Site-Selective C(sp³)-H and Switchable C(sp³)-H/C(sp²)-H Functionalization Enabled by Electron-Deficient...

Area of Science:

• Organic Chemistry
• Catalysis
• Photochemistry

Background:

• Selective C-H bond functionalization is crucial in organic synthesis.
• Directing group-assisted C-H activation often faces challenges with competing reactive sites.
• Oxime ethers are versatile directing groups, but their application in selective C(sp3)-H functionalization requires precise control.

Purpose of the Study:

• To develop a strategy for site-selective C(sp3)-H bond functionalization over more reactive C(sp2)-H bonds.
• To utilize photo-induced E/Z isomerization of oxime ethers for controlling directing group orientation.
• To expand the scope of oxime ethers in iridium(III)-catalyzed C(sp3)-H functionalization.

Main Methods:

• Employing a photo-induced E/Z isomerization of oxime ethers to control directing group orientation.
• Utilizing an electron-deficient Cp*CF3Ir(III) catalyst for C-H activation.
• Investigating switchable C-H activation sequences for sequential double functionalization.

Main Results:

• Achieved site-selective C(sp3)-H functionalization in the presence of C(sp2)-H bonds by controlling directing group geometry.
• Expanded the substrate scope of oxime ethers in C(sp3)-H functionalization through E/Z isomerization and catalysis.
• Demonstrated switchable C-H activation order, enabling successive C(sp3)-H/C(sp2)-H and C(sp2)-H/C(sp3)-H double functionalizations.

Conclusions:

• Photo-induced E/Z isomerization of oxime ethers provides a powerful tool for controlling site-selectivity in C-H functionalization.
• The developed strategy enables the construction of complex molecules through sequential and switchable double C-H functionalizations.
• This work offers new possibilities for synthesizing densely functionalized organic structures.