Acylation of indole

Section C of Table 11,5 gives some examples of Friedel-Crafts and Vilsmeier-Haack acylations of indoles. 

Yoshino reports a novel and general method for the C-3 acylation of indoles with acyl chlorides in the presence of dialkylaluminium chloride which obviates the need for prior N-protection . Interestingly, as described in this preliminary communication, the unprotected indoles 147 are first treated with the Lewis acids prior to addition of the acid chlorides, yielding the desired 3-acyl derivatives 148. In reactions more typical of indoles under acidic conditions, Nakatsuka determined the structures of the dimers and trimers of 1-trimethylacetylindole produced in the presence of aluminium chloride . 

Negishi methodology can also be used to achieve the 3-acylation of indoles. Thus, Faul used this tactic to prepare a series of 3-acylindoles 83 from indole 82 [107], Indole 82 could also be iodinated cleanly at C-3 with iV-iodosuccinimide (78%). 

Whereas intramolecular acylation of indole 88 takes place only in moderate yield, the analogous alkylation of indole 101 gives the dihydrodibenzpyrrol-izine (102) in excellent yield. The reaction conditions for conversion of acid 88 to the tosylate (101) are, however, critical.23 A conversion of tosylate 103 to dihydropyrrolizine 104 was reported.69... 

N-Acylation of indole.1 Indole can be N-acylated by a carboxylic acid in the presence of boric acid (0.3 equiv.) in 45-80% yield. 

Several different methods for the acylation of lFf-pyrrolo[2,3-6]pyridine (1) have been reported <82JHC665> and the results are summarized in Table 40. When reaction conditions which gave a 90% yield for the acylation of indole were tested on compound (1), an excellent yield (91%) of 1-acetylpyrrolo[2,3-6]pyridine was obtained <52JCS3592>. Other acylation methods afforded the 3-acyl derivative as the major product. 

Acylated indoles are important building block for pharmaceutical synthesis. The chloroaluminate ionic liquids have been applied as the eco-friendly catalysts and reaction mediums to the acylation of indoles and substituted indoles. Yeung et al. have investigated the acylation of poor electron indole ring with acidic ionic liquid,... 

Yeung KS, Farkas ME, Qiu Z et al (2002) Fiiedel-Crafts acylation of indoles in acidic imida-zolium chloroaluminate ionic liquid at room temperature. Tetrahedron Lett 43 5793-5795... 

While it can be questioned how green ILs are, they are certainly useful chemically. They have numerous uses as Lewis or protic acid catalysts, for example aluminium chloride in [emim][Cl] is a superior catalyst for the Friedel-Crafts acylation of indoles bearing electron-withdrawing groups and of azaindoles. ... 

The direct and selective 3-acylation of both acid- and base-sensitive indoles 6 can be efficiently achieved using acyl chlorides and alkyl aluminum chlorides without NH protection (Scheme 2.3). When acyl chlorides are used for the acylation of indoles, liberation of hydrogen chloride is unavoidable, and the reaction results in the production of tar materials mainly due to polymerization of indole. Alkylaluminum compounds are utilized to scavenge the acid in the acylation with acyl chlorides. The reaction proceeds cleanly to give 3-acylindoles 7 without any by-product formation. The use of triethylaluminum leads to lower yields, probably because a nucleophilic attack of the alkyl group to acyl chloride occurs competitively. As expected, the use of aluminum... 

Okauchi, T., Itonaga, M., Minami, T., Owa, T., Kitoh, K., and Yoshino, H. 2000. A general method for acylation of indoles at the 3-position with acyl chlorides in the presence of dialkylaluminum chloride. Org. Lett. 2 1485-1487. 

A regioselective Friedel-Crafts 3-acylation of indoles was reported that utilized diethyl aluminum chloride as a Lewis acid mediator <04S2277>. A facile, 3-cyanoacetylation of indoles has been reported <04S2760>. Treatment of indole substrates with cyanoacetic acid in acetic anhydride led to the formation of the corresponding 3-cyanoacetylindoles. This reaction was also investigated with pyrroles and anilines. 

Acylindoles Friedel-Crafts acylation of indoles at C-3 with acid chlorides is catalyzed by R2AICI (R = Me, Et). 

New conditions for intramolecular acylation of indoles have been found in the course of exploration of intramolecular Friedel-Crafts acylation of 3- and... 

Acylation of Amines. Acylation of amines is also faster in the presence of DMAP, as is acylation of indoles, phosphorylation of amines or hydrazines, and conversion of carboxylic acids into anilides by means of Phenyl Isocyanate /3-Lactam formation from /3-amino acids has been carried out with DCC-DMAP, but epimerization occurs. ... 

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