Ligand‐Enabled β‐C(sp3)−H Lactamization of Tosyl‐Protected Aliphatic Amides Using a Practical Oxidant. (14th July 2022)

• Record Type: Journal Article
• Authors: Zhuang, Zhe; Liu, Shuang; Cheng, Jin‐Tang; Yeung, Kap‐Sun; Qiao, Jennifer X.; Meanwell, Nicholas A.; Yu, Jin‐Quan
• Is Part Of: Angewandte Chemie. Volume 134:Number 34(2022)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-07-14
• Subjects: C−H Activation -- Carboxylic Acids -- Lactamization -- Ligand Design -- Palladium; Chemistry -- Periodicals; 540
• DOI: 10.1002/ange.202207354
• Languages: English
• ISSNs: 0044-8249

Abstract

Abstract: The development of C(sp 3 )−H functionalization reactions that use common protecting groups and practical oxidants remains a significant challenge. Herein we report a monoprotected aminoethyl thioether (MPAThio) ligand‐enabled β‐C(sp 3 )−H lactamization of tosyl‐protected aliphatic amides using tert ‐butyl hydrogen peroxide (TBHP) as the sole oxidant. This protocol features exceedingly mild reaction conditions, reliable scalability, and the use of practical oxidants and protecting groups. Further derivatization of the β‐lactam products enables the synthesis of a range of biologically important motifs including β‐amino acids, γ‐amino alcohols, and azetidines. Abstract : Pd II ‐catalyzed β‐C(sp 3 )−H lactamization of aliphatic amides is reported. This protocol features the use of practical and inexpensive oxidants and protecting groups, mild conditions, and reliable scalability. Further derivatization of β‐lactam products enables synthesis of a range of biologically important motifs such as β‐amino acid, γ‐amino alcohol, and azetidine.