Direct trifluoro-methoxylation of aromatics with perfluoro-methyl-hypofluorite

The reactivity of CF3OF (FTM) has been widely studied especially in halogenated olefinic systems and its use in pharmaceutical synthesis as a mild radical and electrophilic fluorinating agent is well documented. On the other hand, the chemical behavior of the perfluoro-methyl-hypofluorite with aromatic substrates is much less studied. Up to now few and scattered data regarding its use as electrophilic fluorinating agent of variously substituted aromatic compounds are found in the literature. In this work the reactivity of CF3OF with simple electron rich and electron poor aromatics (α,α,α-trifluoro-toluene, toluene, benzene, chloro-benzene, methoxybenzene) has been investigated. The possibility of selectively bind the trifluoro-methoxy group (via radical mechanism) or the fluorine atom (via electrophilic addition) by varying the reaction conditions has been explored. In particular we have observed that the trifluoro-methoxy free radical substitution can be the main synthetic pathway if the reaction is promoted by an independent and steady source of CF3O radical.

The reaction pathway between hypofluorites and aromatics is strongly dependent on the nature of the unsaturation but by changing the experimental conditions it is possible to force the reaction to follow preferentially the radical pathway and obtain the trifluoro-methoxylated aromatic.Figure optionsDownload as PowerPoint slideHighlights
► Bind, in one synthetic step, the trifluoro-methoxy group to a mono-substituted aromatic substrate.
► In the experimental condition adopted the free radical process is favored against the electrophilic addition.
► Rearomatization is a very efficient propagation reaction.
► The olefin-induced radical mechanism increases the production of trifluoromethoxy radicals and hence the amount of aromatic ether.