Substitution anchimeric assistance

As shown by the relative rates of methanolysis of thioethers PhS(CH2)nCl (Scheme 4.50), the same substrate can react with or without neighboring-group participation, depending on the nucleophile and on the reaction conditions. Under conditions which favor bimolecular substitution, anchimeric assistance by neighboring groups is observed only rarely. 

Table 15 shows that peroxyester stabiUty decreases for the alkyl groups in the following order tert — butyl > tert — amyl > tert — octyl > tert — cumyl > 3 — hydroxy — 1,1 dimethylbutyl. The order of activity of the R group in peroxyesters is also observed in other alkyl peroxides. Peroxyesters derived from benzoic acids and non-abranched carboxyUc acids are more stable than those derived from mono-a-branched acids which are more stable than those derived from di-a-branched acids (19,21,168). The size of the a-branch also is important, since steric acceleration of homolysis occurs with increasing branch size (236). Suitably substituted peroxyesters show rate enhancements because of anchimeric assistance (168,213,237). 

More mechanistic work undoubtedly will be done on the stereochemistry of solvolysis, particularly of simple alkyl-substituted acyclic vinyl systems. The questions of concerted anchimerically assisted or nonconcerted rearrangements both to the double bond and across the double bond need further development. 

Within the past several years, we have examined the synthesis and reactions of several classes of polymers related to PECH. We have adopted three simple approaches to the preparation of polymeric substrates more reactive than PECH toward nucleophilic substitution. We have i). removed the 8-branch point by extension of the side chain, ii). replaced the chloride leaving group by a more reactive bromide and iii). replaced the backbone oxygen atom by a sulfur atom that offers substantial anchimeric assistance to nucleophilic... 

Three different mechanisms of perester homolytic decay are known [3,4] splitting of the weakest O—O bond with the formation of alkoxyl and acyloxyl radicals, concerted fragmentation with simultaneous splitting of O—O and C—C(O) bonds [3,4], and some ortho-substituted benzoyl peresters are decomposed by the mechanism of decomposition with anchimeric assistance [3,4]. The rate constants of perester decomposition and values of e = k l2kd are collected in the Handbook of Radical Initiators [4]. The yield of cage reaction products increases with increasing viscosity of the solvent. 

All these kinetic features may be readily taken into account within the 3 following assumptions a) because of lower steric hindrance, isotactic triads exhibit a better accessibility than the syndiotactic ones kQ(AmAmA)>kQ(ArArA) b) autoretarded kinetics arises from increasing steric hindrance around the reaction sites as the substitution proceeds further, and from electrostatic repulsion between the anionic reagent j RCH2 ) and the modified negatively charged chain (AAB and AAB-AB-) c) this electrostatic effect is partly canceled in isotactic triads by anchimeric assistance of the substituted B unit to the SN2 step WVmAJ-MAmV -). 

Halogen displacement from 2-halo-tetrahydropyrans and -hexahydropyrimidines is extremely easy, being assisted, in the SnI process, by the electron pairs on the heteroatom (equation 124). 3-Halohexahydropyridines can also show accelerated halogen displacement (anchimeric assistance from nitrogen equation 125). Apart from these and other (normal) substitutions, eliminations of H—Hal are also commonly found. 

An Sn2 reaction with anchimeric assistance (via formation of a bicyclic aziridinium ion intermediate) has been proposed for the nucleophilic substitution of trans-2-substituted 3-piperidinol mesylates by nitrogen nucleophiles with retention of trans... 

Salaiin, J.-P. Durst, F. Anchimerically assisted substitution of a sulfmyl function in a-sulfi-nylhydrazones by thiols. Tetrahedron Lett. 

Toshimitsu, A. Hirosawa, C. Tamao, K. Retention of configuration in the Ritter-type substitution reaction of chiral /j-arylthio alcohols through the anchimeric assistance of the arylthio group. Tetrahedron 1994, 50, 8997— 9008. 

