C-F Bond Insertion: An Emerging Strategy for Constructing Fluorinated Molecules.

C-F Insertion reactions, where an organic fragment formally inserts into a carbon-fluorine bond in a substrate, are highly attractive, yet largely unexplored, methods to prepare valuable fluorinated molecules. The inherent strength of C-F bonds and the resulting need for a large thermodynamic driving force to initiate C-F cleavage often leads to sequestering of the released fluoride in an unreactive by-product. Recently, however, several groups have succeeded in overcoming this challenge, opening up the study of C-F insertion as an efficient and highly atom-economical approach to prepare fluorinated compounds. In this article, the recent breakthroughs are discussed focusing on the key conceptual advances that allowed for both C-F bond cleavage and subsequent incorporation of the released fluoride into the product.

Direct synthesis of acyl fluorides from carboxylic acids using benzothiazolium reagents.

2-(Trifluoromethylthio)benzothiazolium triflate (BT-SCF3) was used as deoxyfluorinating reagent for the synthesis of versatile acyl fluorides directly from the corresponding carboxylic acids. These acyl fluorides were reacted with amines in a one-pot protocol to form different amides, including dipeptides, under mild and operationally simple conditions in high yields. Mechanistic studies suggest that BT-SCF3 can generate acyl fluorides from carboxylic acids via two distinct pathways, which allows the deoxyfluorinating reagent to be employed in sub-stoichiometric amounts.