Grubbs-Hoveyda Second-Generation Catalysts Activated by the Introduction of a Light Fluorous Tag onto the Bidentate Ligands

Article abstract of DOI:10.1055/s-0036-1588686

Various novel Grubbs-Hoveyda second-generation catalysts activated by a fluorous tag on the ligands were prepared. The catalyst bearing the 1-naphthyl group on the bidentate ligand exhibited the highest catalytic activity among the studied catalysts for the ring-closing-metathesis reaction of diethyl 2-allyl-2-(2-methylallyl)malonate.

Full text of DOI:10.1055/s-0036-1588686

SYNTHESIS
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©
Georg Thieme Verlag Stuttgart · New York
2017, 49, A–L
A
paper
Synthesis
Y. Kobayashi et al.
Paper
Grubbs–Hoveyda Second-Generation Catalysts Activated by the
Introduction of a Light Fluorous Tag onto the Bidentate Ligands
Yuki Kobayashi
Naoki Suzumura
Yuki Tsuchiya
MesN
Cl
NMes
MesN
Cl
NMes
Ru
O
R2
Ru
O
Cl
Cl
Machiko Goto
C8F17
Rf
Yuya Sugiyama
Takayuki Shioiri
Masato Matsugi*
1
2
R1
R = OMe, R = H
R1 = iPrO, R2 = H
Rf = C8F17
2 8 17
Rf = (CH ) C F
1
1
1
1
2
R
R
R
R
= Ph, R = H
= 1-naphthyl, R = H
= 2-naphthyl, R = H
= H, R = F
2
2
2
2
Faculty of Agriculture, Meijo University, 1-501 Shiogamaguchi,
Tempaku-ku, Nagoya 468-8502, Japan
matsugi@meijo-u.ac.jp
EtO2C
CO2Et
EtO2C
CO2Et
light fluorous GH 2nd generation catalyst
CDCl3 (0.03 M), 23 °C, 45 min
up to 92% conversion
6
Received: 16.11.2016
Accepted after revision: 13.12.2016
Published online: 11.01.2017
cyclability and activation have been reported. Several rep-
resentative light fluorous GH catalysts are shown in Figure
1 (1b, 1c, and 2b–d). Among these catalysts, 2d exhibits the
DOI: 10.1055/s-0036-1588686; Art ID: ss-2016-f0798-op
highest catalytic activity for the ring-closing metathesis
Abstract Various novel Grubbs–Hoveyda second-generation catalysts
activated by a fluorous tag on the ligands were prepared. The catalyst
bearing the 1-naphthyl group on the bidentate ligand exhibited the
highest catalytic activity among the studied catalysts for the ring-
closing-metathesis reaction of diethyl 2-allyl-2-(2-methylal-
lyl)malonate.
7
(RCM) reaction. To the best of our knowledge, 2d has the
highest activity among all the known light fluorous cata-
lysts. Since the light fluorous tag can be employed as an
electron-withdrawing group, it is possible to shift the equi-
librium of the ligation to the dissociated state, thus improv-
ing the reaction rate.8 Furthermore, the perfluoroalkyl
group exhibits strong hydrophobicity, and it may be sepa-
rated from the organic component by its fluorophilicity via
Key words catalyst, metathesis, ligands, fluorous, activation
9
Olefin metathesis is one of the most attractive and pow-
erful tool for the formation of C=C bonds in the field of syn-
fluorous solid-phase extraction. Thus, the introduction of
the light fluorous tag allows the creation of interesting and
useful metathesis catalytic systems.
1
thetic organic chemistry. Among the ruthenium-based
complexes that are able to catalyze this transformation,
first and second generation Grubbs–Hoveyda catalysts (GH
I: 1a and GH II: 2a ) are particularly suited for this process
because they exhibit high functional group tolerance, excel-
lent air tolerance, and thermodynamic stability (Figure 1).4
Using these characteristics, we recently developed a flu-
orous GH second-generation catalyst supported on Teflon
powder, where the catalyst could be shuttled between the
solid Teflon phase and the liquid DMF phase by simply con-
2
3
10
trolling the water content of the reaction media. Here, we
present a comparison of the catalytic activities of various
novel light fluorous-tagged GH II type catalysts.
