Transition state repulsive

Wheland intermediate (see below) as its model for the transition state. In this form it is illustrated by the case mentioned above, that of nitration of the phenyltrimethylammonium ion. For this case the transition state for -nitration is represented by (v) and that for p-substitution by (vi). It is argued that electrostatic repulsions in the former are smaller than in the latter, so that m-nitration is favoured, though it is associated rvith deactivation. Similar descriptions can be given for the gross effects of other substituents upon orientation. 

A more eflicient and general synthetic procedure is the Masamune reaction of aldehydes with boron enolates of chiral a-silyloxy ketones. A double asymmetric induction generates two new chiral centres with enantioselectivities > 99%. It is again explained by a chair-like six-centre transition state. The repulsive interactions of the bulky cyclohexyl group with the vinylic hydrogen and the boron ligands dictate the approach of the enolate to the aldehyde (S. Masamune, 1981 A). The fi-hydroxy-x-methyl ketones obtained are pure threo products (threo = threose- or threonine-like Fischer formula also termed syn" = planar zig-zag chain with substituents on one side), and the reaction has successfully been applied to macrolide syntheses (S. Masamune, 1981 B). Optically pure threo (= syn") 8-hydroxy-a-methyl carboxylic acids are obtained by desilylation and periodate oxidation (S. Masamune, 1981 A). Chiral 0-((S)-trans-2,5-dimethyl-l-borolanyl) ketene thioketals giving pure erythro (= anti ) diastereomers have also been developed by S. Masamune (1986). 

A sterically restricted nucleophile is less reactive than a more accessible one because of nonbonded repulsions which develop in the transition state. The trigonal bipyramidal geometry of the 8 2 transition state is sterically more demanding than the tetrahedral reactant, so steric congestion increases as the transition state is approached. 

The dependence on steric bulk is attributed to the steric requirements imposed by the bulky trimefliylamine leaving group. In the transition state for anti elimination, steric repulsion is increased as R and increase in size. When the repulsion is sufficiently large, the transition state for syn elimination is preferred. 

Extensions of the enamine alkylation to a-tetralones have also been used (245-248), but product yields were lower, presumably due to steric crowding in a transition state where generation of an imonium salt gives rise to a repulsion between a methylene group on nitrogen and a peri aromatic proton. 

Transition-state stabilization in chymotrypsin also involves the side chains of the substrate. The side chain of the departing amine product forms stronger interactions with the enzyme upon formation of the tetrahedral intermediate. When the tetrahedral intermediate breaks down (Figure 16.24d and e), steric repulsion between the product amine group and the carbonyl group of the acyl-enzyme intermediate leads to departure of the amine product. 

Backside attack may be favored for electrostatic reasons. Examine electrostatic potential maps fox bromide + methyl bromide frontside attack and bromide + methyl bromide backside attack, transition states involving frontside and backside attack of Br (the nucleophile) onto CHsBr, respectively. Which atoms in the transition states are most electron-rich Which trajectory better minimizes electrostatic repulsion ... 

Section II, A) and to an increase in the electrostatic repulsion of attack by anionic methoxide in the transition state shown in 11. 

The eleetron repulsion between the nueleophile and the eleetron-rieh ring-nitrogens is postulated to make the aetivation energy slightly lower for transition states where the eleetron-rieh eenters (nueleophile and ring-nitrogen) are farthest apart. 

In addition to the effects of a cyclic transition state, of lone-pair repulsions, and of rate of removal of hydride ion mentioned above, the position of nucleophilic substitution can be altered by a) hydrogen... 

The general principle that activation of para substitution is greater than of ortho substitution holds true also for an azinium moiety in the one instance studied. Thus, the activation energy for the 4-chloropyridine quaternary salt 280 (Table II, line 9) is 1 kcal lower than that for the 2-isomer (line 5). The rate relation (2- > 4-isomer) is controlled by the entropies of activation in this reaction due to electrostatic attraction in the transition state (281). The reverse rate relation (4- > 2-position) is predicted for aminations of such quaternary compounds due to electrostatic repulsion (282) plus the difference in E. A kinetic study of the 2- and 4-pyridine quaternary salts... 

It is notable that pyridine is activated relative to benzene and quinoline is activated relative to naphthalene, but that the reactivities of anthracene, acridine, and phenazine decrease in that order. A small activation of pyridine and quinoline is reasonable on the basis of quantum-mechanical predictions of atom localization encrgies, " whereas the unexpected decrease in reactivity from anthracene to phenazine can be best interpreted on the basis of a model for the transition state of methylation suggested by Szwarc and Binks." The coulombic repulsion between the ir-electrons of the aromatic nucleus and the p-electron of the radical should be smaller if the radical approaches the aromatic system along the nodal plane rather than perpendicular to it. This approach to a nitrogen center would be very unfavorable, however, since the lone pair of electrons of the nitrogen lies in the nodal plane and since the methyl radical is... 

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