Iridium-catalyzed reactions of trifluoromethylated compounds with alkenes: A Csp3-H bond activation α to the trifluoromethyl group

Article abstract of DOI:10.1002/anie.200805852

(Chemical Equation Presented) Catalytic convenience: The use of iridium or ruthenium catalysts for C_sp3-H bond activation has led to the addition reaction of trifluoromethylated compounds to alkenes (see scheme). This atom-economical reaction o

Full text of DOI:10.1002/anie.200805852

Angewandte
Chemie
DOI: 10.1002/anie.200805852
À
C H Activation
Iridium-Catalyzed Reactions of Trifluoromethylated Compounds with
À
Alkenes: A Csp3 H Bond Activation a to the Trifluoromethyl Group**
Yong Guo, Xiaming Zhao, Dazhi Zhang, and Shun-Ichi Murahashi*
Trifluoromethylated compounds play an important role in
medicinal,[1] agrochemical,[2] and material science;[3] there-
fore, exploitation of a general method for the synthesis of
these compounds is highly desirable. Introduction of an a-
trifluoromethyl group into the target molecule relies on either
trifluoromethyl reagents or trifluoromethylated synthetic
building blocks.[4] It has been difficult to achieve carbon–
carbon bond formation via a-trifluoromethyl carbanions
because these carbanions and related organometallic species
spontaneously release fluoride species to produce 1,1-
difluoroolefins.[4–5] This notorious decomposition of a-tri-
fluoromethyl carbanions has hindered the development of
this species for use in organic synthesis.[6] Only few methods
on the synthetic use of a-trifluoromethyl carbanions, under
specific reaction conditions, have been reported.[6–7]
iridium and ruthenium catalyzed the reaction highly effi-
ciently (Table 1). [IrH5(PiPr3)2] (4) proved to be the best
catalyst among those examined. In the presence of 1 mol% of
Table 1: The reaction of methyl 1,1-bis(trifluoromethyl) acetate (1a) with
acrylonitrile (2a) in the presence of Ru/Ir catalysts or conventional
bases.[a]
Entry[a] Catalyst
Mol Solvent
[%]
t
Conv. Yield
Our research group has developed the transition-metal-
[h] [%]
[%][b]
À
catalyzed Csp3 H functionalization reaction stemming from
the a heteroatom effect.[8] In light of the potent ability of the
transition-metalated carbon nucleophiles to promote carbon–
carbon bond forming reactions under neutral reaction con-
1
2
3
4
5
6
7
8
[IrH5(PiPr3)2]
1
5
1
1
1
toluene 22
99
92 (89)
97 (94)
[IrH5(PiPr3)2]
[Cp*Ru(PPh3)2]
[CpRuH(PPh3)2]
[RuH2(PPh3)4]
[RuH2(CO)(PPh3)3]
PiPr3
PPh3
DBU
tBuOK
MeONa
toluene
3
100
94
38
18
0
16
11
40
50
50
toluene 24
toluene 24
toluene 24
toluene 24
94
84
78
0
19
0
10
0
0
À
ditions, we examined the activation of a Csp3 H bond a to a
trifluoromethyl group. Herein, we report the iridium- or
ruthenium-catalyzed reactions of trifluoromethylated com-
pounds with alkenes to afford alkylated products in an atom-
economic and selective manner under neutral reaction
conditions without the formation of any defluorinated by-
product.
1
10
toluene
3
100 THF
100
100 THF
100
100
100
24
9
toluene 16
10
11
12
13
16
16
MeOH
Et3N
MeCN
MeOH
64 100
16 100
27
0
We found that [IrH5(PiPr3)2] acts as an efficient catalyst
for the reaction of trifluoromethyl compounds (1) with
alkenes (2) at room temperature or at higher temperatures
BnNMe3+OHÀ[c]
[a] Unless specified, the reaction was carried out with 1a (0.2 mmol,
0.5m in toluene) and acrylonitrile 2a (0.6 mmol, 3 equiv) in the presence
of a catalyst at room temperature. [b] Yield determined by 19F NMR
spectroscopy using 1,3-bis(trifluoromethyl)benzene as an internal
standard. Yield of the isolated product is shown in parenthesis.
[c] 40% methanol solution. Bn=benzyl, Cp=cyclopentadienyl, Cp*=
À
[Eq. (1)]. To our knowledge, no example of C H bond
activation a to a trifluoromethyl group with transition metal
catalysts has been reported. Although recent progress on the
transition-metal-catalyzed activation of carbon–fluorine
bonds is striking.[9]
pentamethylcyclopentadienyl,
ene.
DBU=1,8-diazabicyclo[5.4.0]undec-7-
Initially, we examined the reaction of methyl 1,1-trifluoro-
methyl acetate (1a) with acrylonitrile (2a) at room temper-
ature and found that the low valent hydride complexes of
the catalyst 4 in toluene, the reaction gave methyl 4-cyano-
2,2-bis(trifluoromethyl)butyrate (3a) in 92% yield and with
99% conversion of 1a (Table 1, entry 1). [Cp*RuH(PPh3)2]
was also useful as a catalyst (Table 1, entry 3). Notably, the
desired product 3a was not obtained by the reaction of 1a in
the presence of conventional bases such as DBU, tBuOK,
[*] Dr. Y. Guo, Dr. X. Zhao, Dr. D. Zhang, Prof. Dr. S.-I. Murahashi
Department of Chemistry
Okayama University of Science
1-1, Ridai-cho, Okayama 700-0005 (Japan)
Fax: (+81)86-256-4292
+
MeONa, Et3N, or BuNMe3 OHÀ (Table 1, entries 9–13).
E-mail: murahashi@high.ous.ac.jp
Phosphines such as PiPr3 and PPh3 were not effective
