Preparation and Application of Solid, Salt-Stabilized Zinc Amide Enolates with Enhanced Air and Moisture Stability.
The treatment of various N-morpholino amides with TMPZnCl⋅LiCl (TMP=2,2,6,6-tetramethylpiperidyl) and Mg(OPiv)2in THF at 25 °C provides solid zinc enolates with enhanced air and moisture stability (t1/2in 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.
Ludwig-Maximilians-Universität München, Department Chemie, Butenandtstrasse 5-13, Haus F, 81377, München, Germany.
Yi-Hung
YH
Chen
Ludwig-Maximilians-Universität München, Department Chemie, Butenandtstrasse 5-13, Haus F, 81377, München, Germany.
Mario
M
Ellwart
Ludwig-Maximilians-Universität München, Department Chemie, Butenandtstrasse 5-13, Haus F, 81377, München, Germany.
Georgios
G
Toupalas
Department of Chemistry, Graduate School of Science, Kyoto University, Sakyo, Kyoto, 606-8502, Japan.
Yusuke
Y
Ebe
Ludwig-Maximilians-Universität München, Department Chemie, Butenandtstrasse 5-13, Haus F, 81377, München, Germany.
Paul
P
Knochel
cross-coupling; solid zinc reagents; synthetic methods; zinc amide enolates; α-arylation