Synthesis of dienes from pyrrolidines using skeletal modification

Area of Science:

• Organic Chemistry
• Synthetic Chemistry
• Medicinal Chemistry

Background:

• Saturated N-heterocyclic pyrrolidines are prevalent scaffolds in natural products, pharmaceuticals, and agrochemicals.
• Reconstructing pyrrolidine skeletons to access novel chemical entities is synthetically challenging due to limited methodologies.

Purpose of the Study:

• To develop a novel skeletal modification strategy for pyrrolidines.
• To convert polar cyclic pyrrolidines into nonpolar linear dienes.
• To explore new chemical space through N-atom removal and deconstruction.

Main Methods:

• N-atom removal and deconstruction of pyrrolidine rings.
• N-sulfonylazidonation followed by rearrangement of sulfamoyl azide intermediates.
• Formation of C-C π bonds and cleavage of C-N and C-C σ bonds.

Main Results:

• Successful conversion of pyrrolidines into versatile conjugated and nonconjugated dienes with varying linker lengths.
• Demonstration of the method's applicability in late-stage skeletal modification of bioactive compounds.
• Exploration of formal traceless C(sp2)-H functionalization and N-atom deletion.

Conclusions:

• The developed method offers a unique approach for skeletal modification of pyrrolidines.
• This strategy enables access to diverse linear dienes, expanding synthetic possibilities.
• The methodology holds potential for drug discovery and development through late-stage functionalization.