Metal-promoted aromatic acylation

The first mention of a metal-promoted aromatic acylation appeared in 1873 in a preliminary communication by Grucarevic and Merz/ closely followed by a note of Zincke, who described the reaction of benzoyl chloride with metals such as copper, silver, and zinc in benzene with the goal of producing benzil 1 (Scheme 1.1). 

In aromatic acylation, present industrial practice involves stoichiometric amounts of metal halides as "catalysts" and of acylating agents. Aromatic heterocycles present exceptions. For example, catalytic amounts of SnCU promote the reaction of benzofuran with acetic anhydride to give 4()% 2-acetyl-benzofuran [1]. 

Apparent anomalies in reactivity have appeared to exist for a number of reactions. It is not generally known that under conventional EQ conditions, an electrophile can promote aromatic metalation during the quench step. It was stated in an early report [130] that the reaction of phenothiazine 31 with 2 equivalents of n-BuLi proceeds with formation of dilithio intermediate 33 via monoUthio amide 32 (Scheme 26.8). The fact that the regioselectivity of the reaction is dependent on the electrophile used was not properly analyzed by the authors whereas trapping experiments with RCOX=DME, PhCONMe, MeCO Li, PhCO Li, and CO give C(7j-acylation products 34, the reaction of RX = MeCOCl, Mel, and ethylene oxide provides lVjf70)-substitution products 35. 

BenzoMoxazoles (130) undergo a base-promoted formal arylation using an aromatic acyl chloride, giving product (131) in up to 91% yield. " The reaction proceeds via N-acylation of oxazole to form an iminium intermediate, which hydrates to give a Lewis acetal, ring-opens, extrudes CO, ring-closes and then dehydrates. The reaction avoids the previous use of transition metal ion catalysis, and one example of an alkyl acid chloride is also reported. 

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... 

Trifluoroacetic and triflic anhydrides can be utilized to promote acylation of aromatics with carboxylic acids without any metal catalyst. Thus, the trifluoroacetic anhydride (TFAA)-promoted cycloacylation of conveniently functionalized carboxylic acids prepared from Baylis-Hillman adducts... 

Imines are reduced by triethylsilane to their amines when the proper Ir orNi catalysts areemployed. Non-metal-mediated reductions of C=N groups by EtsSiH are also possible. Among these, the trifluorosulfonic acid promoted reductive amidation of aliphatic and aromatic aldehydes with EtsSiH is an excellent way to mono (V-alkylate aliphatic and aromatic amides, thioamides, carbamates, and ureas (eq 26). It is also worth noting that trifluorosulfonic acid/EtsSiH reduces acyl- and tosylhydrazones to hydrazines and 2-aminopyrimidines to 2-amino-dihydro-or 2-aminotetrahydropyrimidines (eq 27). ... 

---