Product influencing transition structure

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. 

Ab initio calculations at the MP2/6-31+ G level have been performed for gas-phase El elimination reactions of CH3CH2X (X = NH3"1", Br, Cl, F, SH) promoted by NH . OH-, F-, PH2. SH-, and Cl- in order to determine how changes in transition-state geometry, from reactant-like to product-like, influence kinetic isotope effects.9 Secondary isotope effects (a-H) on leaving group departure are correlated with the hybridization at C7 in the transition state, whereas there is no such correlation between secondary (/5-H) isotope effects and the transition state hybridization at C/ . The primary deuterium isotope effect is influenced markedly by the nucleophilic atom concerned but approach to a broad maximum for a symmetric transition structure can be discerned when due allowance is made for the element effect. 

The polarity of the solvent will influence different types of reactions in different ways, depending upon whether they involve ions, dipoles or polarisable molecules. At the simplest level, we can analyse the effects of the solvent in terms of the different degrees of solvation of species in the initial state and the transition state. For example, in the reaction between pyridine and methyl iodide (Equation 3.24) the reactants are separate neutral molecules, the products are separate fully formed ions, but the transition structure is a single molecular entity with an appreciable degree of polarity. 

Kinetic studies of the Midland reduction confirmed that the reduction of aldehydes is a bimolecular process and the changes in ketone structure have a marked influence on the rate of the reaction (e.g., the presence of an EWG in the para position of aryl ketones increases the rate compared to an EDG in the same position). However, when the carbonyl compound is sterically hindered, the rate becomes independent of the ketone concentration and the structure of the substrate. The mechanism with sterically unhindered substrates involves a cyclic boatlike transition structure (similar to what occurs in the Meerwein-Ponndorf-Verley reduction). The favored transition structure has the larger substituent (Rl) in the equatorial position, and this model correctly predicts the absolute stereochemistry of the product. 

The next level of stereoselection pertains to the existence of stereocenters resident in either of the reactants. In these scenarios, illustrated in Scheme 10-1 (Eqs. (10.2)-(I0.5)), the newly formed centers are created under the influence of these covalently bound subunits and will be referred to as arising from internal stereoselection. The resident stereocenter can be anywhere on the aldehyde or al-lylmetal, and this kind of selection process is easy to identify when the stereocenters persist in both the educts and the product (Eqs. (10.2), (10.3)). However there are two important cases where they do not, namely, when the resident stereocenter bears the metal subunit (Eq. (10.4)) or is the metal subunit (Eq. (10.5)). Because these stereocenters are covalently bound in the educts and (to the extent that they influence the stereochemical outcome) in the transition structure, they will be considered under internal stereocontrol [5]. 

The results obtained from the cyclization of model 5 indicated that the size of the Lewis acid-aldehyde complex influences the selectivity of the reaction. For model system 10 it appears that the steric bulk of the Lewis acid does not play a significant role in determining the stereochemical outcome of the reaction. In model system 10 no external methylene unit exists which could interact with the Lewis acid-aldehyde complex. In fact, the silane is fixed in an anti orientation with respect to the approaching aldehyde (anti Se ). The cyclization of model system 10 with fluoride ion affords primarily the distal product resulting from cyclization through an antiperiplanar transition structure. Thus, the antiperiplanar transition structure is accessible, but is not favored in reactions with the Lewis acids. 

The cause of the scatter is the non-systematic influence of the substituent on the microscopic environment of the transition structure. The linear free energy relationship between product state XpyH (Equation 22) and the transition structure (Xpy. .. PO32 . . . isq) will be modulated by second-order non-systematic variation because the microscopic environment of the reaction centre in the standard (XpyH ) differs slightly from that (Xpy-PO ) in the reaction under investigation giving rise to specific substituent effects. These effects are mostly small. An unusually dramatic intervention of the microscopic medium effect may be found in Myron Bender s extremely scattered Hammett dependence of the reaction of cyclodextrins with substituted phenyl acetates.22 The cyclodextrin reagent complexes the substrate and interacts... 

The familiar explanation for this example of site selectivity is that reaction at the 9,10-position creates two isolated benzene rings, whereas reaction at the 1,4-position would create a naphthalene nucleus, which is a less stable arrangement of two benzene rings. This explanation relies on the influence of product-like character in the transition structure, but we may also note that the same product is accounted for by looking at the frontier orbital coefficients of the starting materials the largest coefficients in the HOMO of 6.287 are at the 9,10-positions (see p. 174). 

When the alkenyl component is an O-terf-butyldimethylsilyl (TBDMS) enol ether, another anomaly occurs independent of enol ether geometry, the anti product is favored (Scheme 6.8) [62]. With trimethylsilylpropargyl ethers, the anti selectivity is 95-98%, making this reaction an excellent route for the preparation of anti 1,2-diols. In these cases, transition structures similar to Figure 6.6c and d are operative, the dominant influence being mutual repulsion between the carbanion substituent, R, and the 0-silyl group. 

A different influence of pressure on an intramolecular [4 + 2] cycloaddition and a 1,5-sigmatropic rearrangement is responsible for a pressure-induced increase in selectivity in the thermolysis of (Z)-l,3,8-nonatriene 35 to give 36 and 37 as shown by Klamer et al. (Scheme 8.11) [28]. At 0.1 MPa the rearrangement is favored and the products 36 and 37 are formed in a 31 69 ratio. Applying 770 MPa of pressure, the selectivity is reversed favoring the Diels-Alder product 36 in a ratio of 73 27. It can be assumed that 36 is formed via the bicyclic transition structure 38, whereas 37 evolves through the monocyclic transition structure 39 (cf. Chapter 2). 

Another interesting example of the influence of high pressure on the regioselec-tivity in organic reactions has been observed for the Mukaiyama aldol reaction of unsaturated silyl ketene acetals (51) with aromatic aldehydes by Bellassoued, Dumas and coworkers (Scheme 8.14) [33]. The desired y-adduct 52 was the major compound up to 0.5 GPa (52 53 = 83 17) while the preference was reversed at 1.7 GPa, making the a-adduct 53 the predominant product (52 53 = 25 75). This pressure dependence of the regioselectivity may imply that the transition structure leading to the linear aldol product 52 is less compact than that in the formation of the branched aldol product 53. 

The discussion of elimination reactions considers the classical E2, El, and Elcb eliminations that involve removal of a hydrogen and a leaving group. We focus on the kinetic and stereochemical characteristics of elimination reactions as key indicators of the reaction mechanism and examine how substituents influence the mechanism and product composition of the reactions, paying particular attention to the nature of transition structures in order to discern how substituent effects influence reactivity. We also briefly consider reactions involving trisubstituted silyl or stannyl groups. Thermal and concerted eliminations are discussed elsewhere. 

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