Nucleophilic Arylation of N,O‐Ketene Acetals with Triaryl Aluminum Reagents: Access to α‐Aryl Amides through an Umpolung Process

• Published in: Angewandte Chemie International Edition 2017-12, Vol.56 (51), p.16342-16346
• Main Authors: Takeda, Norihiko, Futaki, Erika, Kobori, Yukiko, Ueda, Masafumi, Miyata, Okiko
• Format: Article
• Language: English
• Subjects: aluminum; amides; ketene acetals; nucleophilic addition; umpolung
• ISSN: 1433-7851; 1521-3773
• DOI: 10.1002/anie.201708665

A novel approach for the umpolung α‐arylation of amides is presented. By the nucleophilic phenylation of O‐silyl N,O‐ketene acetals, generated in situ from N‐alkoxy amides, a phenyl group can be introduced onto the α‐carbon atom of amides through N−O bond cleavage in a two‐step, one‐pot process. The asymmetric synthesis of α‐aryl amides through the diastereoselective arylation of a chiral N,O‐ketene acetal is also described. Changing the rules to win the game: By means of an umpolung strategy involving the generation of O‐silyl N,O‐ketene acetals in situ from N‐alkoxyamides, a phenyl group could be introduced onto the α‐carbon center of amides through N−O bond cleavage in a two‐step, one‐pot process (see scheme). The asymmetric synthesis of α‐aryl amides through the diastereoselective arylation of a chiral N,O‐ketene acetal is also described.