Intramolecular electrophilic aromatic

Detailed mechanistic studies by Fodor demonstrated the intermediacy of both imidoyl chlorides (6) and nitrilium salts (7) in Bischler-Napieralski reactions promoted by a variety of reagents such as PCI5, POCI3, and SOCh)/ For example, amide 1 reacts with POCI3 to afford imidoyl chloride 6. Upon heating, intermediate 6 is converted to nitrilium salt 7, which undergoes intramolecular electrophilic aromatic substitution to afford the dihydroisoquinoline 2. Fodor s studies showed that the imidoyl chloride and nitrilium salt intermediates could be generated under mild conditions and characterized spectroscopically. Fodor also found that the cyclization of the imidoyl chlorides is accelerated by the addition of Lewis acids (SnCU, ZnCh), which provides further evidence to support the intermediacy of nitrilium salts. ... 

A more practical solution to this problem was reported by Larson, in which the amide substrate 20 was treated with oxalyl chloride to afford a 2-chlorooxazolidine-4,5-dione 23. Reaction of this substrate with FeCL affords a reactive A-acyl iminium ion intermediate 24, which undergoes an intramolecular electrophilic aromatic substitution reaction to provide 25. Deprotection of 25 with acidic methanol affords the desired dihydroisoquinoline products 22. This strategy avoids the problematic nitrilium ion intermediate, and provides generally good yields of 3-aryl dihydroisoquinolines. 

Intramolecular electrophilic aromatic substitution to give tricyclic products 142 is also a viable process, with trapping efficiency related to the electron density of the arene trap (equation 3)67. With a simple phenyl group pendant, rearrangement to the 2-pyrone was... 

Thus /i-carbolincs can be obtained in a tandem hydroformylation/Pictet-Spengler-type intramolecular electrophilic aromatic substitution of polymer bound olefins (Scheme 26) [80]. 

In a similar fashion, hydroformylation of N-allyl-pyrrols leads to 5,6-dihydroindolizines via a one-pot hydroformylation/cyclization/dehydration process (Scheme 27) [81,82]. The cyclization step represents an intramolecular electrophilic aromatic substitution in a-position of the pyrrole ring. This procedure was expanded to various substrates bearing substituents in the al-lyl and in the pyrrole unit. 

Several chain transfer to polymer reactions are possible in cationic polymerization. Transfer of the cationic propagating center can occur either by electrophilic aromatic substituation or hydride transfer. Intramolecular electrophilic aromatic substituation (or backbiting) occurs in the polymerization of styrene as well as other aromatic monomers with the formation of... 

Dibenzo[f,. ]cinnolines 259 have been obtained from 2-naphthylanilines 258 via diazotization followed by intramolecular electrophilic aromatic substitution (Equation 65) <2003BMC1475>. 

A nucleophilic attack of an N-tethered phenethyl substituent is shown in Scheme 50. The protonated thiazine ring brings about an intramolecular electrophilic aromatic substitution on the aryl substituent, whether this is a phenyl <1992CHE832> or a veratryl ring <1980JHC449>. 

An equally important general type of synthesis which proceeds via heterocyclization with formation of a ring bond y to the heteroatom involves acid-catalyzed intramolecular electrophilic aromatic substitution, especially those in which a carbonyl group functions as the electrophile. The most common structural requirements are summarized in (18)-(2l) ... 

By far the most common methods for the preparation of dibenzoselenophenes and 2-benzoselenophenes, like the synthesis of 1-benzoselenophenes, rely upon the annulation of the heterocyclic ring system onto a preformed benzene ring and mostly involve the formation of one or two Se-C bonds as their key steps, with only a few exceptions [1, 119, 120], Intramolecular electrophilic aromatic substitution of biphenyl-2-yl trifluoromethylselenide to 5-(trifluoromethyl)dibenzoselenopheni um triflate (62) [99, 143] and synthesis of tetramethoxydibenzoselenophene (95) (Scheme 26) [144, 145] are examples. 

The imine salt is perfectly placed for an intramolecular electrophilic aromatic substitution by the electron-rich dihydroxyphenyl ring. This closes the isoquinoline ring in a Mannich-like process (Chapter 27) with the phenol replacing the enol in the pyrrolidine alkaloid biosynthesis. 

Treatment of P3C3Bu 3 with [(CO)sW <—PMe], generated / si/u by thermal decomposition of 56b (R = Ph) at 110°C, furnished a 2 1 mixture of quadricyclane 58b and the tricyclic compound 59, which were separated by fractional crystallization as colorless or yellow crystals in 39% and 25% yield, respectively. The presence of a three-membered ring in 59 agrees with an initial attack of the phosphinidene complex at a P=C bond of the triphosphinine to give transient 60. An intramolecular electrophilic aromatic substitution furnished product 59, whereas rearrangement of 60 to tetraphosphanorbornadiene 57a and its intramolecular [2+2] cycloaddition would rationalize the formation of 58b (Scheme 22) <2001CEJ3545>. 

Example 4.21. A metal-catalyzed, intramolecular, electrophilic aromatic substitution. 

Similar intramolecular electrophilic aromatic substitution reactions are common, especially when five- or six-membered rings are formed. 

SCHEME 7.27 C-Glycosidation via intramolecular electrophilic aromatic substitutions. 

With Mn(OAc)3, generated by oxidation of Mn(OAc)2 as mediator, a tandem reaction consisting of an intermolecular radical addition followed by an intramolecular electrophilic aromatic substitution can be accomplished [Eq. (21b)] [225b]. Further Mn(III)-mediated additions of 1,3-dicarbonyl compound to olefins are shown in Table 11 (numbers 8b,c, and 9a). Mediated by in situ generated Mn(III), methyl dibromoacetate, trichloro-bromomethane, perfluoroctyl iodide, dimethyl bromomalonate, and active methylene compounds have been added via radicals to olefins [225d]. 

The salts (219) have been prepared advantageously by action of anilines on 3-chloroacraldehydes (218) obtained in a Vilsmeier-Haack-Arnold formylation25 of methyleneketones without intermediate isolation94. The ring-closure has been accounted for by an intramolecular electrophilic aromatic substitution, as shown in the following scheme ... 

With silver salts, 1-bromocyclopropyl 2-phenylethyl sulfide [60, R = (CH2)2Ph] and 1-bromo-cyclopropyl benzyl sulfide (60, R = Bn) produce relatively stable thiocyclopropyl cations, which undergo intramolecular electrophilic aromatic substitution to afford spiro compounds 61 and 62.1 ... 

Scheme 2.4.16 C-Glycosidation via Intramolecular Electrophilic Aromatic Substitutions...

One of the most powerful methods for the construction of tetrahydroisoquinoline systems is the Pictet-Spengler cyclisation. The reaction consists of the condensation of a b-phenylethylamine derivative with a carbonyl compound, generating an imine (Schiffs base), which undergoes cyclisation via an intramolecular electrophilic aromatic substitution yielding the isoquinoline derivative. The Pictet-Spengler reaction is traditionally carried out in a protic solvent with acid catalysts, usually acetic acid or trifluoroacetic acid. 

Intramolecular electrophilic aromatic substitutions. 3.4 Pericyclic reactions Formation of Two New Bonds... 

An alternate route to fused ring pyrroles involves an interesting cyclization of (5-N-pyrrolyl-2-hydroxypentyl)cobaloxime (31), which proceeds by intramolecular electrophilic aromatic substitution of a cobaloxime n-cation onto the pyrrole ring to provide 6-exo cyclization product 32 enroute to a formal synthesis of (-)-tashiromine (33) <97TL7007>. 

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