Elimination stereoelectronic effects

The term stereoelectronic refers to the effect of orbital overlap requirements on the steric course of a reaction. Thus, because of stereoelectronic effects, the Sw2 substitution gives inversion (see Section 4.2) and E2 elimination proceeds most readily when the angle between the leaving groups is 0° or 180° (see Chapter 7, p. 369). Stereoelectronic effects also play an important role in pericyclic reactions, which are the subject of Chapters 11 and 12. 

In principle, stereoelectronic effects should play an important role in the formation of double-bonds in base-promoted eliminations of HX. 

It would appear safe to conclude that where stereoelectronic effects alone are operating, the anti elimination process is favored over the syru There are however several other parameters which are also important, such as the effects of the nucleophile, the solvent, the alkyl structure of the substrate and the nature of the leaving groups. Any of these variables is capable of completely reversing the stereochemical course of a concerted elimination reaction (83). 

Trans-elimination is therefore clearly stereochemically favored over cis-elimination indicating that stereoelectronic effects must play a decisive role in these reactions. Ingold (1) has pointed out that ... 

In the previous subsection, it was shown that the Ferrier reaction offers an opportunity to convert glycal derivatives into unsaturated sugar derivatives, which have an isolated double bond between C(2) and C(3). The Tipson-Cohcn reaction is another important reaction for the introduction of isolated double bonds.29 In this procedure, a cis or tram diols are converted into disulfonates (mesylates or tosylates) which are reductively eliminated with sodium iodide and zinc in refluxing DMF (Scheme 3.6a). In this reaction, the C(3) sulfonate is substituted by an iodide, which then is reductively removed by zinc with concomitant elimination of the second sulfonate moiety, introducing a double bond. Stereoelectronic effects make nucleophilic substitutions at C(3) more favourable than similar reactions at C(2) (see Section 3.2.3). Probably, the elimination proceeds through a boat conformation. In this case, the iodide and tosylate are in a syn relation. In most cases, E2 elimination proceeds via a transition state involving an anti orientation. Nevertheless, syn elimination becomes the dominant mode of reaction when structural features prohibit an anti orientation. 

The relatively easy elimination of axial anomeric groups in glycosides may also be a demonstration of a similar stereoelectronic effect (66MI1 74OMS480). 

Figure 7.25. Stereoelectronic effects on the Norrish type II reaction. Presumed optimal orbital alignments a) for cyclization and b) for elimination.

The stereochemistry of 3-C-nitro glycals has been studied in some detail [210]. For example, when nitroanhydroglucitol 106 was subjected to reaction with triethylamine, it gave the elimination product 107, which was then rearranged to an equilibrated mixture of glycals 108 and 109 (O Scheme 36) [211,212]. Some researchers have tried to explain this equilibrium shift by arguing that the quasi-equatorial anomeric proton is made more acidic by the stereoelectronic effect [213]. 

The acetal RCH(OMe)2 can have a total of nine conformers, 30a-30i. We may ignore the broken red bonds, which are included to allow a quick conformational match with that of the cyclohexane chair and, thus, ascertain the geometrical relationships rather easily. The conformers 30a and 30e have two methyl groups within van der Waals distance and, hence, their contributions to the overall conformational equilibrium will be small, if not zero. We can therefore eliminate these conformers from further discussion. The conformers 30b and 30d, 30c and 30 g, and 30f and 30 h are mirror images and, thus, we need to consider only one conformer of each pair. Thus, we are left with four distinct conformers, namely 30b, 30c, 30f, and 30i, to consider for acid hydrolysis. The relative contributions of these conformers could be estimated from the understanding that they are laced with two, one, one and zero stereoelectronic effects, respectively. The conformers 30b and 30i are, respectively, the most contributing and the least contributing. The conformers 30c and 30f contribute at the medium level. 

Let us examine each step of the orthoester hydrolysis under the operating stereoelectronic effects that vary with the variation in the conformational profile. Consider the acetal 92 and the nine well-defined conformers 92a-92i. The con-formers 92c and 92e suffer from severe steric interactions between the methyl groups as shown and, hence, their concentration at equilibrium should be expected to be negligible. Likewise, conformers 92g-92i also suffer from severe steric interactions between the methyl of the axial methoxy group and the axial hydrogen atoms on ring positions 4 and 6 as shown for 92 g. The equilibrium concentration of each of these conformers also should be expected to be negligible like those of 92c and 92e. We may eliminate all these conformers from further discussion. 

The loss of an alkoxy group, after protonation, is the starting point of hydrolysis. An orthoester can provide for this loss to take place with the assistance from one or two stereoelectronic effects, the latter being obviously favored over the former. The conformer 92d does not allow any stereoelectronic effects. This conformer may therefore be treated as the slow reacting or even as the neutral conformer. This prediction has been verified experimentally by studying the hydrolysis of 93, a rigid 92d conformer, which was found to be stable to the normally employed mild acidic conditions for orthoester hydrolysis [2-5]. Therefore, the conformer 92d is also eliminated from further discussion. 

Thus, both the trans-addition and tram-elimination are strongly favored over the corresponding civ-variants due to stereoelectronic effects. In 1,2-migrations, the migrating group is always anti to the leaving group on the adjacent carbon. 

The second factor is the structure of the tetrahedric intermedier, in which the leaving methoxy group should have axial orientation (structures (S.S -TSt) and (3i -75t) in Fig. (17)), since in this case the double stereoelectronic effect coming from the non-bonding electronpair of both the N atom and the geminal hydroxy group (see curved arrows at the reaction center) could facilitate the elimination. However, this intermediate is rather crowded in the S31 conformer because, like in the final lactam, the benzene ring is in axial orientation. R12 is flat in both cases. 

Many examples of stereoelectronic effects have been proposed in numerous areas of organic chemistry. The textbook example is perhaps the requirement for the anti conformation of the electrons of the scissile C—H bond with the leaving group in the E2 elimination reaction. However, over the past decade, the term stereoelectronic effect has become synonymous with an effect otherwise termed the kinetic anomeric effect or the antiperiplanar lone-pair hypothesis. While it is quite erroneous to label this hypothesis as the stereoelectronic effect , the fact that this situation has come about does serve to emphasize the ascendency of this hypothesis in the minds of many organic chemists. 

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