Iron-catalyzed trifluoromethylation with concomitant C-C bond formation via 1,2-migration of an aryl group

Article abstract of DOI:10.1039/c3cc43936d

Iron-catalyzed trifluoromethylation with concomitant 1,2-migration of an aryl group starting from diaryl allyl alcohol was achieved under mild conditions. This reaction system affords α-substituted-β- trifluoromethyl carbonyl compounds in high efficiency.

Full text of DOI:10.1039/c3cc43936d

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Iron-catalyzed trifluoromethylation with concomitant
C–C bond formation via 1,2-migration of an aryl
group†
Cite this: Chem. Commun., 2013,
49, 7346
Received 25th May 2013,
Accepted 16th June 2013
Hiromichi Egami,ab Ryo Shimizu,ac Yoshihiko Usuiac and Mikiko Sodeoka*abcd
DOI: 10.1039/c3cc43936d
www.rsc.org/chemcomm
Iron-catalyzed trifluoromethylation with concomitant 1,2-migration of
an aryl group starting from diaryl allyl alcohol was achieved under mild
conditions. This reaction system affords a-substituted-b-trifluoromethyl
carbonyl compounds in high efficiency. In the case of substrates bearing
different aryl groups, selective migration was observed.
Fluorine chemistry has profoundly contributed to the pharma-
ceutical, agrochemical and material science industries, and many
methodologies for the synthesis of fluorine-containing molecules
have been developed.1 Among the known fluorine-containing
units, the trifluoromethyl group is currently attracting significant
attention due to its unique properties.1 Although recent progress
in trifluoromethylation reactions has provided various types of
Scheme 1 Carbotrifluoromethylation reactions of alkenes.
C–CF3 bond formation reactions,2 new types of trifluoromethyla- carbocycles and heterocycles bearing a trifluoromethyl group, such
tion reactions are required to generate a diversity of compounds as tetraline, indoline and oxindole derivatives. For the carbotri-
bearing a trifluoromethyl group.
fluoromethylation of acryloanilides, Liu et al. have reported elegant
Since the representative reports on the deprotonative tri- work using the combination of palladium–ytterbium catalysts
fluoromethylation of alkenes by Buchwald, Liu and Wang et al. under oxidative conditions in 2012.10
in 2011,3 trifluoromethylation of alkenes has become a topic of
b-Trifluoromethylated carbonyl compounds are versatile
growing interest, and several successful examples have been building blocks for bioactive compounds bearing a trifluoro-
reported so far.4 One of the main approaches has been the use methyl group. Thus, we embarked on the development of a
of Togni’s reagent5 system. We have studied metal-catalyzed synthetic method for a-substituted-b-trifluoromethylated carbonyl
trifluoromethylation reactions using Togni’s reagent 1 since compounds from our studies on trifluoromethylation reactions.
2010.6 Our recent focus has been on the difunctionalization- We hypothesized that a semipinacol-type rearrangement11
type trifluoromethylation, and we have already achieved the would be applicable to meet this purpose. Herein, we report
oxytrifluoromethylation of styrene derivatives,7 the aminotri- the 1,2-migration driven carbotrifluoromethylation of alkenes
fluoromethylation of alkenyl amines,8 as well as the carbotri- catalyzed by iron acetate (Scheme 1b).
fluoromethylation of alkenes using Cu–Togni’s reagent system
Allylic alcohol 2a was used as the substrate for screening the
(Scheme 1a).9 Our carbotrifluoromethylation methodology provided reaction conditions (Table 1). We first examined trifluoromethyla-
tion under the same conditions as those for our previous
carbotrifluoromethylation (entry 1).9 The desired compound
3a was obtained in 40% yield. CuCl and CuOAc both worked as
a Synthetic Organic Chemistry Laboratory, RIKEN, 2-1 Hirosawa, Wako,
Saitama 351-0198, Japan. E-mail: sodeoka@riken.jp; Fax: +81 48 462 4666
b Sodeoka Live Cell Chemistry Project, ERATO, Japan Science and Technology
Agency, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan
c Graduate School of Science and Engineering, Saitama University,
255 Shimo-Okubo, Sakura-ku, Saitama 338-8570, Japan
d RIKEN Center for Sustainable Resource Science, 2-1 Hirosawa, Wako,
Saitama 351-0198, Japan
catalysts, and moderate yields were observed (entries 2 and 3).
Iron salts were also tested as we and some other groups have
identified that iron salts could catalyze trifluoromethylation
using Togni’s reagent.6a,12 Fe(OAc)2 was found to be a good
catalyst for the desired trifluoromethylation, and 71% of 3a was
afforded (entry 5). Interestingly, addition of base accelerated
the reaction. Among the additives tested (entries 8–11), K2CO3
† Electronic supplementary information (ESI) available: Experimental procedures
and spectral data. See DOI: 10.1039/c3cc43936d
c
7346 Chem. Commun., 2013, 49, 7346--7348
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Table 1 Screening of reaction conditionsa
Table 3 Trifluoromethylation of asymmetrical substratesa
Cat.
Entry
Additive
Temp. [1C]
3a b [%]
Ar2
Entry
Ar1
5 : 6b
5c [%]
6c [%]
1
2
3
4
CuI
CuCl
CuOAc
FeCl2
Fe(OAc)2
Fe(OAc)2
Fe(OAc)2
Fe(OAc)2
Fe(OAc)2
