Tight transition state, nucleophilic reactions

When Sn2 reactions are carried out on these substrates, rates are greatly increased for certain nucleophiles (e.g., halide or halide-like ions), but decreased or essentially unaffected by others. For example, a-Chloroaceto-phenone (PhCOCH2Cl) reacts with KI in acetone at 75°C 32,000 times faster than l-Chlorobutane, ° but a-bromoacetophenone reacts with the nucleophile triethylamine 0.14 times as fast as iodomethane. The reasons for this varying behavior are not clear, but those nucleophiles that form a tight transition state (one in which bond making and bond breaking have proceeded to about the same extent) are more likely to accelerate the reac-tion. ... 

It is significant to note that this reaction is highly unusual since the prochiral element resides entirely on the nucleophile. The chiral Lewis acid exerts control of en-antiofacial selectivity by proctor through tight control of the presumed heterocycloaddition transition state, Scheme 27. In effect, extremely high fidelity is necessary to orient the 2n component with respect to the 4ji component coordinated to the chiral Lewis acid. The factors that control the diastereoselectivity in the Mukaiyama Michael reaction of crotonylimides could also control enantioselectivity in the amination reaction. That selectivities on the order of 99% ee are observed in this reaction is testament to the level of control exerted by these catalysts. 

Second-order rate constants have been measured for the S 2 reactions of benzyl bromide and p-nitrobenzyl bromide with hydroxy nucleophiles. The values of (HOO )//c(HO ) are very small (1.3 and 1.2, respectively) for the two substrates. Thus the a-effect is very small and it is suggested that this may be due to the lack of tight a-bond formation at the transition state. 

Other phosphoryl transfer mechanisms are an associative, two-step mechanism (An + Dn) and a concerted mechanism (ANDN) with no intermediate. The AN+DN mechanism is an addition-elimination pathway in which a stable pentacoordinate intermediate, called a phosphorane, is formed. This mechanism occurs in some reactions of phosphate triesters and diesters, and has been speculated to occur in enzymatic reactions of monoesters. In the concerted ANDN mechanism, bond formation to the nucleophile and bond fission to the leaving group both occur in the transition state. This transition state could be loose or tight, depending upon the synchronicity between nucleophilic attack and leaving group departure. The concerted mechanism of Fig. 2 is drawn to indicate a loose transition state, typical of phosphate monoester reactions. 

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