Smiles-Truce Cascades Enable Heteroaryl Cyclopropane and Sultine Synthesis

Area of Science:

• Organic Chemistry
• Synthetic Chemistry
• Medicinal Chemistry

Background:

• Cyclopropanes are valuable structural motifs in pharmaceuticals.
• Heteroaryl cyclopropanes are particularly important building blocks.
• Sultines are an under-explored class of heterocycles with potential bioisosteric applications.

Purpose of the Study:

• To develop a novel cascade process for synthesizing heteroaryl cyclopropanes.
• To explore new synthetic methodologies for creating complex organic molecules.
• To investigate the potential of sultines as bioisosteres.

Main Methods:

• A triple C─C bond cascade reaction was employed.
• The reaction involved vinyl sulfonium salts and sulfones under mild conditions.
• Key steps included conjugate addition, Smiles-Truce rearrangement, and 3-exo-tet ring closure.

Main Results:

• Efficient synthesis of heteroaryl cyclopropanes was achieved through a three-step cascade process.
• A novel reaction pathway was discovered, leading to the formation of sultines.
• The reaction conditions were mild, indicating a practical synthetic approach.

Conclusions:

• The developed cascade reaction provides a versatile route to heteroaryl cyclopropanes.
• The serendipitous discovery of sultine synthesis opens new avenues for medicinal chemistry.
• This work expands the synthetic toolkit for accessing valuable heterocyclic compounds.