Stereoelectronic effect nucleophilic substitution

The presence of a stereogenic center on the aldehyde can strongly inlinence the diastereoselectivity in allylboration reactions, especially if this center is in the a-position. Predictive rules for nucleophilic addition on snch a-snbstitnted carbonyl substrates such as the Felkin model are not always snitable for closed transition structures.For a-substituted aldehydes devoid of a polar substituent, Roush has established that the minimization of ganche-ganche ( syn-pentane ) interactions can overrule the influence of stereoelectronic effects. This model is valid for any 3-monosubstituted allylic boron reagent. For example, althongh crotylboronate (E)-7 adds to aldehyde 39 to afford as the major prodnct the diastereomer predicted by the Felkin model (Scheme 2), " it is proposed that the dominant factor is rather the minimization of syn-pentane interactions between the Y-snbstitnents of the allyl unit and the a-carbon of the aldehyde. With this... 

Moreover, product formation was not the same. Dibenzyl ethylsulfonium salt 72 gave only benzyl ethyl sulfide (73) and benzyl thiocyanate 74, but no dibenzyl sulfide or ethyl thiocyanate. By contrast, the cyclic sulfonium salt 75 gave a mixture containing chiefly (80%) dihydroisothianaphthene (76) with an equivalent amount of ethyl thiocyanate (77) and a minor amount (20%) of the sulfide-thiocyanate 78. This work represents the first direct experimental information on the rate of bimolecular nucleophilic substitution and relative orientation of the benzene ring and the leaving group and it demonstrates clearly the importance of stereoelectronic effects in these reactions. 

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. 

Theoretical studies of tetrahedral carbon species have played an important role in the formulation of ALPH and the anomeric effect. Similarly, molecular-orbital calculations have been the touchpaper for development of the stereoelectronic effect in phosphorus chemistry. Early theoretical calculations indicated the influence of the anomeric and gauche effects in phosphates (Newton, 1973). But without doubt, the foray of Lehn and Wipff (1975) into this field provided the inceptive piece of research that was the impetus for a series of studies resulting in the proposition of a stereoelectronic theory with a far-reaching impact on nucleophilic substitution reactions at phosphorus. 

The principle of microscopic reversibility brings the above stereoelectronic effects back into play in the reactions of o-benzynes with nucleophilic trapping species (Figure 10.17). For example, control of relative stabilities of aryl lithiums by substitution allows selective preparation of halosubstituted biphenyls. In the... 

The addition of nucleophiles to cyclic acetals and hemiacetals is an efficient method to access substituted THFs in high diastereoselectivity which is, in general, predictable and can be explained by stereoelectronic effects (1999JA12208). In this transformation, the intermediate is an oxocarbe-nium, which preferentially adopts an envelope conformation, and the nucleophile attacks on the inside face of the envelope. In the presence of a methyl at C3, the conformer possessing pseudoequatorial substituents is favored and the, 2>-trans product is obtained as the major product (63 64) (Scheme 33). It is worthy of note that when an alkoxy group is present at C3, the 1,3-ds product, resulting from an inside attack on the diaxial conformer, is favored (65 66) (Scheme 33). 

Fig. 4.30) with various substitution pattern at Cl and C2 were investigated. Experiments with alkyl substituents at C2, in place of the sulfur heteroatoms, eliminate the viability of a chelation-controlled selectivity and reveal the significance of geminal substitution [geminal substitution influenced the selectivity in other oxocarbenium ion systems [108]]. Perturbation of the Cl substituent of the oxocarbenium ion intermediate has little effect on reaction stereoselectivity, and analysis of this observation lends additional support for stereoelectronically preferred inside attack of the nucleophile. The results demonstrate that selective formation of the 1,4-c/s product 84 does not require a chelated transition stracture, reinforcing the utility of the inside attack model to analyze the reactivity of complex five-membered ring oxocarbenium ion intermediates. 

Formation and reactivity of o-benzynes o-benzynes serve as illustrative stereoelectronic models due to two features a) structural rigidity that restricts orbital interactions exclusively to syn-periplanar geometries and b) distortion of the in-plane x-system. These features are translated in the interplay of two related stabilizing effects controlling the structure of substituted benzynes and their reactivity towards nucleophiles 1) interaction of o-acceptors with bent bonds and 2) interaction of o-acceptors with anionic centers. 

Anomeric and double anomeric effects in phosphates The unusual stereoelectronic properties of negatively charged oxygen as a source of donor orbitals play a role in the formation of tetrahedral intermediates in nucleophilic addition/substitution at carbonyl. It also has important consequences for phosphate transfer reactions - one of the key types of chemical events in biology. 

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