RESEARCH
| REPORT
yielded exclusively the cyclized alkyl-CF3 product
in good yield (59, 60% yield). The 1-to-1 diaster-
eomeric ratio of the cyclized product 59, along
with the absence of the CF3-arene product 60,
further support the hypothesis of aryl radical
generation during the course of the reaction
(33, 34). Previously reported copper-mediated
aryl halide trifluoromethylation protocols did
not exhibit aryl radical characteristics when sim-
ilar radical clock experiments were used as a
mechanistic probe (24, 25). In addition, whereas
aryl radical generation has previously been shown
to be operative under light-irradiated copper ca-
talysis (33), the open-shell aryl species under
our optimized conditions is generated by a silyl
radical halogen abstraction, independent of the
copper catalyst (43).
Use of aryl radical trapping to circumvent the
sluggish nature of conventional oxidative addition
in copper catalysis has allowed for the devel-
opment of a general dual copper/photoredox-
catalyzed trifluoromethylation protocol for aryl
bromides. We expect this method to be widely
adopted by the synthetic community as a com-
plementary tool to existing trifluoromethylation
platforms. Perhaps most important, we see this
halide abstraction/radical capture mechanism
(at room temperature) as an approach to over-
come the copper oxidative addition problem and
in doing so provide a general paradigm to the
development of many, previously unknown, copper-
catalyzed coupling reactions.
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ACKNOWLEDGMENTS
The authors thank C. Kraml, N. Byrne, and L. Wilson (Lotus
Separations) for compound purification and P. Jeffrey for
assistance with x-ray structure determination. Funding: Research
reported in this publication was supported by the NIH National
Institute of General Medical Sciences (R01 GM103558-03) and
gifts from Merck, Bristol-Myers Squibb, Eli Lilly, Genentech, Pfizer,
and Johnson & Johnson. C. L. thanks Bristol-Myers Squibb for a
graduate fellowship. Author contributions: D.W.C.M. conceived
and directed the project. D.W.C.M., C.L., T.Q.C., T.L., and P.Z.
designed the experiments. C.L., T.Q.C., and T.L. performed and
analyzed the experiments. T.Q.C. obtained x-ray quality crystals for
trifluoromethylating reagent 8. P.Z. discovered silanol reagent 4
as a new silyl radical source. D.W.C.M., C.L., T.Q.C., T.L., and P.Z.
prepared the manuscript. Competing interests: The authors
declare no conflicts of interest. Data and materials availability:
Crystallographic parameters for compound 8 are available
free of charge from the Cambridge Crystallographic Data
Centre under CCDC 1833832. Data are available in the
supplementary materials.
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SUPPLEMENTARY MATERIALS
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