Visible Light-Driven Copper-Catalyzed Asymmetric Synthesis via Sequential C(sp³)─C(sp³) Bond Scission

Area of Science:

• Organic Chemistry
• Photochemistry
• Catalysis

Background:

• Selective cleavage of C(sp3)─C(sp3) bonds is a significant challenge in synthetic chemistry.
• Existing methods often lack control over chemo-, regio-, and stereoselectivity.
• Asymmetric synthesis of quaternary carbon centers remains a key goal.

Purpose of the Study:

• To develop a visible light-driven catalytic system for selective C(sp3)─C(sp3) bond cleavage.
• To achieve high chemo-, regio-, and stereoselectivity in the formation of quaternary carbon stereocenters.
• To establish a streamlined and efficient method for complex molecule synthesis.

Main Methods:

• Utilized a chiral bisoxazoline copper complex as a multifunctional catalyst.
• Employed a sodium sulfoxylate additive to modulate the catalyst's coordination sphere.
• Developed a visible light-driven cascade reaction involving C(sp3)─C(sp3) fragmentation and radical addition.
• Integrated experimental and computational studies to elucidate the reaction mechanism.

Main Results:

• Achieved twofold C(sp3)─C(sp3) fragmentation of cyclobutanols and subsequent coupling with imines.
• Successfully constructed quaternary carbon stereocenters with up to 99% enantioselectivity (ee).
• Demonstrated a cascade mechanism initiated by photoinduced ligand-to-metal charge transfer (LMCT) and copper-mediated β-cleavage.
• Identified the crucial role of sodium sulfoxylate in controlling selectivity and preventing premature radical trapping.

Conclusions:

• Established a new paradigm for photochemical asymmetric synthesis through controlled C(sp3)─C(sp3) bond cleavage.
• Presented a photosensitizer-free system for efficient and enantioselective synthesis.
• The developed methodology offers a powerful tool for accessing complex chiral molecules.