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(Het)aryl Difluoromethyl‐Substituted β‐Alkoxyenones: Synthesis and Heterocyclizations
Author(s) -
Bugera Maksym Ya.,
Tarasenko Karen V.,
Kondratov Ivan S.,
Gerus Igor I.,
Vashchenko Bohdan V.,
Ivasyshyn Viktor E.,
Grygorenko Oleksandr O.
Publication year - 2020
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.201901833
Subject(s) - chemistry , aryl , electrophile , nucleophile , acylation , nitrogen atom , combinatorial chemistry , medicinal chemistry , organic chemistry , stereochemistry , ring (chemistry) , catalysis , alkyl
An efficient approach to the preparation of β‐alkoxyenones bearing (het)aryl difluoromethyl substituents is described. The method included acylation of acyclic or cyclic vinyl ethers with (het)aryl difluoroacetyl chlorides. The method worked well for most substrates, except aryl‐substituted derivatives bearing electron‐donating groups in o ‐ or p ‐positions, and heteroaromatic compounds bearing sufficiently basic nitrogen atom. Synthetic utility of (het)aryl difluoromethyl‐substituted β‐alkoxyenones as CCC bis‐electrophiles was demonstrated by heterocyclizations with common 1,2‐ and 1,3‐bis‐nucleophiles leading to compounds with (het)aryl–CF 2 –(het)aryl motif, in particular (het)aryl difluoromethyl‐substituted pyrazoles, isoxazoles, and pyrimidines – promising chemotypes for drug discovery.