1a2 : L = PCy3, R1 = H, R2 = H
L
Cl
Cl
5
1
2
1
b : L = PCy3, R = H, R = (CH2)3C8F17
Ru
5
1
2
The new set of light fluorous catalysts 2e–j used in this
study are shown in Figure 2. The light fluorous catalysts 2e–
i are all characterized by the presence of a bulky substitu-
ent ortho to the isopropoxyl group. Blechert et al. reported
that an increase in steric hindrance ortho to the isopropoxyl
group on the ligand enhances the rate of metathesis reac-
tions.11 In the case of catalyst 2j, the perfluoroalkyl substit-
uent on the aromatic ring of the fluorous ligand is retained
in the same position that it occupies in the known catalyst
1c : L = PCy3, R = H, R = (CH2)2C8F17
1d : L = NHC, R1 = H, R2 = C6F13
6a
O
R2
2
2
2
2
a3 : L = NHC, R1 = H, R2 = H
5
1
2
b
c
: L = NHC, R = H, R = (CH2)2C8F17
R1
7
7
: L = NHC, R1 = H, R2 = C8F17
d
: L = NHC, R1 = F, R2 = C8F17
PCy3 =
3P
NHC =
Mes
N
N
Mes
Figure 1 Grubbs–Hoveyda first- (GH I) and second-generation (GH II)
catalysts 1a and 2a, and known light fluorous GH catalyst variants 1b–d
and 2b–d
2d; however, the ortho fluoro group is replaced to the meta
position. Concurrently, we also prepared the light fluorous
Since we introduced a light fluorous tag into 2a for the
first time in 2005, several light fluorous-tagged rutheni-
chromane-ligand catalysts 3a and 3b based on Glrela’s pio-
neering work, which revealed that the conformational
5
12
um-based catalysts for olefin metathesis with improved re-
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Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–L

B
Synthesis
Y. Kobayashi et al.
Paper
constraint of the chelating ether linkage leads to an unex-
pected disturbance of the catalyst geometry and a vast im-
provement in activity.
OH
OH
R1
CHO
R1
CHO
a
4
a : R1 = OMe
C8F17 5a : R1 = OMe
1
1
MesN
Cl
NMes
MesN
Cl
NMes
4b : R = H
5b : R = H
i
OPr
R2
Ru
O
R1
Ru
O
b, c
g
Cl
Cl
2e
C8F17
Rf
C8F17 6a : R1 = OMe
R1
5a
1
2
OiPr
2
2
2
2
2
2
e: R = OMe, R = H
3a: Rf = C8F17
3b: Rf = (CH2)2C8F17
1
i
2
f: R = PrO, R = H
R1
g
g: R1 = Ph, R2 = H
1
2f
2
d, b, c
h: R = 1-naphthyl, R = H
1
2
i: R = 2-naphthyl, R = H
j: R = H, R2 = F
1
C8F17 6b : R1 = OPr
i
i
Figure 2 Novel light fluorous GH second-generation catalysts used in
this study
OPr
2g
or
2h
or
g
R1
e, b, c, f
5b
2
i
6c : R1 = Ph
Scheme 1 shows the synthetic route to the light fluo-
C8F17
1
6
6
d : R = 1-naphthyl
e : R = 2-naphthyl
rous catalysts 2e–i. In all cases, the light fluorous tag was
1
13
introduced by direct perfluoroalkylation via phenoxyl
1
4
Scheme 1 Synthesis of the light fluorous GH second-generation cata-
lysts 2e–i. Reagents and conditions: (a) V-70L (1.0 equiv), C8F17I (1.5
equiv), Cs CO (8.0 equiv), DMF, r.t., 18–20 h, 5a: 59%, 5b: 36%; (b) i-PrI
radical formation of 4 with the radical initiator V-70 L,
which we have developed previously.15 The perfluoroal-
2
3
kylation of 4a and salicylaldehyde (4b) under mildly basic
conditions provided the monoperfluoroalkylated com-
pounds 5a and 5b in 59% and 36% yield, respectively. In the
synthesis of 2e, isopropyl ether formation followed by
(
10.0 equiv), K CO (8.0 equiv), DMF, 60 °C, 2 h; (c) (Ph PMe)Br (4.0
2
3
3
equiv), NaHMDS (8.0 equiv), anhyd THF, –78 °C → r.t., 3 h, 6a: 69% (2
steps), 6b: 66% (3 steps); (d) BBr (10.0 equiv), CH Cl , r.t., 20 h; (e) Br
2
3
2
2
1
(10.0 equiv), AcOH, 50 °C, 3 h; (f) R B(OH) (1.3–1.5 equiv), K CO (3
2
2
3
equiv), Pd(OAc) /S-Phos (0.05 equiv), 1,4-dioxane, 90 °C, 6–7 h, 6c:
16
2
Wittig olefination provided ligand 6a in 69% yield over the
two steps. Ligand exchange with a standard Grubbs second-
generation catalyst (not the GH catalyst) provided the tar-
get catalyst 2e in 37% yield. In the synthesis of catalyst 2f,
demethylation of 5a, diisopropyl ether formation, and sub-
sequent Wittig olefination provided ligand 6b in 66% yield
over the three steps. Then, ligand exchange provided 2f in
5
7%, 6d: 65%, 6e: 30% (4 steps); Grubbs II catalyst (0.9–1.1 equiv), CuCl
(
2 equiv), anhyd CH Cl , r.t., 3 h, 2e: 37%, 2f: 50%, 2g: 25%, 2h: 34%, 2i:
2
2
46%.
