Late-Stage Aryl C-H Bond Cyclopropenylation with Cyclopropenium Cations

Area of Science:

• Organic Chemistry
• Medicinal Chemistry

Background:

• Late-stage functionalization is crucial for drug discovery and development.
• Cyclopropene rings are strained motifs with potential in medicinal chemistry.
• Efficient methods for introducing cyclopropene rings are limited.

Purpose of the Study:

• To develop a novel method for late-stage cyclopropenylation of (hetero)aryl C-H bonds.
• To explore the utility of cyclopropenylation in modifying complex organic molecules.
• To investigate the application of cyclopropene installation in drug design.

Main Methods:

• Late-stage (hetero)aryl C-H bond cyclopropenylation using cyclopropenium cations (CPCs).
• Demonstration of regio-, site-, and chemoselectivity.
• Application to densely-functionalized drug molecules, natural products, agrochemicals, and fluorescent dyes.

Main Results:

• The first successful regio-, site-, and chemoselective late-stage cyclopropenylation method was established.
• The reaction is fast, operationally simple, and exhibits excellent functional group tolerance.
• Cyclopropene installation can enhance metabolic stability and access sp³-rich scaffolds in drug molecules.

Conclusions:

• This novel cyclopropenylation method provides a powerful tool for late-stage modification of complex molecules.
• The introduction of cyclopropene rings offers a strategy to improve drug properties and create novel chemical entities.
• The strained cyclopropene ring can be leveraged for further synthetic transformations to access medicinally relevant scaffolds.