Generation and Reaction of Carbamoyl Anions in Flow: Applications in the Three-Component Synthesis of Functionalized α-Ketoamides

• Published in: Angewandte Chemie (International ed.) Vol. 55; no. 17; pp. 5327 - 5331
• Main Authors: Nagaki, Aiichiro, Takahashi, Yusuke, Yoshida, Jun-ichi
• Format: Journal Article
• Language: English
• Published: Germany Blackwell Publishing Ltd 18.04.2016
• Subjects: amides; carbonyl groups; flow chemistry; lithiation; microreactors; amides; lithiation; carbonyl groups; microreactors; flow chemistry
• ISSN: 1433-7851; 1521-3773
• DOI: 10.1002/anie.201601386

Using a flow microreactor system, carbamoyllithium compounds were successfully generated and used for reactions with electrophiles to give various amides, including α‐ketoamides. The present method could be applied to the three‐component synthesis of functionalized α‐ketoamides using a carbamoyllithium compound, methyl chloroformate, and a functionalized organolithium reagent. Go with the flow: Using a flow microreactor system, carbamoyllithium compounds were successfully generated and used to react with electrophiles to give various amides, including α‐ketoamides. The method was applied to the three‐component synthesis of functionalized α‐ketoamides using a carbamoyllithium compound, methyl chloroformate, and a functionalized organolithium reagent. PMB=p‐methoxybenzyl; FG=functional group.