Intramolecular electrophilic

A similar mechanism operates in the reaction of 3,3,3-trifluoropropene with benzene and aluminum chloride [12 13] Perfluorophenylpropene undergoes intramolecular electrophilic attack m a rare example of ring closure at a C -F bond [14] (equation 11)... 

The key step in syntheses of if/-quebrachamine (122-127) and if/-dihydro-cleavamine (12S) is the oxidation of tertiary amines with mercuric acetate to cyclic imonium salts, which give rise to an intramolecular electrophilic attack on an indole. 

In the reactions of arylsulfenyl chlorides with enamines one encounters an unusual result for enamine chemistry, in that the formation of 2,6-disubstituted cyclohexanone enamines predominates over the formation of monosubstitution products 474). A rationalization of this result suggests the formation of an intermediate which can act as an intramolecular electrophile in formation of the second carbon-sulfur bond. 

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. 

Those syntheses of pyrido[3,2-d]pyrimidines in which pyrimidines are the starting materials are completed either by an intramolecular electrophilic cyclization of a pyrimidine with a vacant 4-position (route i) or by the addition of the C-5 and C-6 atoms to a 4-substituted-5-aminopyrimidinc (route ii). 

The most satisfactory method involving this type of intramolecular electrophilic cyclization was the thermal ring-closure of aminomethylenemalonates (e.g., 119, R = COOEt) to yield the pyrido[3,2-d]pyrimidine-2,4,8(l/7,3/f,5/f)-trione (120, R = COOEt). 

The mechanism for the conversion of the A -oxide (94) to the o-methylaminophenylquinoxaline (96) involves an initial protonation of the A -oxide function. This enhances the electrophilic reactivity of the a-carbon atom which then effects an intramolecular electrophilic substitution at an ortho position of the anilide ring to give the spiro-lactam (98). Hydrolytic ring cleavage of (98) gives the acid (99), which undergoes ready dehydration and decarboxylation to (96), the availability of the cyclic transition state facilitating these processes. ... 

The second part of lanosterol biosynthesis is catalyzed by oxidosqualene lanosterol cyclase and occurs as shown in Figure 27.14. Squalene is folded by the enzyme into a conformation that aligns the various double bonds for undergoing a cascade of successive intramolecular electrophilic additions, followed by a series of hydride and methyl migrations. Except for the initial epoxide protonation/cyclization, the process is probably stepwise and appears to involve discrete carbocation intermediates that are stabilized by electrostatic interactions with electron-rich aromatic amino acids in the enzyme. 

Protonation on oxygen opens the epoxide ring and gives a tertiary carbocation at C4. Intramolecular electrophilic addition of C4 to the 5,10 double bond then yields a tertiary monocyclic carbocation at C10. 

An alternative approach to thienothienopyridines involves intramolecular electrophilic attack at C-3 of the thiophene ring. In this way, the thienothiophene 82 can be cyclized to the benzothieno[2,3-/]thieno[2,3-c]pyridine 83 upon treatment with polyphosphoric acid (PPA) at 150°C (Equation 3). Similarly, treatment of the amide 84 with POCI3 gives the corresponding 1-alkyl-3,4-dihydro-benzothieno[3,2-g]thieno[3,2-f]pyridine 85 <1999PS(153)401> (Equation 4). 

Benzo-fused pyridopyrrolizines can be prepared by an acid-induced cyclodehydration of the appropriately substituted hydroxypyrrolopyridines. In the case of 124 (Equation 7), this is best rationalized as an intramolecular electrophilic substitution at the o-carbon of the benzyl substituent <1988CC623, 1990J(P1)1757, 2001J(P1)1446>. 

Access to oxadiazolopyrimidinium salts, for example, compound 93, was achieved via intramolecular electrophilic attack of the 2-nitrogen of the 1,2,4-oxadiazole 92 in the presence of HCIO4 (Equation 9). Competing reaction at N-4 also occurs and the products are often not isolated, but used as intermediates for hydrolysis, thereby producing pyrimidines <2006T1158>. 

The reaction of 2-chloro-4,5-dihydroimidazole 347 with hydroxylamine-O-sulfonic acid gives 2-hydroxylamino-4,5-dihydroimidazolium-O-sulfonate 348, which reacts with aldehydes and cyclic ketones to give the imidazo[l,2-f] fused 4,5-dihydro-l,2,4-oxadiazoles 350 (Scheme 58). Mechanistically, the reaction may be explained by the reaction of an imidazoline NH with the carbonyl followed by intramolecular electrophilic amination of the anionic oxygen present in the resultant intermediate 349 and elimination of the sulfate group <2003JOC4791>. 

