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Published on: August 16, 2018
Preparation and Application of Solid, Salt-Stabilized Zinc Amide Enolates with Enhanced Air and Moisture Stability
Yi-Hung Chen1, Mario Ellwart1, Georgios Toupalas1
1Ludwig-Maximilians-Universität München, Department Chemie, Butenandtstrasse 5-13, Haus F, 81377, München, Germany.
Abstract:
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 (t1/2 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 LaCl3 ⋅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.
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