Carbocations trifluoromethyl

Methyl group releases electrons, stabilizes carbocation than than Trifluoromethyl group withdraws electrons, destabilizes carbocation... 

Since these methoxylated and acetoxylated sulfides have an acetal structure, it is expected that Lewis acid catalyzed demethoxylation should generate a carbocation intermediate which is stabilized by the neighboring sulfur atom. In fact, nucleophilic substitution with arenes has been successfully achieved as shown in Scheme 6.7 [43], This procedure is useful for the preparation of trifluoroethyl aromatics. As already mentioned, generation of carbocations bearing an a-trifluoromethyl group is difficult due to the strong electron-withdrawing effect. Therefore, this carbon-carbon bond formation reaction is remarkable from both mechanistic and synthetic aspects. 

The thus prepared /l-trifluoromethylated 0,S-acetal 4 allows us to make a carbon-carbon bond via a carbocation at the -position to the CF 3 group as shown in Scheme 6.9 [48]. Interestingly, Lewis acid-mediated allylation and cyanation can be achieved efficiently only when electrogenerated acids (EGA) are employed. 

The first long-lived fluorine-containing carbocation was discovered by Olah and coworkers.32 Thus, the fluorodimethylcarbcnium ion [Me2CF+] was obtained by protonation of 2-fluoropropene and also from 2,2-difluoropropane by reaction with antimony(V) fluoride. In the course of these investigations it was found that a-F stabilizes a cationic state, whereas fi-F is destabilizing. Attempts to prepare the simplest member of this class, the trifluoromethyl carbocation CF3+ failed. The ionization of trifluoromethyl halides with antimony(V) fluoride at — 80 C yielded only carbon tetrafluoride. 

Unlike a methyl group, which is slightly electron-releasing, a trifluoromethyl group is a powerful electron-withdrawing substituent. Consequently, a CF3 group destabilizes a carbocation site to which it is attached. 

Trifluoromethyl group withdraws electrons, destabilizes carbocation... 

The mechanism for the cyclization of these perfluoro ketones, proposed by German and coworkers5 and discussed in the review by Krcspan and Petrov.4 involves initial activation of the carbonyl with antimony V) fluoride and a 1.4-fluorine shift from the /1-trifluoromethyl group. The resultant difluoromethylene carbocation then cyclizes with the carbonyl oxygen to give the tetrahydrofuran. 

This behavior is exceptional. Nevertheless, the assumption that pAR and p AR measure equivalent trends in carbocation stability needs to be treated with caution. Richard and coworkers measured values of pAR to assess the influence of (3-fluoro substituents on the stability of the a-methyl /)-mcUioxybcn/yi cation 58 (R = Me). As indicated in Scheme 29, replacement of an a-methyl by an a-trifluoromethyl group decreases the stability of the carbocation by 7 powers of 10 in AR. 221... 

A further dependence of the selectivity between different nucleophiles on the stability and reactivity of carbocations was found by Richard and Amyes in a study of reactions of alcohols and carboxylate anions with -substituted a-trifluoromethyl benzyl cations (75, X = Me, OMe, SMe, N(Me)CH2CF3, and NMe2) monitored using the azide clock.305 Apart from the methyl-substituted substrate, for which the reactions approached diffusion control,... 

It seems clear therefore that more reactive cations than those for which Ritchie s N+ relationship was developed, show a distinct dependence of selectivity between nucleophiles upon the stability and reactivity of the carbocation. Richard has confirmed that for a very stable benzylic carbocation, represented by the bis-trifluoromethyl quinone methide 57, the N+ regime is restored and that a plot of log k against N+ for reactions of nucleophiles, including amines, oxygen and sulfur anions, the azide ion, and a-effect nucleophiles, shows a good correlation with N+.219... 

The interpretation of reactivities here provides a particular challenge, because differences in solvation and bond energies contribute differently to reaction rates and equilibria. Analysis in terms of the Marcus equation, in which effects on reactivity arising from changes in intrinsic barrier and equilibrium constant can be separated, is an undoubted advantage. Only rather recently, however, have equilibrium constants, essential to a Marcus analysis, become available for reactions of halide ions with relatively stable carbocations, such as the trityl cation, the bis-trifluoromethyl quinone methide (49), and the rather less stable benzhydryl cations.19,219... 

In a study by Berti et al., acid-catalyzed hydrolysis of styrene oxide was reported to occur with 67% inversion and 33% retention at the benzyl carbon.45 In a later study, it was reported that the styrene glycol product formed in the acid-catalyzed hydrolysis of chiral styrene oxide is completely racemic, which would indicate an A-l mechanism.46 As these two results indicate quite different mechanisms for this reaction, the glycol product from acid-catalyzed hydrolysis of chiral styrene oxide was converted to its bis-( + )-a-(methoxy-a-trifluoromethyl)phenylacetate diester derivative, and the composition of the diastereomeric diester mixture was determined by H NMR.47 This study agreed with those of Berti et al. and showed that acid-catalyzed hydrolysis of styrene oxide occurs with 67% inversion and 33% retention at the benzyl carbon. Acid-catalyzed methanolysis of styrene oxide is reported to occur with 89% inversion at the benzyl carbon.48 The fact that the diol product from acid-catalyzed hydrolysis of chiral styrene oxide is not completely racemic demonstrates that the lifetime of the carbocation is not sufficiently long for it to become symmetrically solvated. 

Both inductive and resonance effects are involved. The favored reaction proceeds through the most stabilized (or least destabilized) intermediate carbocation. Study carefully the resonance forms pictured for the possible cations derived from electrophilic attack on methylbenzene and (trifluoromethyl)benzene (Section 16-2), and on benzenamine (aniline), benzoic acid, and a halobenzene (Section 16-3). Notice the types of groups that fall into the different categories in Table 16-1. In particular, notice the following two general trends ... 

---