Remote difunctionalization of 2H-indazoles using Koser's reagents

Area of Science:

• Organic Chemistry
• Synthetic Methodology
• Heterocyclic Chemistry

Background:

• Unreactive C-H bonds in heterocyclic compounds like 2H-indazole present synthetic challenges.
• Selective functionalization of these positions is crucial for developing new molecules.
• Existing methods often require harsh conditions or metal catalysts.

Purpose of the Study:

• To develop an efficient, metal-free protocol for the remote difunctionalization of 2H-indazoles.
• To achieve regioselective introduction of sulfonyloxy and iodo groups at specific positions.
• To provide a versatile synthetic route to novel 4,7-disubstituted 2H-indazole derivatives.

Main Methods:

• Utilized Koser's reagents as dual sulfonyloxylating and iodinating agents.
• Performed reactions under ambient air conditions, avoiding inert atmospheres.
• Employed a range of 2H-indazole substrates to assess scope and tolerance.

Main Results:

• Achieved efficient and regioselective C-4 sulfonyloxylation and C-7 iodination of 2H-indazoles.
• Demonstrated wide functional group tolerance and broad substrate scope.
• Obtained desired 4,7-disubstituted 2H-indazole derivatives in good to excellent yields.
• Confirmed the utility of the products as precursors for further C-4,7-functionalization.

Conclusions:

• Established a novel, efficient, and metal-free protocol for remote difunctionalization of 2H-indazoles.
• The developed methodology offers facile access to valuable 4,7-disubstituted 2H-indazoles.
• This approach provides a versatile platform for synthesizing diverse functionalized indazole derivatives.