A gallium-catalyzed cycloisomerization/Friedel-Crafts tandem

Area of Science:

• Organic Chemistry
• Catalysis
• Synthetic Methodology

Background:

• 1,6-Arenynes are versatile precursors for constructing cyclic organic molecules.
• Metal-catalyzed cycloisomerization reactions are crucial in organic synthesis.
• Achieving regiocontrol in cascade reactions remains a synthetic challenge.

Purpose of the Study:

• To investigate the catalytic activity of noble and group 13 metals in the cycloisomerization of 1,6-arenynes.
• To explore the potential for tandem cycloisomerization-Friedel-Crafts reactions.
• To synthesize complex polycyclic compounds, such as tetrahydroisoquinolines and tetrahydrobenzoazepines, using a novel catalytic approach.

Main Methods:

• Catalysis using noble metals (Au, Pt, Ru) and group 13 metals (Ga, In).
• Reactions involving 1,6-arenynes and electron-rich arenes.
• Density Functional Theory (DFT) calculations to elucidate reaction mechanisms.
• Synthesis of N-tethered 1,6-arenynes for selective cyclizations.

Main Results:

• High-yielding, regiocontrolled cycloisomerization of 1,6-arenynes to 1,2-dihydronaphthalenes was achieved with Au, Pt, Ru, Ga, and In catalysts.
• Gallium(III) salts uniquely catalyzed sequential cycloisomerization and Friedel-Crafts addition reactions.
• Selective synthesis of tetrahydroisoquinolines and tetrahydrobenzoazepines was demonstrated.
• DFT calculations provided mechanistic insights into regioselectivity and the role of the tether in stabilizing intermediates.
• Complementary reactivities of gold and gallium catalysts were observed for different substrates.

Conclusions:

• Gallium catalysts exhibit unique reactivity for tandem cycloisomerization-Friedel-Crafts reactions, enabling the synthesis of complex polycyclic structures.
• The developed methodology offers a powerful route to valuable heterocyclic compounds that are otherwise difficult to access.
• DFT calculations elucidated the mechanistic basis for the observed regioselectivity and catalytic behavior.