Carbocations acyl-substituted

The sp hybridized carbon of an acyl chloride is less sterically hindered than the sp hybridized carbon of an alkyl chloride making an acyl chloride more open toward nude ophilic attack Also unlike the 8 2 transition state or a carbocation intermediate m an Stvfl reaction the tetrahedral intermediate m nucleophilic acyl substitution has a stable arrangement of bonds and can be formed via a lower energy transition state... 

Besides avoiding carbocation rearrangements, another advantage of preparing alkyl-substituted benzenes by acylation-reduction rather than by direct alkylahon is that a large excess of benzene does not have to be used (Sechon 15.14). Unlike alkyl-substituted benzenes, which are morereachve than benzene (Section 16.3), acyl-substituted benzenes are less reactive than benzene, so they will not undergo addihonal Friedel-Crafts reactions. 

Treated with trifluoroacetic anhydride, sulfoxides 218 undergo conversion to triazapentalenes 219 with high yields. The process must involve acylation of the sulfoxide oxygen atom and generation of a carbocation that attacks the N-2 atom of benzotriazole. Hydrogenation over Raney nickel cleaves the C-S and one of the N-N bonds to generate >rtfe -substituted anilines 220 (Scheme 27) <2002EJ0493>. 

In continuation of our investigations on asymmetric nucleophilic acylations with lithiated a-aminonitriles [40], we envisaged the asymmetric synthesis of 3-substituted 5-amino-4-oxo esters A, bearing both a-amino ketone and 5-amino ester functionalities (Scheme 1.1.14) [41]. Since a-amino ketones are precursors of chiral p-amino alcohols [42, 43] and chiral amines [43], their asymmetric synthesis has the potential to provide valuable intermediates for the synthesis of biologically active compounds, including peptidomimetics [44]. The retrosynthetic analysis of A leads to the a-aminoacyl carbanion B and p-ester carbocation... 

A carbocation is strongly stabilized by an X substituent (Figure 7.1a) through a -type interaction which also involves partial delocalization of the nonbonded electron pair of X to the formally electron-deficient center. At the same time, the LUMO is elevated, reducing the reactivity of the electron-deficient center toward attack by nucleophiles. The effects of substitution are cumulative. Thus, the more X -type substituents there are, the more thermodynamically stable is the cation and the less reactive it is as a Lewis acid. As an extreme example, guanidinium ion, which may be written as [C(NH2)3]+, is stable in water. Species of the type [— ( ) ]1 are common intermediates in acyl hydrolysis reactions. Even cations stabilized by fluorine have been reported and recently studied theoretically [127]. 

Shi and coworkers found that vinyl acetates 68 are viable acceptors in addition reactions of alkylarenes 67 catalyzed by 10 mol% FeCl2 in the presence of di-tert-butyl peroxide (Fig. 15) [124]. (S-Branched ketones 69 were isolated in 13-94% yield. The reaction proceeded with best yields when the vinyl acetate 68 was more electron deficient, but both donor- and acceptor-substituted 1-arylvinyl acetates underwent the addition reaction. These reactivity patterns and the observation of dibenzyls as side products support a radical mechanism, which starts with a Fenton process as described in Fig. 14. Hydrogen abstraction from 67 forms a benzylic radical, which stabilizes by addition to 68. SET oxidation of the resulting electron-rich a-acyloxy radical by the oxidized iron species leads to reduced iron catalyst and a carbocation, which stabilizes to 69 by acyl transfer to ferf-butanol. However, a second SET oxidation of the benzylic radical to a benzylic cation prior to addition followed by a polar addition to 68 cannot be excluded completely for the most electron-rich substrates. 

Besides being an enolate anion equivalent, the lithium dimethylhydrazone can also serve as an acyl carbocation equivalent57,95 (equation 24). In this way, the a-substituted... 

Formation of a Nitrene. The decomposition of acyl azides is one of several ways in which acyl nitrenes 3 are formed (see p. 293). After the migration has taken place, the atom at the migration origin (A) must necessarily have an open sextet. In the third step, this atom acquires an octet. In the case of carbocations, the most common third steps are combinations with a nucleophile (rearrangement with substitution) and loss of H" " (rearrangement with elimination). 

The coupling of an allyl or acyl moiety onto carbon atoms is achieved by anodic oxidation of a-heteroatom substituted organostannanes or Oj -acetals in the presence of allylsilanes or silyl enol ethers. The reaction probably involves carbocations as intermediates that undergo electrophilic addition to the double bond [245c]. 

