Optimizing ligand structure for low-loading and fast catalysis for alkynyl-alcohol and -amine cyclization

Area of Science:

• Organometallic Chemistry
• Catalysis
• Synthetic Organic Chemistry

Background:

• Ruthenium complexes are versatile catalysts in organic synthesis.
• Alkyne cyclization reactions are important for heterocycle synthesis.
• Tuning the ligand sphere of metal catalysts impacts reactivity and selectivity.

Purpose of the Study:

• To synthesize novel Ruthenium(II) complexes with varying primary coordination spheres.
• To evaluate the catalytic activity of these complexes in intramolecular alkyne cyclization.
• To understand the influence of steric and electronic ligand properties on catalyst performance.

Main Methods:

• Synthesis of [Ru(Cp/Cp*)(P^R₂N^R'₂)(MeCN)]PF₆ complexes with diverse R and R' groups.
• Catalytic testing in intramolecular cyclization of alkynes with amines or alcohols.
• Analysis of catalyst performance, including turnover number and reaction temperature.

Main Results:

• The prepared Ruthenium complexes demonstrated catalytic activity in forming 5- and 6-membered heterocycles.
• Increased steric bulk around the Ruthenium center significantly enhanced catalytic rates at lower temperatures.
• The catalyst [Ru(Cp)(P^t-Bu₂N^Ph₂)(MeCN)]PF₆ exhibited >10-fold higher activity than previous catalysts for 2-ethynylaniline cyclization.
• This optimized catalyst efficiently produced various substituted indoles with good functional group tolerance.

Conclusions:

• Steric factors in the primary coordination sphere are critical for developing highly active Ruthenium catalysts.
• The developed Ruthenium catalyst offers a superior method for synthesizing substituted indoles.
• This work provides insights into ligand design for efficient alkyne cyclization catalysis.