γ-Carboline synthesis enabled by Rh(iii)-catalysed regioselective C-H annulation

Area of Science:

• Organic Chemistry
• Catalysis
• Medicinal Chemistry

Background:

• Indolyl oximes are versatile precursors in organic synthesis.
• Rhodium(iii)-catalyzed C-H activation offers efficient bond formation.
• γ-carbolines are important heterocyclic scaffolds with diverse biological activities.

Purpose of the Study:

• To develop a novel redox-neutral Rh(iii)-catalyzed C-H annulation of indolyl oximes.
• To utilize alkynyl silanes as effective alkyne surrogates.
• To achieve regioselective synthesis of C3-substituted γ-carbolines.

Main Methods:

• Redox-neutral Rh(iii)-catalyzed C-H annulation reaction.
• Employing various alkynyl silanes as terminal alkyne surrogates.
• Deuterium-labelling and kinetic analysis to probe the reaction mechanism.

Main Results:

• Successful development of a Rh(iii)-catalyzed C-H annulation of indolyl oximes.
• Exclusive synthesis of C3-substituted, substituent-free γ-carbolines.
• High efficiency and broad substrate scope demonstrated with various alkynyl silanes.

Conclusions:

• The developed catalytic system provides an efficient and regioselective method for synthesizing γ-carbolines.
• Alkynyl silanes serve as effective surrogates for terminal alkynes in this transformation.
• Preliminary mechanistic studies offer insights into the catalytic cycle.