Equatorial substituents reactivity

Reactions such as catalytic hydrogenation that take place at the less hindered side of a reactant are common m organic chemistry and are examples of steric effects on reactivity Previously we saw steric effects on structure and stability m the case of CIS and trans stereoisomers and m the preference for equatorial substituents on cyclo hexane rings... 

The axial or equatorial nature of a substituent has a bearing on its reactivity, or ability to interact with its environment. Equatorial substituents are more stable and less reactive than their axial counterparts. For example, equatorial carboxyl groups are stronger acids than axial ones because of the higher stability of the carboxylate ion, whereas equatorial esters are hydrolyzed more slowly than axial ones because they are less accessible to protons or hydroxyl ions during acid- or base-catalyzed hydrolysis. 

In cyclohexanyl haloketones 21, 22, 23, and 24 the very bulky equatorial substituents 1,3 to the halogen prohibit the existence of any chair-chair equilibration. However, these derivatives can adopt a boat conformation in which the axial halogen is not sterically hindered, except in the case of derivative 24, which does not ring contract in the presence of sodium methoxide in methanol.When zwitterion formation is favored under such conditions, its disrotatory in or out cyclization can give rise to both a- and cyclopropanones. Ring opening of the latter will lead to esters with configurations opposite to those of the initial carbon-bromine bond. Such a hypothesis is in accord with the reactivity observed in the case of 23. ... 

It has been validated [69] that the axial or equatorial nature of a substituent has a bearing on its reactivity or abiUty to interact with its environment. Moreover, equatorial substituents are an index of greater stability and less reactivity in comparison to their axial counterparts. In this direction our group has analyzed some of the N-iiee, N-alkyl, and N-positions substituted by the electron withdrawing groups such as formyl, ethoxy carbonyl, and nitroso group piperidine derivatives with various substituents at different positions in a piperidine ring to understand the stereochemistry of the system (Table 1). 

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... 

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). 

The relationship between conformation and chemical reactivity was first pointed out by D.H.R. Barton in 1950. In a paper he drew attention to the difference in chemical behavior when substituents were placed hi equatorial and axial properties in cyclohexanes. This will become clear from some of the following examples ... 

The presence of the two spirotetrahydrofuran rings in these reactive intermediates is obviously not condudve to the stereocontrolled synthesis of 14. This problem was resolved by making recourse to 22, a precursor to 15, the silyl-protected (3-hydroxypropyl) substituent which was viewed to be sufficiently bulky to guarantee its equatorial occupancy in the lowest energy conformation (Scheme 3-4). Furthermore, treatment of 22 with Grignard reagent should be met with rapid deprotonation of the hydroxyl and formation of chelate 23. At this point, customary equatorial... 

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