Transition-state species steric effect

On the basis of ESl-MS observation as well as positive nmilinear effects of this system, we assumed that p-oxo-p-aiyloxy-trimer complex is the most enantiose-lective active species (Fig. 3). Therefore, Sm50(0-/Pr)i3 with a well-ordered structure would have beneficial effects for the formation of desired trimer species. Postulated catalytic cycle of the reaction based on the initial rate kinetic studies and kinetic isotope effect studies is shown in Fig. 4. In this catalyst system, both Cu and Sm are essential. We assume that the cooperative dual activation of nitroalkanes and imines with Cu and Sm is important to realize the syn-selective catalytic asymmetric nitro-Mannich-type reaction. The Sm-aryloxide moiety in the catalyst would act as a Brpnsted base to generate Sm-nitronate. On the other hand, Cu(ll) would act as a Lewis acid to control the position of iV-Boc-imine. Among possible transition states, the sterically less hindered TS-1 would be more favorable. Thus, the stereoselective C-C bond formation via TS-1 followed by protonation with phenolic proton affords syn product and regenerates the catalyst. 

In summary, a number of effective chiral reducing agents have been developed based on the modification of LAH. Excellent results have been obtained with aryl alkyl ketones and a,p-acetylenic ketones. However, dialkyl ketones are reduced in much lower enantiomeric excess. This clearly indicates that steric effects alone do not control stereoselectivity in these reductions. Systematic studies have been carried out with the objective of designing improved reagents. A better understanding of the mechanisms and knowledge of the active species is required in order to provide more accurate models of the transition states of the key reduction steps. 

The tertiary a-ester (26) and a-cyano (27) radicals react about an order of magnitude less rapidly with Bu3SnH than do tertiary alkyl radicals. On the basis of the results with secondary radicals 28-31, the kinetic effect is unlikely to be due to electronics. The radical clocks 26 and 27 also cyclize considerably less rapidly than a secondary radical counterpart (26 with R = H) or their tertiary alkyl radical analogue (i.e., 26 with R = X = CH3), and the slow cyclization rates for 26 and 27 were ascribed to an enforced planarity in ester- and cyano-substituted radicals that, in the case of tertiary species, results in a steric interaction in the transition states for cyclization.89 It is possible that a steric effect due to an enforced planar tertiary radical center also is involved in the kinetic effect on the tin hydride reaction rate constants. 

Steric effects result from repulsions between valence electrons or non-bonded atoms. Steric effects always increase the energy of a chemical species in which they are present. The overall steric effect on a chemical reaction may be either favorable or unfavorable. If steric effects in the reactant are larger then in the product (or transition state) then the reaction is favored (steric augmentation). If the reverse is the case the reaction is disfavored (steric diminution). This is also true of a dynamic physical property involving initial and final states, such as ionization potential. We may expect the same result in biological systems for the formation of the bas-receptor complex, and when it occurs, for the subsequent chemical reaction of the complex. 

Since the radical motions are unlikely to involve changes in bonding, the effects of deuterium in the P positions are almost certainly steric, but the sense of the effect (kH > kD) is opposite the steric isotope effects that are normally observed. Given the standard interpretation of steric isotope effects, which assumes that the transition state survives several periods of normal vibration [98], the present results imply that the smaller size of deuterium reduces the driving force for radical motion. That is, the P methylene group is under more stress in Species A24 than in the transition state leading to the next intermediate structure. 

It is reasonable to consider that in titanium silicate-catalyzed reactions the oxidizing species also acts as an electrophile. The different order of reactivity of the C4 olefins in the presence of titanium silicates relative to that observed with soluble catalysts must therefore arise from the fact that alkyl substitution at the double bond is responsible not only for inductive effects, but also for increases in the size and the steric requirements of the molecules. Since the rates of diffusion of the different butenes cannot be the cause of the different reaction rates, a restricted transition-state selectivity must be operating. 

However, since epoxidation occurs within pores of cross-section comparable to that of the olefin, steric restrictions generally prevail over inductive effects, leading to anomalous reactivity orders. They result from restrictions to diffusion in the pores (reactant shape selectivity) and to the approach of the double bond to the active species (transition state shape selectivity). The first is sufficient to explain... 

Any explanation of facial selectivity must account for the diastereoselection observed in reactions of acyclic aldehydes and ketones and high stereochemical preference for axial attack in the reduction of sterically unhindered cyclohexanones along with observed substituent effects. A consideration of each will follow. Many theories have been proposed [8, 9] to account for experimental observations, but only a few have survived detailed scrutiny. In recent years the application of computational methods has increased our understanding of selectivity and can often allow reasonable predictions to be made even in complex systems. Experimental studies of anionic nucleophilic addition to carbonyl groups in the gas phase [10], however, show that this proceeds without an activation barrier. In fact Dewar [11] suggested that all reactions of anions with neutral species will proceed without activation in the gas phase. The transition states for reactions such as hydride addition to carbonyl compounds cannot therefore be modelled by gas phase procedures. In solution, desolvation of the anion is considered to account for the experimentally observed barrier to reaction. 

Numerous investigations of reactions of allyfic stannanes with aldehydes have demonstrated that changes in steric interactions and electronic effects are introduced by the coordination of Lewis acids. In fact, the oxocarbenium species serves as the reactive partner in the allylation process, and deficiencies of detailed knowledge regarding the structure, reactivity, and steric requirements of oxocarbenium complexes leads to some uncertainties in providing a simple model to forecast stereoselectivity. Based upon a body of results accumulated from a variety of investigators, the pre-complexation with a specific Lewis acid and aldehyde may sustain the inherent attributes of the synclinal transition state, or the coordination complex may present features that override this tendency in favor of antiperiplanar arrangements. 

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