Three-Component Synthesis of Isoquinolone Derivatives via Rh(III)-Catalyzed C–H Activation and Tandem Annulation

Abstract

A one-pot three-component synthesis of multifunctionalized isoquinolones from 2-oxazolines, iodonium ylides, and carboxylic acids via Rh(III)-catalyzed oxazolinyl-directed C−H activation and tandem annulation under redox-neutral conditions has been developed. This catalytic system is characterized by readily available starting materials, a wide tolerance of functional groups, a short reaction time, and high yields. The synthetic utility of the cascade reaction was further demonstrated by a gram-scale synthesis and derivatization of the obtained products.

Redox-Neutral Three-Component Coupling of Phenacyl Azides, Aldehydes, and 1,3-Dicarbonyls to Access β-Enaminodiones

“…Various synthetic methodologies to access β-enaminones from 1,3-dicarbonyls are depicted and compared with our work in Scheme . The uniqueness of our three-component synthetic strategy lies in its redox-neutral status and high yields of β-enaminones without using any catalyst, additives, or solvents …”

Three-Component Chemo-Selective Synthesis of N-(o-Alkenylaryl) Pyrazoles by Pyrazole Annulation and Rh-Catalyzed Chemo-Selective Aryl C–H Addition Cascade

“…In fact, the application of MCRs in C–H activation reactions has already been proved to be powerful in many valuable synthetic reactions. , For example, the Catellani reaction − is a typical protocol enabling the synthesis of diverse organic products in the fashion of multicomponent C–H activation. In addition, multicomponent C–H activation also has shown versatile application in other reactions such as the synergistic light/Ni-catalyzed olefin dicarbofunctionalization, , Rh-catalyzed enantioselective carboamination of dienes, Co-catalyzed enantioselective enone dicarbofunctionalization, Ni/NHC-catalyzed ring fusion, as well as more other reactions. − The success in the MCR-based C–H activation provides convictive support for the space in finding more valuable synthetic methodologies benefiting the step economy and/or new reaction pathways. As typical examples of widespread C–H activation synthesis, the Rh-catalyzed reactions of N -aryl pyrazoles with alkynes have been disclosed to be capable of providing diverse products depending on the reaction conditions and substrate structures. − However, as reported by Miura and Satoh et al, when the N -phenyl pyrazoles and internal alkynes were employed to rhodium catalysis, the N -naphthyl pyrazoles resulting from the benzannulation of the two adjacent aryl C–H bonds with two alkyne molecules were the products (Scheme A).…”