Nucleophiles electron-rich aromatic

Experimental observations indicate that electron-rich aromatic nucleophiles, such as phenoxide, add to phenyl diazonium ion in the same way as dimethylamine. 

Scheme 6.35 Cu(l)-catalyzed enantioselective addition of electron-rich aromatic nucleophiles to imino esters, as described by Johannsen [48].

The postulated mechanism for the reaction involves activation of the alkyne by jt-coordination to the cationic (IPr)Au% followed by direct nucleophilic attack by the electron-rich aromatic ring to form product 111. Alternatively, two 1,2-acetate migrations give the activated aUene complex, which can be cyclised to product 110 by nucleophilic attack of the aromatic ring on the activated aUene (Scheme 2.21) [92]. 

The formation of 151 from the phosphonate 171 could be proved only by indirect means. Electron-rich aromatic compounds such as N,N-diethylaniline and N,N,N, N -tetraethyl-m-phenylenediamine U0 1I9> and N-methylaniline 120> are phosphorylated in the para- and in the ortho- plus para-positions by 151. Furthermore, 151 also adds to the nitrogen lone pair of aniline to form the corresponding phosphor-amidate. Considerable competition between nucleophiles of various strengths for the monomeric methyl metaphosphate 151 — e.g. aromatic substitution of N,N-diethylaniline and reaction with methanol or aromatic substitution and reaction with the nitrogen lone pair in N-methylaniline — again underline its extraordinary non-selectivity. 

Preparation of Copolymers Containing Both Electrophilic and Nucleophilic Groups. Our first implementation of this reaction scheme involved the preparation of a series of copolymers incorporating both a latent electrophile and an electron-rich aromatic moiety which, being phenolic, also provides access to swelling-free development in aqueous medium. The copolymers are prepared as shown in Figure 1 by copolymerization of 4-t-butyloxycarbonyloxy-styrene with 4-acetyloxymethyl-styrene. Although the reactivity ratios of these two monomers are different [11], our study of this system has confirmed that they copolymerize essentially in random fashion. 

Pandey and co-workers have generated arene radical cations by PET from electron-rich aromatic rings [119]. The photoreaction is apparently initiated by single-electron transfer from the excited state of the arene to ground state 1,4-dicyanonaphthalene (DCN) in an aerated aqueous solution of acetonitrile. Intramolecular reaction with nucleophiles leads to anellated products regio-specifically. The author explains the regiospecifidty of the cyclization step from... 

In a series of important papers, MacMillan described the alkylation of electron rich aromatic and heteroaromatic nucleophiles with a,P-unsaturated aldehydes, using catalysts based upon the imidazoUdinone scaffold, further establishing the concept and utility of iminium ion activation. In line with the cycloaddition processes described above, the sense of asymmetric induction of these reactions can be rationalised through selective (F)-iminium ion formation between the catalyst and the a,P-unsaturated aldehyde substrate, with the benzyl arm of the catalyst blocking one diastereoface of the reactive Jt-system towards nucleophilic attack (Fig. 3). 

The synthetically most valuable intermediate in heterofullerene chemistry so far has been the aza[60]fulleronium ion C59N (28). It can be generated in situ by the thermally induced homolytic cleavage of 2 and subsequent oxidation, for example, with O2 or chloranil [20-24]. The reaction intermediate 28 can subsequently be trapped with various nucleophiles such as electron-rich aromatics, enolizable carbonyl compounds, alkenes and alcohols to form functionalized heterofullerenes 29 (Scheme 12.8). Treatment of 2 with electron-rich aromatics as nucleophilic reagent NuH in the presence of air and excess of p-TsOH leads to arylated aza[60]fullerene derivatives 30 in yields up to 90% (Scheme 12.9). A large variety of arylated derivatives 30 have been synthesized, including those containing cor-annulene, coronene and pyrene addends [20, 22-25]. 

Y.S. Ding, C.Y. Shiue, J.S. Fowler, A.P. Wolf, A. Plevenaux, No carrier added (nca) aryl [F-18]fluorides via the nucleophilic aromatic-substitution of electron-rich aromatic rings, J. Fluor. Chem. 48 (1990) 189-205. 

E.D. Hostetler, S.D. Jonson, M.J. Welch, J.A. Katzenellenbogen, Synthesis of 2-[F-18]fluoroestradiol, a potential diagnostic imaging agent for breast cancer Strategies to achieve nucleophilic substitution of an electron-rich aromatic ring with [F-18]F, J. Org. Chem. 64 (1999) 178-185. 

