Merging C-H Bond Activation, Alkyne Insertion, and Rearrangements by Rh(III)-Catalysis: Oxindole Synthesis from...

Area of Science:

• Organic Chemistry
• Catalysis
• Synthetic Methodology

Background:

• Oxindoles are crucial heterocyclic scaffolds in medicinal chemistry and natural products.
• Efficient synthesis of oxindoles, particularly those with quaternary stereocenters, remains a significant challenge in organic synthesis.

Purpose of the Study:

• To develop a new Rh(III)-catalyzed C-H functionalization strategy for constructing 3,3-disubstituted oxindoles.
• To explore the utility of nitroarenes as versatile starting materials in C-H functionalization reactions.
• To achieve the synthesis of oxindoles bearing a quaternary carbon stereocenter.

Main Methods:

• Rhodium(III)-catalyzed ortho-C-H bond functionalization of nitroarenes with 1,2-diarylalkynes and carboxylic anhydrides.
• Utilized a specifically designed functionalized cyclopentadienyl (CpTMP*)-ligated Rh(III) catalyst.
• Employed mechanistic investigations, including isolation of rhodacycle intermediates and density functional theory (DFT) calculations.

Main Results:

• Successfully synthesized 3,3-disubstituted oxindoles with formal reduction of the nitro group under redox-neutral conditions.
• Demonstrated good functional group tolerance in the developed transformation.
• Achieved the preparation of oxindoles with a quaternary carbon stereocenter using nonsymmetrical 1,2-diarylalkynes.
• Identified nitrosoarene intermediates and a cascade mechanism involving C-H activation, O-atom transfer, aryl migration, deoxygenation, and N-acylation.

Conclusions:

• The developed Rh(III)-catalyzed protocol provides an efficient and versatile route to complex oxindole derivatives.
• The use of a tailored CpTMP*-Rh(III) catalyst is key to the reaction's success.
• Mechanistic studies elucidated a novel reaction pathway involving nitroarene reduction and cascade processes.