Transition state conformation

STO-3G calculations find the corresponding transition state to be more stable than other possible conformations by several kilocalories per raole. The origin of the preference for this transition-state conformation is believed to be a stabilization of the C=0 LUMO by the a orbital of the perpendicularly oriented substituent. 

Regioselectivity in opening of a-functionalized epoxides by treatment with trimethylamine dihydrofluoride has been observed. Thus, cw-isophorol epoxide gives exclusively 3-fluoro-l,2-diol, whereas from the trans isomer, 2-fluoro-l,3-diol is obtained as the main product together with 3-methylenecyclohexane-l,2-diol. This behavior has been discussed m terms of the influence of a-substituents on the transition state conformations [7 J] (equations 11 and 12). 

We can conclude that anti elimination is generally favored in the E2 mechanism, but that steric (inability to form the anti-periplanar transition state), conformational, ion pairing, and other factors cause syn elimination to intervene (and even predominate) in some cases. 

Intramolecular cyclopropanation is a useful method for construction of [n.l.0]-bicyclic compounds.17-21 225 275 As a matter of course, alkenyl and diazo groups of the substrate are connected by a linker and the transition-state conformation of intramolecular cyclization is influenced by the length and the shape of the linker. Thus, the enantioselectivity of the reaction often depends upon the substrates used. Use of a catalyst suitably designed for each reaction is essential for achieving high enantioselectivity. 

Claisen rearrangement presumably was the boat-like form 156 (bj0) with minimized 1,3 repulsive interactions resulting in the lactams 157. However, the 2,4-as disubstituted pyrrolidine 159 (R =OTBS, R, R =H) gave the expected lactam diastereomer 158 via a chair-like transition state conformation 160 (entry 16, Table 8) (Scheme 31). 

It is now recognized that among the proposed folded envelope transition state conformations the Rautenstrauch model (A) best accommodates the experimental... 

The Cope rearrangement is the conversion of a 1,5-hexadiene derivative to an isomeric 1,5-hexadiene by the [3,3] sigmatropic mechanism. The reaction is both stereospecific and stereoselective. It is stereospecific in that a Z or E configurational relationship at either double bond is maintained in the transition state and governs the stereochemical relationship at the newly formed single bond in the product.137 However, the relationship depends upon the conformation of the transition state. When a chair transition state is favored, the EyE- and Z,Z-dienes lead to anli-3,4-diastereomcrs whereas the E,Z and Z,/i-isomcrs give the 3,4-syn product. Transition-state conformation also... 

A large number of nitrile oxide cycloadditions to chiral olefins were reported from several groups in the early 1980s (16,18,20). A clear rationale of regioselec-tivity was developed only when the traditional view, which focused on ground-state conformers, was abandoned and calculational approaches to identify transition states and transition state conformations were refined (158,159). Calculations... 

Exceptionally high diastereoselectivity has been found for the methylation of 23 and the protonation of 2610. These enolates were prepared by 1,4-addition of a bulky nucleophile 28 or 29. Both reactions, i.e., methylation of 23 and protonation of 26, are in agreement with a transition state conformation 21 as discussed previously. The bulkiness of the nucleophiles 28 and 29, respectively, is the reason for the much higher diastereoselectivity as compared to those in references 7-9. 

Conformation has a major influence on the chemical reactivity of cycloalkanes. To understand its effect in any one reaction, we first need to know what the conformation is of the transition state, and this requires a knowledge of the reaction mechanism. Next, we have to decide what amount of energy is required for the reactants to achieve transition-state conformations. For example, consider the E2 elimination discussed in Section 8-8D. The preferred transition state requires the leaving groups to be antarafacial and coplanar ... 

For cyclohexane derivatives to react in this way, the transition-state conformation must have both leaving groups axial ... 

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