Lewis acid catalysis acylation

A more important variation is the Friedel-Crafts acylation with acid chlorides and AICI3. As you saw in Chapter 13, add chlorides can give the rather stable acylium ions even in hydrolytic reactions and they do so readily with Lewis acid catalysis. Attack on a benzene ring then gives an aromatic ketone. The benzene ring has been acylated. 

Electrophiles for aromatic substitution include the halonium ion, the nitronium ion and the carbonium ion. The latter may be generated from alkyl and acyl halides using Lewis acid catalysis in the Friedel-Crafts reactions. 

Acyclic C-acyl imines have recently been studied as dienophiles.32-34 p j example, Prato and coworkers examined the reaction of imines (41) (equation 13) with several cyclic and acyclic 1,3-dienes. Under neutral conditions, (41) is unreactive as a dienophile. However, under Lewis acid catalysis these imines react to afford mixtures of adducts. With 1,3-cyclohexadiene, bicyclic adducts (42) and (43) are produced along with (44) in which the imine has acted as an azadiene. The ratios of these sorts of products are dependent upon the particular imine and diene used. The formation of adducts of type (43) proved to be both regio- and stereo-selective. Product formation in these cases can be rationalized lx>th by concerted and by stepwise ionic mechanisms. ... 

The acylation is limited to the use of acid chlorides due to their unique ability to oxidatively add palla-dium(0) other acylating agents are not generally useful in this context. It was also known that acid chlorides do not react with organotins without Lewis acid catalysis and more importantly organotins do not generally react with the expected product, the ketone, except under very strong Lewis acidic conditions. Even diacid chlorides may be utilized in this process (equation 77) however, oxalyl chloride cannot be used due to the indicated decarbonylation of the intermediate acid chloride (equation 78). ... 

The first total synthesis of the cytotoxic agent (+)-euplotin A was completed by the research team of R.L. Funk. The key step of the synthetic effort was the intramolecular hetero DIels-Alder cycloadditlon of a 3-acyl oxadiene (generated from 5-acyl-4H-1,3-dioxins via thermal retrocycloaddition) with a substituted dihydrofuran to afford the tricyclic skeleton of the natural product. The correct relative stereochemistry of the required dihydrofuran substrate was established using the Paterno-Buchi reaction between ethyl glyoxylate and furan. Subsequently, the oxetane ring was opened stereoselectively under Lewis acid catalysis. 

Simplified nucleoside synthesis,8 The known synthesis of nucleosides from silylated heterocycles and a protected sugar derivative in the presence of (CHjijSiClO or (CH3)3SiOTf (6, 639-640) has been adapted to a one-pot synthesis based on in situ silylation and Lewis acid catalysis. The reagent (1) is prepared in situ (equation I) and is added to the free base and acylated sugar then triflic acid, potassium nonaflate, or SnCl4 is added as catalyst. The last Lewis acid is fhe most active and allows condensation to proceed at 24°. Acetonitrile is the most useful solvent. The method is generally applicable and yields are about the same as those obtained in the two-step procedure. 

Aldol reactions with specific enol equivalents Contrast with equilibrium methods Aldols with Lewis acid catalysis silyl enol ethers Application to the synthesis of gingerol Reaction at O or C Silylation, Acylation and Alkylation Naked enolates... 

Controlled oxidation of A-acyl-piperidines and -pyrrolidines can be used to prepare 2-alkoxy derivatives or the equivalent enamides, which are useful general synthetic intermediates. The former are susceptible to nucleophilic substitution under Lewis-acid catalysis, via Mannich-type intermediates, and the latter can undergo electrophilic substitution at C-3 or addition to the double bond. 

Scheldt and co-workers reported a cooperative eatalysis process integrating Ti and triazolium-derived NHCs, providing a facile synthesis of cis cyclopentenes with a broad substrate scope. Using the cooperative system that successfully integrates Lewis acid catalysis and NHC catalysis, previously inaeeessible substituted cyclopentenes were provided directly with excellent levels of enantio- and diastereoselectivity (up to 81% yield, 99% ee). The addition of 2-propanol might facilitate the disassociation of the tertiary alkoxide, and therefore accelerate the acylation step to regenerate the NHC catalyst and Ti(0 Pr)4 (Scheme 7.54). 

The Stolle reaction of arylamines with oxalyl chloride has provided interesting avenues into dioxoindoles. As shown below, reaction of 4,5-dihydro-[l,2]dithiolo[3,4-c]quinoline-l-thiones 18 with oxalyl chloride in refluxing toluene gave the corresponding quinoline-4,5-diones 20. The reaction did not require Lewis acid catalysis, as the HCl generated in the acylation step provided sufficient conditions for the cyclization step. ... 

There is one type of Lewis acid catalysis with which we should be very familiar—a range of Lewis acids such as AICI3, SnCl, and FeClj catalyze the Friedel-Crafts alkylation and acylation of aromatic compounds (Figure 23.6 see Section 12.2.2). 

The scope of this reaction is similar to that of 10-21. Though anhydrides are somewhat less reactive than acyl halides, they are often used to prepare carboxylic esters. Acids, Lewis acids, and bases are often used as catalysts—most often, pyridine. Catalysis by pyridine is of the nucleophilic type (see 10-9). 4-(A,A-Dimethylamino)pyridine is a better catalyst than pyridine and can be used in cases where pyridine fails. " Nonbasic catalysts are cobalt(II) chloride " and TaCls—Si02. " Formic anhydride is not a stable compound but esters of formic acid can be prepared by treating alcohols " or phenols " with acetic-formic anhydride. Cyclic anhydrides give monoesterified dicarboxylic acids, for example,... 

Acylation of aromatic compounds (Friedel-Crafts (FC) acylation), of great industrial interest, suffers from an important catalysis problem [69]. Most of the Lewis acids used as catalysts (traditionally metal chlorides such as A1C13) complex preferentially... 

Lewis acid-catalyzed ene reactions proceed between allenyl sulfides, e.g. 330, and aldehydes 329 to afford cis-trans mixtures of 1,3-butadienes 331 (Scheme 8.90) [168, 175b], Similar ene reactions observed with imines such as 332 provide the corresponding allylamines [168,177]. It was also found that the ene reaction of 1-silylated allenyl sulfide 333 with various aldehydes (or acetals) furnishes a,/l-unsaturatcd acyl compounds such as 334 and 335 under BF3-etherate catalysis [175b]. 

An interesting bifunctional system with a combination of In(OTf)3 and benzoyl-quinine 65 was developed in p-lactam formation reaction from ketenes and an imino ester by Lectka [Eq. (13.40)]. High diastrereo- and enantioselectivity as well as high chemical yield were produced with the bifunctional catalysis. In the absence of the Lewis acid, polymerization of the acid chloride and imino ester occurred, and product yield was moderate. It was proposed that quinine activates ketenes (generated from acyl chloride in the presence of proton sponge) as a nucleophile to generate an enolate, while indium activates the imino ester, which favors the desired addition reaction (66) ... 

In electrophilic catalysis, the metal ion acts as a Lewis acid. An example from organic chemistry is the formation of an acylium ion from aluminum chloride and an acid chloride in Friedel-Crafts acylation reactions (Figure 2). In this case substrate activation results in cleavage of the C—Cl bond. In most cases, however, substrate activation by Lewis acids involves electron redistribution without bond breaking (Figure 3). 

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