Picolinamides and Iodoalkynes Enable Palladium‐Catalyzed syn‐Aminoalkynylation of Di‐ and Trisubstituted Alkenes to Give Pyrrolidines. (17th May 2022)

• Record Type: Journal Article
• Authors: Müller, Nicolas; Schreib, Benedikt S.; Leutenegger, Sebastian U.; Carreira, Erick M.
• Is Part Of: Angewandte Chemie. Volume 134:Number 38(2022)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-05-17
• Subjects: Alkenes -- Alkynes -- C−C Coupling -- Nitrogen Heterocycles -- Pd Catalysis; Chemistry -- Periodicals; 540
• DOI: 10.1002/ange.202204535
• Languages: English
• ISSNs: 0044-8249

Abstract

Abstract: Palladium‐catalyzed aminoalkynylation of electronically unbiased olefins with iodoalkynes is reported. The picolinamide auxiliary enables for the first time the syn ‐selective aminoalkynylation of mono‐, di‐ and trisubstituted alkenes to afford the corresponding pyrrolidines in up to 97 % yield and as single diastereomers. Furthermore, through a C−H activation approach, the picolinamide allows the rapid synthesis of functionalized olefins, which are suitable cyclization precursors. Facile and orthogonal deprotection of the amides and Si i Pr3 ‐acetylenes in the products, and a subsequent Pictet–Spengler reaction is demonstrated. Abstract : A palladium‐catalyzed, syn ‐selective aminoalkynylation of mono‐, di‐ and trisubstituted olefins to afford pyrrolidines is developed. The combination of iodoalkynes and a picolinamide as nucleophile is shown to be essential for the observed reactivity. Furthermore, the picolinamide enables the rapid synthesis of cyclization substrates through a C−H activation approach.