DOI: 10.1002/chem.201403447
Communication
&
Trifluoromethylation
Dual Catalysis with Copper and Rhenium for Trifluoromethylation
of Propargylic Alcohols: Efficient Synthesis of a-
Trifluoromethylated Enones
Hiromichi Egami,[a, b, c] Takafumi Ide,[c] Masashi Fujita,[c] Toshifumi Tojo,[a, d]
Yoshitaka Hamashima,*[c] and Mikiko Sodeoka*[a, b, e]
methyl group. However, suitable synthetic methods have not
yet been well established for the synthesis of a-trifluoromethy-
lated enones.[8]
Abstract: Trifluoromethylation of propargylic alcohols to
provide (Z)-a-trifluoromethylated enones and b-unsubsti-
tuted a-trifluoromethylated enones proceeded with high
yield and selectivity in the presence of CuI/Re2O7. The Z
isomer was formed under kinetic control, though it is less
stable than the E isomer in terms of steric repulsion.
Allenol derivatives are expected to be good substrates for
electrophilic trifluoromethylation (Scheme 1). However, allenols
are usually unstable and preparation of allenol derivatives is
sometimes difficult. Thus, we planned to utilize the Meyer–
Schuster rearrangement, which provides enones from propar-
gylic alcohols via an allenol intermediate.[9] The Meyer–Schus-
ter rearrangement has been well studied from the viewpoint
of the synthesis of highly substituted enones. However, there
are only a few reports describing electrophilic trapping of alle-
nol intermediates and their equivalents.[10] For example, Trost
et al. developed a dual catalysis using a combination of p-allyl
palladium chemistry and vanadium-catalyzed rearrangement of
propargylic alcohols.[11] Recently, Gaunt and co-workers report-
ed an arylative Meyer–Schuster rearrangement using diaryl io-
donium salts with a copper catalyst to afford a variety of a-aryl
a,b-unsaturated carbonyl compounds.[12] During the prepara-
tion of this paper, Liu and Tan reported the E-selective trifluor-
omethylation of propargylic alcohols via a Meyer–Schuster re-
arrangement using a copper catalyst alone, though a much
longer reaction time and higher temperature were generally
required.[13] As part of our research program to develop se-
quential reactions involving trifluoromethylation, we independ-
ently focused on a putative allenol intermediate and found
a novel dual-catalytic system that is more effective than the
single use of a copper catalyst alone. It is noteworthy that our
reaction is Z-selective, and is thus complementary to Liu and
Tan’s work. Herein we disclose a stereoselective trifluoromethy-
lation of propargylic alcohols to provide (Z)-a-trifluoromethy-
The trifluoromethyl group has unique properties, and trifluoro-
methylation reactions have attracted significant interest in the
pharmaceutical and agrochemical fields.[1,2] Addition of a tri-
fluoromethyl group to a C=C bond under oxidative conditions
or with photo-redox catalysts has been actively investigat-
ed.[2–4] We have reported novel trifluoromethylations of simple
alkenes, alkynes, and heteroaromatic compounds,[5] in which
a copper or iron salt acts as an efficient catalyst for the trifluor-
omethylation reaction with Togni’s reagent 1.[6]
Enone is also an important functional group in organic syn-
thesis due to its versatile reactivity, and many methodologies
have been developed for its construction.[7] Therefore, a-tri-
fluoromethylated enones would serve as useful building blocks
for the synthesis of bioactive compounds having a trifluoro-
[a] Dr. H. Egami, T. Tojo, Prof.Dr. M. Sodeoka
Synthetic Organic Chemistry Laboratory
RIKEN
2-1 Hirosawa, Wako, Saitama 351-0198 (Japan)
[b] Dr. H. Egami, Prof.Dr. M. Sodeoka
Sodeoka Live Cell Chemistry Project, ERATO
Japan Science and Technology Agency
2-1 Hirosawa, Wako, Saitama 351-0198 (Japan)
[c] Dr. H. Egami, T. Ide, M. Fujita, Prof.Dr. Y. Hamashima
School of Pharmaceutical Sciences
University of Shizuoka
52-1 Yada, Suruga-ku, Shizuoka 422-8526 (Japan)
[d] T. Tojo
Department of Bioengineering
Tokyo Institute of Technology
B52, Nagatsuta-cho 4259, Midori-ku, Yokohama 226-8501 (Japan)
[e] Prof.Dr. M. Sodeoka
RIKEN Center for Sustainable Resource Science
2-1 Hirosawa, Wako, Saitama 351-0198 (Japan)
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/chem.201403447.
Scheme 1. Trifluoromethylation of propargylic alcohol
Chem. Eur. J. 2014, 20, 12061 – 12065
12061
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