Lactone radical cyclizations and cyclization cascades mediated by SmI2-H2O

Area of Science:

• Organic Chemistry
• Synthetic Chemistry
• Stereoselective Synthesis

Background:

• Unsaturated lactones are versatile precursors in organic synthesis.
• Controlling stereochemistry in cyclic compounds is crucial for drug discovery.
• Reductive radical cyclizations offer powerful C-C bond-forming strategies.

Purpose of the Study:

• To develop a novel method for synthesizing decorated cycloheptanes.
• To achieve highly stereoselective construction of multiple contiguous stereocenters.
• To explore cascade reactions for accessing complex molecular scaffolds.

Main Methods:

• Reductive radical cyclization using samarium diiodide (SmI2) and water.
• Employing unsaturated lactones with various unsaturated functionalities (alkenes, alkynes, allenes).
• One-pot cascade processes for sequential C-C bond formation.

Main Results:

• Selective formation of decorated cycloheptanes from unsaturated lactones.
• Generation of up to three contiguous stereocenters in a single operation.
• Cascade reactions enabled the construction of up to four contiguous stereocenters in biologically significant scaffolds.
• Mechanism involves trapping of radical anions from SmI2 reduction of the lactone carbonyl.

Conclusions:

• Samarium diiodide-mediated reductive radical cyclization is an effective strategy for stereoselective cycloheptane synthesis.
• The developed method provides efficient access to complex molecular architectures with multiple stereocenters.
• This approach offers a powerful tool for the synthesis of biologically relevant compounds.