Iridium(III)-Catalyzed Asymmetric Site-Selective Carbene C-H Insertion during Late-Stage Transformation

Area of Science:

• Organic Chemistry
• Catalysis
• Synthetic Methodology

Background:

• Late-stage C-H functionalization is crucial for modifying bioactive compounds and creating novel molecules.
• Carbene transfer reactions offer stereoselective C-H to C-C bond conversion but have limitations in late-stage material transformations.

Purpose of the Study:

• To develop an efficient catalytic system for asymmetric carbene C-H insertion reactions.
• To expand the application of C-H functionalization in late-stage transformations.

Main Methods:

• Utilized an iridium-salen complex (catalyst 6) for asymmetric carbene C-H insertion reactions.
• Optimized reaction conditions to achieve high stereoselectivity and regioselectivity.
• Investigated reaction mechanisms through mechanistic studies.

Main Results:

• The iridium-salen complex demonstrated efficient catalysis in asymmetric carbene C-H insertion.
• Benzylic, allylic, and propargylic C-H bonds were converted to C-C bonds with excellent stereoselectivity.
• High regioselectivity was achieved with both simple substrates and natural products.

Conclusions:

• The developed iridium-catalyzed reaction provides a powerful tool for stereoselective C-C bond formation.
• The method is applicable to complex molecules, including natural products, in late-stage functionalization.
• Mechanistic studies revealed a unique C-H insertion pathway involving rate-determining asynchronous concerted processes.