Palladium‐Catalyzed Ring‐Closing Aminoalkylative Amination of Unactivated Aminoenynes

• Published in: Angewandte Chemie 2023-01, Vol.135 (3), p.n/a
• Main Authors: Zou, Suchen, Yu, Bangkui, Huang, Hanmin
• Format: Article
• Language: English
• Subjects: Aldehydes; Amination; Amines; Asymmetric Catalysis; Catalysts; Chemistry; Chirality; Enantiomers; Enynes; Exocyclic Allenes; Palladium; Spirodiamines
• ISSN: 0044-8249; 1521-3757
• DOI: 10.1002/ange.202215325

An efficient strategy for preventing the β‐hydride elimination of alkylpalladium species by ligation of the palladium with adjacent amino‐group was developed, which enabled a novel palladium‐catalyzed ring‐closing aminoalkylative amination of unactivated aminoenynes. The reaction is amenable to aminals, as well as aliphatic aldehydes with secondary amines, which provides straightforward access to structurally diverse exocyclic allenic amines bearing 5 to 12‐membered N‐heterocycles. With chiral phosphoramidite‐ligated palladium complex as the catalyst, an enantioselective variant was achieved with up to 93 % ee. Simultaneously, synthetic transformations of the chiral products were also conducted to afford structurally unique spirodiamines including one pharmaceutically active molecule via axial‐to‐central chirality transfer. A highly chemo‐, regio‐ and enantioselective aminoalkylative amination of unactivated aminoenynes by using aminals or aldehydes and amines as coupling partners has been developed, which permits facile synthesis of various chiral exocyclic allenic amines bearing 5 to 12‐membered N‐heterocycles. Synthetic transformations of the chiral products were also conducted to afford structurally unique chiral spirodiamines via axial‐to‐central chirality transfer.