A wide variety of products had been isolated over the years, beginning with Bamberger s own research, that could be thought of as arising from nucleophilic attack of a neutral electron-rich aromatic on either the N or ortho- and para-carbons of a nitrenium ion (Schemes 2, 10, 12, 15) i3-i5.24.36.38.43... 

The acid-catalyzed dimerization of pyrroles and indoles also involves electrophilic attack by the 2H- or 3//-protonated species upon the non-protonated heterocycles (Schemes 6, 7 and 8, Section 3.05.1.2.2), and 3,3-dimethyl-3//-indole has been reported to react with 7r-electron-rich aromatic compounds to yield the 2-ary.l-3,3-dimethyl-2,3-dihydroindoles (77S343). In the absence of a nucleophile strong acids promote the interchange of substituents at the 2- and 3-positions of 2,3,3-trisubstituted 3//-indoles, e.g. (510) (511) (62JOC1553). 

Finally, electron rich aromatic rings can also act as nucleophiles towards arynes, e.g. 2-phenylanisole is the major product of Ag+-catalyzed decomposition of benzenediazonium carboxylate in anisole (equa-... 

Additions to aromatic rings can become useful when radicals and acceptors are electronically paired. The additions of electrophilic radicals to electron rich aromatic rings are growing in importance and the additions of nucleophilic radicals to electron poor alkenes have long been of preparative value. This chapter can provide only a few representative examples of each class. Giese s book is recommended as a more thorough overview of additions to aromatic rings.232... 

The functionalization of electron rich aromatics rings is often accomplished by electrophilic aromatic substitution. However, electrophilic substitutions require stringent conditions or fail entirely with electron deficient aromatic rings. Nucleophilic aromatic substitutions are commonly used but must usually be conducted under aprotic conditions. In contrast, nucleophilic radicals can add to electron deficient aromatic rings under very mild conditions. 

Various nucleophiles, such as alcohols, fluoride ion, amides, allylsilane, and electron-rich aromatic rings, have been successfully used in this reaction in either an inter- or intra-molecular mode. A recent example of a new C-C bond formation in this reaction in the inter-molecular mode includes the preparation of derivatives 17 by the oxidation of 2-alkoxynaphthols 16 in the presence of an allylsilane or a silyl enol ether as a carbon-based nucleophile (Scheme 7) [22]. 

Nucleophilic attack of the electron-rich aromatic ring 124 to the cationic complex 123, and intramolecular amination afforded the intermediate 125 for the synthesis of discorhabdin and prianosin alkaloids [29]. 

When first reported in 1905, the Reissert reaction demonstrated the addition of KCN to quinoline in the presence of benzoyl chloride, but many new modifications since then have employed other nucleophiles and catalytic promotion by a Lewis acid. Shibasaki reported in 2001 the first catalytic enantioselective Reissert-type reaction. Optimized reaction conditions involving an electron-rich aromatic acid chloride in a low-polarity solvent, and use of catalyst 14, were found to suppress the racemic pathway and resulted in good enantioselectivity (Scheme 2) <2001JA6801>. 

In the previous sections, the reactions of nucleophilic alkyl and acyl radicals with electron-deficient aromatics via SOMO-LUMO interaction have been described. At this point, we introduce the reactions of electrophilic alkyl radicals and electron-rich aromatics via SOMO-HOMO interaction, though the study is quite limited. Treatment of ethyl iodoacetate with triethylborane in the presence of electron-rich aromatics (36) such as pyrrole, thiophene, furan, etc. produces the corresponding ethyl arylacetates (37) [50-54]. 

This reaction comprises firstly of SH2 reaction on the iodine atom of ethyl iodoacetate by an ethyl radical, formed from triethylborane and molecular oxygen, to form a more stable Chester radical and ethyl iodide. Electrophilic addition of the a-ester radical to electron-rich aromatics (36) forms an adduct radical, and finally abstraction of a hydrogen atom from the adduct by the ethyl radical or oxidation by molecular oxygen generates ethyl arylacetate (37), as shown in eq. 5.20. Here, a nucleophilic ethyl radical does not react with electron-rich aromatics (36), while only an electrophilic a-ester radical reacts with electron-rich aromatics via SOMO-HOMO interaction. 

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