OH
Br
i
OH
OPr
a
b, c, d
e
2j
5
0% yield. The other catalysts 2g–i were prepared via a syn-
F
F
F
17
thetic route using Suzuki–Miyaura coupling as the key re-
action. After bromination of 5b, isopropyl ether formation,
and Wittig olefination, the subsequent Suzuki–Miyaura
coupling with each corresponding aryl borate provided the
ligands 6c–e in 30 to 65% yields over the four steps. Then,
ligand exchange provided 2g–i in 25–46% yields.
C8F17
C8F17
7
8
9
Scheme 2 Synthesis of the light fluorous GH II catalyst 2j. Reagents and
conditions: Cu powder (25.4 equiv), C8F17I (2.0 equiv), anhyd DMF, 110
°
C, 3 h, 73%; (b) Br (1.1 equiv), AcOH, 50 °C, 3 h; (c) i-PrI (10 equiv),
2
K CO (8.0 equiv), DMF, 60 °C, 2 h; (d) potassium vinyltrifluoroborate
(1.1 equiv), Cs CO (3.0 equiv), Pd(PPh ) (0.05 equiv), THF/H O, 85 °C,
2
3
2
3
3
4
2
The synthesis of catalyst 2j is shown in Scheme 2. The
coupling of 4-bromo-3-fluorophenol (7) with perfluorooc-
22 h, 49% (3 steps); (e) Grubbs II catalyst (1.0 equiv), CuCl (2.0 equiv),
anhyd CH Cl , 30 °C, 2 h, 41%.
2
2
18
tyl iodide by the Ullmann reaction provided perfluoro-
phenol 8 in 73% yield. Subsequent regioselective monobro-
mination and isopropylation of the phenolic hydroxyl
group, followed by Suzuki–Miyaura coupling using potassi-
um vinyltrifluoroborate, provided the ortho-fluorinated
fluorous ligand 9 in 49% yield over the three steps. A similar
ligand exchange with the standard Grubbs II catalyst pro-
vided 2j in 41% yield.
the Ullmann reaction provided the corresponding perfluo-
rophenols 11a and 11b in 61% and 28% yield, respectively.
Subsequent ortho-dibromination and chloropropanation of
the phenolic hydroxyl group gave 12a and 12b in 82% and
87% yield (two steps), respectively. Then, intramolecular
cyclization and formylation via a lithiation process followed
by Wittig reaction provided the fluorous ligands 13a and
13b in 15% and 29% yield (two steps), respectively. Finally,
ligand exchange with the standard Grubbs II catalyst pro-
vided the target catalysts 3a and 3b in 35% and 78% yield,
respectively.
