Iridium‐Catalyzed Reductive Alkylations of Secondary Amides

• Published in: Angewandte Chemie International Edition Vol. 57; no. 35; pp. 11354 - 11358
• Main Authors: Ou, Wei, Han, Feng, Hu, Xiu‐Ning, Chen, Hang, Huang, Pei‐Qiang
• Format: Journal Article
• Language: English
• Published: WEINHEIM Wiley 27.08.2018; Wiley Subscription Services, Inc
• Edition: International ed. in English
• Subjects: Alkylation; Amides; Amines; Chemistry; Chemistry, Multidisciplinary; Functional groups; homogeneous catalysis; Iridium; Nucleophiles; Physical Sciences; reductive alkylation; Science & Technology; synthetic methods; amides; ASYMMETRIC-SYNTHESIS; INTERMOLECULAR ADDITION-REACTIONS; NUCLEOPHILIC-ADDITION; IMINIUM ION; TERTIARY; METHOXYAMIDES; iridium; ORGANOZINC REAGENTS; N-ACYLIMINIUM IONS; homogeneous catalysis; DIRECT TRANSFORMATION; AMINES; reductive alkylation; synthetic methods
• ISSN: 1433-7851; 1521-3773
• DOI: 10.1002/anie.201806747

Reported herein is the first direct, metal‐catalyzed reductive functionalization of secondary amides to give functionalized amines and heterocycles. The method is shown to have exceptionally broad scope with respect to suitable nucleophiles, which cover both hard and soft C nucleophiles as well as a P nucleophile. The reaction exhibits good chemoselectivity and tolerates several sensitive functional groups. A soft touch: A versatile, direct, metal‐catalyzed reductive functionalization reaction of secondary amides, to give functionalized amines and heterocycles, was developed. A broad substrate scope for both the amide and nucleophile was observed. Viable nucleophiles include reactive and soft C nucleophiles as well as a P nucleophile. The reaction exhibits good chemoselectivity and tolerates several sensitive functional groups (FGs).