Copper‐Catalyzed Carbonylative Hydroamidation of Styrenes to Branched Amides

• Published in: Angewandte Chemie Vol. 132; no. 50; pp. 22627 - 22631
• Main Authors: Yuan, Yang, Wu, Fu‐Peng, Schünemann, Claas, Holz, Jens, Kamer, Paul C. J., Wu, Xiao‐Feng
• Format: Journal Article
• Language: English
• Published: Weinheim Wiley Subscription Services, Inc 07.12.2020
• Subjects: Amides; carbonylation; Carbonyls; Catalysis; Chemical synthesis; Chemistry; Copper; Enantiomers; enantioselectivity; Functional groups; hydroamidation; Phosphine; Phosphines; Styrenes
• ISSN: 0044-8249; 1521-3757
• DOI: 10.1002/ange.202010509

Amides are one of the most ubiquitous functional groups in synthetic and medicinal chemistry. Novel and rapid synthesis of amides remains in high demand. In this communication, a general and efficient procedure for branch‐selective hydroamidation of vinylarenes with hydroxyamine derivatives enabled by copper catalysis has been developed for the first time. The reaction proceeds under mild conditions and tolerates a broad range of functional groups. Applying a chiral phosphine ligand, an enantioselective variant of this transformation was achieved, affording a variety of chiral α‐amides with excellent enantioselectivities (up to 99 % ee) and high yields. The first Cu‐catalyzed hydroamidation of vinylarenes with hydroxyamine derivatives has been developed. The method displays broad functional‐group tolerance and proceeds under mild conditions to afford branched amides. The asymmetric variant of this transformation was also achieved by applying (R,R)‐Ph‐BPE as the ligand, delivering the α‐chiral amides in good yields with excellent enantioselectivities (up to 99 % ee).