Size, of substituents

Some workers in this field have used Eyring s equation, relating first-order reaction rates to the activation energy d(7, whereas others have used the Arrhenius parameter E. The re.sults obtained are quite consistent with each other (ef. ref. 33) in all the substituted compounds listed above, AG is about 14 keal/mole (for the 4,7-dibromo compound an E value of 6 + 2 keal/mole has been reported, but this appears to be erroneous ). A correlation of E values with size of substituents in the 4- and 7-positions has been suggested. A/S values (derived from the Arrhenius preexponential factor) are... 

Unfortunately, an increase in the size of substituents at the a- and p-C atoms of nitro olefin (72) leads to a sharp decrease in the yield of target nitronates. It casts doubt on the importance of this method or at least on the procedure suggested. 

The stereoselectivity of the reaction can be rationalized in terms of the relative stabilities of the products 133 and 134. The stereoselectivity was more pronounced in the cyclohexane series. The stereoselectivity increases with increasing size of substituent R, and the reaction becomes a stereospecific process for the rert-butyl derivatives. The equatorial position of a bulkier substituent is preferred, and thus in the phenyl series the steric requirement of the phenyl group is smaller than that of the methyl group. 

Allylboronates of type 103 react with equivalent amounts of aldoximes 102 (equation 73) giving allylhydroxylamines 104 in good yields. Similar reactions of aldoximes and glyoxylate oxime ethers with allyl bromide and indium also provide hydroxylamines. Additions of substituted allyl boronates to oximes produce mixtures of stereoisomers with ratio highly dependent on the steric size of substituents in both molecules. Addition of allyltri-n-butyltin to aldoxime ether 105 (equation 74) was found to proceed with a considerable diastereoselectivity. 

Ring-inversion barriers in tetrahydro-l,3-oxazines (Table XXI) decrease with increasing size of substituent. Inclusion of a 4-methyl substituent also decreases A G for the process. 

From the H-NMR spectra the barrier to ring inversion was estimated as AG1 13.2 0.2 kcal mol-1 at — 5°C and the barrier to /V-inversion as AG1 7.2 + 0.1 kcal moP1 at — 123.5°C.363 Barriers to ring inversion in 1,3,5-trialkyl derivatives 470 decrease with increasing size of substituent,297 365-366 and AG values for nitrogen inversion (determined by 13C-NMR spectroscopy355) follow a similar trend (Table XXIX). The barriers to N-inversion... 

These findings imply that the use of probabilities for i-ad formation at a given temperature in a given solvent is insufficient to describe the monomer constitutions influence on the stereocontrol in free radical polymerizations. The lack of correlation is either the result of the combined action of more than one parameter (size of substituent, resonance stabilization and/or structure of propagating radicals, etc.) or the result of noncomparable experimental conditions. 

A limited number of 1,1-disubstituted olefins have been subjected to catalytic AD, and these are listed in Table 6D.4 [26,29,31,46], The results shown there indicate that selected members of this class of olefins can be dihydroxylated with high enantioselectivity but it should be recognized that these olefins all have relatively dissimilar substituents. As the two substituents becomes more alike, the discriminatory capability of the catalyst is expected to lessen and lower enantioselectivities to be observed. Such a trend may be found in the comparison of entries 1 and 5 with entry 3. The difference in size of substituents clearly is greater in the case of entry 3 and the diol derived from this olefin has the highest enantiomeric purity. 

The examples in Table 4 again demonstrate the effect of increasing size of substituents, reflected both by the deviation of [Pg.129]

Cytotoxicity of 3 -CF3-taxoids 71 and 72a-h thus obtained were evaluated against human cancer cell lines and the results are summarized in Table ll.45 As Table 11 shows, all these taxoids possess excellent activities, and are substantially more potent than either paclitaxel or docetaxel in virtually every case. The most remarkable results are, however, one order of magnitude better activities of the 10-acylated taxoids 72a-h as compared to paclitaxel and docetaxel against the drug-resistant breast cancer cell line, MCF7-R. The marked difference in cytotoxicity observed between 3 -(2-CF3-ethyl) taxoid, 68 or 69, and 3 -CF3-taxoids 72 reconfirms high sensitivity of the C-3 position to the size of substituent for the biological activity. 

The open transition state is preferred, but the outcome of the reaction (syn/anti) depends on the size of substituents and on the Lewis acid. New modified protocols allow syn- or anti-selective transformations and even the selective preparation of enantiomers. 

A clear correlation between the stabilisation of the endo-transition structure and the size of substituent at the 2-position of an 1-oxa-1,3-butadiene is again seen in the cycloaddition of the N-acetyl-enaminoketone 8-20 to 8-12. As expected, the reaction of 8-20 a to give 8-21 a and 8-22 a shows only a very small AAV, whereas with growing bulkiness of R as in 8-20 b and 8-20 c an increase of AAV is observed with the formation of the trans-cycloadduct 8-22 as the major product under high pressure. Because of the pressure effect it can clearly be deduced that 8-22 is formed via an endo-Z-anti-transition structure, presumably due to a strong hydrogen bond in the (Z)-diastereomer and a steric discrimination of the ( )-diastereomer of 8-20. However, an exo-E-anti-transition structure would give the same product (Fig. 8-7) [548]. 

Asymmetric synthesis of ketones (7, 17). Meyers and Williams have extended the asymmetric alkylation of cyclohexanones via the imines formed from 1 to acyclic ketones. Initially optical yields were only 3-44%, but they can be increased to 20-98% by heating the lithioenamines to reflux (THF) prior to alkylation at -78°. Evidently the lithioenamines formed at —20° are mixtures of (E)- and (Z)-isomers. The optical yields are lowered as the size of substituents on the ketone increases. Example ... 

---