Shining light on tryptamine-derived isocyanides: access to constrained spirocylic scaffolds

Area of Science:

• Organic Chemistry
• Synthetic Chemistry
• Medicinal Chemistry

Background:

• Dearomatization of indoles via charge transfer complexes is a key strategy for building complex 3D structures.
• The synthesis of spirocyclic scaffolds from tryptamine-derived isocyanides using this method is currently underdeveloped.

Purpose of the Study:

• To develop a novel protocol for the dearomatization of tryptamine-derived isocyanides.
• To generate conformationally constrained spirocyclic scaffolds with potential applications in drug discovery.

Main Methods:

• Formation of aggregates by tryptamine-derived isocyanides at higher concentrations.
• Initiation of single electron transfer to generate carbon-based radical intermediates.
• Utilizing optical, HRMS, and computational studies to understand photophysical properties.

Main Results:

• Demonstrated the aggregation of tryptamine-derived isocyanides enabling single electron transfer.
• Successfully generated carbon-based radical intermediates.
• Elucidated key photophysical properties of the isocyanides.

Conclusions:

• Developed an operationally simple and robust protocol for synthesizing spirocyclic scaffolds.
• Presented a novel approach to access conformationally constrained spirocyclic structures.
• Highlighted the potential of these scaffolds in drug discovery.