Conformations of the transition state

The fact that with acetal 1 (R1 = H R2 = CH3) a lower stereoselectivity is observed than with the acetals where R1 = Ft or C6II5 suggests that the bulkiness of the substituent at the acetal center also plays an important role in fixing the conformation of the transition state. With 1 bearing a hydrogen atom at the acetal center (R1 = II), the acetyl group is allowed to occupy the quasiequatorial position (3B) and the addition reaction therefore proceeds with no or only a weak chelation control. The same presumably holds for the elyoxal monoacetal 1 (Ri = R2 = M). 

For reactions of A-acyliminium ions with alkenes and alkynes one has to distinguish between A-acyliminium ions locked in an s-trans conformation and those which (can) adopt an s-cis conformation. The former type reacts as a (nitrogen stabilized) carbocation with a C —C multiple bond. Although there are some exceptions, the intramolecular reaction of this type is regarded as an anti addition to the 7t-nucleophile, with (nearly) synchronous bond formation, the conformation of the transition state determining the product configuration. 

The molecules most profitably studied in connection with purely steric isotope effects have been isotopically substituted biphenyl derivatives. Mislow et al. (1964) reported the first more or less clearcut example of this kind in the isotope effect in the configurational inversion of optically active 9,10-dihydro-4,5-dimethylphenanthrene (7), for which an isotopic rate ratio ( d/ h) of 1-17 at 295-2°K in benzene solution was determined. The detailed conformation of the transition state is not certain in this case, as it involves the mutual passage of two methyl groups, and thus it is difficult to compare the experimental results with... 

Fig. 16. Preferred conformations of the transition states for the absorption of endocyclo-olefins.

Figure 11 Chorismate-prephenate rearrangement catalyzed by antibody 1F7 raised against a bicyciic hapten that mimics the chair conformation of the transition state of the reaction and X-ray structure of the corresponding antibody 1 F7-hapten compiex.

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... 

Electron densities of ortho- and para-positions of biphenyl are higher than that of meta-posltions. Sterically non-controlled isopropylatlon of biphenyl at low temperature occurred predominantly at ortho and para-posltlons to give 2-and 4-IPBP because of the electrophilic nature of the alkylation. However, selective formation of 4-IPBP over HM is controlled by the sterlc restrictions depending on the elliptical pore of the zeolite and on the conformation of the transition state for the formation of products. The molecule 2-IPBP has approximately 0.75 nm of diameter In a twisted bulky conformation with an angle of 64°[8]. The formation of 2-IPBP is prevented over HM because the corresponding transition state with bulky conformation requires more space than is available at the acidic sites of HM. On the other hand, the formation of 4-IPBP proceeds unhindered because of its smaller transition state. The formation of 3-IPBP Is also less hindered because of flexible conformations at transition states In HM pore. 

Diastereoselectivities in complex systems are determined by conformation of the transition states which are affected by chelation and steric effects of substituents and reaction conditions. For example, the stereochemistry of a hydroxyl group derived from a ketone is determined by coordination of hydroxyl and other functional groups, and depends on the presence or absence of HMPA (Equation (42)). 

In 2003, Molander reported the synthesis of (+ )-isoschizandrin using the Sml2-mediated 8-endo-trig carbonyl-alkene cyclisation of ketone 71 (Scheme 7.30).69 The axial chirality of the biaryl system efficiently controls the central chirality of the product. The (Z)-alkene geometry is also vital to the stereochemical outcome and the presence of HMPA in the reaction mixture helps control the conformation of the transition state by increasing the steric demands of the alkoxysamarium substituent.69... 

The aldol formed from the favoured transition state structure, with R pseudoequatorial, is shown below—first in the conformation of the transition state, and then flattened out on to the page, and it is syti. 

The stereochemistry comes from an all-chair arrangement in the conformation of the transition state. The methyl group will adopt an equatorial position in this conformation, fixing the way the other bonds are formed. Again, colour coding should make it clearer what has happened. 

Consequently, the Y-T equation is incapable of directly correlating the effects of the full range of X-substituents in any fixed Y series of [29(X,Y)], except for the symmetrically substituted series [29(X = Y)]. The bilinear correlation obtained in the unsymmetrical series with X =7 Y indicates a change in the substituent interaction mechanism within the range of substituents involved. The non-linear correlations of substituent effects in this system can be related to the substituent-induced change in conformation of the transition state. 

The effect of substitution is also evident in the epoxidation of verticillene (21)153 at the 7,8-double bond giving 22. Once again, the conformation of the transition state for the preferred mode of attack is, ideally, puckered. The additional three-carbon bridge prevents total ring inversion additional substitution of the double bonds limits conformational mobility. Thus, even for this 14-membered ring system high diastereoselectivity is predicted. Experimental evidence so far, however, indicates only that no second diastcrcomcr of the 7,8-cpoxidc 22 has been isolated from the reaction mixture. 

There is no way of determining between this choice, but, where the various contributions to the energies of 1 and 2 have been Hsted then these contributions are of the same relative importance for 1 and 2. Thus it is possible to make a useful discussion of barrier heights, though, unaware of the conformation of the transition state. We shall discuss ring inversion in terms of 1 on the understanding that 2 ought also to be considered on similar terms mutatis mutandi. 

As pointed out earlier, the aliphatic Claisen reairangement and its variants are powerful means to effect stereocontrolled C,C-bond formation. Highly ordered transition states effect a reliable transfer of stereochemistry from starting materials to products. Naturally, the geometry of the vinyl ether bond and the conformation of the transition state are crucial parameters in this process. The former issue is strongly dependent on the Claisen variant that is employed, whereas the transition state geometry is controlled by both steric and electronic features of the Claisen system. Additionally, the choice between... 

Figure 8.30. Conformations of Penicillin and a Normal Substrate. The conformation of penicillin in the vicinity of its reactive peptide bond (A) resembles the postulated conformation of the transition state of R-d-Ala-d-Ala (B) in the transpeptidation reaction. [After B. Lee. J. Mol. Biol. 61(1971) 464.]...

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