Intramolecular electrophilic reaction

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 reaction of imines using a 2-propylidene-l,3-bis(silane) unit as nucleophile can lead to bridged heterocyclic frameworks. ... 

Intramolecular electrophilic reaction of (y3-silylmethyl)allylsilane with an imino group is an efficient approach to an l-azabicyclo[3.2.1]octane framework [32]. For example, treatment of 94 with formaldehyde in CH3CN at room temperature and then with trifluoroacetic acid produces 97 as a trifluoroacetate salt, presumably through domino cydization through 95 and then of 96 (Scheme 5.24). 

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)... 

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. 

The molecule below has four stereoisomeric forms exoO exoCH2Br, exoO endoCH2Br, and so on. Examine electrostatic potential maps of the four ions and identify the most nucleophilic (electron-rich) atom in each. Examine the electron-acceptor orbital (the lowest-unoccuped molecular orbital or LUMO) in each and identify electrophilic sites that are in close proximity to the nucleophilic. Which isomers can undergo an intramolecular E2 reaction Draw the expected 8 2 and E2 products. Which isomers should not readily undergo intramolecular reactions Why are these inert ... 

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. 

The enolate of the 1,4-adduct, obtained after the stereoselective Michael addition step, as discussed in the previous sections, may be quenched in situ with various electrophiles. The fact that additional stereogenic centers may be formed via such tandem Michael addition/quench-ing procedures, giving products with high diastereoselectivity in many cases, extends the scope of these methods substantially. Furthermore these procedures occasionally offer the possibility of reversing the syn/anti diastereoselection. In the next sections pertinent examples of diastereoselective inter- and intramolecular quenching reactions will be discussed. 

Given their extraordinary reactivity, one might assume that o-QMs offer plentiful applications as electrophiles in synthetic chemistry. However, unlike their more stable /tora-quinone methide (p-QM) cousin, the potential of o-QMs remains largely untapped. The reason resides with the propensity of these species to participate in undesired addition of the closest available nucleophile, which can be solvent or the o-QM itself. Methods for o-QM generation have therefore required a combination of low concentrations and high temperatures to mitigate and reverse undesired pathways and enable the redistribution into thermodynamically preferred and desired products. Hence, the principal uses for o-QMs have been as electrophilic heterodienes either in intramolecular cycloaddition reactions with nucleophilic alkenes under thermodynamic control or in intermolecular reactions under thermodynamic control where a large excess of a reactive nucleophile thwarts unwanted side reactions by its sheer vast presence. 

For very electrophilic carbene ligands bound to a metal center which also has coordinated an aromatic phosphine ligand,there is the possibility of the following intramolecular substitution reaction leading to a metallacycle ... 

The Yao group has made use of a Ic type intramolecular Heck reaction to prepare the C2-symmetric dimeric indole core of chloptosin <06OL4919>. A solvent-free variation of the Bischler indole synthesis, electrophilic cyclization of a-arylamino imine tautomers prepared from aniline derived a-arylamino ketones, has been used by Menendez and co-workers for the preparation of 2-arylindoles <06SL91>. 

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>. 

According to the stepwise electrophilic reaction mechanism, the differences in the stereochemistries of the products from the reactions of alkenes with cyclic 49 and acyclic 51 disulfonium dications can be explained by the larger rates of the intramolecular reactions. In the case of a cyclic dication, the carbocationic center in intermediate 94, which is formed as the result of initial attack by a S-S dication on a double C=C bond reacts with nucleophile intramolecularly, thus conserving the configuration of the substituents at the double bond. On the other hand, an acyclic dication undergoes transformation to two separate particles (95 and dimethylsulfide) with a consequent loss of stereoselectivity. Additional experiments with deuteretad alkenes confirm that reaction is not stereoselective, lending further support to the stepwise mechanism (Scheme 36).106... 

Presumably, the oxidative cyclization of 3 commences with direct palladation at the a position, forming o-arylpalladium(II) complex 5 in a fashion analogous to a typical electrophilic aromatic substitution (this statement will be useful in predicting the regiochemistry of oxidative additions). Subsequently, in a manner akin to an intramolecular Heck reaction, intermediate 5 undergoes an intramolecular insertion onto the other benzene ring, furnishing 6. (i-Hydride elimination of 6 then results in carbazole 4. 

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. 

As we have seen (Section 4, p. 191) the range of effective molarities associated with ring-closure reactions is very much greater than that characteristic of intramolecular general acid-base catalysis the main classification is therefore in terms of mechanism. By far the largest section (I, Tables A-D) gives EM s for intramolecular nucleophilic reactions. These can be concerted displacements (mostly at tetrahedral carbon), stepwise displacements (mostly addition-elimination reactions at trigonal carbon), or additions, and they have been classified in terms of the nucleophilic and electrophilic centres. 

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