Site-selective Ru-catalysed saturation of unactivated arenes via directed 6π activation

Area of Science:

• Organic Chemistry
• Catalysis
• Synthetic Methodology

Background:

• Directing group strategies are effective for functionalizing various bonds but not unactivated aromatic systems.
• Catalytic hydrogenation of arenes increases molecular 3D character and sp3 carbons but lacks site-selectivity for unbiased arenes.

Purpose of the Study:

• To develop a site-selective arene saturation method using ruthenium catalysis.
• To achieve high cis selectivity and chemoselectivity in the reduction of aromatic systems.

Main Methods:

• Ruthenium-catalyzed reaction employing a removable directing group for arene saturation.
• Exploration of reaction conditions to ensure chemoselectivity and tolerance of other functional groups.

Main Results:

• Selective reduction of the aryl group adjacent to the directing moiety with excellent cis selectivity.
• High chemoselectivity observed, with tolerance for functional groups like alkenes, heteroarenes, ketones, and aryl bromides.
• Demonstrated synthetic utility in synthesizing cis-Atovaquone and late-stage functionalization of complex molecules.

Conclusions:

• The developed Ru-catalyzed directed arene saturation is a powerful new synthetic tool.
• The method offers a straightforward approach to increase molecular complexity and sp3 carbon content.
• The reaction proceeds via homogeneous catalysis, potentially involving a eta(6)-arene-ruthenium intermediate.