Substitution reactions intramolecular

The selectivity relationship merely expresses the proportionality between intermolecular and intramolecular selectivities in electrophilic substitution, and it is not surprising that these quantities should be related. There are examples of related reactions in which connections between selectivity and reactivity have been demonstrated. For example, the ratio of the rates of reaction with the azide anion and water of the triphenylmethyl, diphenylmethyl and tert-butyl carbonium ions were 2-8x10 , 2-4x10 and 3-9 respectively the selectivities of the ions decrease as the reactivities increase. The existence, under very restricted and closely related conditions, of a relationship between reactivity and selectivity in the reactions mentioned above, does not permit the assumption that a similar relationship holds over the wide range of different electrophilic aromatic substitutions. In these substitution reactions a difficulty arises in defining the concept of reactivity it is not sufficient to assume that the reactivity of an electrophile is related... 

Overall the stereospecificity of this method is the same as that observed m per oxy acid oxidation of alkenes Substituents that are cis to each other m the alkene remain CIS m the epoxide This is because formation of the bromohydrm involves anti addition and the ensuing intramolecular nucleophilic substitution reaction takes place with mver Sion of configuration at the carbon that bears the halide leaving group... 

Benzenediazonium fluoroborate, 2-carboxy-xanthone synthesis from, 3, 838 Benzenediazonium ions phenyl azide formation from, 5, 839 Benzenediazonium salts, o-(imidazol-l-yl)-intramolecular diazo coupling, 5, 404 Benzene-1,2-disulfonimides N-substituted reactions, 6, 930 Benzene episulfide formation, 7, 577 Benzeneimine... 

Substitution, addition, and group transfer reactions can occur intramolecularly. Intramolecular substitution reactions that involve hydrogen abstraction have some important synthetic applications, since they permit functionalization of carbon atoms relatively remote from the initial reaction site. ° The preference for a six-membered cyclic transition state in the hydrogen abstraction step imparts position selectivity to the process ... 

Photochemical substitution reactions of this type which involve selective hydrogen abstractions from intramolecular sites by the m.tt ketone oxygen, are reviewed in chapter 12. ... 

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. 

An a ,/3-epoxycarboxylic ester (also called glycidic ester) 3 is formed upon reaction of a a-halo ester 2 with an aldehyde or ketone 1 in the presence of a base such as sodium ethoxide or sodium amide. Mechanistically it is a Knoevenagel-type reaction of the aldehyde or ketone 1 with the deprotonated a-halo ester to the a-halo alkoxide 4, followed by an intramolecular nucleophilic substitution reaction to give the epoxide 3 ... 

An a-halosulfone 1 reacts with a base by deprotonation at the a -position to give a carbanionic species 3. An intramolecular nucleophilic substitution reaction, with the halogen substituent taking the part of the leaving group, then leads to formation of an intermediate episulfone 4 and the halide anion. This mechanism is supported by the fact that the episulfone 4 could be isolated. Subsequent extrusion of sulfur dioxide from 4 yields the alkene 2 ... 

The following reaction involves a hydrolysis followed by an intramolecular nucleophilic acyl substitution reaction. Write both steps, and show their mechanisms. 

On the other hand, in the case of a-halogenoethyl sulphoxides 503 an SN2-type displacement occurs with mercaptide anions and leads to a-alkylthioethyl sulphoxides 504, while the elimination-addition mechanism is operative with alkoxide anions, affording jS-alkoxyethyl sulphoxides577,596 505 (equation 306). Finally, the reaction of 1-halogeno-l-methylethyl derivatives with both nucleophiles mentioned above occurs via the elimination-addition mechanism596 (equation 307). The substitution reaction can also take place intramolecularly (equation 308) and it proceeds very easily (cf. Section IV.A.2.C)484,600. 

Heterocyclic sulphoxides 65 mass spectra of 130-132 Hexahydronaphthalenols, synthesis of 310 Hofmann elimination 953 HOMO energies 1048, 1049 Homolytic substitution 1109 intramolecular 846 Horner-Wittig reaction 333 Hot electrons 892, 893 HSAB theory 282, 549 Hydrides, as reducing agents 934-941, 959 Hydrogen abstraction, photochemical 874, 876, 877, 879, 880... 

The synthesis of highly substituted rigid tricyclic nitrogen heterocycles via a tandem four-component condensation (the Ugi reaction)/intramolecular Diels-Alder reaction was investigated in both solution and solid phase [24]. The Ugi reaction in MeOH (Scheme 4.2) involves the condensation of furylaldehydes 17, benzylamine 18, benzyl isocyanide 19 and maleic or fumaric acid derivatives 20, and provides the triene 21 which immediately undergoes an intramolecular Diels-Alder reaction, affording the cycloadduct 22 in a diastereoisomeric mixture with high yield. 

