Catalytic Turnover with Rate Acceleration

This new process has one unexpected benefit the rates and turnover numbers are increased substantially with the result that the amount of the toxic and expensive 0s04 is considerably reduced (usually 0.002 mole %). The rate acceleration is attributed to formation of an Os04-alkaloid complex, which is more reactive than free osmium tetroxide. Increasing the concentration of 1 or 2 beyond that of 0s04 produces only negligible increase in the enantiomeric excess of the diol. In contrast quinuclidine itself substantially retards the catalytic reaction, probably because it binds too strongly to osmium tetroxide and inhibits the initial osmylation. Other chelating tertiary amines as well as pyridine also inhibit the catalytic process. 

Both imprinted polymers showed an enhancement in the catalytic activity that was about 50-fold higher than the control polymer (P0) and turnover of the catalytic cavities was also demonstrated. However, when comparison was made with a polymer containing Co(II) but which was not imprinted with the template (PI), the rate acceleration dropped to about fourfold. In addition, the control of the enantioselectivity of the reaction was very low. In fact, the polymer, imprinted with the diketone derived from the / -camphor, was able to catalyse the reaction, between the 5-camphor and benzaldehyde, with an acceleration rate almost identical to that obtained with the polymer imprinted with the opposite enantiomer. The rate enhancement between the two polymers was in fact equal to 1.04. 

Phosphonate ester 30 can also be considered as a mimic of the transition state for subsequent esterolysis and aminolysis of the 8-lactone. In fact, the antibody that promotes ring formation was shown to catalyze the stereoselective reaction between 29 and 1,4-phenylenediaminc.39 The kinetic mechanism of the bimolecular process involves random equilibrium binding of lactone and amine, and the observed turnover rate could be approximated from the measured difference between the binding of reactants and the TSA. Again, entropic factors are presumed largely responsible for the observed rate acceleration, with minimal contributions derived from specific catalytic groups at the active site. 

Keck [89a-c], Tagliavini [89d,e], and Yu [89f] have extensively studied the BINOL-Ti- or binol-Zr promoted reactions of achiral aldehydes with allylstan-nanes. The initial studies employed BINOL and either Ti(Oi-Pr)4 or TiCl2(0/-Pr)2 as the Lewis acid promoter in the reaction of achiral aldehydes with allyltributyl-stannane. The reaction affords good yields of the desired homoallylic alcohol with a high degree of enantioselectivity even with as little as 10 mol% of the chiral catalyst (Scheme 10-49) [89a]. The rate and turnover of the catalytic, asymmetric allylation reaction have also been optimized. It was found that when /-PrSSiMe3 is added to the reaction, a rate acceleration occurs, allowing as little as 1-2% of the catalyst to be used [89 fj. 

Kinetic templates accelerate reaction of bound substrates, which makes it tempting to quantify template effects in terms of rate enhancement . In this section, we will show how this can be misleading because such rate enhancements are concentration dependent. We will elucidate the parameters which determine the rate enhancement achieved with a kinetic template, by analyzing the thermodynamic and kinetic behavior of simple theoretical models, and applying these models to published template systems. Our theoretical models are similar to the Michaelis-Menten analysis of enzyme catalyzed reactions [51], except that we assume there is no catalytic turnover. First, we consider linear templates, then cyclization templates. In general, the rate of reaction varies as the reaction proceeds whenever we refer to rates in the following discussion, we mean initial rates. 

One of the interesting goals in this field is to produce amino acids with high enantiomeric excesses (ee) as well as high rate accelerations and catalytic turnovers. An opening effort in... 

There are three main criteria for design of this catalytic system. First, the additive must accelerate the cyclopropanation at a rate which is significantly greater than the background. If the additive is to be used in substoichiometric quantities, then the ratio of catalyzed to uncatalyzed rates must be greater than 50 1 for practical levels of enantio-induction. Second, the additive must create well defined complexes which provide an effective asymmetric environment to distinguish the enantiotopic faces of the alkene. The ability to easily modulate the steric and electronic nature of the additive is an obvious prerequisite. Third, the additive must not bind the adduct or the product too strongly to interfere with turnover. 

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