Visible-light-induced synthesis of a variety of trifluoromethylated alkenes from potassium vinyltrifluoroborates by photoredox catalysis

Article abstract of DOI:10.1039/c3cc39235j

A facile synthesis of trifluoromethylated alkenes by the radical-mediated trifluoromethylation of vinyltrifluoroborates has been developed. Togni's reagent serves as a CF₃ radical precursor in the presence of the photoredox catalyst [Ru(bpy)₃](PF₆)₂ under visible light irradiation. This new photocatalytic protocol can be applicable to a wide variety of vinylborates containing electronically diverse substituents and hetero-aromatics. The Royal Society of Chemistry 2013.

Full text of DOI:10.1039/c3cc39235j

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Visible-light-induced synthesis of a variety of
trifluoromethylated alkenes from potassium
vinyltrifluoroborates by photoredox catalysis†
Cite this: Chem. Commun., 2013,
49, 2037
Received 28th December 2012,
Accepted 22nd January 2013
Yusuke Yasu, Takashi Koike* and Munetaka Akita*
DOI: 10.1039/c3cc39235j
www.rsc.org/chemcomm
A facile synthesis of trifluoromethylated alkenes by the radical-
mediated trifluoromethylation of vinyltrifluoroborates has been
developed. Togni’s reagent serves as a CF3 radical precursor in the
presence of the photoredox catalyst [Ru(bpy)3](PF6)2 under visible
light irradiation. This new photocatalytic protocol can be applicable
to a wide variety of vinylborates containing electronically diverse
substituents and hetero-aromatics.
The trifluoromethyl (CF3) group is a useful structural motif in
many biologically active molecules as well as materials.1,2 Thus,
the development of new methodologies for highly efficient and
selective incorporation of a CF3 group into diverse skeletons has
attracted great interest of synthetic chemists.3 Over the past few
years, a variety of transition-metal-catalyzed trifluoromethylations
of aromatic molecules have been well developed.4 On the other
hand, effective construction of Calkenyl–CF3 bonds is significantly
more limited although trifluoromethylated alkenes are promising
building blocks for pharmaceuticals, agrochemicals and func-
tional materials.2a,3b,5–7
The strategies for trifluoromethylation using electrophilic
trifluoromethylating (+CF3) reagents such as Togni’s reagents 1a
(1-trifluoromethyl-1,2-benziodoxol-3-(1H)-one), 1b (1-trifluoromethyl-
1,3-dihydro-3,3-dimethyl-1,2-benzioxodole) and Umemoto’s reagent
Scheme 1 Photoredox-catalysed trifluoromethylation using electrophilic tri-
fluoromethylating reagents (1a–c).
1c (S-(trifluoromethyl)dibenzothiophenium tetrafluoroborate) have of vinyltrifluoroborates (Scheme 1b).11c In addition, there are
attracted great attention because the reagents are easy-to-handle a few reports on copper-mediated trifluoromethylation of
chemicals in terms of being shelf-stable solid compounds at room a,b-unsaturated carboxylic acids,11d alkynes11e and enamides.11f These
temperature.8–10 Over the past few years, several catalytic synthetic methods, however, exhibit limited substrate scopes with respect to
methods for construction of Calkenyl–CF3 bonds with ‘‘+CF3’’ reagents hetero-aromatics and functional groups. Therefore, a new protocol for
have been reported.11 The groups of Shen and Liu have shown non- construction of Calkenyl–CF3 bonds with broad scope as well as in an
stereoselective trifluoromethylation of vinylboronic acids by Cu(I) efficient and stereoselective manner is highly desirable.
catalysis (Scheme 1a).11a,b Furthermore, Buchwald and co-workers
Recently, there have been several reports on radical trifluoro-
reported an Fe(II)-catalyzed stereoselective trifluoromethylation methylation by photoredox catalysis, which is regarded as a useful
redox tool for organic compounds via single electron transfer (SET)
Chemical Resources Laboratory, Tokyo Institute of Technology, 4259 Nagatsuta,
Midori-ku, Yokohama 226-8503, Japan.
