The development of new applications for pentafluoropyridine in organic chemistry.

Abstract

Esters are a class of organic compounds, that have uses in a wide variety of industries including, fragrances, lubrication, and medicine. One of the most common ways to approach ester synthesis is through a reactive acyl chloride moiety which is accessed by employing reagents such as thionyl chloride. Acyl fluorides are of similar reactivity to their chloride counterparts but have largely remained unexplored for ester preparation as the synthetic methods required to access them can require toxic conditions. This work primarily describes the utilisation of pentafluoropyridine (PFP) to prepare acyl fluorides which were subsequently used to produce esters and thioesters. Recent studies have shown that PFP can be used in a carboxylic acid deoxyfluorination process for the in-situ preparation of acyl fluorides. Herein, this methodology is expanded to one-pot esterification and thioesterification reactions. High yields were readily obtained in the esterification (92%) and thioesterification (89%) processes. The methods reported are mild and easily adaptable for any lab, requiring no specialist handling equipment such as plastic reaction vessels which can often be required for reactions utilising fluorine.

Following this successful esterification work, one of the proposed intermediates of the reaction process was explored and tetrafluoropyridyl esters were successful synthesised. A novel sulfonyl reagent was prepared and successfully shown to be able to access tetrafluoropyridyl esters directly from carboxylic acids which negates the need for acid anhydrides or acid chlorides.

In-situ preparations of acyl fluorides were then used to successfully demonstrate in-situ Suzuki-Miyaura cross-couplings which prepared ketones from acyl fluorides and boronic acids in less-than-optimal yields.