Electrophilic arenes

Addition-elimination could occur. PhBr is not an electrophilic arene, but the very high nucleophilicity of -BuLi may compensate. 

The synthetic application of vicarious nucleophilic substitution, whereby hydrogen of an electrophilic arene is replaced by an a-functionalized alkyl substituent, has been reviewed 177 the sequence usually involves attack on a nitroalkene by a carbanion containing a leaving group X at the carbanionic centre, /i-elimination of HX from the er-adduct, and rearomatization on subsequent protonation. 

Figure 3 Examples of electrophilic arene-metal complexes...

The [(OEP)Rh]+ scaffold, while efficient at the metalation of arenes, is ill-suited for catalytic biaryl bond formation. The generation of an intermediate bearing two aryl groups cis to each other as a typical precursor to biaryls through reductive elimination is impossible due to the ligand-imposed geometry at the metal center. Nonetheless, other highly electron-deficient Rh(III) complexes can offer suitable entries into catalytic routes for electrophilic arene arylation. This is especially the case if the electrophilic Rh(III) center can be accessed in situ from the oxidative addition of Ar-X to a Rh(I) complex (Scheme 4). 

Nucleophilic substitution of halogen atoms in highly electrophilic arenes (most often nitroarenes) by carbanions proceeds efficiently under PTC conditions. However, the catalytic process operates only with methynic carbanions, when the products do not possess an acidic hydrogen atom. In the case of methylenic carbanions, introduction of nitroaryl substituents gives products that are much stronger C-H acids thus, they are immediately converted into nitrobenzylic carbanions which, associated with the lipophilic TAA cations of the catalyst, stay in the organic phase. The low nucleophilic activity of these carbanions prevents their further reactions. In this situation the catalytic process is arrested. 

Electrophilic arene CH activation is classic for metals such as Hg(II), Au(I) and Rh(III). For example, [Rh(oep)]+ reacts with CeHsOMe to give the [(p-MeOC6H4)Rh(OEP)]+ [131]. The reagent, being very bulky, avoids ortho substitution. 

The key problem of all kinds of the Sn reactions is how to eliminate hydrogen with pair of electrons. External oxidant is usually needed to perform the Sn reactions however, in some cases, highly electrophilic arenes can play the role of internal... 

For the double-functionalized arenes applied, in general, they can be divided into three main analogues (Table l.l). One is 1,2-dihaloarenes, also called 1,2-di-electrophilic arenes (DBA) the next is orf/ro-halogen activated arenes, also called 1,2-electrophilic-nulceophilic coexisted arenes (ENA) the third is called 1,2-di-nulceophilic arenes (DNA). 

The preceding reactions dealt with the use of chiral auxiliaries linked to the electrophilic arene partner. The entering nucleophile can also serve as a chiral controller in diastereoselective SjjAr reactions. This approach was successfully employed for the arylation of enolates derived from amino acids. To illustrate the potential of the method, two examples have been selected. Arylation of Schollkopf s bislactim ether 75 with aryne 77 as electrophilic arylation reagent was demonstrated by Barrett to provide substitution product 81 with good yield (Scheme 8.18) [62, 63]. Aryne 77 arises from the orf/jo-lithiation of 76 between the methoxy and the chlorine atom followed by elimination of LiCl. Nucleophilic attack of 77 by the lithiated species 78 occurs by the opposite face to that carrying the i-Pr substituent. Inter- or intramolecnlar proton transfer at the a-face of the newly formed carbanion 79 affords the anionic species 80. Subsequent diastereoselective reprotonation with the bulky weak acid 2,6-di-f-butyl-4-methyl-phenol (BHT) at the less hindered face provides the syn product 81. Hydrolysis and N-Boc protection give the unnatural arylated amino acid 82. The proposed mechanism is supported by a deuterium-labeling experiment. Unnatural arylated amino acids have found application as intermediates for the construction of pharmaceutically important products such as peptidomi-metics, enzyme inhibitors, etc. [64, 65]. 

ONSH is an efficient tool for introduction of perfluoroalkyl groups into electron-deficient arenes. Due to moderate nucleophilicity and stability of perfluoroalkyl carbanions, the reaction proceeds only with highly electrophilic arenes such as azinium salts (Scheme 11.10) [20, 21]. 

It turns out that there actually is an electrophile present. We said that the enolate is in equilibrium with the ketone (and there is a lot of ketone present). Well, ketones are electrophilic, aren t they We devoted an entire chapter to the reactions that take place when ketones get attacked. So, what happens when an enolate attacks a ketone ... 

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