Crowding transition

The steric rather than the inductive origin of the secondary deuterium KIE is also suggested because kH/kD = 0.994 per deuterium found in the per-deuteropyridine-methyl iodide reaction is smaller (less inverse) than the kH/kn = 0.988 per deuterium found for the 4-deuteropyridine reaction. A secondary inductive KIE should be more inverse when a deuterium is substituted for a hydrogen nearer the reaction centre, i.e. at the meta- or ortho-rather than at the para-position of the pyridine ring. Thus, if the KIE were inductive in origin, the KIE in the perdeuteropyridine reaction should be more inverse than that observed for the 4-deuteropyridine reaction. If the observed KIE were the result of a steric KIE, on the other hand, a less inverse KIE per deuterium could be found in the perdeuteropyridine reaction, i.e. a less inverse KIE per deuterium would be expected if there were little or no increase in steric hindrance around the C—H(D) bonds as the substrate was converted into the SN2 transition state. Since the KIE per D for the perdeuteropyridine reaction is less than 1%, the transition state must not be sterically crowded and the KIE must be steric in origin. Finally, the secondary deuterium KIEs observed in the reactions between 2-methyl-d3-pyridine and methyl-, ethyl- and isopropyl iodides (entries 3, 7 and 9, Table 17) are not consistent with an inductive KIE. If an inductive KIE were important in these reactions, one would expect the same KIE for all three reactions because the deuteriums would increase the nucleophilicity of the pyridine by the same amount in each reaction. The different KIEs for these three reactions are consistent with a steric KIE because the most inverse KIE is observed in the isopropyl iodide reaction, which would be expected to have the most crowded transition state, and the least inverse KIE is found in the methyl iodide reaction, where the transition state is the least crowded. 

The vinylcarbenoid [3-1-4] cycloaddition was applicable to the short stereoselective synthesis of ( )-tremulenolide A 73 and ( )-tremulenediol A 74 (Scheme 14.7) [81]. The key step is the cyclopropanation between the cyclic vinyldiazoacetate 69 and the functionalized diene 70, which occurs selectively at the ds-double bond in 70. Because of the crowded transition state for the Cope rearrangement of the divinylcyclopropane 71, forcing conditions are required to form the fused cycloheptadiene 72. The stereo-... 

The carbonyl C of RCOOH and RCOOR is trigonal sp -hybridized, but that of the intermediate is tetrahedral sp -hybridized. If R in R OH or R in RCOOH is extensively branched, formation of the unavoidably crowded transition state has to occur with greater difficulty and more slowly. 

In the second step, achiral 9-borabicyclo[3.3.1]nonane (9-BBN) adds to the less hindered diastereotopic face of a-pinene to yield the chiral reducing agent Alpine-Borane. Aldehydes are rapidly reduced to alcohols. The reaction with deuterio-Alpine-Borane, which yields (R)-a-d-henzy alcohol in 98% enantiomeric excess ( ) reveals a very high degree of selectivity of the enantiotopic faces of the aldehyde group in a crowded transition state ... 

A bulky substituent close to the reaction centre may increase the non-bonded compression energy as the transition state is formed this will cause an increase in A//. It will also hinder the close approach of solvent molecules to the reaction centre, thus reducing the maximum amount of stabilization possible (steric inhibition of solvation). This will result in a further increase in AH, but since decreased solvation means less ordering of solvent molecules about the transition state, there is a compensating increase in AS. Another effect of the bulky substituent may be to block certain vibrational and rotational degrees of freedom more in the (more crowded) transition state than in the initial state, and so to reduce AS. These are the most important of the simple effects of a bulky substituent and can be used to explain most of the relationships of Table 25. 

However, the results should be taken as an exception, since in our understanding of enantioface differentiating transformations enantioselectivity is obtained by discrimination of one of the two enantiofaces of a molecule usually due to steric hindrance. Since under high pressure the sterically more crowded transition structure is preferred, a decrease in enantioselectivity should be observed under high pressure. This indeed was found for the intermolecular all-carbon Diels-Alder reaction of 2-methyl-1,3-butadiene to a crotonic acid derivative [552], A divergent result may be obtained if the differentiation is caused by electrostatic reasons. 

The bottom half of Figure 19-11 shows the conformations along the Cl —C2 bond. Any of the three staggered conformations of the Cl —C2 bond provides an anti relationship between one of the protons and the leaving group. The Hofmann product predominates because elimination of one of the Cl protons involves a lower-energy, more probable transition state than the crowded transition state required for Zaitsev (C2—C3) elimination. 

Although the figure of 10% coverage is a rough one, it is clear that the surface is still very open when the crowding transition occurs. One possible interpretation... 

There is a dichotomy in the sense of syn-anti diastereofacial preference, dictated by the bulkiness of the migrating group [94]. The sterically demanding silyl group results in syn diastereofacial preference but the less demanding proton leads to anti preference (Sch. 35). The anti diastereoselectivity in carbonyl-ene reactions can be explained by the Felkin-Anh-like cyclic transition-state model (Ti) (Sch. 36). In the aldol reaction, by contrast, the now inside-crowded transition state (Ti ) is less favorable than Tg, because of steric repulsion between the trimethylsilyl group and the inside methyl group of aldehyde (Ti ). The syn-diastereofacial selectivity is, therefore, visualized in terms of the anti-Felkin-like cyclic transition-state model (T2 )-... 

The reaction was always accompanied by retroaldolization. In the solvent (HMPT) in which the extent of reversibility of the aldolization was the highest, isomer 73 was formed practically quantitatively, via the least-crowded transition state. These results are in contrast with those obtained with benzaldehyde and chloroaceto-nitrile, where stereoselectivity was not observed in HMPT. 

It is, of course, the carbonyl group that makes acyl compounds more reactive than alkyl compounds. Nucleophilic attack (Sn2) on a tetrahedral alkyl carbon involves a badly crowded transition state containing pentavalent carbon a bond must be partly broken to permit the attachment of the nucleophile ... 

Figure 4.21 E2 elimination regioisomers and stereoisomers. The cis-2-alkene has the most crowded transition state, and the l-alkene has the least crowded transition state.

It is also important to note that several factors influence both the stereoselectivity of hydrogen exchange and enolate formation in base-promoted reactions. Houk, Ando and co-workers found that differing conju-gative stabilization by CH p-orbital overlap does not directly influence stereoselectivity.205 Steric effects only dominate is exceptionally crowded transition structures, but torsional strain involving vicinal bonds contributes significantly to the stereoselectivity of all cases studied. 

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