Stereoelectronic effects, elimination reactions

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. 

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. 

These effects are minimized for n-o fragmentations, especially those where the intramolecular electron transfer takes place between spatially adjacent orbitals. Somewhat related stereoelectronic considerations apply to nucleophile or base assisted fragmentations where certain three-dimensional dispositions of existing bonds may favor the assistance, in a way related to, for example, the anti stereochemistry of elimination reactions (Sect. 5.2). 

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 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. 

Although this is the only chapter in which stereoelectronics appears in the title, you will soon recognize the similarity between the ideas we cover here and concepts like the stereospecificity of E2 elimination reactions (Chapter 17) and the effect of orbital overlap on NMR coupling constants (Chapter 18). We will also use orbital alignment to explain the Karplus relationship (Chapter 32), the Felkin-Anh transition state (Chapter 33), and the conformational requirements for rearrangement and fragmentation reactions (Chapter 36). 

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