Synthesis of Isoquinolines and Heterocycle-Fused Pyridines via Three-Component Cascade Reaction of Aryl Ketones, Hydroxylamine, and Alkynes

• Published in: Journal of organic chemistry 2012-07, Vol.77 (13), p.5794-5800
• Main Authors: Zheng, Liyao, Ju, Jia, Bin, Yunhui, Hua, Ruimao
• Format: Article
• Language: English
• Subjects: Alkynes - chemistry; Chemistry; Exact sciences and technology; Heterocyclic compounds; Heterocyclic Compounds - chemical synthesis; Heterocyclic Compounds - chemistry; Heterocyclic compounds with n hetero atom and also o and/or s, se, te hetero atoms; Heterocyclic compounds with only one n hetero atom and condensed derivatives; Heterocyclic compounds with several n hetero atoms in the same ring, in separated rings or in fused rings; Hydroxylamine - chemistry; Isoquinolines - chemical synthesis; Isoquinolines - chemistry; Ketones - chemistry; Molecular Structure; Organic chemistry; Preparations and properties; Pyridines - chemical synthesis; Pyridines - chemistry; Stereoisomerism
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/jo3010414

An efficient one-pot synthesis of isoquinolines and heterocycle-fused pyridines by three-component reaction of aryl ketones, hydroxylamine, and alkynes is developed. The reaction involves condensation of aryl ketones and hydroxylamine, rhodium(III)-catalyzed C–H bond activation of the in situ generated aryl ketone oximes, and cyclization with internal alkynes. This protocol enables rapid assembly of multisubstituted isoquinolines as well as γ-carbolines, furo[2,3-c]pyridines, thieno[2,3-c]pyridines, and benzofuro[2,3-c]pyridines from readily available substrates.