Influence of Stereoelectronic Effects on Reactions

For the E2 reaction to succeed, ctc. h and ctc L bonds must be antiperiplanar to each other as shown. This structural feature allows for oc h — ff c-L interaction which is responsible for the enhanced acidic character of the hydrogen to allow its 

An electron pair orbital that is not engaged in anomeric effect is more electron rich and, hence, more vulnerable to protonation than an electron pair orbital that is involved in anomeric effect. This translates into the understanding that two electron pair orbitals on the same heteroatom are likely to be different from each other on account of whether or not the electron pair is engaged in anomeric effect. 

In the transformation 16 14, water attacks the oxonium ion on the axial face. The electron pair of the cleaved n bond ends up in the axial orbital on the ring oxygen that exerts anomeric effect on the crc () bond that is just formed. An attack from the equatorial site will generate 19, where the new ctc o bond formed is not in anomeric effect with any of the electron pair orbitals of the ring oxygen. Both the formation and the cleavage of a bond under anomeric control are more facile than when the anomeric effect is absent. We shall continue to learn this aspect through the discussions below as well. 

We know that the reaction of an aldehyde with an alcohol under dehydrating conditions generates an acetal as shown in Eq. 7. The details regarding the progress 

Let us consider the reverse of acetal formation, i.e., acid hydrolysis of an acetal within the ambit of stereoelectronic effects and explore the underlying features. We begin by understanding the conformational profile and the associated conformational effects by representing the acetal in such a way that it appears to be part of a cyclohexane chair. In doing so, we understand the geometrical relationship of various bonds on this ring system much better. 

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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... 

These reactions likely proceed vi a the formation of an intermediate carban-ion. Indeed, the carbanion 496 generated by treatment of 491 and 492 with lithium di isopropyl amide gave 81% of 491 (H=D) and 19% of 492 (H=0). The preferential formation of 491 can be explained on the basis of stereoelectronic effects which influence the reactivity of the intermediate carbanion... 

Since the importance of entropic factors in the kinetics of reactions controlled by stereo-electronic interactions discussed in this chapter is well recognized now (6h, 10,11,315a), the influence of these interactions on the rates should preferably be discussed in terms of enthalpies of activation (cf. Section II.F). This seems to be especially important when stereoelectronic effects are deduced from rates of reactions of nonisomeric compounds. 

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. 

In organic chemistry it is well known that a substituent directly linked to a reaction center has a profound effect on the latter s reactivity. The influence of a remote substituent has also received much attention as more organic molecules are being scrutinized. Thus, neighboring group participations in solvolysis are generally observed. Certainly, the full attribution of a substituent must be the sum of electronic, steric, and stereoelectronic factors. 

Different silyl groups in substrates exert steric influence on organic reactions in various degrees. Evidence for this exists in the following 29 types of important organic reactions, which can be controlled by bulky silyl groups. Their steric effect often dominates the outcome of those reactions. Nevertheless, the electronic or the stereoelectronic effect may simultaneously also play a minor role. 

Before completing this section on the SN2 reaction, we must also consider the influence of the stereoelectronic effects caused by the electron pairs of atoms which are linked to the carbon bearing the leaving group. 

Stereoelectronic effects should also play an important role in the nucleophilic 1,4-additions of anions to conjugated systems. These effects should therefore influence the Michael reaction as well as the hydrocyanation of a,6-unsaturated ketones. Studies on these reactions provided evidence that the kinetically controlled addition of a nucleophile to a cyclohexenone derivative is indeed subject to stereoelectronic effects. 

The effect of substituents on the stereoselectivity has been studied in the acid-catalyzed hydrolysis of a series of aryloxiranes. Work on the influence of temperature on the steric course of the reaction has demonstrated that the tendency towards retention is explained by the high degree of carbocationic nature in the transition state leading to the cis products, the favorable entropy content of the transition state of cis addition, and the relatively low enthalpy barrier of the benzyl C-0 bond. At the same time, almost complete tram selectivity can be observed in aliphatic and cycloaliphatic oxiranes and ionization of the C-0 bond is associated with high enthalpy values. Attempts have been made to separate the inductive, conformational, and stereoelectronic effects. 3,4-Epoxytetrahydropyran was used to study the inductive effect while the corresponding cis- and trans-methyl derivatives were employed to examine the stereochemical and conformational factors. ... 

Similarly photocycloaddition of ethylene with chiral 5-alkoxyfuranones 181 proceeds with facial diastereoselection [153], Although selectivity remains low, the reaction has been used for the enantiospecihc synthesis of grandisol because it is easy to separate the initial diastereoisomers [154]. Selectivity is greatly influenced by temperature and by substituents on the ethylenic bond of the furanone ring. It was concluded that steric hindrance of the alkoxy group and stereoelectronic effects of substituents on the conjugated system are responsible for the selectivity observed. It was also proposed that the diastereoselection of the photocycloaddition of ethylene with 181 was dominated by the approach of ethylene to the vibrationally relaxed (71,71 ) excited furanone rather than by the selectivity of the reactions of biradicals. 

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. 

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