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Medium‐Ring Nitrogen Heterocycles through Migratory Ring Expansion of Metalated Ureas
Author(s) -
Hall Jessica E.,
Matlock Johnathan V.,
Ward John W.,
Gray Katharine V.,
Clayden Jonathan
Publication year - 2016
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201605714
Subject(s) - lithium diisopropylamide , chemistry , ring (chemistry) , substituent , deprotonation , nitrogen , urea , stereochemistry , combinatorial chemistry , medicinal chemistry , organic chemistry , ion
Simple benzo‐fused nitrogen heterocycles (indolines, tetrahydroquinolines, and their homologues) undergo migratory ring expansion through deprotonation of their benzylic urea derivatives with lithium diisopropylamide (LDA) in the presence of N,N′‐dimethylpropylideneurea (DMPU). The products of the reactions are benzodiazepines, benzodiazocines, and their homologues, with ring sizes of 8–12. The reactions tolerate a range of substituent patterns and types, and may exhibit enantiospecificity or diastereoselectivity. Considerable complexity is rapidly generated in an efficient synthesis of these otherwise difficult‐to‐obtain medium‐ring nitrogen heterocycles.