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Consecutive Ring Expansion and Contraction for the Synthesis of 1‐Aryl Tetrahydroisoquinolines and Tetrahydrobenzazepines from Readily Available Heterocyclic Precursors
Author(s) -
Hill Jessica E.,
Matlock Johnathan V.,
Lefebvre Quentin,
Cooper Katie G.,
Clayden Jonathan
Publication year - 2018
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201802188
Subject(s) - chemistry , ring (chemistry) , aryl , contraction (grammar) , combinatorial chemistry , bicyclic molecule , stereochemistry , organic chemistry , medicine , alkyl
Tetrahydroisoquinolines and tetrahydrobenzazepines were prepared by acid‐promoted ring contraction of cyclic ureas, which were themselves formed by ring expansion of indolines and tetrahydroquinolines. The consequent overall one‐carbon insertion reaction gives these 6‐ and 7‐membered heterocyclic scaffolds in three steps from readily available precursors. Other ring sizes may be formed by an alternative elimination reaction of bicyclic structures. Scalability of the method was demonstrated by operating it in a flow system.