A mild two-step propargylation of aromatic bioactive small molecules

Area of Science:

• Organic Chemistry
• Medicinal Chemistry

Background:

• Aromatic bioactive small molecules are crucial in drug discovery.
• Introducing functional groups like propargyl can modulate molecular properties.
• Existing methods may lack efficiency or compatibility with sensitive substrates.

Purpose of the Study:

• To develop a mild and efficient two-step method for propargyl group introduction into aromatic bioactive small molecules.
• To ensure the method's applicability to acid- and/or oxidant-sensitive compounds.

Main Methods:

• Propargylation of aromatic groups using a cationic propargyl hexacarbonyl complex and cesium carbonate.
• Decomplexation of cobalt complexes using 2,2,6,6-tetramethylpiperidine-1-oxoammonium tetrafluoroborate.
• Performing reactions under mild conditions.

Main Results:

• Successful introduction of propargyl groups onto aromatic bioactive small molecules.
• Demonstrated compatibility with acid- and/or oxidant-sensitive substrates.
• The two-step process is efficient and proceeds under mild reaction conditions.

Conclusions:

• A new, mild two-step synthetic route for propargylating aromatic bioactive molecules has been established.
• This method offers a valuable tool for medicinal chemists working with sensitive molecular structures.
• The developed protocol expands synthetic possibilities in drug discovery and development.