Preparation and Application of Solid, Salt‐Stabilized Zinc Amide Enolates with Enhanced Air and Moisture Stability

Abstract

The treatment of various N-morpholino amides with TMPZnCl⋅LiCl (TMP=2,2,6,6-tetramethylpiperidyl) and Mg(OPiv) in THF at 25 °C provides solid zinc enolates with enhanced air and moisture stability (t 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 ⋅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.

Lewis‐Säure‐dirigierte regioselektive Metallierungen an Pyridazin

“…Hçhere Ausbeuten wurden erhalten wenn das kovalentere Metallamid TMPZnCl·LiCl (5)v erwendet wurde (Einträge 3-6). [16] Eine niedrige Regioselektivitätd er Zinkierung wurde in Abwesenheit von BF 3 ·OEt 2 beobachtet (Eintrag 3). In Anwesenheit von BF 3 ·OEt 2 (1.1 ¾quiv.)…”

Cobalt‐Catalyzed Electrophilic Amination of Aryl‐ and Heteroarylzinc Pivalates with N‐Hydroxylamine Benzoates

“…Over the past two decades,t he development of palladiumcatalyzed Buchwald-Hartwig nucleophilic aminations [2] allowed the facile synthesis of aryl amines.H owever,t hese reactions usually require expensive catalysts and ligands. [10][11][12] These reagents were used to improve the efficiency of cobalt-catalyzed Negishi crosscoupling reactions [11] and were useful for the synthesis of biologically active molecules [12] as well as high-throughput screenings. [3] This amination [4] has been extended to organometallic compounds derived from Mg, [3d] Zn, [5] Al, [6] B, [7] Si, [8] and Cu [9] by using Cu or Ni as catalysts.Despite the impressive progress made,the use of air-sensitive reagents,ligands,ortoxic Ni catalysts still represent drawbacks.R ecently,w er eported an ew class of highly functionalized organozinc reagents with enhanced airand moisture-stability.…”

Allyl‐Palladium‐Catalyzed α,β‐Dehydrogenation of Carboxylic Acids via Enediolates

“…Slightly improved yields could be obtained using our recently disclosed procedure,w hich avoids transmetallation utilizing either commercial Zn(TMP) 2 (entry 3) [10c] or Zn(TMP) 2 , prepared as the LiCl adduct from LiTMP and ZnCl 2 (entry 4). While addition of 6.0 equivalents LiCl to these reaction conditions resulted in al ow yield of 19 %( entry 5), the optimal protocol involved pre-mixing Zn(TMP) 2 ·2 LiCl with excess ZnCl 2 , [16] and remarkably resulted in complete conversion and 90 %y ield ( 1 HNMR) with ay ield of 85 % upon isolation and greater than 20:1 E/Z diastereoselectivity (entry 6). It is noteworthy that the analogous procedure using commercial Zn(TMP) 2 with added ZnCl 2 results in comparable 1 HNMR yield (88 %).…”