Benzylic cations electron-withdrawing substituents

To avoid any loss of benzyl ester protection during acidolytic removal of the benzyloxy-carbonyl and ferf-butoxycarbonyl groups, electron-withdrawing substituents were used to destabilize the intermediate benzyl cation and thus to increase the acid stability. In addition to the very useful 4-nitrobenzyl esters (vide infra), the picolyl ester (see Section 2.2.1.2.2.3) as well as halo-P l or cyano-P°°l substituted benzyl esters have been reported, the latter being rarely used for a-carboxy protection. Conversely, an increase in sensitivity toward acids can be achieved by introduction of electron-releasing substituents, such as methoxy or methyl groups. Addition of scavengers to quench intermediate carbocations and to prevent electrophilic substitutions at sensitive amino acid side chains is beneficial in the deprotection of such esters. 

Electron-withdrawing substituents in anionic polymerizations enhance electron density at the double bonds or stabilize the carbanions by resonance. Anionic copolymerizations in many respects behave similarly to the cationic ones. For some comonomer pairs steric effects give rise to a tendency to altemate. The reactivities of the monomers in copolymerizations and the compositions of the resultant copolymers are subject to solvent polarity and to the effects of the counterions. The two, just as in cationic polymerizations, cannot be considered independently from each other. This, again, is due to the tightness of the ion pairs and to the amount of solvation. Furthermore, only monomers that possess similar polarity can be copolymerized by an anionic mechanism. Thus, for instance, styrene derivatives copolymerize with each other. Styrene, however, is unable to add to a methyl methacrylate anion, though it copolymerizes with butadiene and isoprene. In copolymerizations initiated by w-butyllithium in toluene and in tetrahydrofuran at-78 °C, the following order of reactivity with methyl methacrylate anions was observed. In toluene the order is diphenylmethyl methacrylate > benzyl methacrylate > methyl methacrylate > ethyl methacrylate > a-methylbenzyl methacrylate > isopropyl methacrylate > t-butyl methacrylate > trityl methacrylate > a,a -dimethyl-benzyl methacrylate. In tetrahydrofuran the order changes to trityl methacrylate > benzyl methacrylate > methyl methacrylate > diphenylmethyl methacrylate > ethyl methacrylate > a-methylbenzyl methacrylate > isopropyl methacrylate > a,a -dimethylbenzyl methacrylate > t-butyl methacrylate. 

Benzyl esters are cleaved by catalytic hydrogenation and also by acidolysis albeit only under fairly drastic conditions. Electron-withdrawing substituents, such as the nitro group in / -nitrobenzyl esters, destabilize the benzyl cation and render the benzyl group even more resistant to acids. In contrast, the action of moderately strong acids, like dilute solutions of HCl in acetic acid or neat trifluoroacetic acid is sufficient for the acidolytic cleavage of /7-methoxybenzyl esters and, of course, of tert.butyl esters. 

The difluorobenzyl cation (Figure 4.20) is stable under conditions in which the benzyl cation undergoes rapid polymerisation [57] and and NMR studies [58] have shown that, as the electron demand of the aromatic ring increases (i.e. R is electron-withdrawing), the TT(p-p) donation of fluorine to the carbocation centre also increases, leaving the electron density at relatively constant for a variety of aromatic substituents. 

The extent of the rate enhancement due to adjacent substituents is dependent on the nature of the transition state. The most important factor is the nature of the TT-type orbital which develops at the trigonal bipyramidal carbon in the transition state. If this carbon is cationic in character, electron donation from adjacent substituents becomes stabilizing. If bond formation at the transition state is far advanced, electron withdrawal should be more stabilizing. Substituents such as carbonyl therefore have their greatest effect on reactions with strong nucleophiles. Adjacent alkoxy substituents can stabilize Sn2 transition states that are cationic in character. Since the vinyl and phenyl groups can stabilize either type of transition state, the allyl and benzyl systems show enhanced reactivity toward both strong and weak nucleophiles. ... 

---