Palladium‐Catalyzed Direct Carbonylation of Bromoacetonitrile to Synthesize 2‐Cyano‐N‐acetamide and 2‐Cyanoacetate Compounds

• Published in: Angewandte Chemie International Edition Vol. 62; no. 19; pp. e202301671 - n/a
• Main Authors: Bao, Zhi‐Peng, Wu, Xiao‐Feng
• Format: Journal Article
• Language: English
• Published: WEINHEIM Wiley 02.05.2023; Wiley Subscription Services, Inc
• Edition: International ed. in English
• Subjects: Amides; Atmospheric pressure; Bromoacetonitrile; Carbonylation; Carbonyls; Catalysts; Chemistry; Chemistry, Multidisciplinary; Esters; Palladium; Physical Sciences; Science & Technology; Carbonylation; NATURAL-PRODUCT SYNTHESIS; COUPLING REACTIONS; Amides; Esters; Palladium; BROMIDES; Bromoacetonitrile
• ISSN: 1433-7851; 1521-3773
• DOI: 10.1002/anie.202301671

Nitrile compounds containing ester and amide groups are important functionalized chemicals in synthetic and medicinal chemistry. In this article, an efficient and convenient palladium‐catalyzed carbonylative procedure toward 2‐cyano‐N‐acetamide and 2‐cyanoacetate compounds has been developed. The reaction proceeds under mild conditions via radical intermediate which is suitable for late‐stage functionalization. Gram‐scale experiment was performed successfully under low catalyst loading and gave the target product in excellent yield. Additionally, this transformation can be performed under atmospheric pressure and provide alternative routes to 7 drug precursors. A new and convenient procedure for the palladium‐catalyzed carbonylation of bromoacetonitrile has been developed. A variety of valuable 2‐cyano‐N‐acetamide and 2‐cyanoacetate compounds were obtained in good to excellent yields under mild reaction conditions. Furthermore, this transformation can be carried out under atmospheric pressure and provides an alternative route to 7 drug compounds.