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. 2019 Aug 19;58(34):11704-11708.
doi: 10.1002/anie.201905247. Epub 2019 Jul 11.

1,2-(Bis)trifluoromethylation of Alkynes: A One-Step Reaction to Install an Underutilized Functional Group

Shuo Guo  1 , Deyaa I AbuSalim  1 , Silas P Cook  1
Affiliations

1,2-(Bis)trifluoromethylation of Alkynes: A One-Step Reaction to Install an Underutilized Functional Group

Shuo Guo et al. Angew Chem Int Ed Engl. .

Abstract

Modifying the electronic properties of olefins is the quintessential approach to tuning alkene reactivity. In this context, the exploration of trifluoromethyl groups as divergent electronic modifiers has not been considered. In this work, we describe a copper-mediated 1,2-(bis)trifluoromethylation of acetylenes to create E-hexafluorobutenes (E-HFBs) under blue light in a single step. The reaction proceeds with high yield and E/Z selectivity. Since the alkyne captures two trifluoromethyl groups from each molecule of bpyCu(CF3 )3 , mechanistic studies were conducted to illuminate the role of the reactants. Interestingly, E-HFBs exhibit remarkable stability to standard olefin functionalization reactions in spite of the pendant trifluoromethyl groups. This finding has significant implications for medicine, agroscience, and materials.

Keywords: alkynes; copper; difunctionalization; persulfate; trifluoromethylation.

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Conflict of interest statement

Conflicts of Interest

The authors declair no conflicts of interest.

Figures

Figure 1.
Figure 1.
Computed geometries (uM06/LACVP**) and ΔGsol energies for 2, 32, and bipyCu (CF3)2. Bond lengths are measured in angstroms (Å).
Figure 2.
Figure 2.
Computed ΔGsol energies (with uM06/cc-pVTZ(-f)–LACV3P**//uM06/LACVP**) for all intermediates and transition states along the reaction pathway from I to IV.
Figure 3.
Figure 3.
Both UV and blue light excite to the same σ* orbital (LUMO +1). This results in the formation of 32 leading to CF3 bond homolysis.
Scheme 1.
Scheme 1.
(a-c) Previous studies have established the capture of one trifluoromethyl group from bpyCu(CF3)3; (d-e) the combination of persulfate and light enable the capture of two trifluoromethyl groups from bpyCu(CF3)3.
Scheme 2.
Scheme 2.
Late-Stage 1,2-(Bis)trifluoromethylation of Bioactive Moleculesa a All reactions were with alkyne substrate (0.16 mmol) and 2 (0.16 mmol) in 2.8 mL of solvent for 1 h.
Scheme 3.
Scheme 3.
Control Experiments
See this image and copyright information in PMC

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