(Table 1, entries 7 and 8). Changing the solvent effect had a
dramatic effect. The best yield was obtained in a nonpolar
solvent such as toluene. The reactions of 1a in DME (1,2-
dimethoxyethane) and THF (tetrahydrofuran) gave 3a in
[**] This work was supported by Grants-in-aid for Scientific Research,
Ministry of Education, Culture, Sports, Science and Technology of
Japan.
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.200805852.
Angew. Chem. Int. Ed. 2009, 48, 2047 –2049
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Communications
92% and 88% yield, respectively. Meanwhile, the same
reaction in acetonitrile resulted in 5% yield.
(Table 2, entry 5). The reactions of trifluoromethylated com-
pounds 1 with methyl vinyl ketone (2b) also proceeded but
required a higher reaction temperature in comparison to the
reaction with acrylonitrile (Table 2, entries 6 and 7). Thus, the
reactions of 1a and 1b with 2b at 1108C gave the corre-
sponding compounds 3 f and 3g in 82% and 61% yields,
respectively. The reaction of trifluoromethyl compounds
The representative results of the iridium-catalyzed reac-
tion of trifluoromethylated compounds with alkenes are
shown in Table 2. The substrates bearing nitrile (1b) and
ester (1c) functionalities were converted into the correspond-
ing products in excellent yields (Table 2, entries 1–3). Nota-
bly, reactions that involved a substrate bearing an electron-
donating substituent, such as a methoxy group, occurred
readily. Thus, the iridium-catalyzed reaction of 1,1,1,3,3-
À
bearing two C H bonds a to the trifluoromethyl group gave
the double alkylation products exclusively. Thus, the reaction
of 3,3,3-trifluoropropionitrile (1 f) with 2a gave 4-cyano-4-
(trifluoromethyl)-heptane-1,7-dinitrile (3h) in 77% yield
(Table 2, entry 8), and the reaction of 4,4,4-trufluoro-2-
butanone (1g) with 2a gave 4-acetyl-4-trifluoromethylhep-
tane-1,7-dinitrile (3i) in good yield (Table 2, entry 9).
pentafluoro-2-(trifluoromethyl)-3-methoxypropane
(1d)
gave the product 3d in 56% yield (Table 2, entry 4).
The reaction of 2-(trifluoromethyl)cyclohexanone (1e)
with acrylonitrile gave the product (3e) in 65% yield
The products obtained are highly useful intermediates for
the synthesis of industrially important trifluoromethylated
compounds.[9] Next, we demonstrated the catalytic production
of polyamides bearing trifluoromethyl groups (which are
useful for material science) by using our unique environ-
mentally benign ruthenium-catalyzed method.[10] The poly-
condensation of the dinitrile compound bearing a trifluor-
omethyl group 3i with 1,6-hexanediamine (6) in the presence
of [RuH2(PPh3)4] catalyst (3 mol%) and two equivalents of
water in DMF at 1608C gave the trifluoromethylated
polyamide 7 in 96% yield along with ammonia as shown in
Table 2: Iridium-catalyzed reaction of a-trifluoromethylated compounds
(1) with alkenes (2).[a]
Entry Substrate
Alkene
2
Product
3
T
t
Yield
1
[8C] [h] [%][b]
1
25
50
3
1
97
1a
2a
2a
3a
3b
3c
(94)
2
(91)
(93)
1b
Equation (2). The GPC analysis of 7 showed Mn =
2592 gmolÀ1 and Mw = 10878 gmolÀ1, as well as PDI = 4.20.
3
25
5
2a
2a
1c
4
25 40 81
(56)
1d
3d
5[c]
50 40 76
2a
1e
3e
3 f
3g
3h
3i
(65)
6
110 18 (82)
1a
2b
2b
The present iridium-catalyzed reaction can be rational-
À
ized by assuming that the Csp3 H bond a to the trifluoro-
methyl group is activated with low valent iridium or
ruthenium species,[7] and subsequent insertion to alkenes
and reductive elimination gives the product. It is oteworthy
that the reaction occurs under heating conditions without the
formation of defluorinated by-products. The lack of by-
products may result from the stability of the fluoromethyl–
iridium complex against decomposition that involves b-fluoro
elimination, particularly under neutral reaction conditions.[11]
In conclusion, we have found a novel and efficient
iridium- or ruthenium-catalyzed reactions of trifluoromethy-
lated compounds with alkenes without the formation of
defluorinated by-products. The reaction is highly useful and
will provide scope for finding other new types of catalytic
reactions in fluorine chemistry.
7
110 16 (61)
1b
8
110
50
7
5
(77)
(70)
2a
2a
1 f
9
1g
[a] The reaction was carried out with 1 (0.2 mmol) and 2 (0.3 mmol) in the
presence of [IrH5(PiPr3)2] (5 mol%) in toluene (0.5 mL) under argon or in a
sealed tube. [b] Yield determined by 19F NMR spectroscopy using 1,3-
bis(trifluoromethyl)benzene as an internal standard. Yield of the isolated
product is shown in parenthesis. [c] The ratio of 1e/2a is 1.5:1 and the
conversion was 86%.
Received: December 2, 2008
Published online: January 29, 2009
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Chemie
À
Takaya, T. Naota, S.-I. Murahashi, J. Am. Chem. Soc. 1998, 120,
Keywords: alkenes · C H activation · fluorides · iridium ·
ruthenium
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