Benzylic C(sp³)-H Phosphonylation via Dual Photo and Copper Catalysis

Area of Science:

• Organic Chemistry
• Medicinal Chemistry
• Synthetic Chemistry

Background:

• Alkyl phosphonates are crucial in medicinal chemistry.
• Efficient synthesis of alkyl phosphonates via direct C(sp³)-H functionalization is challenging.

Purpose of the Study:

• To develop a straightforward method for synthesizing benzylic phosphonates.
• To achieve direct C(sp³)-H functionalization using readily available starting materials.

Main Methods:

• Cross-dehydrogenative-coupling reaction between alkylarenes and phosphites.
• Utilizing non-specialized alkylarenes and unfunctionalized phosphites as substrates.
• Employing C-H substrates as the limiting reagents.

Main Results:

• Broad scope of benzylic C-H substrates successfully functionalized.
• Mild reaction conditions with good functional group tolerance achieved.
• Reaction proceeds via a radical pathway, distinct from previous methods.

Conclusions:

• This study provides efficient access to benzylic phosphonates.
• The developed method offers a versatile tool for medicinal chemistry.
• The radical pathway offers new insights into C-H functionalization mechanisms.