Ian Hotham, Daniel W. Widlicka, Robert A. Singer*, David J. Bernhardson and Zheng Wang,
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Cu-Catalyzed C–N Couplings with Benzilamide Ligands
A linker fragment used in the preparation of an oncology candidate is efficiently synthesized via Cu-catalyzed C–N coupling. The original route required a Cu-catalyzed coupling, followed by an oxidation and protection sequence. After the evaluation of hydroxypicolinamide ligands and other amide ligands as inefficient for a more desirable C–N coupling sequence, screening of new ligands commenced. With a new catalyst derived from Cu salts and dimethoxyphenylbenzilamide (DMPB), the linker fragment can be directly prepared with commodity chemicals, avoiding oxidation. The DMPB ligand for the Cu catalyst is readily prepared from benzilic acid and 2,6-dimethoxyaniline. A brief survey of the scope of this Cu-DMPB system is explored for secondary and primary amines.
期刊介绍：
The journal Organic Process Research & Development serves as a communication tool between industrial chemists and chemists working in universities and research institutes. As such, it reports original work from the broad field of industrial process chemistry but also presents academic results that are relevant, or potentially relevant, to industrial applications. Process chemistry is the science that enables the safe, environmentally benign and ultimately economical manufacturing of organic compounds that are required in larger amounts to help address the needs of society. Consequently, the Journal encompasses every aspect of organic chemistry, including all aspects of catalysis, synthetic methodology development and synthetic strategy exploration, but also includes aspects from analytical and solid-state chemistry and chemical engineering, such as work-up tools，process safety, or flow-chemistry. The goal of development and optimization of chemical reactions and processes is their transfer to a larger scale; original work describing such studies and the actual implementation on scale is highly relevant to the journal. However, studies on new developments from either industry, research institutes or academia that have not yet been demonstrated on scale, but where an industrial utility can be expected and where the study has addressed important prerequisites for a scale-up and has given confidence into the reliability and practicality of the chemistry, also serve the mission of OPR&D as a communication tool between the different contributors to the field.
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