Ruthenium-Catalyzed Carbocycle-Selective Hydrogenation of Fused Heteroarenes

Area of Science:

• Organic Chemistry
• Catalysis
• Heterocyclic Chemistry

Background:

• Homogeneous hydrogenation of benzo-fused heteroarenes typically reduces the heteroaryl ring, yielding partially hydrogenated products like 1,2,3,4-tetrahydroquinoline.
• Selective reduction of the carbocyclic ring in these systems remains a significant challenge in synthetic chemistry.

Purpose of the Study:

• To develop a catalytic system for carbocycle-selective hydrogenation of fused N-heteroarenes.
• To achieve high chemoselectivity for the formation of 5,6,7,8-tetrahydro products.
• To explore the applicability of the catalyst for asymmetric hydrogenation of functionalized heteroarenes.

Main Methods:

• Utilized a ruthenium complex with a chiral spiroketal-based diphosphine (SKP) ligand as the homogeneous catalyst.
• Investigated the hydrogenation of various fused N-heteroarenes including quinoline, isoquinoline, and quinoxaline.
• Employed experimental studies and Density Functional Theory (DFT) calculations to elucidate the catalytic mechanism.

Main Results:

• Achieved high chemoselectivity for carbocycle hydrogenation of fused N-heteroarenes, producing 5,6,7,8-tetrahydro products.
• Demonstrated the catalyst's effectiveness in asymmetric carbocycle hydrogenation of fused heteroarenes with boryl or amino substituents.
• Provided strong experimental evidence for homogeneous catalysis and proposed an inner-sphere hydrogenation mechanism.

Conclusions:

• The developed Ru-SKP catalytic system enables selective carbocycle hydrogenation of fused N-heteroarenes.
• The proposed mechanism involves initial η⁴-coordinative activation of the carbocycle by the Ru dihydride complex.
• This work offers a valuable synthetic strategy for accessing specific tetrahydroheteroarene derivatives.