Synthesis of Indoles by Domino Reaction of 2-(Tosylamino)benzyl Alcohols with Furfurylamines: Two Opposite Reactivity Modes of the α-Carbon of the Furan Ring in One Process

• Published in: European journal of organic chemistry 2014-04, Vol.2014 (12), p.2508-2515
• Main Authors: Uchuskin, Maxim G., Molodtsova, Natalia V., Lysenko, Sergey A., Strel'nikov, Vladimir N., Trushkov, Igor V., Butin, Alexander V.
• Format: Article
• Language: English
• Subjects: Electrophilic substitution; Nitrogen heterocycles; Nucleophilic substitution; Oxygen heterocycles
• ISSN: 1434-193X; 1099-0690
• DOI: 10.1002/ejoc.201301762

An unusual domino reaction where the same furan α‐carbon atom reacts initially as a nucleophile and then as an electrophile is reported. In the presence of acid, N‐tosylfurfurylamines react with 2‐(tosylamino)benzyl alcohols to afford 2‐(2‐acylvinyl)indoles. The reaction proceeds by Friedel–Crafts alkylation at the C(2) atom of furan followed by acid‐catalyzed intramolecular nucleophilic attack of the ortho‐amino group onto the same carbon atom. The replacement of the tosylamino leaving group by phthalimide enables generation of a different type of indole yet allows the ambiphilic nature of C(2) to be retained. Both types of indoles were obtained when N‐furfurylbenzamides were employed. Furfurylamines react with 2‐(tosylamino)benzyl alcohols affording 2‐(2‐acylvinyl)indoles by a domino reaction sequence in which the same furan α‐carbon atom behaves initially as an electron‐rich center and then as an electron deficient one. In addition, substitution of the tosylamino leaving group with a phthalimido group furnishes a change in chemoselectivity.