A New Robust and Versatile Tetradentate Linker for Amides To be Cleaved under Mild Conditions by Unusual Complexation of the Amide Nitrogen to Cu⁺⁺

Abstract

The concept of weakening amide bonds by the rather unusual forced complexation of nitrogen to Cu++ is not limited to tridentate ligands and was extended in this work to tetradentate ligands as well. The use of cyclic tetradentate ligands was to no avail, but an open‐chain and more‐flexible tetradentate ligand allowed mild cleavage by methanolysis after complexation. The principle was applied to the development of a new linker for solid‐phase chemistry, which was proven to be extremely robust, yet allowed mild cleavage after activation by Cu++ complexation. Its stability and versatility was demonstrated by the successful application to a whole plethora of different types of reactions. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)

Chelatbildende Carbonsäureamide als stabile Relay‐Schutzgruppen für Carbonsäuren und ihre Spaltung unter milden Bedingungen

“…Kürzlich haben wir zwei neue Linker für die Festphasensynthese entwickelt, die die Anbindung von Carbonsäuren an die Festphase über eine stabile Amidbindung ermöglichen und zugleich durch eine ungewöhnliche Komplexierung von Cu 2+ an das Amid‐Stickstoffatom eine Abspaltung als Methylester durch Methanolyse ermöglichen 3. 4 Trotz der ausgesprochenen Stabilität des Linkers unter stark basischen, sauren und einer ganzen Reihe weiterer Bedingungen konnte die Abspaltungsreaktion auf sehr milde Art und Weise erreicht werden. Neben zahlreichen Modifikationen am ursprünglichen Carbonsäureteil konnten wir auch vielstufige Synthesen durchführen.…”

Chelating Carboxylic Acid Amides as Robust Relay Protecting Groups of Carboxylic Acids and their Cleavage under Mild Conditions

“…After modifications by followup reactions, treatment with Cu 2+ in methanol would lead to the methyl ester of the carboxylic acid (4). As in the linker systems mentioned above, activation for methanolysis would proceed by an unusual complexation involving the nitrogen atom of the amide bond.…”

“…[3,4] These enable the attachment of carboxylic acids to the solid phase through an amide bond and release after an unusual complexation of the amide nitrogen atom with Cu 2+ ions followed by methanolysis. This sequence yields the methyl ester of the originally bound carboxylic acid.…”

Pyridine–hydrazone ligands in enantioselective palladium-catalyzed Suzuki–Miyaura cross-couplings

“…, 1-bromo-2-methoxynaphthalene (3a), 1bromo-2,3-dimethoxynaphthalene (3b), 1-naphthylboronic acid (4a) and 2-tolylboronic acid (4b) were purchased from Aldrich and used as received. (2S,5S)-1-Amino-2,5-diphenylpyrrolidine (1A), 8 (2R,5R)-1-amino-2,5-diphenylpyrrolidine (ent-1A), 8 (2S,6S)-1-amino-2,6-diphenylpiperidine (1B), 8 (2S,5S)-1-amino-2,5-diisopropylpyrrolidine (1C), 11 pyridine aldehydes 2b,d 18 2c, 19 and 2e, 20 and pyridine-hydrazones L1-L8 12 were prepared according to the literature procedures.…”