AlMe₃‐Mediated Regio‐ and Chemoselective Reactions of Indole with Carbamoyl Electrophiles

Abstract

Herein, we report the regio‐ and chemoselective reactions of indole with carbamoyl electrophiles in presence of AlMe3. Indole‐3‐carboxamide was prepared in one‐step from a reaction of indole with tertiary carbamoylimidazole in the presence AlMe3. Under conditions for the formation of an aluminium ate complex, the reaction was diverted to the indole nitrogen. Secondary carbamoyl electrophiles in the presence of AlMe3 regiospecifically yielded trisubstituted ureas. The regiospecificity and chemoselectivity of the indole nitrogen towards ester and tertiary carbamoylimidazole functionalities were also studied.

Copper(I)‐Catalyzed N‐Carboxamidation of Indoles with Isocyanates: Facile and General Method for the Synthesis of Indole‐1‐carboxamides

“…However, only few methods for the synthesis of indole‐1‐carboxamides have been reported so far . Although the N‐carboxamidation of indoles with isocyanates was the most direct method for indole‐1‐carboxamides, these N‐carboxamidation reactions always occurred under harsh conditions, due to the use of NaH[17c] or AlMe 3 (Scheme b). Transition metal‐catalyzed cyclization of 1‐(2‐ethynylphenyl)‐3‐alkylurea or 2‐alkynylbenzenamides with isocyanates to form indole‐1‐carboxamides was also described.…”

Copper‐Catalyzed Synthesis of 5‐Arylindolo[1,2‐c]quinazolin‐6(5H)‐ones from 2‐(2‐Bromoaryl)indoles and Aryl Isocyanates under Microwave Irradiation

“…[17][18][19][20] The intermediate 4 could be prepared by AlMe 3 -mediated nucleophilic addition of 1 a to 2 a under an ambient reaction temperature using a reported method and used to identify such a CÀ N bond formation. [21] Treatment of 4 in DMF at 130 °C for 2 h in the presence of Cs 2 CO 3 and CuI/Cs 2 CO 3 under microwave irradiation produced 3 a in 12 % and 49 % yields, respectively (eq 2). Lower reactivity of the reaction of 1 a and 2 a compared to that of 2-(2-bromoaryl)benzimidazole 9 and 2 a under transition metal-free condition seems to be due to the stability of a Meisenheimer complex resulting from electronegativity difference between carbon and nitrogen (Scheme 2).…”

A Simple, Effective, Green Method for the Regioselective 3-Acylation of Unprotected Indoles

“…3-Acylindoles are useful intermediates in the synthesis of various pharmaceuticals [1][2][3][4]. Regioselectivity in the 3-acylation of indoles has been an interesting and challenging subject in organic synthesis.…”

“…Regioselectivity in the 3-acylation of indoles has been an interesting and challenging subject in organic synthesis. A wide range of 3-acylindoles was synthesized by several methods such as Friedel-Crafts acylation [5][6][7][8][9][10][11][12], Vilsmeier-Haack type reaction [4,13], α-aminocarbonyl compounds with palladium [14], carbamoyl electrophiles [2], α-oxocarboxylic acids [15][16][17], and nitrilium salt with palladium [18]. Among those, Friedel-Crafts acylation of free (NH) indoles is definitely the simplest way [19], however, low yields were observed due to competing substitution at the 1-position.…”