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Preparation and Application of Solid, Salt‐Stabilized Zinc Amide Enolates with Enhanced Air and Moisture Stability
Author(s) -
Chen YiHung,
Ellwart Mario,
Toupalas Georgios,
Ebe Yusuke,
Knochel Paul
Publication year - 2017
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.201700216
Subject(s) - chemistry , amide , zinc , reagent , allylic rearrangement , halide , aryl , yield (engineering) , salt (chemistry) , acylation , solvent , moisture , organic chemistry , combinatorial chemistry , medicinal chemistry , nuclear chemistry , catalysis , materials science , alkyl , metallurgy
The treatment of various N‐morpholino amides with TMPZnCl⋅LiCl (TMP=2,2,6,6‐tetramethylpiperidyl) and Mg(OPiv) 2 in THF at 25 °C provides solid zinc enolates with enhanced air and moisture stability ( t 1/2 in air: 1–3 h) after solvent evaporation. These enolates undergo Pd‐ and Cu‐catalyzed cross‐couplings with (hetero)aryl bromides as well as allylic and benzylic halides. The arylated N‐morpholino amides were converted into various ketones by LaCl 3 ⋅2 LiCl mediated acylation with Grignard reagents. The new, solid enolates were used to prepare a potent anti‐breast‐cancer drug candidate in six steps and 23 % overall yield.