Nickel(II)/Salox-Catalyzed Enantioselective C-H Functionalization

Area of Science:

• Organic Chemistry
• Catalysis
• Asymmetric Synthesis

Background:

• Nickel catalysts are effective in asymmetric catalysis.
• Controlling stereochemistry in nickel-catalyzed C-H activation/alkene insertion is challenging.
• Divalent nickel catalysts offer cost-effectiveness and sustainability.

Purpose of the Study:

• To develop a nickel(II)-catalyzed enantioselective C-H/N-H annulation.
• To synthesize chiral [2,2,1]-bridged bicyclic compounds with multiple stereocenters.
• To address challenges in stereochemical control during nickel-catalyzed transformations.

Main Methods:

• Utilized a nickel(II) catalyst system.
• Employed a sterically hindered chiral salicyloxazoline (Salox) ligand, specifically TMS-Salox.
• Performed C-H/N-H annulation with oxabicyclic alkenes.
• Conducted mechanistic investigations.

Main Results:

• Achieved straightforward synthesis of chiral [2,2,1]-bridged bicyclic compounds.
• Generated products with four consecutive stereocenters.
• Obtained high enantioselectivity, up to 96% ee.
• Identified a chiral Ni(III)-metalacyclic intermediate.

Conclusions:

• The TMS-Salox ligand is crucial for achieving high enantioselectivity.
• In situ oxidation and ligand coordination form a chiral Ni(III) intermediate.
• A tailored chiral pocket dictates alkene approach and stereochemistry.
• This protocol provides efficient access to complex chiral bicyclic structures.