One-pot ester and thioester formation mediated by pentafluoropyridine (PFP)

Area of Science:

• Organic Chemistry
• Synthetic Chemistry

Background:

• Acyl fluorides are valuable synthetic intermediates but are often difficult to handle and isolate due to degradation.
• Existing methods for acyl fluoride preparation often require isolation and are incompatible with in situ generation, limiting their application.
• Acyl fluorides are under-investigated in nucleophilic substitution reactions due to substrate scope limitations.

Purpose of the Study:

• To develop a mild and efficient method for in situ generation of acyl fluorides.
• To expand the utility of acyl fluorides in nucleophilic substitution reactions.
• To establish a one-pot synthesis for esters and thioesters from carboxylic acids.

Main Methods:

• Utilizing pentafluoropyridine for the in situ generation of acyl fluorides under mild conditions.
• Subsequent reaction of the in situ generated acyl fluorides with nucleophiles to form esters and thioesters.
• One-pot reaction sequence directly from parent carboxylic acids.

Main Results:

• Pentafluoropyridine effectively generates acyl fluorides in situ under mild conditions.
• The in situ generated acyl fluorides are reactive intermediates for synthesizing a range of esters and thioesters.
• A simple one-pot procedure for ester and thioester synthesis directly from carboxylic acids was established.

Conclusions:

• Pentafluoropyridine provides a convenient reagent for mild, in situ acyl fluoride generation.
• This method overcomes challenges associated with acyl fluoride handling and isolation.
• The developed methodology offers a versatile and efficient one-pot synthesis of esters and thioesters.