Mechanistic divergence

Subsequent mechanistic studies suggested that the abovementioned effect of ethylene on reaction efficiency is connected to a mechanistic divergence that exists for reactions of terminal styrenyl ethers versus those of disubstituted styrene systems [13b]. Whereas with monosubstituted styrenyl substrates the initial site of reaction is the terminal alkene, with disubstituted styrene systems the cyclic ji-systems react first. This mechanistic scenario suggests two critical roles for ethylene in the catalytic reactions of disubstituted styrenes ... 

Fig. 74 Mechanistic divergence of copper(I)-catalyzed diamination reactions...

Desymmetrization with halogen nucleophiles was effectively demonstrated with two mechanistically-divergent chiral catalysts. Denmark disclosed a Lewis-base activated delivery of chloride that was catalyzed by the enantiopuxe phos-phoramide 16. Binding of the phosphoramide was believed to induce dissociation of SiCl4 into the chiral phosphorus/silicon cation and chloride anion, which subsequently ring-opened the activated epoxide. The best enantioselectivity was observed with cfs-stilbene oxide, which was formed in 94% yield and 87% ee (Scheme 14) [28]. 

The mechanistic divergence in this group of phosphines makes them attractive candidates for further study, particularly in cases where secondary binding sites are available. Rationalization and Summary... 

Shortly after the discovery of enyne metathesis, Trost began developing cycloisomerization reactions of enynes using Pd(ll) and Pt(ll) metallacyclic catalysts (429-433), which are mechanistically divergent from the metal-carbene reactions. The first of these metal catalyzed cycloisomerization reactions of 1,6-enynes appeared in 1985 (434). The reaction mechanism is proposed to involve initial enyne n complexation of the metal catalyst, which in this case is a cyclometalated Pd(II) cyclopentadiene, followed by oxidative cyclometala-tion of the enyne to form a tetradentate, putative Pd(IV) intermediate [Scheme 42(a)]. Subsequent reductive elimination of the cyclometalated catalyst releases a cyclobutene that rings opens to the 1,3-diene product. Although this scheme represents the fundamental mechanism for enyne metathesis and is useful in the synthesis of complex 1,3-cyclic dienes [Scheme 42(fe)], variations in the reaction pathway due to selective n complexation or alternative cyclobutene reactivity (e.g., isomerization, p-hydride elimination, path 2, Scheme 40) leads to variability in the reaction products. Strong evidence for intermediacy of cyclobutene species derives from the stereospecificity of the reaction. Alkene... 

The stereochemical consequences of the reactions catalyzed by these two phosphodiesterases are the opposite of those determined for the reactions catalyzed by SNase and DNase I. The structural and mechanistic divergence already noted for the two phosphodiesterases, which require Ca for activity and probably involve general base-assisted attack of water on the substrate, is expanded on by the finding that the phosphodiesterases from snake venom and spleen utilize mechanisms that have retention as their stereochemical outcomes. Clearly, the stereochemical and structural studies of phosphodiesterases reported to date reveal mechanistic complexity that contrasts with the stereochemical (and mechanistic) uniformity that has been discovered for all of the kinases studied to date. The diversity in the phosphodiesterases is perhaps even more surprising when it is realized that the substrates for all of the enzymes that have been stereochemi-... 

The mechanism of the Gibbs reaction, an assay for phenols using, e.g., 2,6-dichlorobenzoquinone iV-chloroimine, has been probed for a wide range of imines and phenols. The first step of single-electron transfer to produce the iV-chloroimine radical anion is followed by a mechanistic divergence into three routes, depending on the reactivity of the pair of reactants. 

Detailed kinetic investigations on several systems have been carried out and have helped to unravel many of the factors involved in the divergent reaction pathways discussed above (14,87-93). The mechanistic pathways involved in the aminolysis reactions of chlorocyclophospha-zenes are summarized in Fig. 8. 

Mechanistic studies on this system have demonstrated that the reaction does not follow a simple stepwise condensation pathway as first assumed. Instead, the authors have proposed a divergent mechanism by which the production of 2 and 3 are linked by a common intermediate (see Scheme 3). In such a mechanism, hydrogen-bonding interactions between the donor molecular moieties and the templating halide (acceptor) play an important role. 

Lipscomb has commented that glutamic acid-245 might act either as a general base or a nucleophile. The available mechanistic information has been reviewed by Kaiser and Kaiser (1972), who postulated that the carboxylate anion of glutamic acid-245 acts as a nucleophile forming an anhydride intermediate [equation (29)]. The divergent D2O solvent isotope effects, =... 

Four chapters towards the end of the book diverge from the other mechanism-oriented chapters. They have a strong biochemical theme and will undoubtedly overlap with what may be taught separately by biochemists. These topics are approached here from a chemical viewpoint, using the same structural and mechanistic principles developed earlier, and should provide an alternative perspective. It is probable that some of the material described will not be required during the first 2 years of study, but it could sow the seeds for more detailed work later in the course. 

The undefined mechanism of the aldol-type Mukaiyama and Sakurai allylation reactions arose the discussion and interest in mechanistic studies [143-145]. The proposed mechanism was proved to proceed through the catalytic activation of the aldehyde and its interaction with the silyl ketene acetal or allylsilane producing the intermediate. From that point the investigation is complicated with two possible pathways that lead either to the release of TMS triflate salt and its electrophihc attack on the trityl group in the intermediate or to the intramolecular transfer of the TMS group to the aldolate position resulting in the evolution of the trityl catalyst and the formation of the product (Scheme 51). On this divergence, series of experimental and spectroscopic studies were conducted. 

The CIEEL mechanism has been utilized to explain the catalyzed decomposition of several cyclic and linear peroxides, including diphenoyl peroxide (4), peroxyesters and 1,2-dioxetanones. Special interest has focused on this mechanism when it was utilized to explain the efficient excited state formation in the chemiexcitation step of the firefly s luciferin/luciferase bio luminescence. However, doubts have been voiced more recently about the validity of this mechanistic scheme, due to divergences about the... 

The mechanistic pathways then diverge. By the associative scheme, a solvated deuteron attacks the 7r-complexed benzene (Fig. 1, step 3). A proton is then lost (step 4), as is deuterated benzene (step 5) with regeneration of the catalyst. The intermediate produced at step 3 is similar to that of a conventional electrophilic attack at benzene, except... 

Scheme 39 Mechanistic explanation for the radical divergent formation of bicyclic P-lactams 112 and 113...

J. A. Gerlt and P. C. Babbitt, Divergent evolution of enzymatic function mechanistically diverse superfamilies and functionally diverse suprafamilies, Annu. Rev. Biochem. 2001, 70, 209-246. 

The dammarenyl cation (21) represents the first branch point from which numerous mechanistic pathways of triterpene synthesis diverge. A detailed and interesting study of molecular modelling and conformational analysis indicates that the formation and... 

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