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Synthesis of 3‐Benzazepines by Metal‐Free Oxidative C–H Bond Functionalization–Ring Expansion Tandem Reaction
Author(s) -
Gini Andrea,
Bamberger Julia,
LuisBarrera Javier,
Zurro Mercedes,
MasBallesté Rubén,
Alemán José,
Mancheño Olga García
Publication year - 2016
Publication title -
advanced synthesis and catalysis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.541
H-Index - 155
eISSN - 1615-4169
pISSN - 1615-4150
DOI - 10.1002/adsc.201600985
Subject(s) - chemistry , benzazepines , ring (chemistry) , reagent , combinatorial chemistry , surface modification , tandem , salt (chemistry) , stereochemistry , organic chemistry , materials science , composite material
A metal‐free synthesis of biologically important benzazepines is achieved through a single synthetic operation involving an oxidative C–H bond functionalization and ring expansion with diazomethanes as key reagent. This represents a new, strong methodology for the straightforward construction of the seven‐ring N‐heterocyclic structures under mild conditions using a 2,2,6,6‐tetramethylpiperidine 1‐oxyl (TEMPO) oxoammonium salt as oxidant. Moderate to good yields are achieved from simple, readily available tetrahydroisoquinolines, and this methodology has been further successfully applied for the synthesis of the 3‐benzazepine drug Lorcaserin. A possible mechanistic pathway for the ring expansion step, comprising the extrusion of nitrogen in a concerted asynchronic process, is proposed based on both mechanistic proof and density function theory (DFT) calculations.