Premium
Synthesis of 4,5,6,7‐Tetrahydro‐1 H ‐indole Derivatives Through Successive Sonogashira Coupling/Pd‐Mediated 5‐ endo ‐ dig Cyclization
Author(s) -
Andreev Ivan A.,
Belov Dmitry S.,
Kurkin Alexander V.,
Yurovskaya Marina A.
Publication year - 2013
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.201201417
Subject(s) - sonogashira coupling , chemistry , dig , aryl , combinatorial chemistry , indole test , stereochemistry , nitrogen atom , catalysis , medicinal chemistry , palladium , organic chemistry , ring (chemistry) , alkyl , computer security , computer science
A one‐pot Sonogashira cross‐coupling/5‐ endo ‐ dig cyclization procedure leading to 2‐aryl‐4,5,6,7‐tetrahydroindoles was developed. This short (only two steps from commercially available compounds) sequence avoids harsh conditions and expensive catalysts. Our procedure is highly tolerant to a range of functional groups (amino, nitro, carboxy, cyano, hydroxy, and bromo). A family of 21 tetrahydroindoles was synthesized on a gram scale in a good to excellent yields, which is indicative of the general character and scalability of this reaction. This methodology allows access to indoles bearing miscellaneous substituents at the C2 position (by variation of ArI) and at the nitrogen atom (by variation of RNH 2 , including chiral moieties).