in the presence of well-defined ruthenium(II) polypyridine complexes
(e.g. [Ru(bpy)3]2+) and the relevant cyclometalated iridium(III) deriva-
tives under visible light irradiation,12–16 and conventional trifluoro-
methyl radical (ꢀCF3) sources such as CF3SO2Cl 1d and gaseous CF3I
were used. These ‘‘ꢀCF3’’ precursors, however, require operational
carefulness and special apparatus. In contrast, we have previously
E-mail: koike.t.ad@m.titech.ac.jp,makita@res.titech.ac.jp; Fax: +81-45-924-5230;
Tel: +81-45-924-5230
† Electronic supplementary information (ESI) available: Experimental details,
spectral data, and crystallographic results. CCDC 900630. For ESI and crystal-
lographic data in CIF or other electronic format see DOI: 10.1039/c3cc39235j
c
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reported the photoredox-catalyzed oxytrifluoromethylation of
The scope and limitations of the present photocatalytic
alkenes with ‘‘+CF3’’ reagents based on usual laboratory tech- trifluoromethylation of vinyltrifluoroborates are summarized
niques and equipment.14c Importantly, easy-to-handle ‘‘+CF3’’ in Table 2. (E)-Styrylborates with electron-donating substituents,
reagents can serve as ‘‘ꢀCF3’’ precursors in the presence of Me (2b, l) and MeO (2c), smoothly produced the corresponding
photoredox catalysts under visible light irradiation.
b-CF3-styrene products with high E/Z selectivities in good yields
Herein we disclose highly efficient and stereoselective (3b, c, l). In addition, this reaction can be applied to vinylborates
deboronated trifluoromethylation of vinyltrifluoroborates with bearing a variety of electron-withdrawing functional groups, F
commercially available and air-stable Togni’s reagent 1a by (2i), Cl (2d), Br (2e), CF3 (2f, j), OCF3 (2g), CN (2h), and NHBoc
visible-light-driven photoredox catalysis (Scheme 1c). In parti- (2k). The corresponding trifluoromethylated alkene products
cular, this new photocatalytic protocol is effective in the selec- (3d–k) were obtained without deterioration by the functional
tive and large-scale synthesis of (E)-trifluoromethylated alkenes groups with excellent E/Z selectivities (>94/o6) in high yields
bearing a p-electron-deficient hetero-aromatic moiety, which (68–93%). This broad applicability of vinylborates is remarkable.
are difficult to access by previous catalytic systems.
The above-mentioned Buchwald’s catalytic system is ineffective
We initially examined the photocatalytic trifluoromethylation of for electron-deficient substrates.11c
(E)-styrylboronic acid derivatives 2 with 1.1 equiv. of Togni’s reagent
1a as the CF3 source in the presence of 5 mol% photoredox catalyst
Table 2 The scope of the present trifluoromethylation of vinylboratesa,b
17
Ir(ppy)3 in MeOH under visible light irradiation (blue LEDs:
lmax = 425 nm) for 2 h. Every entry resulted in formation of b-
trifluoromethylstyrene 3a (Table 1, entries 1–3). As a result, the
choice of the boron auxiliary turned out to be crucial for better yield
and selectivity. The reaction of potassium (E)-styryltrifluoroborate
2a afforded the product 3a with an E/Z ratio of 94/6 in 85% yield
(entry 3). In contrast, the substrates with B(OH)2 and Bpin groups
gave mixtures of 3a and methoxytrifluoromethylated by-product.
Next, examination of the CF3 reagents revealed that 1a is the best
choice in terms of yield and selectivity. The use of 1b and 1c
provided product 3a in good yields, but did not improve the E/Z
selectivity (entries 4 and 5). A typical CF3 radical source 1d gave a
mixture of product 3a, styrene and unidentified by-products
(entry 6). Finally, the Ru photocatalyst [Ru(bpy)3](PF6)2 also pro-
moted the present reaction, providing the product 3a with excellent
E/Z selectivity (98/2) in 81% yield upon 5 h irradiation (entry 7).
Notably, the product 3a was not obtained at all either in the
dark or in the absence of the photoredox catalyst (entries 8
and 9), strongly supporting that the photoexcited species of the
photoredox catalyst play key roles in the reaction.
Table 1 Optimization of photocatalytic trifluoromethylation of (E)-styrylboronic
acid derivatives 2
Entry CF3 reagent BXn
Photoredox catalyst E/Za
Yielda/%
1
2
3
4
1a
1a
1a
1b
1c
B(OH)2 Ir(ppy)3 57/43 53
Bpin Ir(ppy)3 54/46 36
94/6 85
BF3K 2a Ir(ppy)3
BF3K 2a Ir(ppy)3
BF3K 2a Ir(ppy)3
90/10 83
85/15 79
5
6b
7c
8
CF3SO2Cl 1d BF3K 2a Ir(ppy)3
99/1
98/2
—
27
81
0
1a
1a
1a
BF3K 2a [Ru(bpy)3](PF6)2
BF3K 2a none
9d
BF3K 2a [Ru(bpy)3](PF6)2
—
0
For reaction conditions, see the ESI. a Isolated yields. E/Z ratios were
b
determined by 1H and 19F NMR spectroscopies of the crude product
ppy = 2-phenylpyridine, bpy = 2,20-bipyridine. For reaction conditions,
see the ESI.a Yields and E/Z ratios were determined by 1H and 19F NMR
c
d
mixtures. Photocatalyst Ir(ppy)3 (0.5 mol%) was used. Reaction
b
c
e
spectroscopies. CD3CN was used as solvent. Reaction time = 5 h.
time = 2 h. 1.1 equiv. of vinylborate with respect to 1 was used.
d
f
g
In the dark.
