Axial substituents reactivity

Strong 1 3 interactions between the axial substituent at C-6 with 8j5- and 2ji (5a-series) hydrogens and 10 -substituents decrease the reactivity of the 6-ketone as compared to saturated 3-ketones. The 6-ketone does not react with methanol to give a dimethyl ketal, even in the absence of the C-19 methyl group. Thus the 19-nor-5a-3,6-dione (75) gives selectively the 3,3-dimethyl-ketal (76). ... 

It is often possible to predict the reactivity of a chlorosulfonyloxy group by a consideration of the steric and polar factors affecting the formation of the transition state,27-28 as indicated in Section 11,1 (see p. 227) for nucleophilic-replacement reactions of sulfonic esters of carbohydrate derivatives. Thus, it has been found that the presence of a vicinal, axial substituent or of a (3-trans-axial substituent on a pyranoid ring inhibits replacement of a chlorosulfonyloxy group also, a chlorosulfate group at C-2 has been observed to be deactivated to nucleophilic substitution by chloride ion. 

The low reactivity of l,6-anhydro-2,3,4-tri-0-benzyl-/3-D-allopyra-nose is also of interest.106 This monomer has 1,3-interaction between substituents on C-2 and C-4 in the C4(d) conformation. However, when conversion into a boat conformation, as proposed, occurs on reaction with a propagating cation, eclipsed bonds develop at C-2, C-3, and C-4. It is, therefore, not surprising that the D-allo anhydride is less reactive than those of D-mannose, D-glucose, or D-galactose. The corresponding, D-altrose derivative has only one axial substituent in addition to the anhydro ring, and these are on opposite sides of the pyranose ring, and therefore do not interact it would be expected to be, and has proved to be, of very low polymerizability.106... 

The conversion of the chair to the half-chair conformation will be helped by the recession of the C2 and C5 axial substituents away from the C4 and C3 axial substituents, respectively. This effect will be more powerful as the size of these axial substituents increases. Consequently, on comparing methyl D-glycopyranosides which differ only at C2, C3, and C4 (that is, all in the Cl form), it can be predicted that the order of reactivity will be D-idose (three axial substituents) > D-altrose, D-gulose (two axial substituents) > D-allose, D-mannose, D-galactose (one axial substituent) > d-glucose (no axial substituents). Similarly, D-l3 ose > D-arabinose >d-... 

These data extend to the pyranoside series the relationship between steric strain and reactivity, and indicate that the conformational instability and non-bonded interaction of the axial substituents in the favored chair conformation result in a higher rate of hydrolysis. Another aspect of these theoretical considerations is that the methyl /3-d and fi-L aldopyranosides are only hydrolyzed faster than their corresponding a anomer when the normal chair conformation is favored, and thus, when the glycosidic group of the (3 anomer assumes an exposed, equatorial position (see page... 

The physical, chemical cind biological properties of a molecule often depend critically upo the three-dimensional structures, or conformations, that it can adopt. Conformational analysi is the study of the conformations of a molecule and their influence on its properties. Th development of modem conformational analysis is often attributed to D H R Bcirton, wh showed in 1950 that the reactivity of substituted cyclohexanes wcis influenced by th equatoricil or axial nature of the substituents [Beirton 1950]. An equcilly important reaso for the development of conformatiorml analysis at that time Wcis the introduction c analytic il techniques such as infreired spectroscopy, NMR and X-ray crystaillograph] which actucilly enabled the conformation to be determined. 

The incorporation of heteroatoms can result in stereoelectronic effects that have a pronounced effect on conformation and, ultimately, on reactivity. It is known from numerous examples in carbohydrate chemistry that pyranose sugars substituted with an electron-withdrawing group such as halogen or alkoxy at C-1 are often more stable when the substituent has an axial, rather than an equatorial, orientation. This tendency is not limited to carbohydrates but carries over to simpler ring systems such as 2-substituted tetrahydropyrans. The phenomenon is known as the anomeric ect, because it involves a substituent at the anomeric position in carbohydrate pyranose rings. Scheme 3.1 lists... 

The stereoselectivity of these reactions has been interpreted in terms of chair-like six-membered ring transition states in which the substituents a to tin adopt an axial position, possibly because of steric and anomeric effects. The cc-substituted (Z)-isomers are less reactive because the axial preference of the a-substituent would lead to severe 1,3-diaxial interactions17. 

This section deals with reactions which involve only the organo-ligand, whether unmodified or modified by the loss or gain of a proton, and the cobalt. After considering established and possible mechanisms (Section B,l) we list examples to show how reactivity is influenced by different functional groups and substituents (Section B,2), and by changes in the axial and equatorial ligands (Section B,3). 

---