Visible Light-Induced Sulfonamidation of [1.1.1]Propellane Promoted by Energy Transfer Catalysis

Area of Science:

• Organic Chemistry
• Medicinal Chemistry
• Photocatalysis

Background:

• Sulfonamides are crucial structural motifs in many drugs.
• Limited synthetic methods for bicyclo[1.1.1]pentanesulfonamides hinder their application.
• Bicyclo[1.1.1]pentane (BCP) scaffolds offer unique properties for drug design.

Purpose of the Study:

• To develop an efficient photocatalytic strategy for synthesizing bicyclo[1.1.1]pentanesulfonamides.
• To overcome the limitations posed by the scarcity of synthetic routes.
• To broaden the applicability of BCP-sulfonamides in drug discovery.

Main Methods:

• Utilized an energy transfer (EnT) promoted photocatalytic strategy.
• Employed N-nitrososulfonamides as precursors for sulfonamide radical generation.
• Facilitated radical addition to [1.1.1]propellane followed by coupling reactions.

Main Results:

• Successfully synthesized a variety of C3-substituted bicyclo[1.1.1]pentanesulfonamides.
• Demonstrated efficient sulfonamidation of [1.1.1]propellane.
• Achieved synthesis under mild conditions with operational simplicity and high atomic utilization.

Conclusions:

• The developed EnT photocatalytic strategy provides an efficient route to C3-versatile-substituted BCP sulfonamides.
• This method significantly broadens the potential applications of bicyclo[1.1.1]pentanesulfonamides in drug discovery.
• The approach offers a valuable tool for medicinal chemists seeking novel BCP-containing drug candidates.