Aldehydes Friedel-Crafts addition

Aromatic and heterocycHc compounds are formylated by reaction with dialkyl- or alkylarylformamides in the presence of phosphoms oxychloride or phosgene (Vilsmeier aldehyde synthesis) (125). The Vilsmeier reaction is a Friedel-Crafts type formylation (126), since the intermediate cation formed by the interaction of phosphoms oxychloride with formamide is a typical electrophilic reagent. Ionic addition compounds of formamide with phosgene or phosphoms oxychloride are also known (127). 

While the Friedel-Crafts acylation is a general method for the preparation of aryl ketones, and of wide scope, there is no equivalently versatile reaction for the preparation of aryl aldehydes. There are various formylation procedures known, each of limited scope. In addition to the reactions outlined above, there is the Vdsmeier reaction, the Reimer-Tiemann reaction, and the Rieche formylation reaction The latter is the reaction of aromatic compounds with 1,1-dichloromethyl ether as formylating agent in the presence of a Lewis acid catalyst. This procedure has recently gained much importance. 

Diastereoselective domino Michael addition/Friedel-Crafts/SN-type cyclizations which allow the synthesis of bridged tetrahydroquinolines such as 2-405 have been observed by Yadav and coworkers when a mixture of anilines 2-403 and 6-hydroxy-a, 3-unsaturated aldehydes 2-404 were treated with catalytic amounts of Bi(OTf)3 or InClj in MeCN at 80 °C (Scheme 2.96) [222],... 

Friedel-Crafts acylation reactions of aromatics are promoted by Tilv complexes.104 In some cases, a catalytic amount of the titanium compound works well (Scheme 28). In addition to acyl halides or acid anhydrides, aldehydes, ketones, and acetals can serve as electrophile equivalents for this reaction.105 The formylation of aromatic substrates in the presence of TiCl4 is known as the Rieche-Gross formylation metalated aromatics or olefins are also formylated under these conditions.106... 

An intermediate acylnickel halide is first formed by oxidative addition of acyl halides to zero-valent nickel. This intermediate can attack unsaturated ligands with subsequent proton attack from water. It can give rise to benzyl- or benzoin-type coupling products, partially decarbonylate to give ketones, or react with organic halides to give ketones as well. Protonation of certain complexes can give aldehydes. Nickel chloride also acts as catalyst for Friedel-Crafts-type reactions. 

For preparative purposes the method of obtaining aldehydes from the primary alcohols is preferable by far, at least in the aliphatic series. The simple aromatic aldehydes can be obtained by alkaline hydrolysis of the arylidene chlorides, R.CHC12, which are produced from the hydrocarbons by substitution with chlorine (technical method for the preparation of benzaldehyde). In addition to these methods the elegant synthesis of Gattermann and Koch should be mentioned here. This synthesis, which proceeds like that of Friedel-Crafts, consists in acting on the aromatic hydrocarbon with carbon monoxide and hydrogen chloride in the presence of aluminium chloride and cuprous chloride. 

Fig. 13). The cross-linked scandium-modified dendrimer was tested in a number of Lewis acid-catalyzed reactions, including Mukaiyama aldol additions to aldehydes and aldimines, Diels-Alder reactions, and Friedel-Crafts acylations. The dendritic catalyst was recovered by a simple filtration. The Mukaiyama aldol... 

In 1977, an article from the authors laboratories [9] reported an TiCV mediated coupling reaction of 1-alkoxy-l-siloxy-cyclopropane with aldehydes (Scheme 1), in which the intermediate formation of a titanium homoenolate (path b) was postulated instead of a then-more-likely Friedel-Crafts-like mechanism (path a). This finding some years later led to the isolation of the first stable metal homoenolate [10] that exhibits considerable nucleophilic reactivity toward (external) electrophiles. Although the metal-carbon bond in this titanium complex is essentially covalent, such titanium species underwent ready nucleophilic addition onto carbonyl compounds to give 4-hydroxy esters in good yield. Since then a number of characterizable metal homoenolates have been prepared from siloxycyclopropanes [11], The repertoire of metal homoenolate reactions now covers most of the standard reaction types ranging from simple... 

Reactions 1-22 to 1-26 involve the introduction of a CH2Z group, where Z is halogen, hydroxyl, amino, or alkyithio. They are all Friedel-Crafts reactions of aldehydes and ketones and, with respect to the carbonyl compound, additions to the C=0 double bond. They follow mechanisms discussed in Chapter 16. 

Friedel-Crafts acylation of aromatics is of considerable practical value owing to the importance of aryl ketones and aldehydes as chemical intermediates.346 Whereas alkylation of aromatics with alkyl halides requires only catalytic amounts of catalysts, acylation to ketones generally necessitates equimolar or even some excess of the Friedel-Crafts catalysts. Usually one molar equivalent of catalyst combines with an acyl halide, giving a 1 1 addition compound, which then acts as the active acylating agent [Eq. (5.137)]. 

The sequence 32—>33—>34—>35 (Scheme 8) also illustrates in-between DoM but, in addition, the important conversion of amides into more useful FG and a method to override the normal Friedel-Crafts reactivity by use of a carbo-desilyla-tion reaction (37) [31]. Amide DMG which have been tested in developing methods for conversion to corresponding acid derivatives and masked aldehyde DMG and the parent carboxylic acid are useful to consider (36). 

The use of other nucleophilic species to perform Friedel-Crafts alkylations to a,/ -unsaturated aldehydes has also been investigated, with success. For example, indoles [14, 83] and anilines [18, 84] have been added to a,/ -unsaturated aldehydes, providing 1,4-addition products in good yields and excellent enantioselec-tivities. Again, the importance of such an approach is demonstrated by the suc-... 

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. 

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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