The Formal Cross‐Coupling of Amines and Carboxylic Acids to Form sp3–sp3 Carbon–Carbon Bonds
Year: 2021
Type: article
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.
Source: Angewandte Chemie
Authors: Zirong Zhang, Tim Cernak
Institution: University of Michigan
Language: English
Subfield: Organic Chemistry
Field: Chemistry
Domain: Physical Sciences
Open Access status: green
OpenAlex ID: W4297734749