Transition structure modelling

Finally, force field methods are zero-dimensional . It is not possible to asses the probable error of a given result within the method. The quality of the result can only be judged by comparison with other calculations on similar types of molecules, for which relevant experimental data exist. 

Finally, force field methods are zero-dimensional . It is not possible to asses the probable error of a given result within the method. The quality of the result can only be judged by comparison with other calculations on similar types of molecules, for which relevant experimental data exist.----------------------------------------------------- 

One of the early applications of TS modelling was the work on steric effects in Sn2 

2 Modelling the TS as a Minimum Energy Structure on the Reactant/Product Energy Seam 

There are two principal problems with the above modelling technique. First, the TS is 

Both of these problems are eliminated in the intersecting potential energy surface 

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Jensen F 1994 Transition structure modeling by intersecting potential energy surfaces J. Comput. Chem. 15 1199... 

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-... 

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). 

A density functional study of the transition structures of Ti-catalyzed epoxidation of allylic alcohol was performed, which mimicked the dimeric mechanism proposed by Sharpless et al.5 Importance of the bulkiness of alkyl hydroperoxide to the stereoselectivity, the conformational features of tartrate esters in the epoxidation transition structure, and the loading of allylic alcohol in the dimeric transition structure model were pointed out. 

The Lewis acid-promoted reaction of the allylsilane (R)-43 with either of the (5)-a-alkoxy aldehydes provides some surprising insights (Scheme I0-19) [34]. The BF3-OEt2-promoted reaction of the silane (R)-43 and either (S)-26 or (S)-46 afforded predominantly the syn homoallylic alcohols 50 and 51, even though this is presumed to be a mismatched combination of reagents. The TiCL-promoted reaction of ( )-43 with (5)-26 or (S )-46 also produces the syn homoallylic alcohols, presumably through a Cram chelate transition structure model (albeit with lesser selectivity for 46). These experiments indicate that the chirality of the R-silane re-... 

Figure 10-10. Transition structure models for substituted allylic indium reagents.

Abstract This chapter deals with the facial selectivity of nucleophilic additions to carbonyl compounds. This is explained using models such as the Cram s model, Anh-Felkin modification of Cram s model, Houk s transition structure model, Houk s electrostatic model, Cieplak s a —> cr model, and cation coordination model. The intricacies, variations, and predicted selectivities of these models are elaborated with examples. It has been argued that the Cieplak s cr > cr model is applicable to only those reactions that proceed through product-like transition structures. Using the cation coordination model, the facial selectivities of a number of substrates, including the better anrf-selectivity of endo,endo-2,3-die hyl-l -norbomanone in comparison to that of en[Pg.71]

Keywords Cram s model Anh-Felkin modification Houk s transition structure model Houk s electrostatic model Cieplak s a —> a model Cation coordination model (a —> n model) Carbonyl pyramidalization a —> interaction Reactant-like and product-like transition structures... 

Equation (12) illustrates the following general principle electrophiles able to form a chelated complex with the Lewis acid e.g. 28) control (usually invert) the simple stereoselection of the reaction . The major isomer (29) is, in fact, syn. Adducts (29) and (30) were then transformed, by simple functional group chemistry, into (+)-PS-5, a carbapenem antibiotic. Transition structure models for this process are discussed in detail in Section 2.4.4.1. 

Organoyttrium catalysts have been utilized to effect the cyclization of dienes under reductive conditions [39]. Excellent selectivity is achieved in these reactions between two monosubstituted alkenes leading to a single regioisomeric product (Eq. 40), and the diastereoselectivity is consistent with the simple chair transition structure model (Fig. 7). Both acetals and thioacetals are tolerated (Eq.41), whereas nitriles, esters, and sulfones preclude product formation (Eq.42). 

Haloetherification is closely related to halolactonization although it is used less often. Its main application is the diastereoselective synthesis of synthetically useful substituted tetrahy-drofurans. The mechanism of the asymmetry transfer of the reaction has been investigated using a transition-structure model based on AM1 calculations167. The strong correlation between model and experimental results makes the proposed rationale extremely attractive. 

In their work, Houk and coworkers applied the so-called MM2 transition structure modelling , a method originally developed in the same group [57]. At the time this work was performed, the reaction mechanism was not yet established. Nevertheless, envisioning the future, the authors assumed that the transition state was the symmetrical five-membered ring. 

Potential Energy Surfaces. An Application to Transition Structure Modeling. 

Transition structure models for hydroboration of an alkene with one alkyl substituent. 

Scheme 12.34 Transition structure models of the three-component coupling.

Based on mechanistic studies and on the reasonable expectation that both the aldehyde carbonyl and the ephedrine NMe2 group tend to bind to TiCl4, which usually ligates two electron-donating molecules to form cis-octahedral six-coordinate complexes, the transition structure models shown below were proposed for the asymmetric aldol reaction. ... 

As 19 and the (S) aldehyde fonn a matched pair (they cooperate to realize the same stereochemical result) while 19 and the (R) aldehyde form a mismatched pair, only the (S) enantiomer of the starting 95.5/4.5 S/R mixture of aldehyde 44 reacts with 19, and the condensation occurs with concomitant kinetic resolution. The relative configuration of the three contiguous chiral centers is a result of chelation control (C-3,C-4 anti) and syn simple stereoselection (C-2,C-3 syn) in agreement with the transition structure model A (Figure 3). An example of the mismatched pair is shown below here the (lR,2S)-N-methylephedrine derived silyl ketene acetal 16 reacts with (S) 44 (e.e. 91%) to give a mixture of the adducts 46 and 47 in poor yield. 

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