Diylide 1, by reaction with a phosphorus electrophile, Ph2PCl, lead instantaneously via a nucleophilic substitution and intramolecular prototropy to the formation of functionalized monoylides 10 (Scheme 11). 

Aldol addition and related reactions of enolates and enolate equivalents are the subject of the first part of Chapter 2. These reactions provide powerful methods for controlling the stereochemistry in reactions that form hydroxyl- and methyl-substituted structures, such as those found in many antibiotics. We will see how the choice of the nucleophile, the other reagents (such as Lewis acids), and adjustment of reaction conditions can be used to control stereochemistry. We discuss the role of open, cyclic, and chelated transition structures in determining stereochemistry, and will also see how chiral auxiliaries and chiral catalysts can control the enantiose-lectivity of these reactions. Intramolecular aldol reactions, including the Robinson annulation are discussed. Other reactions included in Chapter 2 include Mannich, carbon acylation, and olefination reactions. The reactivity of other carbon nucleophiles including phosphonium ylides, phosphonate carbanions, sulfone anions, sulfonium ylides, and sulfoxonium ylides are also considered. 

Reaction of the same neutral borabenzene-ligand adduct, C5H5B-PMe3, with a transition, rather than an alkali, metal alkyl or amide can furnish r 6-boratabenzene complexes in a single step (Scheme 8).17 This efficient transformation presumably proceeds through initial ir-coordination of CsHsB-PMes to the transition metal, followedby an intramolecular substitution reaction. In contrast to other approaches to the synthesis of T 6-boratabenzene complexes, this synthetic route does not have a parallel in if-cyclopentadienyl chemistry. 

Additional experimental, theoretical, and computational work is needed to acquire a complete understanding of the microscopic dynamics of gas-phase SN2 nucleophilic substitution reactions. Experimental measurements of the SN2 reaction rate versus excitation of specific vibrational modes of RY (equation 1) are needed, as are experimental studies of the dissociation and isomerization rates of the X--RY complex versus specific excitations of the complex s intermolecular and intramolecular modes. Experimental studies that probe the molecular dynamics of the [X-. r - Y]- central barrier region would also be extremely useful. 

As shown in Scheme 2.20, selective lithiation of substrate 2-87 by treatment with LDA in THF at -78 °C triggers an intramolecular Michael/intermolecular aldol addition process with benzaldehyde to give a mixture of diastereomers 2-90 and 2-91. 2-91 was afterwards transformed into 2-92, which is used as a chiral ligand for Pd-catalyzed asymmetric allylic substitution reactions [29]. 

Aromatic nitro compounds undergo nucleophilic aromatic substitutions with various nucleophiles. In 1991 Terrier s book covered (1) SNAr reactions, mechanistic aspects (2) structure and reactivity of anionic o-complexes (3) synthetic aspects of intermolecular SNAr substitutions (4) intramolecular SNAr reactions (5) vicarious nucleophilic substitutions of hydrogen (VNS) (6) nucleophilic aromatic photo-substitutions and (7) radical nucleophilic aromatic substitutions. This chapter describes the recent development in synthetic application of SNAr and especially VNS. The environmentally friendly chemical processes are highly required in modem chemical industry. VNS reaction is an ideal process to introduce functional groups into aromatic rings because hydrogen can be substituted by nucleophiles without the need of metal catalysts. 

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 ... 

While nitrogen sources such as chloramine-T and PhI=NTs have been used for aziridination reactions, TsNC12 has not been explored until now. The reaction of TsNCL, with Pd(OAc)2 and K2C03 provides the expected N-tosyl aziridines in good yields <06TL7225>. This reaction presumably proceeds through an initial amidohalogenation reaction catalyzed by palladium. The chloroamide is then converted to the aziridine via an intramolecular substitution reaction. 

In 1984, we demonstrated that A-alkoxy-A-acyl nitrenium ions 15 could be generated by the reaction of A-alkoxy-A-chloroamides 14 with Lewis acids such as Ag + and Zn2+ and used these to form heterocycles by intramolecular aromatic substitution reactions (Scheme 2).90 In this manner, several novel A-acyl-3,4-dihydro-2,l-benzoxazines 16a and A-acyl-4,5-dihydro-( I //,3//)-2,1-benzoxazepines 16b were made. Subsequent work91,92 and that of Kikugawa93 96 produced numerous syntheses involving alkoxynitrenium ions including formation of natural products.97 99... 

Both inter- and intramolecular Heck reactions of indoles have been pursued and these will be considered in turn. Appropriately, Heck and co-workers were the first to use Pd-catalyzed vinyl substitution reactions with haloindoles [239]. Thus, l-acetyl-3-bromoindole (217) gave a 50% yield of 3-indolylacrylate 218. A similar reaction with 5-bromoindole yielded ( )-methyl 3-(5-indolyl)acrylate (53% yield), but 3-bromoindole gave no identifiable product. 

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