The fluorous chromane-ligand catalysts 3a and 3b were
12
synthesized according to Glrela’s method, as shown in
Scheme 3. The coupling reaction of 4-bromophenol (10)
with perfluorooctyl iodide or perfluorooctylethyl iodide by
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Synthesis
Y. Kobayashi et al.
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OH
OH
Rf
O
Cl
Br
Br
a
b, c
Br
Rf
1
1
1a : Rf = C8F17
1b : Rf = (CH2)2C8F17
12a : Rf = C8F17
12b : Rf = (CH2)2C8F17
10
O
d, e
f
3a
or
3b
Rf
1
1
3a : Rf = C8F17
3b : Rf = (CH2)2C8F17
Scheme 3 Synthesis of the light fluorous GH II chromane-type cata-
lysts 3a and 3b. Reagents and conditions: Cu powder (19.9–45.9 equiv),
C F17I or C8F17(CH ) I (2.0 equiv), anhyd DMF, 110 °C, 3 h, 11a: 61%,
8
2 2
Figure 3 Comparison of the catalytic activities of 2e and 2f for the
RCM reaction of 14
1
1b: 28%; (b) Br (10.0 equiv), AcOH, 50 °C, 3 h; (c) 1-bromo-3-chloro-
2
propane (10 equiv), Bu NHSO (1.0 equiv), K CO (8.0 equiv), MeCN, 45
4
4
2
3
°C, 20 h, 12a: 82% (2 steps), 12b: 87% (2 steps); (d) n-BuLi (10 equiv),
anhyd THF, –78 °C, 10 min, anhyd DMF, –40 °C, 1 h; (e) (Ph PMe)Br (4.0
3
equiv), NaHDMS (8.0 equiv), anhyd THF, –78 °C → r.t., 3 h, 13a: 15% (2
steps), 13b: 29% (2 steps); (f) Grubbs II catalyst (0.9 equiv), CuCl (2.0
equiv), anhyd CH Cl , 30 °C, 2 h, 3a: 35%, 3b: 78%.
tions and protocol were the same as those for the experi-
ments conducted with 2e and 2f. The data for GH II catalyst
2
2
2a and fluorous catalyst 2c were also plotted as controls in
this case. It is apparent that 2h has the highest activity
among the studied catalysts because it reaches 90% conver-
sion after 40 minutes, whereas the control catalyst 2c takes
55 minutes to reach the same conversion. The catalysts 2g
and 2i are deactivated after 20 minutes of the reaction. The
catalyst 2h bearing a 1-naphthyl group shows higher reac-
tivity than 2g bearing a phenyl group (Figure 4). Thus, the
introduction of the 1-naphthyl group onto the bidentate li-
gand is an effective means for improving catalytic activity.
Furthermore, we added the result of the reaction in which
The relative turnover rates of catalysts 2e and 2f were
determined by comparing the RCM reaction rates of these
catalysts in the conversion of diethyl 2-allyl-2-(2-methylal-
lyl)malonate (14) to diethyl 3-methylcyclopent-3-ene-1,1-
dicarboxylate (15).1 This substrate was used because of its
moderate reactivity for the RCM reaction. It has suitable re-
activity for comparison with the original catalyst, and the
catalytic activities can be compared at room temperature
9
(
23 °C). The reactions were conducted with CDCl as the
3
1
2
3
solvent to allow for NMR monitoring of reaction aliquots.
Separate reactions with the catalysts 2e and 2f were set up
under identical conditions and with identical catalyst load-
ings (0.03 M). At given time points the percentage conver-
the non-fluorous version (2k: R = 1-naphthyl, R = H, R =
20
20
H ) of catalyst 2h was used, which we recently reported,
in order to evaluate the effect of the fluorous activation. It is
clear that the introduction of the fluorous tag onto the li-
gand promotes the catalytic activity, as we have reported
1
sion of the reaction was determined by recording the H
7
NMR spectra of the reaction mixtures and calculating the
relative integrals of the corresponding methylene protons
of product 15. A plot of percentage conversion versus time
is shown in Figure 3, and confirms that 2e exhibits slightly
higher activity than 2f in the RCM reaction of 14. The data
for GH II catalyst 2a and fluorous catalyst 2c are also plotted
as controls in the same graph in Figure 3. The results indi-
cate that the insertion of an alkoxy group ortho to the iso-
propoxyl group on the bidentate ligand is effective for acti-
vation during the first 50 minutes of the reaction. However,
the activity of these catalysts begins to decrease at around
previously. In the RCM reactions using the GH catalysts,
the rate-determining step is the release step of the biden-
50 minutes. This is because the catalysts begin to decom-
pose at this time, as indicated by the disappearance of their
1
characteristic proton signals from the H NMR spectra.
