Angewandte
Chemie
DOI: 10.1002/anie.201201095
À
C CF3 Bond Formation
Copper-Catalyzed Trifluoromethylation of Allylsilanes**
Ryo Shimizu, Hiromichi Egami, Yoshitaka Hamashima, and Mikiko Sodeoka*
The trifluoromethyl group is of interest in the pharmaceu-
tical and agrochemical fields because it is lipophilic,
hydrophobic, and metabolically stable;[1] thus, great efforts
have been made to develop reactions to introduce this
group into organic molecules.[2] The formation of Csp2 CF3
À
bonds is now a well-developed field of study.[3] On the other
À
hand, Csp3 CF3 bond formation is still generally achieved
only through carbonyl groups,[4] by one of a variety of
protocols.[2] New synthetic methods are still needed for the
À
construction of Csp3 CF3 bonds in a wider range of
molecular contexts.
In 2010, we reported the trifluoromethylation of indole
derivatives using CuI and Togniꢀs reagent 2 (1-trifluoro-
methyl-1,2-benziodoxol-3-(1H)-one)[5] in MeOH (Sch-
eme 1a).[6] As an extension of that work, we next focused
=
on C C bond trifluoromethylation. Groups led by Buch-
wald,[7] Liu,[8] and Wang[9] have recently reported the
trifluoromethylation of unactivated olefins with a copper
(I) salt and either Togniꢀs reagent 2[5] or Umemotoꢀs
reagent 2’[10] (Scheme 1b). Although these reactions can
provide structures bearing a trifluoromethyl group at the
allylic position, the reported substrates are mostly limited to
monosubstituted terminal olefins. We also independently
investigated the trifluoromethylation of unactivated olefins,
but when we applied our original CuI/2/MeOH system[6] to the
trifluoromethylation of unactivated olefins, we also found the
substrate scope to be limited. To overcome this problem, we
focused on allylsilanes as substrates, anticipating that they
would be more nucleophilic than unactivated olefins. Herein,
we disclose the trifluoromethylation of allylsilanes to afford
either gem-disubstituted terminal olefins or vinylsilanes
bearing a trifluoromethyl group in the allylic position
(Scheme 1c).
Scheme 1. CuI-catalyzed trifluoromethylation. CuTc=Copper(I)-thiophene-
2-carboxylate, DMAc=N,N-dimethylacetamide, OTf=trifluoromethanesul-
fonate.
We initially examined the reaction of (2-phenylallyl)tri-
methylsilane 1a with CuOAc and Togniꢀs reagent 2 in
MeOH.[6] The desired trifluoromethylation product was
obtained in low yield along with the recovery of 65% of the
starting material (Table 1, entry 1).[11] Other copper (I) salts
were examined in order to increase the effectiveness of this
reaction. The use of [Cu(CH3CN)4]PF6 or CuCl gave slightly
better results, but the yield was still low (entries 2 and 3).
However, CuI was found to afford the desired product 3a in
Table 1: Screening of reaction conditions.[a]
[*] R. Shimizu, Dr. H. Egami, Dr. Y. Hamashima, Prof. Dr. M. Sodeoka
RIKEN Advanced Science Institute
2-1 Hirosawa, Wako-shi, Saitama 351-0198 (Japan)
E-mail: sodeoka@riken.jp
Entry
Catalyst
Solvent
Yield [%][b]
R. Shimizu, Prof. Dr. M. Sodeoka
Graduate School of Science and Engineering
Saitama University
1
2
3
4
CuOAc
[Cu(CH3CN)4]PF6
CuCl
CuI
CuI
CuI
CuI
CuI
CuI
MeOH
MeOH
MeOH
MeOH
MeOH
EtOH
CH3CN
toluene
CH2Cl2
MeOH
27
39
32
72
63[d]
36
42
31
42
0
255 Shimo-okubo, Sakura-ku, Saitama 338-8570 (Japan)
5[c]
6
Dr. H. Egami, Prof. Dr. M. Sodeoka
Sodeoka Live Cell Chemistry Project, ERATO, JST
2-1 Hirosawa, Wako-shi, Saitama 351-0198 (Japan)
7
8
9
10
Dr. Y. Hamashima
School of Pharmaceutical Science, University of Shizuoka
52-1 Yoda, Suruga-ku, Shizuoka 422-8526 (Japan)
none
[**] This work was supported in part by a Grant-in-aid for Young
Scientists (B) from MEXT (23750116) and by Project Funding for
Basic Science from RIKEN.
[a] The reactions were carried out with catalyst (10 mol%) and Togni’s
reagent 2 (1.2 equiv) in MeOH (2 mL) at room temperature on
a 0.2 mmol scale, unless otherwise mentioned. [b] Determined by
1H NMR analysis using 4-bromoanisole as an internal standard. [c] Run
on a 0.5 mmol scale. [d] Yield of isolated product.
Supporting information for this article is available on the WWW
Angew. Chem. Int. Ed. 2012, 51, 4577 –4580
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
4577