Installing Axial Chirality by Atroposelective C(sp³)-H Bond Oxidation

Area of Science:

• Organic Chemistry
• Catalysis
• Stereoselective Synthesis

Background:

• Biaryl compounds are crucial structural motifs in pharmaceuticals and materials.
• Developing efficient and selective methods for synthesizing chiral biaryls remains a significant challenge in organic chemistry.

Purpose of the Study:

• To report a novel non-directed atroposelective C(sp³)-H bond oxidation for synthesizing optically enriched multifunctionalized biaryl compounds.
• To introduce a new family of manganese catalysts for achieving high chemo- and enantioselectivity in biaryl synthesis.

Main Methods:

• Utilizing a novel family of manganese complexes as catalysts for C-H bond oxidation.
• Employing hydrogen peroxide (H₂O₂) as a green oxidant under mild reaction conditions.
• Developing a non-directed approach, eliminating the need for directing groups on the substrate.

Main Results:

• Achieved synthesis of 42 examples of axially chiral biaryls with diverse functional groups.
• Obtained high yields (up to 88%) and outstanding enantioselectivity (up to >99% ee).
• Demonstrated subsequent site- and chemoselective oxidation of the second methyl group, enabling further functionalization.

Conclusions:

• The developed manganese-catalyzed system provides a powerful and versatile platform for stereoselective synthesis of complex biaryl compounds.
• This approach highlights the strategic use of C-H bond functionalization for accessing valuable chiral molecules.
• The catalysts recognize methyl groups as functional handles for synthetic manipulation, expanding synthetic possibilities.