Transition structures substrates

Although the rationalization of the reactivity and selectivity of this particular substrate is distinct from that for chiral ketals 92-95, it still agrees with the mechanistic conclusions gained throughout the study of Simmons-Smith cyclopropa-nations. StOl, the possibility of the existence of a bimetallic transition structure similar to v (see Fig. 3.5) has not been rigorously ruled out. No real changes in the stereochemical rationale of the reaction are required upon substitution of such a bimetallic transition structure. But as will be seen later, the effect of zinc iodide on catalytic cyclopropanations is a clue to the nature of highly selective reaction pathways. A similar but unexplained effect of zinc iodide on these cyclopro-panation may provide further information on the true reactive species. 

A transition structure model was proposed which accounts for the high selectiv-ities obtained for some of the substrates [80]. In the structure shown in Scheme 6.37 the two phosphorus atoms of the Tol-BINAP ligand and the two car-... 

The theoretical investigations of Lewis acid-catalyzed 1,3-dipolar cycloaddition reactions are also very limited and only papers dealing with cycloaddition reactions of nitrones with alkenes have been investigated. The Influence of the Lewis acid catalyst on these reactions are very similar to what has been calculated for the carbo- and hetero-Diels-Alder reactions. The FMOs are perturbed by the coordination of the substrate to the Lewis acid giving a more favorable reaction with a lower transition-state energy. Furthermore, a more asynchronous transition-structure for the cycloaddition step, compared to the uncatalyzed reaction, has also been found for this class of reactions. 

The rate acceleration achieved by enzymes is due to several factors. Particularly important is the ability of the enzyme to stabilize and thus lower the energy of the transition state(s). That is, it s not the ability of the enzyme to bind the substrate that matters but rather its ability to bind and thereby stabilize the transition state. Often, in fact, the enzyme binds the transition structure as much as 1012 times more tightly than it binds the substrate or products. As a result, the transition state is substantially lowered in energy. An energy diagram for an enzyme-catalyzed process might look like that in Figure 26.8. 

For most dienes, 7r-bonds adjacent to quaternary centers do not undergo insertion reactions. One notable exception is 1,5-diene (75) (Scheme 17) [44], For this substrate, the observed selectivity is inconsistent with a chair-like (in this case a trans decalin-like) transition structure (76 top) leading to the insertion product, which is typically seen in diene cyclizations with 70 [36]. 

Treatment of the enantiopure substrate 4-341 containing a sila-ene moiety with trimethylsilyl trifluoromethanesulfonate (TMS OTf) gave 4-342 in a highly stereoselective fashion and 52% yield. It can be assumed that the reaction passes through the two chairlike transition structures 4-345 and 4-346 (Scheme 4.76). It is of interest that the stereochemistry of the two C-C-double bonds in 4-341 did not influence the configuration of the product. Moreover, when using EtAlCl2 as mediator, a 3 l-mixture of 4-343 and 4-344 is obtained in 40% yield. This can be explained by an axial orientation of the carbonyl moiety in the transition state. 

The presence of a stereogenic center on the aldehyde can strongly inlinence the diastereoselectivity in allylboration reactions, especially if this center is in the a-position. Predictive rules for nucleophilic addition on snch a-snbstitnted carbonyl substrates such as the Felkin model are not always snitable for closed transition structures.For a-substituted aldehydes devoid of a polar substituent, Roush has established that the minimization of ganche-ganche ( syn-pentane ) interactions can overrule the influence of stereoelectronic effects. This model is valid for any 3-monosubstituted allylic boron reagent. For example, althongh crotylboronate (E)-7 adds to aldehyde 39 to afford as the major prodnct the diastereomer predicted by the Felkin model (Scheme 2), " it is proposed that the dominant factor is rather the minimization of syn-pentane interactions between the Y-snbstitnents of the allyl unit and the a-carbon of the aldehyde. With this... 

Cyclic allylic alcohols have different steric requirements than the acyclic substrates discussed above. Sarzi-Amade and coworkers addressed the mechanism of epoxida-tion of 2-cyclohexen-l-ol by locating all the transition structures (TSs) for the reaction of peroxyformic acid (PFA) with both pseudoequatorial and pseudoaxial cyclohexenol con-formers. Geometry optimizations were performed at the B3LYP/6-31G level, and the total energies were refined with single-point B3LYP/6-311- -G //B3LYP/6-31G calculations. 

The results of the dioxirane epoxidation of some 3-alkyl-substituted cyclohexenes and of 2-menthene indicate that the diastereoselectivity control is subject to the steric interactions of the dioxirane with the substituents of the substrate, while the size of the dioxirane substituents has only a minimal effect . In the favored transition structure, the alkyl groups of the dioxirane cannot interact effectively with the substituents at the stereogenic center of the chiral alkene . ... 

Thus it is evident that the modified polyethylenimines provide a matrix for achieving homogeneous catalysis of decarboxylation of activated anionic substrates in an aqueous environment. Clearly, the modified polyethylenimines provide solvation features that stabilize the anionic transition structure in the state with particularly sensitive bonds. Large solvent effects have been observed in kinetic studies of many reactions involving anions.46 47,50,51 Suitable derivatives of polyethylenimine should manifest interesting effects in many of these reactions also. 

FIGURE 37. Prereaction complex (R-a) and transition structure (TS-b) with the natural (enzymatic) orientation of the p-OHB substrate with respect to the F1HO—OH 14... 

Various bimolecular assemblies that have been proposed for the transition state are shown in Scheme 13 (14, 19a, 20g). Bicyclic transition state A involves transfer of bridging alkyl group (R) to the terminally located aldehyde, while transition structure B involves reaction between terminal R and bridging aldehyde. The reaction may proceed via mono-cyclic, boat-like six-membered transition state C. Transition structures of types B and C were originally proposed for the reactions of orga-noaluminum compounds and carbonyl substrates (26, 27). Ab initio calculations suggest that methyllithium dimer reacts with formaldehyde through a bicyclic transition state related to A (28). The dinuclear Zn... 

Olefins react directly at the electron-rich and rather electron-deficient oxygens. If the dimer is much more reactive toward olefins than the monomer, only a small fraction of the alkaloid-Os04 complex need be present as a dimer (94a). Houk developed a symmetrical five-membered transition-structure model on the basis of X-ray crystal structures of Os04-amine complexes and osmate ester products and ab initio transition structures of analogous reactions (Scheme 40). The MM2 calculations based on this [3 + 2] reaction model reproduce the stereoselectivities of the stoichiometric reactions observed with several chiral diamines (94b). The transition state may be stabilized by tt-tt interaction of the alkene substrate and the ligand aromatic ring (95). 

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