Selective ring expansion and C-H functionalization of azulenes

Area of Science:

• Organic Chemistry
• Catalysis
• Synthetic Methodology

Background:

• The Buchner reaction traditionally applies to benzenoid aromatics for carbene insertion.
• Azulenes, nonbenzenoid aromatic compounds, present unique reactivity challenges in cyclopropanation and related reactions.
• Developing selective catalytic methods for azulene functionalization is crucial for accessing novel molecular architectures.

Purpose of the Study:

• To report the first transition metal-catalyzed ring expansion of azulene.
• To investigate the chemoselectivity between ring expansion and C-H functionalization.
• To elucidate the mechanistic differences between copper and silver catalysts in azulene functionalization.

Main Methods:

• Copper(II) bis(hexafluoroacetylacetonate) [Cu(hfacac)2] catalyzed reaction of azulene with a diazo reagent.
• Silver triflate (AgOTf) catalyzed reaction of azulene with a diazo reagent.
• Density Functional Theory (DFT) calculations to model reaction pathways.

Main Results:

• Cu(hfacac)2 successfully catalyzed the ring expansion of azulene, extending the Buchner reaction to nonbenzenoid systems.
• Substitution of copper with AgOTf selectively yielded C-H functionalization products.
• The catalytic system demonstrated high functional group tolerance and obviated the need for ligands or prefunctionalization.
• Theoretical studies explained the divergent reactivity observed with copper and silver catalysts.

Conclusions:

• A novel transition metal-catalyzed ring expansion of azulene has been achieved, broadening the scope of the Buchner reaction.
• Catalyst choice (Cu vs. Ag) dictates chemoselectivity, enabling either ring expansion or C-H functionalization.
• The developed methods offer a versatile and efficient route to substituted 6,7-bicyclic compounds and C-H functionalized azulenes.