Fig. 3: The deoxytrifluoromethylation/aromatization strategy pushes the limits of accessible Ar–CF3 compounds. | Nature Communications

Fig. 3: The deoxytrifluoromethylation/aromatization strategy pushes the limits of accessible Ar–CF3 compounds.

From: Deoxytrifluoromethylation/aromatization of cyclohexan(en)ones to access highly substituted trifluoromethyl arenes

Fig. 3

The transformation enables (A) conversion of readily available ketone substrates to Ar–CF3 derivatives, (B) systematic elaboration of simple precursors to highly functionalized Ar–CF3 products, (C) conversion of natural products into Ar–CF3 derivatives, (D) annulation reactions to access highly substituted substrates that convert to Ar–CF3 products, and (E) conversion of heterocyclic ketones to (Het)Ar–CF3. All reactions were run in 0.5 mmol batch of substrate. Conditions A: i) TMSCF3 (1.1 equiv.), 10 mol% CsF, o-DCB (0.5 M), rt–50 °C, 4–48 h. ii) PTSA•H2O (2 equiv.), DDQ (3 equiv.), o-DCB (0.2 M), 120 °C–140 °C, 12–24 h. Conditions B: (i) TMSCF3 (1.1 equiv.), TBAF (1 equiv.), THF (0.5 M), rt, 4 h. (ii) SOCl2 (3 equiv.), Pyridine (3 equiv.), 10 mol% DMAP, THF (0.5 M), 50 °C, 18 h. Then silica filter. (iii) NBS (4 equiv.), 10 mol% AIBN, o-DCB (0.2 M), 120 °C, 18 h. Conditions C: (i) TMSCF3 (1.1 equiv.), TBAF (1 equiv.), THF (0.25–0.5 M), rt–35 °C, 4–12 h. (ii) SOCl2 (3 equiv.), Pyridine (3 equiv.), 10 mol% DMAP, THF (0.25–0.5 M), rt–60 °C, 8–24 h. Then silica filter. (iii) DDQ (2–3 equiv.), o-DCB (0.2 M), 90–120 °C, 12–48 h. a THF was used instead of o-DCB in step 1 followed by basic alumina plug filter and swapping of solvent with o-DCB. b 1,2–DCE was used as a solvent in step 3.

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