Fe(OAc)2
Fe(OAc)2
(10 mol%)
(10 mol%)
(10 mol%)
(10 mol%)
(10 mol%)
(15 mol%)
(15 mol%)
(15 mol%)
(15 mol%)
(15 mol%)
(15 mol%)
—
—
—
—
—
—
80
80
80
80
80
80
23
23
23
23
23
40
45
49
37
55
71
0
82
0
56
68
1d,e
2 f,g
3d,i
4g, j
5d,g
6 f,g
7d,e
8e, j,l
4-Cl-C6H4
4-F-C6H4
Ph
Ph
Ph
4-Cl-C6H4
Ph
4-Cl-C6H4
2-Cl-C6H4
2-F-C6H4
2-Cl-C6H4
2-Br-C6H4
2-MeO-C6H4
4-MeO-C6H4
C6F5
a
b
c
d
e
f
25 : 1
1 : 1
9 : 1
12 : 1
3 : 1
10 : 1
—
80
42h
79
81
71
80
79
64
4
42h
9
5
7
6c
7c
8c
9c
10c
11c
21
7
—
K2CO3
d
g
h
NDk
NDk
d
Na2CO3d
Cs2CO3
KOAce
Me
—
a
The reactions were carried out with Fe(OAc)2 (15 mol%), K2CO3
(1 equiv.) and 1 (2 equiv.) in 1,4-dioxane (1 ml) on a 0.2 mmol scale,
a
b
unless otherwise mentioned. Determined by 19F NMR analysis of the
The reactions were carried out with catalyst and Togni’s reagent 1
f
crude mixture. c Isolated yield. d Run at 40 1C. e Run for 3 h. Run at 23 1C.
(1.2 equiv.) in 1,4-dioxane (1 ml) for 6 h on a 0.2 mmol scale, unless
b
c
g
Run for 12 h. h Products 5b and 6b were obtained as an inseparable
otherwise mentioned. Isolated yield. Run with 1 (2 equiv.) for 12 h.
d
e
mixture (1 : 1). The numbers are calculated yields. Run for 9 h. j Run at
80 1C. Not detected. Run in the absence of K2CO3.
i
Run with 1 equiv. of additive. Run with 2 equiv. of additive.
k
l
was found to be the most efficient and 3a was obtained in 82%
yield even at 23 1C (entry 8). When the reaction was carried out at
23 1C in the absence of a base, no product was generated (entry 7).
During the course of our studies, we examined other symme-
trical substrates (Table 2). Compound 3b bearing p-tolyl groups
was obtained in 72% yield. Although the electron-donating
groups on the aryl ring reduced the yields to some extent, the
reactions of 2c and 2d proceeded at 80 1C even in the absence of
K2CO3 to provide 3c and 3d in 78% and 80% yields, respectively.
Meanwhile, it was found that substrates bearing electron-
withdrawing groups afforded the corresponding carbonyl com-
pounds in high yields (3e, 3f, 3g). The ortho-substituted aryl
group also worked as a migrating group and 2h was success-
fully converted to 3h. It should be noted that a quaternary
carbon center could be generated by this trifluoromethylation,
and the yield of 3i was 75%.
Inspired by these results, allylic alcohols bearing two different
aryl groups were used as substrates (Table 3). To our delight, the
reaction of 4a, which possesses 2-chlorophenyl and 4-chlorophenyl
groups, proceeded with migration of the 4-chlorophenyl group in a
highly selective manner and 5a was obtained in 80% (entry 1). In
contrast, 4b bearing fluoro-substituted aryl rings did not induce
selective migration and an inseparable mixture of 5b and 6b (1 : 1)
was observed (entry 2). Migration of 2-substituted aryl rings was
slower than that of the phenyl group (entries 3–5), suggesting that
steric hindrance on the aryl ring reduced the migration rate.
Pleasingly, selective migration was observed in the reaction of 4f
bearing 4-chlorophenyl and 4-methoxyphenyl groups (entry 6). This
result suggests that the electronic properties of the aryl ring affect
the migration rate and the electron-withdrawing group accelerates
aryl migration during this particular trifluoromethylation reaction.
On the other hand, we could not detect the pentafluorophenyl
group migration product 6g, and the phenyl migration product 5g
was obtained in 79% yield in the reaction of 4g (entry 7). These
unique results indicate that the reaction mechanism may differ
from a simple semipinacol rearrangement, that is, this reaction
may proceed via a non-cationic intermediate.13 However, the exact
mechanism is not clear at this moment. Finally, we investigated the
trifluoromethylation of allylic alcohol 4h bearing a methyl group in
place of an aryl group. Although the reaction was slower than that
using diaryl-type substrates, 5h was obtained in 64% yield (entry 8).
In addition, migration of the methyl group was not observed and the
hydrotrifluoromethylation product4k,l was observed as a by-product
in the reaction mixture, suggesting that an intermediate of this
reaction was likely to have radical character.
Table 2 Trifluoromethylation of symmetrical substratesa
In summary, we have achieved the iron-catalyzed trifluoro-
methylation with concomitant CAr–Csp3 bond formation via
1,2-migration. This new type of carbotrifluoromethylation
afforded a-substituted-b-trifluoromethylated carbonyl compounds
from diaryl allylic alcohols in high efficiency. In addition, unique
selectivity was observed in the reaction of substrates bearing
different aryl groups. We believe that this reaction provides a
a
The reactions were carried out with Fe(OAc)2 (15 mol%), K2CO3
(1 equiv.) and 1 (2 equiv.) in 1,4-dioxane on a 0.2 mmol scale, unless
otherwise mentioned. Run in the absence of K2CO3.
b
c
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This research was supported in part by Project Funding for
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´
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7348 Chem. Commun., 2013, 49, 7346--7348
This journal is The Royal Society of Chemistry 2013