Migratory C(sp²)-H/C(sp³)-H Cross-Coupling Enabled by Metallaphotoredox Catalysis

Area of Science:

• Organic Chemistry
• Catalysis
• Synthetic Methodology

Background:

• Traditional cross-coupling reactions often require pre-functionalized substrates, limiting step and atom economy.
• Direct C─H functionalization offers a more sustainable approach by utilizing abundant C─H bonds.
• Developing dual catalytic systems can enable novel transformations by combining orthogonal activation modes.

Purpose of the Study:

• To develop a direct twofold C─H cross-coupling reaction.
• To establish a dual catalytic platform combining nickel catalysis and photoredox catalysis.
• To achieve regio- and stereoselective synthesis of substituted alkenes and arenes.

Main Methods:

• Employed a dual catalytic system integrating nickel-catalyzed through-space 1,4-Ni/H shift and photoredox-mediated hydrogen atom transfer (HAT).
• Utilized aryl bromides (or chlorides) and abundant alkanes as substrates.
• Conducted mechanistic studies and density functional theory (DFT) calculations to elucidate the reaction pathway.

Main Results:

• Successfully achieved direct twofold C─H cross-coupling between aryl halides and alkanes.
• Demonstrated excellent chemo- and stereoselectivity in the synthesis of substituted alkenes and arenes.
• Identified HAT as the rate-limiting step and elucidated the roles of radical addition and reductive elimination in regioselectivity.

Conclusions:

• The developed dual catalytic platform provides a powerful and efficient method for direct C─H cross-coupling.
• This strategy significantly improves step and atom economy compared to traditional cross-coupling methods.
• The findings open new avenues for the synthesis of complex organic molecules from simple precursors.