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... 

In this chapter, both intermolecular and intramolecular electrophilic [1] and nucleophilic additions [2, 3] to allenes will be discussed. For electrophilic addition, the regio- and stereoselectivity depend on the steric and electronic effects of the substituents on the allenes and the nature of the electrophiles. However, nucleophilic addition usually occurs at the central carbon atom with very limited exceptions. 

In the presence of an aluminum reagent, 2,3-butadienyltrimethylsilane can also accept the intramolecular electrophilic attack of the ketone-aluminum complex to afford bicyclic products via intermediate 60 [31]. The structures of the products depend on the aluminum reagent used [31]. 

The reactivity of allenyl ketones is also manifested in the Hg(II)-catalyzed ipso substitution that converts 54 to spirodione 55 (Eq. 13.17) [19]. The reaction presumably involves activation of the allene by Hg(II), followed by intramolecular electrophilic attack on the aromatic ring. Hydrolytic cleavage of the metal from the intermediate product of the reaction, followed by rearrangement leads to the observed spirocyclic dione. 

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. 

On the other hand, we also planned alternative completely new approach (Route B) to Nakadomarin A, which involves the spirolactam followed by coupling reaction with furan derivative and subsequent intramolecular electrophilic substitution reaction of an iminium cation generated from an aminal to give highly functionalized tetracyclic core system (Scheme 10.3). 

When imines are the nucleophiles used, the initially formed iminium intermediates can undergo intramolecular electrophilic alkylation of the other ligands (e.g. Entry 2, Table 2.10 see also [143]). In addition to this, carbyne complexes can also react with azides to give metallatriazoles [185,186] (Entry 6, Table 2.10). 

In qualitative terms, the rearrangement reaction is considerably more efficient for the oxime acetate 107b than for the oxime ether 107a. As a result, the photochemical reactivity of the oxime acetates 109 and 110 was probed. Irradiation of 109 for 3 hr, under the same conditions used for 107, affords the cyclopropane 111 (25%) as a 1 2 mixture of Z.E isomers. Likewise, DCA-sensitized irradiation of 110 for 1 hr yields the cyclopropane derivative 112 (16%) and the dihydroisoxazole 113 (18%). It is unclear at this point how 113 arises in the SET-sensitized reaction of 110. However, this cyclization process is similar to that observed in our studies of the DCA-sensitized reaction of the 7,8-unsaturated oximes 114, which affords the 5,6-dihydro-4//-l,2-oxazines 115 [68]. A possible mechanism to justify the formation of 113 could involve intramolecular electrophilic addition to the alkene unit in 116 of the oxygen from the oxime localized radical-cation, followed by transfer of an acyl cation to any of the radical-anions present in the reaction medium. 

Cationic polymerization is, of course, an inter-molecular electrophilic addition process. Intramolecular electrophilic addition involving two double bonds in the same molecule may be used to generate a cyclic system. Thus, the trienone shown is converted into a mixture of cyclic products when treated with sulfuric acid. 

The formation of cyclic terpenoids involves intramolecular electrophilic addition, and this can be exemplified by the following monoterpene structures, again with all reactions being enzyme controlled. 

Isothiocyanate 23 (X = CO), when treated with AICI3 in nitromethane undergoes ring closure by an intramolecular electrophilic substitution between C3 of the pyrrole ring and the isothiocyanate group to afford pyrrolo[3,2-c][l]benzazepine-10(lH)-one-4(5H)-thione 24 (Scheme 2 (2005BMCL3220, 1998MI197)). 

Few examples of the intramolecular electrophilic substitution on a C2py oie site have been reported for benzo[/]pyrrolo[l,2-a]azepinones. Thus, treatment of acid 62 with phosphorous pentachloride results in Friedel-Crafts product 63 (Scheme 13 (2000T9351)). 

Intramolecular electrophilic reactions of substituted pyrrole-2-carboxylic acids or their amides lead to benzo[d]pyrrolo[l,2-a]azepinones. Acid 70 in this fashion undergoes Fiiedel-Crafts cyclization to furnish fused azepine 71 in good yield (Equation (6) (2000JOC2479)). 

Intramolecular electrophilic cyclization of methyl selenoate gives only a 12% yield of benzo[/]pyrrolo[2,l- ][l,3]thiazepin-9(10H)-one 285, while cyclization of an acetate derivative under a variety of the conditions failed (Scheme 61 (1998JMC3763)). An alternate route from pyrrole ketones 286 by oxidation and TFAA induced cyclization proved to be advantageous providing a 40% yield of 285. 

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>. 

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