Protodeboronated by-product was obtained in 2% yield. NMR yield.
c
2038 Chem. Commun., 2013, 49, 2037--2039
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Next, vinylborates containing heteroaryl groups such as thio-
phene, pyridine, quinoline and benzothiazole were examined.
Hetero-aromatic substrates are relevant to pharmaceuticals and
agrochemicals because hetero-arenes are ubiquitous structures in
biologically active compounds.18 Remarkably, the photocatalytic
reactions of 2m–t gave the corresponding CF3-substituted alkenes
3m–t with excellent E/Z selectivities (>96/o4) in good yields
(56–82%). The catalytic formation of Calkenyl–CF3 bonds connected
with p-electron-deficient hetero-aromatics has not been so far
reported,11 thus the present photocatalytic protocol might be attrac-
tive from the viewpoint of regio- and stereoselective introduction of a
CF3 group into these scaffolds. Furthermore, alkylvinylborates (2u
and v) can also be applicable to this photocatalytic system with
moderate selectivities and good yields (3u and v).
As a demonstration of scalability of this transformation, the
trifluoromethylation of 2s was carried out on a gram scale. As a
result, the trifluoromethylated alkene with quinoline moiety 3s,
which is a herbicide-related molecule,7 was obtained in good yield
(64%, 1.06 g) with excellent E/Z selectivity (>99/o1) (see the ESI†).
A plausible reaction mechanism based on a SET photoredox
process (oxidative quenching) is shown in Scheme 2. According to
our previous report,14c,19 ꢀCF3 canꢀbe generated from 1e-reduction of
electrophilic Togni’s reagent 1a. CF3 reacts with a CQC bond of
vinylborates 2 to give b-borato-stabilized radical intermediates20 in
a regioselective manner. Subsequent 1e-oxidation by the high-
oxidation state photocatalyst [Ru(bpy)3]3+ produces b-borato cation
intermediates. Finally predominant Peterson elimination of the
boron-based group with trans-selectivity provides (E)-trifluoro-
methylated alkenes 3.21 However we could not rule out the possibility
that a mechanism including radical chain propagation occurs.
In conclusion, we have developed a new and facile visible-light-
induced synthesis of a variety of trifluoromethylated alkenes using
a Ru photoredox catalyst. Togni’s reagent 1a plays an important
role as a CF3 radical source. This photocatalytic system allows easy
access to (E)-trifluoromethylated alkenes bearing electron-deficient
moieties such as p-electron-deficient hetero-aromatics. We expect
this protocol to be of broad utility in the synthesis of biologically
active organofluorine molecules.
9 T. Umemoto, Chem. Rev., 1996, 96, 1757, and references therein.
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17 The photoexcited state of Ir(ppy)3 is a strong reductant (E1/2
=
ꢁ1.32 V vs. Cp2Fe), see: L. Flamigni, A. Barbieri, C. Sabatini,
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18 http://www.drugs.com/top200.html.
19 Cyclic voltammograms of vinylborate 2a showed a broad irreversible
oxidation wave around E1/2 = +1.01 V vs. Cp2Fe. We excluded
generation of radicals from oxidation of vinylborates by the photo-
excited state of [Ru(bpy)3]2+ (E1/2 = +0.43 V vs. Cp2Fe).
The financial support from the Japanese government
(Grants-in-Aid for Scientific Research: No. 23750174) is grate-
fully acknowledged.
20 H. Kim and D. W. C. MacMillan, J. Am. Chem. Soc., 2008, 130, 398.
21 Elimination of the boron group via a b-borato-radical intermediate
is a highly endothermic pathway and thereby presumed unlikely;
see: J. C. Walton, A. J. McCarroll, Q. Chen, B. Carboni and
R. Nziengui, J. Am. Chem. Soc., 2000, 122, 5455.
Notes and references
1 T. Hiyama, Organofluorine Compounds: Chemistry and Applications,
Springer, Berlin, 2000.
c
This journal is The Royal Society of Chemistry 2013
Chem. Commun., 2013, 49, 2037--2039 2039