Elimination reactions steric acceleration

The most satisfactory method of dehydrating 12a-alcohols appears to be through the sulfonate esters Engel and coworkers have shown (ref. 236 and ref. cited therein) that treatment of such sulfonates with alumina gives A -compounds. The reaction appears to be subject to steric acceleration in that bulky IToc-substituents and cw-fused A-rings aid elimination, and that yields increase with increasing size of the sulfonate employed. 

The study of S -1 reaction in cyclohexane becomes difficult because of the ease with which the elimination reactions occur at the same time. However it has been shown that SN reaction will be sterically accelerated for an axial substituent, because the formation of carbocation will relieve the steric strain due to 1, 3 interactions which is absent with equatorial substituent. 

Many steroid secondary alcohols are resistant to acid-catalysed dehydration, but can be converted into olefins by elimination reactions of their sulphonate esters, usually the toluene 3 -sulphonate ( tosylate ) or methanesulphonate ( mesylate ). These elimination reactions always accompany attempted nucleophilic substitution of the sulphonate (p. 41), and can be made to predominate by appropriate choice of reaction conditions. Activated alkaline alumina has been used to prepare A - and AH-olehns from the sulphonates of 3 - [131] and i2a-alcohols [132]. In the latter case the naphthalene-i-sulphonate was most effective, and the methanesulphonate distinctly less so, suggesting that steric acceleration occurs with the more bulky naphthalenesulphonate [ 132c]. This view is strengthened by the enhanced efficiency of elimination of a i2a-sulphonate in the presence of a 17a-methyl group, which increases the compression at C(i2) [132b]. The mechanism and stereochemical features of these heterogeneous reactions have not been described in detail. 

When the reaction conditions are such that acetate acts as a base, removing the proton at an ortho position, nitrogen is eliminated and benzyne formed. The o-t-butylanilines are especially good substrates for benzyne formation via the N-nitrosoacetanilide, apparently because the t-butyl group sterically accelerates elimination of nitrogen. ... 

Tin Reagents. The presence of a 3-methyl group in the 2-chloroquinoline 202 has a beneficial effect on reaction rates and efficiency in Stille-type alkenylations with terminal stannyl alkenes (Scheme 77). This was attributed to steric acceleration in the reductive elimination of Pd(0) from a Pd(II) complex. The purine 6-position is highly electrophilic. A chloro substituent is readily replaced under Stille conditions using tri(n-butyl)vinylstannane. The 6-vinylpurine product 203 from the coupling is reacted further in situ in Heck couphngs. These reactions proceed readily because of the electron-withdrawing effect from the ir-deficient pyrimidine moiety of the heterocycle.t ... 

The resting state of the propanoate catalysts may well be an acyl complex [60,61], while the attack of alcohol at the acylpalladium complex is considered to be the rate-determining step. It is probably more precise to say that fast preequilibria exist between the acyl complex and other complexes en route to it and that the highest barrier is formed by the reaction of alcohol and acylpalladium complex. The precise course of the reaction is still not known presumably deprotonation of the coordinating alcohol and the migratory elimination are concerted processes, accelerated by the steric bulk of the bidentate ligand. Toth and Elsevier showed that the reaction of an acetylpalladium complex and sodium methoxide is very fast and occurs already at low temperature to give methyl acetate and a palladium(I) hydride dimer [46]. 

In the intramolecular reactions studied by Bruice and Koshland and their co-workers, proximity effects (reduction in kinetic order and elimination of unfavourable ground state conformations) and orientation effects might give rate accelerations of 10 -10 . Hence, these effects can by themselves account for the enhancements seen in most intramolecular reactions. However, a factor of 10 -10 is less than the rate acceleration calculated for many enzyme reactions and certain intramolecular reactions, for example, hydrolysis of benzalde-hyde disalicyl acetal (3 X 10 ) (Anderson and Fife, 1973) and the lactonization reaction of[l] (10 ) where a trimethyl lock has been built into the system. If hydrolysis of tetramethylsuccinanilic acid (Higuchi et al., 1966) represents a steric compression effect (10 rate acceleration), then proximity, orientation, and steric compression... 

If the reaction has second-order kinetics, elimination is preferred if the substrate has a-branching e.g. f-butyl) groups. One reason for this is the statistical factor there are more protons which can be eliminated. Secondly, there is a steric factor the nucleophilic attack on the a-C is hindered. Thirdly, branching at a-C accelerates elimination, due to greater hyperconjugative stabilization of the double bond being formed. 

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