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Synthesis of Functionalized 4‐Fluoropyridazines
Author(s) -
FeraldiXypolia Alexandra,
Fredj Gregory,
Tran Gaël,
Tsuchiya Tomoki,
Vors JeanPierre,
Mykhailiuk Pavel,
Gomez Pardo Domingo,
Cossy Janine
Publication year - 2017
Publication title -
asian journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.846
H-Index - 44
eISSN - 2193-5815
pISSN - 2193-5807
DOI - 10.1002/ajoc.201700216
Subject(s) - difluorocarbene , chemistry , diazo , cycloaddition , combinatorial chemistry , nucleophile , derivative (finance) , nucleophilic aromatic substitution , functional group , nucleophilic substitution , stereochemistry , organic chemistry , catalysis , polymer , financial economics , economics
Abstract A route to 4‐fluoropyridazines by a [2+1]/[3+2] cycloaddition sequence between an acetylenic derivative, a difluorocarbene source, and a diazo compound is reported. This approach is highly modular and compatible with a broad range of functional groups. The protocol does not require the isolation of any reactive intermediates and, thus, allows for access to a wide range of 4‐fluoropyridazines in a single synthetic step from simple alkynes. Furthermore, these fluorinated compounds can be easily diversified by nucleophilic aromatic substitution (S N Ar) to displace the fluoro group to give a wider range of 3,4,6‐trisubstituted pyridazines. As a result of increasing interest in functionalized pyridazines as well as fluorinated derivatives, this efficient and concise approach to 4‐fluoropyridazines should be of value to medicinal chemists.