Iridium‐Catalyzed Asymmetric Allylic Substitution of Methyl Azaarenes

• Published in: Angewandte Chemie International Edition 2022-05, Vol.61 (20), p.e202200164-n/a
• Main Authors: Liu, Xi‐Jia, Zhang, Wen‐Yun, Zheng, Chao, You, Shu‐Li
• Format: Article
• Language: English
• Subjects: Allosteric properties; Allylic Carbonates; Asymmetric Allylic Alkylation; Asymmetry; Catalysis; Enantiomers; Enantioselectivity; Iridium; Iridium - chemistry; Kinases; Methyl Azaarenes; NMR; Nuclear magnetic resonance; Nucleophiles; Oxazole; Protein biosynthesis; Protein kinase; Quinoline; Reagents; Stereoisomerism; Substitution reactions
• ISSN: 1433-7851; 1521-3773
• DOI: 10.1002/anie.202200164

Herein, an Ir‐catalyzed asymmetric allylic substitution reaction of methyl azaarenes is described. Azaarenes such as (benzo)thiazole, oxazole, benzoimidazole, pyridine, and (iso)quinoline are all tolerated. The corresponding chiral azaarene derivatives are obtained in good yields with high enantioselectivity (up to 96 % yield and 99 % ee). The utilization of the Knochel reagent TMPZnBr⋅LiBr warrants the in situ formation of benzylic nucleophiles without additional activating reagents. 1H NMR studies suggested a two‐fold function of the Knochel reagent in this reaction. The synthetic utility of this method has been showcased by a concise enantioselective synthesis of an allosteric protein kinase modulator. An iridium‐catalyzed asymmetric allylic substitution of a variety of methyl azaarenes, including (benzo)thiazole, oxazole, benzoimidazole, pyridine, and (iso)quinoline, is described. The corresponding chiral azaarene derivatives are afforded in good yields with high enantioselectivity (up to 96 % yield and 99 % ee).