Premium
Conformational Regulation of Substituted Azepanes through Mono‐, Di‐, and Trifluorination
Author(s) -
Patel Alpesh Ramanlal,
Hunter Luke,
Bhadbhade Mohan M.,
Liu Fei
Publication year - 2014
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.201301811
Subject(s) - chemistry , ring (chemistry) , fluorine , nuclear magnetic resonance spectroscopy , stereochemistry , conformational change , molecular model , hydroxylation , organic chemistry , enzyme
Substituted azepanes have flexible ring structures and this conformational diversity is important for their bioactivity. We have shown that a single fluorine atom, when installed diastereoselectively on a model azepane ring, can bias its ring to one major conformation. Here the conformational effects of mono‐, di‐, and trifluorination, as well as hydroxylation, on substituted azepanes have been investigated by 1 H NMR spectroscopy and computational modeling in chloroform. Fluorine substitution was found to be more effective than hydroxyl group substitution in reducing conformational disorder; however, multiple fluorinations may not lead to additive conformational control and can result in complex conformational outcomes.