Stereoelectronics, eliminations

When, in the phosphorous oxychloride-pyridine dehydration of an alcohol these rules conflict, the stereoelectronic factor determines the direction of elimination ... 

A further test of the stereoelectronic theory of reactivity of phosphate esters has been attempted using measurements of the rates of displacement of 4-nitrophenate from the esters (23) and (24), their phosphorus epimers, and also (25), in aqueous methanol the introduction of the 4a-Me group into the system would, it was hoped, reduce the the flexibility of the bicyclic structures and so possibly eliminate the participation of twist-boat conformations. The presence of the 4a-Me group has no effect of the rate of displacement of the axial ArO group... 

The selectivity in the Heck reaction of allylic alcohol 111 is interesting, and the factors that lead to the observed preference for (3-hydride elimination toward nitrogen in this system are unclear, although a combination of steric effects and stereoelectronic factors (i.e., alignment of C-H and C-Pd bonds, nN a c H interactions) is likely involved. Examination of related examples from the literature (Scheme 4.20) reveals no clear trend. Rawal and Michoud examined substrate 115, which lacks the influence of both the amine and hydroxyl substituents and also seems to favor (3-hydride elimination within the six-membered ring over formation of the exocyclic olefin under standard Heck conditions [18a]. However, under... 

This means that if a reaction is carried out on a compound that has no stereoisomers, it cannot be stereospecific but at most stereoselective. The concerted reactions, including SN2 displacements, E2 elimination of alkyl halides, anti and Syn addition to alkenes are all stereoselective. In the case of chiral or geometric substrates the nature of the product depends on the unique stereoelectronic requirement of the reaction. These are examples of stereospecific reactions. 

A straightforward explanation for the unexpected stability of / -lactone enolate 2 has been put forward, a stereoelectronic reason in the rigid system 2 the essential orbitals are held orthogonal to each other as in 2 thus, an elimination reaction has a much higher activation energy than in an open system49. 

Suggest an explanation based on orbital interactions for the observed stereochemistry for E2 elimination reactions, that is, the strong stereoelectronic preference that the C—H and C—X bonds be anti-coplanar. 

The crystal structures of thiamin-dependent enzymes (see next section) as well as modeling102 103 suggest that lactylthiamin pyrophosphate has the conformation shown in Eq. 14-21. If so, it would be formed by the addition of the ylid to the carbonyl of pyruvate in accord with stereoelectronic principles, and the carboxylate group would also be in the correct orientation for elimination to form the enamine in Eq. 14-21, step b.82 83a A transient 380- to 440-nm absorption band arising during the action of pyruvate decarboxylase has been attributed to the enamine. 

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. 

The use of cyclic sulfates in synthetic applications has been limited in the past because, although cyclic sulfites are easily prepared from diols, a convenient method for oxidation of the cyclic sulfites to cyclic sulfates had not been developed. The experiments of Denmark [70] and of Lowe and co-workers [71 ] with stoichiometric ruthenium tetroxide oxidations and of Brandes and Katzenellenbogen [72a] and Gao and Sharpless [68] with catalytic ruthenium tetroxide and sodium periodate as cooxidant have led to an efficient method for this oxidation step. Examples of the conversion of several diols (67) to cyclic sulfites (68) followed by oxidation to cyclic sulfates (69) are listed in Table 6D.7. The cyclic sulfite/cyclic sulfate sequence has been applied to 1,2-, 1,3-, and 1,4-diols with equal success. Cyclic sulfates, like epoxides, are excellent electrophiles and, as a consequence of their stereoelectronic makeup, are less susceptible to the elimination reactions that usually accompany attack by nucleophiles at a secondary carbon. With the development of convenient methods for their syntheses, the reactions of cyclic sulfates have been explored, Most of the reactions have been nucleophilic displacements with opening of the cyclic sulfate ring. The variety of nucleophiles used in this way is already extensive and includes H [68], [68,73-76], F" [68,72,74], PhCOCT [68,73,74], NOJ [68], SCN [68],... 

The stereoelectronic requirements of groups undergoing base-promoted elimination is also easily seen by stereochemical studies. Treatment of trans-2-methylcyclohexyl tosylate gives 3-methylcyclohexene as the major product while treatment of czs-2-methylcyclohexyl tosylate gives the more stable 1-methylcyclohexene as tire only product. 

Chandrasekhar and Kirby (93) have observed that the hydrolysis of the axial -nitrophenoxy isomer 1 27 is pH-independent in the pH range 7-10 and found that the rate of this spontaneous hydrolysis is 3.3 times slower than the equatorial isomer 128 under the same conditions. Thus, in a system designed to eliminate all other factors, including the problems of interpretation associated with acid-catalyzed reactions, no evidence was found that acetal cleavage is subject to stereoelectronic control. 

The next operation consists in the analysis of the hydration of lactonium ion 63 and the subsequent breakdown of the resulting hemi-orthoester. A stereoelectronically controlled attack of water on the lactonium ion 63 must take place on the b face yielding the tetrahedral conformer 66 (Fig. 7). As previously discussed for the case of lactones (cf. p. 70), a reaction with water on the a face of 63 would result in a tetrahedral intermediate having a boat conformation, and this process is therefore eliminated. 

The cis bicyclic orthoester 87 can exist in the two different conformations 91 and 92. The conformation 92 corresponds to that of the unreactive tricyclic orthoester 62, i. e. conformer it can therefore be eliminated. Con-former 91 can undergo the cleavage of the axial C —0 bond with stereoelectronic control to produce the lactonium ion 93 which after hydration will give the hemi-orthoester 94. Since the chair inversion in 94 is not favored because the hydroxyalkyl side chain would have to take the axial orientation, it is expected that 94 would give the dihydroxy methyl ester 89 preferentially. 

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

In another study, Buchanan and McLay (104) found that the equatorial oicy- ri clic ketotosylate 36S gave the seven-membered olefinic ester 367 while the,. axial isomeric tosylate 368 gave the seven-membered olefinic ester 371. Again, the reaction of the equatorial tosylate occurs through the fragmen- tation of intermediate 366. The transformation 368- 371 can be explained by the stereoelectronically controlled retro-Dieckmann fragmentation of 369 followed by the elimination of the tosylate group from 370. 

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