Three-Component Olefin Dicarbofunctionalization Enabled by Nickel/Photoredox Dual Catalysis

Area of Science:

• Organic Chemistry
• Catalysis
• Synthetic Methodology

Background:

• Developing efficient methods for olefin functionalization is crucial in organic synthesis.
• Traditional methods often lack selectivity or require harsh conditions.
• Photoredox and Ni dual catalysis offer promising avenues for novel transformations.

Purpose of the Study:

• To develop a novel intermolecular photocatalytic dicarbofunctionalization (DCF) of olefins.
• To merge Giese-type addition with Ni/photoredox dual catalysis for enhanced reactivity and selectivity.
• To enable the synthesis of complex molecules with quaternary and tertiary centers.

Main Methods:

• Utilized a combination of Giese-type radical addition and Ni/photoredox dual catalysis.
• Employed 3° radicals for regioselective addition to alkenes.
• Optimized reaction conditions for mildness and functional group tolerance.

Main Results:

• Achieved successful intermolecular photocatalytic dicarbofunctionalization of olefins.
• Demonstrated regioselective alkylation and arylation of olefins.
• Enabled the installation of quaternary and tertiary carbon centers in a single step.
• Showcased compatibility with various functional groups, including pinacolboronate esters.
• Applied the methodology to synthesize an intermediate for a preclinical candidate (TK-666).

Conclusions:

• The developed dual catalytic method provides an efficient route for olefin dicarbofunctionalization.
• This approach allows for the construction of complex molecular architectures under mild conditions.
• The methodology holds potential for drug discovery and development, as evidenced by its application in synthesizing a preclinical candidate intermediate.