complexes that are prone to imdergo one-electron oxidations tend to undergo oxidative addition by radical patlaways... 

Rnally, it will be remembered that (a) the strong organic acids such as ben-zenesulfonic acid and related aromatic sulfonic acids can be prepared by the sulfo-nation of the aromatic ring (Equation 8.75) through electrophilic aromatic substitution and that (b) add chlorides of these acids (Equation 8.76) on reaction with alcohols will produce aryl sulfonate (e.g., toluenesulfonate) esters (Equation 8.77) used earlier (Chapter 8) to effect alkene formation from alcohols. 

The presently known electrophilic substitution reactions all occur at the 4-position of the isoxazole nucleus, corresponding to the j3-position in pyridine. Thus the influence of the nitrogen atom is predominant. The introduction of alkyl and, particularly, aryl substituents into the isoxazole nucleus markedly increases its reactivity (on the other hand, during nitration and sulfonation the isoxazole nucleus also activates the phenyl nucleus). 

Polar C=Y double bonds (Y = NR, O, S) with electrophilic carbon have been added to suifinic acids under formation of sulfones. As in the preceding section one must distinguish between carbonyl groups and their derivatives on the one hand, and carboxylic acids (possessing leaving groups at the electrophilic carbon) on the other. Aldehydes " of sufficient reactivity—especially mono-substituted glyoxals - —and their aryl or arylsulfonyl imines have been added to suifinic acids (in a reversible equilibrium) to yield a-hydroxy or a-amino sulfones the latter could also be obtained from the former in the presence of primary amines (equation 26). 

Hydrozirconation of terminal alkynes R-C=CH (R= aryl, alkyl) with 1 affords terminally ( )-Zr-substituted alkenes with high efficiency and excellent stereochemical and regiochemical control (>98%). These alkenylzirconocene complexes are of particular interest for synthetic use [136, 143, 144]. Moreover, beside the electropositive halogen sources [145] and heteroatom electrophiles [3] used in the pioneering studies to directly cleave the Zr-C bond, ( )-vinyl-Zr complexes were recently transformed into a number of other trans-functionalized alkenes such as ( )-vinyl-sul-fides[146], vinylic selenol esters [147], vinyl-sulfones [148], vinyl-iodonium [149], vinyl-(R0)2P(0) [150], and vinilic tellurides [143]. 

Several microwave-assisted protocols for soluble polymer-supported syntheses have been described. Among the first examples of so-called liquid-phase synthesis were aqueous Suzuki couplings. Schotten and coworkers presented the use of polyethylene glycol (PEG)-bound aryl halides and sulfonates in these palladium-catalyzed cross-couplings [70]. The authors demonstrated that no additional phase-transfer catalyst (PTC) is needed when the PEG-bound electrophiles are coupled with appropriate aryl boronic acids. The polymer-bound substrates were coupled with 1.2 equivalents of the boronic acids in water under short-term microwave irradiation in sealed vessels in a domestic microwave oven (Scheme 7.62). Work-up involved precipitation of the polymer-bound biaryl from a suitable organic solvent with diethyl ether. Water and insoluble impurities need to be removed prior to precipitation in order to achieve high recoveries of the products. 

Recently, with a view to overcome the difficulty on the preparation of aryl or alkenyl halides or sulfonates, thioamides and their S-alkyl derivatives have been proposed as a new class of electrophilic partners. This palladium cross-coupling methodology was developed by Liebeskind and mostly applied to heteroaromatic templates.118 121... 

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