Similarly, the relative turnover rates of catalysts 2g–i,
which have an aromatic group at the ortho position to the
isopropoxyl group on the bidentate ligand, were deter-
mined by comparing the same RCM reaction. The condi-
Figure 4 Comparison of the catalytic activities of 2g, 2h, and 2i for the
RCM reaction of 14
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Synthesis
Y. Kobayashi et al.
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8
tate ligand on ruthenium, and the reaction rate is thus in-
fluenced by the ligation ability. We believe that the elec-
tron-withdrawing effect of the fluorous tag contributes to
the decrease in the ligation ability on ruthenium. This fluo-
rous activation effect was also obtained in the RCM reaction
of 14 using deuterated dichloromethane (Figure 5).
catalytic activity of the chromane-ligand catalysts by inser-
tion of a fluorous tag. However, fluorous introduction to the
catalyst did not result in any improvement of the catalytic
activity, as shown in Figure 7.
Figure 7 Comparison of the catalytic activities of 3a and 3b for the
RCM reaction of 14
Using a 45 minute time scale, the conversion rates of the
fluorous GH II catalysts were reassessed, which confirmed
their high catalytic activity for the RCM reaction (Figure 8).
The known highly active light fluorous catalyst 2d is also
plotted in the same graph for comparison. Catalyst 2h
shows activity comparable to 2e.
Figure 5 Comparison of the catalytic activities of 2a and 2h for the
RCM reaction of 14 in CD Cl
2
2
Next, we present the results for the RCM reaction of 14
using catalyst 2j under the same conditions, together with
the data for the control catalyst 2c and the regioisomeric
catalyst 2d (Figure 6). Although 2j shows slightly higher
catalytic activity than the GH II catalyst 2a, it shows lower
activity than catalyst 2d. We conclude that the introduction
of a fluoro group ortho to the isopropoxyl group is an im-
portant factor that dramatically improves the catalytic ac-
tivity.
Figure 8 Comparison of the catalytic activities of 2e and 2h for the
RCM reaction of 14
In the RCM reaction of 4-methyl-N,N-bis(2-methylal-
21
lyl)benzenesulfonamide providing a tetra-substituted cy-
clic olefin,20 a similar difference in catalytic activity was ob-
served between GH II catalyst 2a and 2h. Although the tet-
ra-substituted cyclic olefin was obtained in 9% yield when
Figure 6 Comparison of the catalytic activities of 2a, 2c, 2d, and 2j for
the RCM reaction of 14
2a (5 mol%) was used under the 0.1 M condition in chloro-
form at 58 °C, the corresponding cyclic olefin was obtained
We then compared the catalytic activities of the fluo-
rous chromane-ligand catalysts 3a and 3b and the control
catalyst 2a. We have been working towards improving the
in 19% yield when 2h was used.
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Synthesis
Y. Kobayashi et al.
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In summary, we have synthesized eight light fluorous
GH second-generation catalysts 2e–j, 3a, and 3b. Among
these catalysts, 2h exhibited the highest catalytic activity.
We have established that the insertion of a light fluorous
tag onto the bidentate ligand is an effective method for im-
proving the catalytic activity of GH second-generation-type
catalysts for the first 20 minutes of the reaction. However,
this strategy was not successful for the chromane-type cat-
alysts 3a,b. The catalyst 2h bearing a 1-naphthyl group on
the bidentate ligand was found to exhibit high activity. At
present, we believe that 2h is one of the most useful light
fluorous GH second-generation catalysts, and is easily syn-
thesized.
gel (hexane/EtOAc, 5:1) to give 2-isopropoxy-3-methoxy-5-(perfluo-
rooctyl)benzaldehyde as pale yellow crystals; yield: 283.4 mg (88%);
mp 56.6–57.9 °C.
1H NMR (270 MHz, CDCl3): δ = 1.36 (d, J = 6.2 Hz, 6 H), 3.94 (s, 3 H),
4.73–4.87 (m, 1 H), 7.24 (d, J = 1.8 Hz, 1 H), 7.69 (d, J = 2.4 Hz, 1 H),
1
0.46 (s, 1 H).
13
C NMR (68 MHz, CDCl ): δ = 22.4, 56.3, 76.9, 105–124 (m, C F17),
3
8
115.1, 118.4, 124.2, 130.5, 153.4, 153.6, 189.5.
1
9
F NMR (466 MHz, CDCl ): δ = –80.6 (3 F), –110.2 (2 F), –121.2 (2 F),
3
–21.5 (2 F), –121.8 (4 F), –122.7 (2 F), –126.1 (2 F).
