Electrophilic selectivity

In contrast to ethyl diazoacetate, diethyl diazomalonate reacts with allyl bromide in the presence of Rh2(OAc)4 to give the ylide-derived diester favored by far over the cyclopropane (at 60 °C 93 7 ratio). This finding bespeaks the greater electrophilic selectivity of the carbenoid derived from ethyl diazomalonate. For reasons unknown, this property is not expressed, however, in the reaction with allyl chloride, as the carbenoids from both ethyl diazoacetate and diethyl diazomalonate exhibit a similarly high preference for cyclopropanation. 

From the relative reactivities in Table 7.3, we conclude that 7a is dominant for CH3CCI and CCI2, which exhibit electrophilic selectivity toward the alkenes. On the other hand, CH3OCCH3 displays strongly nucleophilic selectivity toward the electron-poor alkenes. Resonance donation from the methoxy oxygen atom to the carbene Ip orbital (8, Fig. 7.7) is sufficiently strong to render CH3OCCH3 a nucleophilic carbene for which a 71 carbene to alkene electron donation is dominant in the transition state (viz., 7b). 

If an aldehyde and an ester group occur together in the presence of a reducing agent like DIB AH (22), the aldehyde is reduced more rapidly as a consequence of Us greater electrophilicity. Selective reduction of an ester to an aldehyde is therefore possible only if product 23 of the first hydride transfer does not collapse to an aldehyde. in nonpolar solvents at low temperature the tetrahedral intermediate 23 is stable and decpolar-coordinating solvent such as THE on the other hand, the O-Al bond is weakened to such an extent by coordination of solvent with the metal atom in 24 that the aldehyde arises even before hydrolysis and is immediately reduced further to an alcohol.15... 

In addition to the variation in the electrophilic selectivity of reagents induced by modification of the structure and charge of the electrophile, the interaction of the reagent with the solvent is also important. The discriminatory properties of molecular chlorine depend on the nature... 

Nevertheless, a small increase in the pfej< e ratio with an increase in St is detectable. (The line in Fig. 9 represents the reactivity of the para position.) The trend is in accord with the electronic interpretation. It is conceivable, however, that the variation is merely the result of the greater sensitivity of the weakly electrophilic, selective reagents to the steric requirements of the methyl group. 

Table 14.2 Reformatsky reactions with less conventional electrophiles selected examples...

The classical example of the selective activation of a reaction site in a substrate with more than one reactive center is acetoacetic ester 168 (Scheme 2.80). Its reactive form is the enolate 169, which reacts with a variety of electrophiles selectively at the central carbon atom. A subsequent hydrolysis and decarboxylation of the product 170 leads to the formation of ketone 171. The structure of 171 corresponds to the coupling of the electrophile with the carbanion 172, or, in other words, with deprotonated acetone. Thus acetoacetic ester is actually employed in this sequence as a synthetic equivalent to 172. 

Compared with results obtained for ethyl diazoacetate, reactions of diazomethane with allyl bromide produce a dramatic reversal in the relative reactivities of the carbenoid species towards the nucleophilic bromide and the carbon-carbon double bond. These results are in accord with a greater electrophilic selectivity of the dialkoxycarbonyl carbenoid intermediate relative to the ethoxycarbonyl carbenoid. That increasing the electrophilicity of the carbenoid intermediate can reverse its reactivity towards the nucleophilic heteroatom relative to the olefin is consistent with the nature of this... 

The metal-carbenes derived from diazomalonates and 2-diazo-l-phenylethanone display a higher electrophilic selectivity, hence a greater tendency for ylide formation, than those derived from diazoacetates. 

Fig. 9.8. Reaction energy profiles for electrophilic aromatic substitution showing variation in ratedetermining step and electrophile selectivity.

We restrict our attention to the reactions of CH bonds with low-valent transition metals that avoid radical or electrophilic selectivity patterns and are therefore considered CH activation in the sense considered at the outset of the review. A number of non-alkane CH activation reactions are included where they derive from concepts developed in alkane work and where they have proved particularly useful. 

Finally, photolysis of the Re(V) oxo-idodide compound (HBpz3)ReO(I)Cl in arene (ArH) solvents gives the aryl complexes (HBpz3)ReO(Ar)Cl [39], Substituted arenes react with electrophilic selectivity and the authors propose that the reactive species is a rhenium(V) 0x0 complex which can add aromatic C-H bonds aaoss the Re=0 linkage. 

With chromium, intermediates other than the anionic cyclohexadienyl complex have not been isolated, but three X-ray structures of the products of interception of anionic cyclohexadienyl chromium complexes with ClSnPh3 provide indirect evidence for the proposed mechanism [37-39]. Electrophile selectivity was established as shown in Scheme 12. 

In terms of transition state 2, we can see that electrophilic selectivity will be greatest when strong resonance interactions of X and Y with the carbenic carbon evoke correspondingly strong 7t-electron donation by the alkene, leading... 

A singlet carbene is inherently both an electrophile and a nucleophile, what is behaviorally decisive is whether, in the carbene/alkene addition transition state, it is the LUMO(carbene)/HOMO(alkene) or HOMO(carbene)/LUMO(alkene) interaction (cf., Fig. 5) which dominates and determines the electronic distribution. If the former interaction dominates, the carbene will exhibit electrophilic selectivity if the latter interaction is more important, nucleophilic selectivity will be observed. If both interactions are comparable, the carbene will display an ambiphilic selectivity pattern, in which it acts as an electrophile toward electron-rich alkenes, but as a nucleophile toward electron-poor alkenes. [8,69]... 

The introduction of phosphorous substituents is easily accomplished by deprotonation of the a positions of terminal thiophene rings of the thiahe-hcene scaffold with wBuLi at —78 °C and reaction with the appropriate phosphorous-based electrophile. As mentioned before, the use of the appropriate equivalents (2 or 4 equiv.) of nBuLi and of the electrophile, selectively leads to mono- or difunctionalization of the terminal thiophene rings (Scheme 31). 

Lewis acidity, electrophilicity, selective binding preferences, hydrolytic chemistry... 

Scheme 17 Reaction of cyclic dianion 31 with electrophiles selective synthesis of multi-substituted 3-cyclopentenone...

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