The Formal Cross-Coupling of Amines and Carboxylic Acids to Form sp3 -sp3 Carbon-Carbon Bonds.
Angew Chem Int Ed Engl
; 60(52): 27293-27298, 2021 12 20.
Article
em En
| MEDLINE
| ID: mdl-34669980
ABSTRACT
We have developed a deaminative-decarboxylative protocol to form new carbon(sp3 )-carbon(sp3 ) bonds from activated amines and carboxylic acids. Amines and carboxylic acids are ubiquitous building blocks, available in broad chemical diversity and at lower cost than typical C-C coupling partners. To leverage amines and acids for C-C coupling, we developed a reductive nickel-catalyzed cross-coupling utilizing building block activation as pyridinium salts and redox-active esters, respectively. Miniaturized high-throughput experimentation studies were critical to our reaction optimization, with subtle experimental changes such as order of reagent addition, composition of a binary solvent system, and ligand identity having a significant impact on reaction performance. The developed protocol is used in the late-stage diversification of pharmaceuticals while more than one thousand systematically captured and machine-readable reaction datapoints are reposited.
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Bases de dados:
MEDLINE
Idioma:
En
Revista:
Angew Chem Int Ed Engl
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Estados Unidos