Flavin-Mediated Photocatalysis Provides a General Platform for Sulfide C-H Functionalization

Area of Science:

• Organic Chemistry
• Chemical Biology
• Materials Science

Background:

• Functionalized sulfides are crucial in diverse scientific fields, including drug discovery and materials chemistry.
• Selective methods for functionalizing simple sulfides or late-stage modification of complex sulfides remain underexplored.
• α-Sulfur functionalization is particularly valuable for introducing reactive groups.

Purpose of the Study:

• To develop a general reaction platform for the selective α-sulfur C-H functionalization of sulfides.
• To showcase three distinct functionalization modes: cyanation, alkenylation, and alkynylation.
• To demonstrate the utility of this platform for both simple and complex sulfides, including peptides.

Main Methods:

• Visible-light photoredox catalysis utilizing riboflavin tetraacetate as a photocatalyst.
• Direct α-sulfur C-H functionalization of various sulfide substrates.
• Demonstration of cyanation, alkenylation, and alkynylation reactions.
• Compatibility studies with amino-acid dopants for peptide functionalization.

Main Results:

• Successful implementation of three distinct α-sulfur C-H functionalization reactions (cyanation, alkenylation, alkynylation).
• High yields and selectivity achieved for both feedstock and complex sulfide substrates.
• Selective functionalization of methionine-containing peptides demonstrated.
• Platform compatibility with most amino-acid side chains confirmed.

Conclusions:

• A general and efficient visible-light-driven platform for sulfide functionalization has been established.
• The method allows for selective α-sulfur C-H functionalization, expanding synthetic capabilities.
• This approach holds significant potential as a tool for bioconjugation and the synthesis of functionalized organic materials.