A general asymmetric copper-catalysed Sonogashira C(sp³)-C(sp) coupling

Area of Science:

• Organic Chemistry
• Catalysis
• Synthetic Methodology

Background:

• The Sonogashira coupling is a vital reaction for C-C bond formation in synthesizing functionalized molecules.
• Asymmetric Sonogashira coupling, especially for C(sp³)-C(sp) bonds, remains an underdeveloped area in synthetic chemistry.

Purpose of the Study:

• To develop a general and stereoconvergent asymmetric Sonogashira coupling reaction for C(sp³)-C(sp) bond formation.
• To enable the synthesis of stereoenriched molecules using readily available starting materials.

Main Methods:

• Copper-catalyzed radical-involved alkynylation of racemic alkyl halides with terminal alkynes.
• Utilized a chiral cinchona alkaloid-based P,N-ligand to control stereochemistry.

Main Results:

• Demonstrated a general method for asymmetric Sonogashira C(sp³)-C(sp) cross-coupling with over 120 examples.
• Successfully incorporated industrially relevant alkynes like acetylene and propyne.
• Facile synthesis of stereoenriched bioactive molecules, medicinal compounds, and natural products.

Conclusions:

• The developed method provides a scalable and economic approach for synthesizing chiral molecules with C(sp³)-C(sp) bonds.
• Highlights the significance of radical intermediates in enantioconvergent transformations.
• Opens new avenues for the synthesis of complex organic compounds and pharmaceuticals.