Divergent Rearrangement of Geminal-Substituted Cyclopropane: Access to Pyran and Spirocyclopropane Scaffolds

Area of Science:

• Organic Chemistry
• Synthetic Chemistry

Background:

• Accessing diverse chemical structures is crucial for drug discovery and materials science.
• Developing efficient synthetic routes from single precursors remains a key challenge in organic chemistry.

Purpose of the Study:

• To report a chemodivergent protocol enabling access to two distinct chemical spaces from a single starting material.
• To explore the synthesis of pyrans and spiro cyclopropanes using modified geminal substituted cyclopropane 1,3 keto-esters.

Main Methods:

• Utilizing modified geminal substituted cyclopropane 1,3 keto-esters as starting materials.
• Employing varied reaction conditions to control enolate formation (O-center vs. C-center).
• Conducting mechanistic and theoretical studies to elucidate reaction pathways.

Main Results:

• Successfully synthesized pyrans and spiro cyclopropanes by manipulating reaction conditions.
• Demonstrated broad functional group tolerance in the developed protocol.
• Identified keto group enolization as the initiation step, guided by the Hard and Soft Acids and Bases (HSAB) principle.

Conclusions:

• The developed protocol provides a flexible route to diverse molecular architectures.
• The reaction's outcome is predictable and controllable through reaction media, adhering to the HSAB principle.
• This method offers significant potential for synthesizing complex organic molecules.