Enantioselective Carbonylative Coupling Reactions: Merging Nickel-Based Selectivity and Photoredox Reactivity

Area of Science:

• Organic Chemistry
• Catalysis
• Synthetic Chemistry

Background:

• Transition metal-catalyzed carbonylative coupling is vital for synthesizing functional molecules.
• Enantioselective carbonylative coupling of alkyl halides remains a significant challenge due to carbon monoxide inhibition.
• Accessing alpha-chiral motifs is critical for pharmaceutical development.

Purpose of the Study:

• To develop a viable method for asymmetric carbonylative coupling of C(sp3)-halides.
• To overcome the limitations imposed by carbon monoxide in traditional carbonylative couplings.
• To enable the synthesis of enantiomerically enriched chiral amides.

Main Methods:

• A combined photoredox and chiral nickel catalysis strategy was employed.
• The approach separates reactivity and stereocontrol for enhanced selectivity.
• Benzylic and related C(sp3)-halides were coupled with amines.

Main Results:

• The first asymmetric carbonylative coupling of benzylic and related C(sp3)-halides with amines was achieved.
• A diverse range of chiral amides were synthesized with excellent enantioselectivity.
• The method overcomes previous limitations associated with carbon monoxide inhibition.

Conclusions:

• The combined photoredox and nickel catalysis approach offers a new strategy for enantioselective carbonylative coupling.
• This work expands the scope of asymmetric catalysis for synthesizing chiral carbonyl-containing compounds.
• The findings have significant implications for drug discovery and synthetic chemistry.