The stereochemical course of solvolysis of a diastereomeric /3-bromo-silane, which was found to be trans elimination, as well as the observation of 1,2-silyl group migration in a process of substitution at the 0 carbon 143) are evidence of anchimeric assistance of the silyl group in ionization of the bond to the /3 carbon. It was further noticed 144) that after quenching the solvolysis reaction of /3-bromo-/3-dideuterioethylsilane the substrate recovered is a mixture of a and /3 deuterated isomers [Eq. (33)]. These... 

The study of the addition of trifluoroacetic acid to several 5-substituted 1-pentyne derivatives 22 led Peterson and Duddey (1963, 1966) and Peterson and Bopp (1967) to the conclusion that for some of the compounds investigated the intermediate resulting from protonation of the triple bond may be a five-membered ring cation of type 23, rather than a linear vinyl cation. This is indicated by the observation of rearranged products deriving from 1-5 shift when Y = Cl, F, OMe, and OAc (see scheme 3). Kinetio data indicate that Y-participation is important in the transition state of the reaction. Anchimeric assistance effects, expressed in terms of the ratio of assisted to unassisted mechanisms, kjjkg (Heck and Winstein, 1957), have been estimated to be 3 4 for Y = Cl and 6 5 for Y = OMe. The entire kinetic picture almost matches... 

Macomber, 1969). The larger anchimeric assistance effect on rate is observed in the case of em-dimethyl substitution at C2. Bly and Koock (1969) estimated rate enhancements due to homoallenic participation of 8-3-58 x 108 for the 2,2-dimethyl brosylate (5a of Table 6) and as large as 1-7 x 105 in the case of 2,2,5,5-tetramethyl substituted brosylate in acetic acid at 75°. It is noteworthy that these rate enhancements are larger by factor of at least 10 than in the case of homoallylio participation in related compounds. 

Substitution of complexed dienols (244) or dienol acetates with carbon or heteroatom nucleophiles, in the presence of a Lewis acid, occurs with retention of configuration (Scheme 69). (Alkyl aluminum reagents act as both nucleophile and Lewis acid in this process). This reaction is believed to proceed via stereospecific ionization, with anchimeric assistance from the iron, to generate the transoid pentadienyl cation (247) followed by attack of the weak nucleophile on the face opposite to iron. The cross-conjugated pentadienyl cation can also be generated the substitution of (2-acetoxymethyl-l,3-butadiene)Fe(CO)3 (193) has previously been discussed (Section 6.1.1). 

The rate of nucleophilic substitution at positions ft to selenium is greatly enhanced. This anchimeric assistance has been ascribed to neighboring group participation with formation of the corresponding seleniranium ion in the ratedetermining step as shown in Equation (11). 

Thus, two types of active esters are of interest those formed from an acid and a substituted phenol (12-15) and those formed from an acid and a substituted hydroxylamine (16-19). Both types are reactive by virtue of the electron-withdrawing properties of the OR moiety in 2. The level of activation of the substituted phenyl esters varies directly with the electronic effect going from 4-nitrophenyl to 2,4,5-trichlorophenyl, pentachlorophenyl, and pentafluorophenyl, which corresponds with the increasing acidity of the phenols. A diminution in the rate of aminolysis is caused by the presence of a substituent in the ortho position of the ring.f l An additional phenomenon contributes to the reactivity of the esters formed from substituted hydroxylamines, namely anchimeric assistance. Since the anoinolysis of active esters is a bimolecular reaction, it is dependent on concentration and can be forced to completion by an excess of one of the reactants. Aminolysis is also characterized by a pronounced dependence on the polarity of the solvent in particular for the esters formed from substituted phenols, the half-life of a 2,4,5-trichlorophenyl ester in the presence of benzylamine being one hundred times less in dimethylformamide than in benzene. Furthermore, aminolysis is catalyzed by mild acid such as acetic acid. The rate of anoinolysis is slowed if the side chain of the active ester contains a P-methyl substituent. 

Scheme 22 Anchimeric Assistance in the Aminolysis of Active Esters Containing a Substituted Hydroxylamine...

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