Nature of the Leaving Group at

Some cephalosporins can be both substrates and inhibitors of /3-lactamases. The acyl-enzyme intermediate can undergo either rapid deacylation (Fig. 5.4, Pathway a) or elimination of the leaving group at the 3 -position to yield a second acyl-enzyme derivative (Fig. 5.4, Pathway b), which hydrolyzes very slowly [35][53], Thus, cephalosporins inactivate /3-lactamases by a mechanism similar to that described above for class-II inhibitors. It has been hypothesized that differences in the rate of deacylation of the acyl-enzyme intermediates derive from their different abilities to form H-bonds. A H-bond to NH in Fig. 5.4, Pathway a, may be necessary to assure a catalytically essential conformation of the enzyme, whereas the presence of a H-bond acceptor in Fig. 5.4, Pathway b, may drive the enzyme to an unproductive conformation. The ratio between hydrolysis and elimination, and, consequently, the relative importance of substrate and inhibitor behaviors of cephalosporins, is determined by the nature of the leaving group at C(3 ). An appropriate substitution at C(3 ) of cephalosporins may, therefore, increase the /3-lactamase inhibitory properties and yield potentially better antibiotics [53]. 

Another important factor affecting the outcome of glycosylations is the nature of the leaving group at the anomeric position. As a result, a large number of glycosyl donors have been developed.39,50 In addition to the traditionally used chlorides... 

If the reaction is performed on two molecules that differ only in the leaving group (for example, /-BuCl and /-BuSMe ), the rates should obviously be different, since they depend on the ionizing ability of the molecule. However, once the carbocation is formed, if the solvent and the temperature are the same, it should suffer the same fate in both cases, since the nature of the leaving group does not affect the second step. This means that the ratio of elimination to substitution should be the same. The compounds mentioned in the example were solvolyzed at 65.3°C in 80% aqueous ethanol with the following results 11... 

The first example of Pd-catalyzed enantioselective allylation to be reported was the reaction of l-(l -acetoxyethyl)cyclopentene and the sodium salt of methyl benzenesulfonylacetate in the presence of 10 mol % of a DIOP-Pd complex, which led to the condensation product in 46% ee (Scheme 85) (200). This reaction used a racemic starting material, but the enantioselection was not a result of kinetic resolution of the starting material, because the chemical yield was above 80%. However, in certain cases, the selectivity is controlled at the stage of the initial oxidative addition to a Pd(0) species. In a related reaction, a BINAP-Pd(0) complex exhibits excellent enantioselectivity the chiral efficiency is affected by the nature of the leaving group of the allylic derivatives (Scheme 85) (201). It has been suggested that this asymmetric induction is the result of the chiral Pd catalyst choosing between two reactive conformations of the allylic substrate. 

Displacement reactions must proceed either with retention or inversion of configuration at silicon. The change in stereochemistry is mainly a function of the nature of the leaving group and of the electronic character of the nucleophile. 

As in substitution at carbon, stereochemical and kinetic data provide the means of differentiating between these two possibilities. The stereochemical data are examined first. Substitution at silicon leads to both retention and inversion of configuration and the stereochemical outcome depends upon the nature of the leaving group, the nucleophile, solvent, complexing agents and whether or not the silicon is part of a ring. 

Rate laws and kinetic parameters for substitution reactions at complexes Cp2TiX2 in acetonitrile solution at 298.2 K have been reported (X = halide or alkoxide). Reactivities are discussed in terms of the nature of the leaving group, the entering group, and the non-leaving Cp ligand. A volume of activation of —15 cm3 mol-1 has been determined for the reaction with thiocyanate.1124... 

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