Friedel-Crafts alkylation reactions carbonyl compounds

Carbonyl compounds, particularly aromatic aldehydes, when activated with electrophilic catalysts, can also react with aromatics.241 The process is often called condensation or reductive alkylation, but it is actually a multistep Friedel-Crafts alkylation reaction. 

As mentioned above, a range of enantioselective transformations have been established using chiral phosphoric acids via the activation of imines and related nitrogen-substituted substrates. In contrast, the activation of carbonyl compounds, including a,P-unsaturated carbonyl compounds, by chiral phosphoric acids has been limited. In 2008, Zhou, He, and coworkers achieved the asymmetric Friedel-Crafts alkylation reaction of indole derivatives with 1,3-diaryl a,p-unsaturated... 

Phenols are such good nucleophiles that protonated carbonyl compounds functionalize two phenol molecules. The first phenol molecule reacts in an Ar-SE reaction by the carboxonium ion formed in an equilibrium reaction. Subsequently, the second equivalent of phenol becomes the substrate of a Friedel-Crafts alkylation. The electrophile is the benzyl cation that is formed from the initially obtained benzyl alcohol and the acid. Protonated acetone is only a weak electrophile for electronic and steric reasons it contains two electron-donating and relatively large... 

So far, most of the reactions presented in the book that are useful in synthesis have made C-O, C-N, or C-halogen bonds and only a few (Wittig, Friedel-Crafts, and reactions of cyanides and alkynes) make C-C bonds. This limitation has severely restricted the syntheses that we can discuss in this chapter. This is by design as we wanted to establish the idea of synthesis before coming to more complicated chemistry. The next four chapters introduce the main C-C bond-forming reactions in the chemistry of enols and enolates. You met these valuable intermediates in Chapter 21 but now you are about to see how they can be alkylated and acylated and how they add directly to aldehydes and ketones and how they do conjugate addition to unsaturated carbonyl compounds. Then in Chapter 30 we return to a more general discussion of synthesis and develop a new approach in the style of the last synthesis in this chapter. 

Problems have been observed when attempting to carry out reactions with either diacid chlorides or half-ester half-acid chlorides when the two carbonyl functions are separated by either two or three carbon atoms. Rearrangement reactions occur with those compounds and so Friedel-Crafts acylation reactions may yield mixtures of products. Optically active methyl 3-methylglutarate was shown to racemize easily Suggested explanations of these effects include the involvement of alkyl diacyloxonium and acyl-oxy-alkoxycarbenium ions. NMR studies have shown that the half methyl ester-half acid chloride from phthalic acid forms the acyloxy-alkoxycarbenium ion very easilyj and that the related ions derived from succinic and glutaric acids can also be generated under stable ion conditions. ... 

Friedel-Crafts reactions are conversions that form one additional carbon-carbon bond with an aromatic compound, catalysed by strong Lewis acids. Inportant reactions are Friedel-Crafts alkylation, Friedel-Crafts acylation and carbonylation. 

Other acids have also been explored. For instance, a heleropoly acid catalyzed Friedel-Crafts alkylation of indole and pyrrole with enones and electron-deficient olefins in water at room temperature, affording good yields at 0.3mol% catalyst loading [112]. Similarly, a carbon-based solid add was shown to catalyze effidendy the reaction of indoles with a,p-unsaturated carbonyl compounds in water, and the... 

Titanium tetrachloride promoted a three-component cyclization involving a carbonyl compound, an allylsilane, and an acetal, as shown in Eq. (69) [188]. The reaction was initiated by allyl addition to the aldehyde this was followed by acetal exchange and intramolecular Friedel-Crafts-type alkylation of the olefinic moiety. 

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