Metal-to-Ligand Ratio-Dependent Chemodivergent Asymmetric Synthesis

Area of Science:

• Organometallic Chemistry
• Asymmetric Synthesis
• Radical Chemistry

Background:

• Developing catalytic systems for selective chemical transformations is crucial in organic synthesis.
• Controlling chemoselectivity and enantioselectivity simultaneously in radical reactions presents a significant challenge.

Purpose of the Study:

• To achieve chemodivergent asymmetric synthesis of alkenes using a dual photoredox and copper catalytic system.
• To demonstrate the ability to control the reaction pathway (oxocyanation vs. aminocyanation) by tuning the metal-to-ligand ratio.

Main Methods:

• Utilized N-(aroyloxy)phthalimide as a precursor for generating oxygen-centered or nitrogen-centered radicals.
• Employed a dual photoredox and copper catalysis strategy.
• Varied the metal-to-ligand ratio to control chemoselectivity.
• Performed mechanistic studies using electron paramagnetic resonance (EPR) spectroscopy.

Main Results:

• Achieved separate enantioselective oxocyanation and aminocyanation of alkenes.
• Demonstrated chemoselective control by adjusting the metal-to-ligand ratio while maintaining high enantiopurity.
• Successfully applied the protocol to chemodivergent asymmetric 1,5-aminocyanation or 1,5-oxocyanation of vinylcyclopropane.
• Reactions were efficient at low catalyst loading (0.2 mol%) and scalable to gram quantities.

Conclusions:

• The metal-to-ligand ratio is a key factor in achieving chemodivergent asymmetric synthesis via radical pathways.
• The developed dual catalytic system offers a versatile and efficient method for enantioselective functionalization of alkenes and vinylcyclopropanes.
• Mechanistic insights support the proposed radical pathways and stereochemical outcomes.