Precise Editing of Indolines at Different Positions via SET and CMD Pathways

Area of Science:

• Organic Chemistry
• Catalysis
• Medicinal Chemistry

Background:

• Developing selective synthetic methods is crucial for drug discovery, especially for late-stage functionalization of complex molecules.
• Achieving precise C-H bond activation in molecules with similar C-H bonds remains a significant challenge.

Purpose of the Study:

• To develop a single, oxidant-tunable catalytic system for regioselective C-H functionalization of indoline derivatives.
• To achieve selective molecular editing at different positions of the indoline core.

Main Methods:

• Rhodium (Rh)-catalyzed thiolation reactions.
• Utilizing different oxidants (Ag3PO4 and Ag2O) to tune reaction pathways.
• Employing mechanistic studies including Fukui function analysis and ABTS assay.

Main Results:

• Ag3PO4 as oxidant enabled C5 thiolation via a single-electron transfer (SET) mechanism, forming indoline radical cations.
• Ag2O as oxidant suppressed the SET pathway, facilitating C7-selective thiolation through a concerted metalation-deprotonation (CMD) process.
• Mechanistic investigations elucidated the regiodivergence, highlighting the dual reactivity of Rh-(III) species.

Conclusions:

• A single Rh-catalyzed system can achieve regioselective C-H thiolation at C5 or C7 positions of indolines by tuning the oxidant.
• The study provides new conceptual insights into oxidant-controlled C-H functionalization and the dual reactivity of Rh-(III) catalysts.