Bridged-Type Selective Intramolecular Nitrone-Alkene Cycloaddition: Computational Chemistry-Inspired Regioselectivity...

Area of Science:

• Organic Chemistry
• Medicinal Chemistry
• Synthetic Chemistry

Background:

• Intramolecular nitrone-alkene cycloadditions are valuable for constructing nitrogen-containing heterocycles.
• Developing regioselective methods for complex scaffold synthesis remains a key challenge in organic chemistry.

Purpose of the Study:

• To report a novel regioselective intramolecular nitrone-alkene cycloaddition for synthesizing oxazabicyclo ring-fused indoles.
• To establish optimal reaction conditions using computational studies and a Lewis acidic reagent.

Main Methods:

• Regioselective intramolecular nitrone-alkene cycloaddition reaction.
• Computational studies to guide reaction optimization.
• Use of Indium(III) triflate (In(OTf)3) as a Lewis acid catalyst.

Main Results:

• Successful synthesis of oxazabicyclo ring-fused indoles.
• Demonstrated broad substrate scope, yielding diverse seven- and eight-membered carbocycles.
• Formation of complex nitrogen-containing scaffolds with various substituents.

Conclusions:

• The developed method provides a versatile and efficient route to valuable nitrogen-containing heterocyclic compounds.
• The synthesized scaffolds hold potential for applications in medicinal chemistry and total synthesis of biologically active molecules.