A general method for site-selective Csp³-S bond formation via cooperative catalysis

Area of Science:

• Organic Chemistry
• Catalysis
• Synthetic Methodology

Background:

• C-H bond functionalization is a key area in synthetic chemistry.
• Developing selective methods for C-S bond formation is crucial for synthesizing sulfur-containing molecules.
• Aliphatic amines are ubiquitous in pharmaceuticals and natural products.

Purpose of the Study:

• To develop a novel copper-catalyzed method for site-selective thiolation of Csp3-H bonds in aliphatic amines.
• To demonstrate the broad substrate scope and functional group tolerance of the developed method.
• To showcase the utility of this methodology for late-stage functionalization and domino reactions.

Main Methods:

• Copper-catalyzed reaction utilizing specific ligands and thiolation reagents.
• Site-selective functionalization of primary, secondary, and tertiary C-H bonds.
• Application in late-stage modification of biologically relevant molecules and domino synthesis of heterocycles.

Main Results:

• Achieved efficient and site-selective thiolation of Csp3-H bonds in various aliphatic amines.
• Demonstrated broad substrate scope and excellent functional group compatibility.
• Successfully applied the method for late-stage modification of complex molecules and one-pot synthesis of pyrrolidine and piperidine derivatives.

Conclusions:

• The developed copper-catalyzed thiolation offers a powerful and versatile tool for C-S bond formation.
• This method provides access to valuable sulfur-containing compounds, including heterocycles.
• The methodology holds significant potential for drug discovery and development through late-stage functionalization.