In the presence of a Lewis acid (such as Et2AlCl), allylsilanes react with electrophiles in a regiospecific manner. The intermediate (3-carbocation is stabilized by (a-Tc)-conjugation with the C-Si bond. The most important feature of this reaction is that the electrophile reacts with the terminus (y-carbon) of the allyl system, and the n-system is relocated adjacent to its original position. Even substituted allylic silanes can be acylated at the more hindered site. Because of this predictability and their high nucleophilicity, allylsilanes are valuable in many synthetic transformations. 

The mechanism of the Pummerer rearrangement consists of four steps 1) acylation of the sulfoxide oxygen to form an acyloxysulfonium salt 2) loss of a proton from the a-carbon to afford an acylsulfonium ylide 3) cleavage of the sulfur-oxygen bond to give sulfur-substituted carbocation (RDS) and 4) capture of the nucleophile by the carbocation. 

By comparison with the reactions with aromatic substrates, the absence of the driving force of rearo-matization by proton loss in electrophilic acylations of alkenes leads to competition between alternative pathways for the carbocation intermediate. In particular, capture of halide to form 3-halo ketones can become dominant. Hence, the aliphatic Friedel-Crafts acylation reaction need not necessarily result in substitution of an acyl residue for a hydrogen atom in an alkene, nor in the formation of unsaturated ketones. Indeed, within this broader scope, acylations of alkynes and some classes of alkanes can be synthetically useful. 

The regioselectivity of Friedel-Crafts acylations of unsymmetrical alkenes can often be predicted simply by consideration of the alternative carbenium ions formed in an initial electrophilic attack. Pathways via tertiary carbocations are generally preferred over those involving secondary ions. It is the subsequent fate of the initially generated ion that determines the products formed. As has been indicated already, elimination of a proton completes a substitution, although there is a predominance of nonconjugated unsaturated ketone formed, and treatment with base is required to form the conjugated product."... 

Aqueous cationic micelles speed and anionic micelles inhibit bi-molecular reactions of anionic nucleophiles. Both cationic and anionic micelles speed reactions of nonionic nucleophiles. Second-order rate constants in the micelles can be calculated by estimating the concentration of each reactant in the micelles, which are treated as a distinct reaction medium, that is, as a pseudophase. These second-order rate constants are similar to those in water except for aromatic nucleophilic substitution by azide ion, which is much faster than predicted. Ionic micelles generally inhibit spontaneous hydrolyses. But a charge effect also occurs, and for hydrolyses of anhydrides, diaryl carbonates, chloroformates, and acyl and sulfonyl chlorides and SN hydrolyses, reactions are faster in cationic than in anionic micelles if bond making is dominant. This behavior is also observed in water addition to carbocations. If bond breaking is dominant, the reaction is faster in anionic micelles. Zwitterionic sulfobetaine and cationic micelles behave similarly. 

In water, N3 is much less reactive in aromatic nucleophilic substitution than expected from its reactivity toward carbocations, that is, its N+value. Ritchie (43) initially developed his N+ scale from nucleophilicities toward preformed carbocations and the scale fits the data for nucleophilicities toward many electrophiles, regardless of their charge. However, in water, and similar hydroxy lie solvents, the nucleophilicity of azide ion, relative to that of other anions, seems to be related to the carbocation-like character of the electrophile. An acyl derivative with its sp2 carbonyl group is somewhat akin to a carbocation stabilized by an alkoxide group, >C=0 <-— >C+-0 , just as a triarylmethyl carbocation is stabilized by electron delocalization into the aryl groups and azide ion is a good nucleophile toward these electrophiles. As compared with anions such as OH- or CN , azide ion, in water, is very reactive toward carbocations and in deacylation but is relatively unreactive toward dinitrohaloarenes (44). 

Benzene s aromaticity causes it to undergo electrophilic aromatic substitution reactions. The electrophilic addition reactions characteristic of alkenes and dienes would lead to much less stable nonaromatic addition products. The most common electrophilic aromatic substitution reactions are halogenation, nitration, sulfonation, and Friedel-Crafts acylation and alkylation. Once the electrophile is generated, all electrophilic aromatic substitution reactions take place by the same two-step mechanism (1) The aromatic compound reacts with an electrophile, forming a carbocation intermediate and (2) a base pulls off a proton from the carbon that... 

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