Synthesis of Mono-Fluoromethyl 6,5-Heteroaromatic Bicycles Using 1,3-Difluoroacetone As a Cyclising Reagent

The development of facile, wide scope synthetic methodologies providing access to fluorinated motifs is important in medic-inal chemistry; for our purposes, we are interested in developing fluorine-tagged compounds to investigate their utility in Huntington’s disease. Here, we describe a novel, operationally simple and mild procedure for the synthesis of mono-fluoromethyl 6,5-heteroaromatic bicycles using 1,3-difluoroacetone (DFA). The scope of the reaction was investigated, and 27 examples synthesized with yields up to 96%.