Metal-Free C-S Bond Formation: Enabling a Wide Array of Sulfides for DEL Synthesis

Area of Science:

• Organic Chemistry
• Medicinal Chemistry
• Photochemistry

Background:

• Sulfur-containing compounds are crucial building blocks in pharmaceuticals.
• Traditional synthesis of unsymmetrical sulfides often suffers from limited substrate scope and low yields.
• Developing efficient and versatile methods for sulfide synthesis is essential for drug discovery.

Purpose of the Study:

• To develop a novel, metal-free photochemical method for synthesizing unsymmetrical sulfides.
• To establish a versatile protocol applicable to a wide range of thiols, disulfides, and aryl/alkyl iodides.
• To facilitate drug discovery efforts by providing access to diverse sulfide structures for DNA-encoded libraries (DELs).

Main Methods:

• A metal-free photochemical reaction was employed.
• Readily available thiols or disulfides were reacted with common aryl or alkyl iodides.
• The reaction conditions were optimized for efficiency and yield.

Main Results:

• The novel method successfully produced various unsymmetrical sulfides.
• The reaction demonstrated broad substrate scope, accommodating diverse functional groups.
• High yields were achieved under mild photochemical conditions.

Conclusions:

• The developed photochemical method offers an efficient and versatile route to unsymmetrical sulfides.
• This metal-free approach overcomes limitations of traditional synthesis, expanding synthetic possibilities.
• The accessibility of diverse sulfide structures through this method significantly aids drug discovery, particularly in the context of DNA-encoded libraries (DELs).