The trifluoromethyl group is a valuable functional group in the field of pharmaceuticals, agrochemicals and material science, as the introduction of this moiety into organic molecules can modify their metabolic and chemical stability, lipophilicity and acid-base properties. A straightforward approach to the synthesis of CF3-containing scaffolds involves the addition of this group across alkenes.&lt;span style="font-size:10.8333px; line-height:17.3333px"&gt; &lt;/span&gt;This addition generally involves the simultaneous formation of a C-CF3 bond combined with a C-H, C-C, C-heteroatom bond, in presence of a transition metal or photocatalyst (a). In this context, the addition of CF3 to alkenes in presence of sulphur heteroatom is extremely rare, in view of facile formation of undesired S-CF3 and S-S adducts. In this context, we discovered a novel thiotrifluoromethylation of alkenes (b). In this process, the thiourea has a dual role, as a S-source and as a reductant for the release of CF3 radicals. This novel methodology provides a straightforward access to CF3-containing aminothiazines and aminothiazoles that have been identified as effective BACE-1 inhibitors for the treatment of the Alzheimer’s disease. This manifold benefits from the mild operating conditions (no use of metal or photo-catalysts, room temperature, high atom economy), the wide scope in terms of alkenes and thioureas, and the exclusive anti-addition across alkenes.

Dual role of thiourea in the thiotrifluoromethylation of alkenes

252nd National Meeting (2016)

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