HRMS (EI): m/z calcd for C19H13F17O : 612.0593; found: 612.0582;
3
Anal. Calcd for C19H13F17O : C, 37.27; H, 2.14. Found: C, 37.07; H, 2.28.
3
6a
To a solution of (Ph PMe)Br (233.3 mg, 0.65 mmol) in anhyd THF
3
(
10.0 mL) was added a 1.9 mol/L THF solution of sodium bis(trimeth-
All laboratory chemicals were purchased from Wako, TCI, Aldrich, and
Kanto Kagaku Co., Ltd. NMR spectra were recorded on Jeol JNM-
ylsilyl)amide (239.1 mg, 0.65 mL, 1.30 mmol) under N at –78 °C and
2
1
13
1
stirred for 30 min. The reaction temperature rose to –10 °C and the
mixture was stirred for an additional 30 min. A solution of 2-isoprop-
oxy-3-methoxy-5-(perfluorooctyl)benzaldehyde (100 mg, 0.16
mmol) in anhyd THF (8.0 mL) was then added and the stirring was
continued for 5 h at r.t. After the addition of aq 1.0 M HCl and dilution
with EtOAc, the organic layer was washed with H O and brine, dried
(Na SO ), filtered, and concentrated. The residue was purified by col-
umn chromatography on silica gel (hexane/EtOAc, 10:1) to give 6a as
a pale yellow oil; yield: 65.3 mg (78%); 69% over 2 steps.
EX270 ( H: 270 MHz, C: 67.8 MHz) and Jeol ECA-500 ( H: 400 MHz,
19
13
F: 466 MHz, C: 124.5 MHz) spectrometers. Chemical shifts (δ) are
given in units of ppm, and coupling constants (J) are given in Hz. IR
spectra were recorded on a Shimadzu FT/IR-4200 spectrometer. The
–1
signals of IR spectra are expressed in wavenumbers (cm ). HRMS was
performed by FAB and EI using a magnetic sector analyzer. The spec-
2
®
2 4
tra were calibrated with Ultramark 1621 and PFK prior to data ac-
quisition. The elemental analyses were performed using a Yanaco
CHN Corder MT-6 instrument.
1
H NMR (270 MHz, CDCl ): δ = 1.29 (d, J = 6.21 Hz, 6 H), 3.87 (s, 3 H),
3
4
1
1
.48–4.57 (m, 1 H), 5.35 (dd, J = 1.2, 11.2 Hz, 1 H), 5.76 (dd, J = 1.0,
7.8 Hz, 1 H), 6.97 (d, J = 1.6 Hz, 3 H), 7.02–7.23 (m, 1 H), 7.35 (d, J =
.6 Hz, 1 H).
Synthesis of Catalyst 2e
2
-Hydroxy-3-methoxy-5-(perfluorooctyl)benzaldehyde (5a)
To a solution of 2-hydroxy-3-methoxybenzaldehyde (4a; 300 mg,
.97 mmol), perfluorooctyl iodide (1.62 g, 2.96 mmol), and 2,2′-azo-
13
C NMR (68 MHz, CDCl ): δ = 22.4, 56.1, 75.9, 106–124 (m, C F17),
3
8
109.4, 116.0, 116.8, 123.9 131.2, 132.9, 147.4, 153.3.
1
19F NMR (466 MHz, CDCl
–121.4 (2 F), –121.6 (4 F), –122.5 (2 F), –125.9 (2 F).
): δ = –80.6 (3 F), –109.9 (2 F), –121.1 (2 F),
bis(4-methoxy-2,4-dimethylvaleronitrile) (V-70L; 308 mg, 1.97
mmol) in DMF (10 mL) was added Cs CO (6.39 g, 19.68 mmol) at r.t.
3
2
3
The mixture was stirred for 20 h at the same temperature. After the
HRMS (EI): m/z calcd for C20H15F17O : 610.0801; found: 610.0784.
2
addition of aq 1.0 M HCl and dilution with Et O, the organic layer was
2
washed with H O and brine, dried (Na SO ), filtered, and concentrat-
2
2
4
(
1,3-Dimesitylimidazolidin-2-yl)[2-isopropoxy-3-methoxy-5-(per-
ed. The residue was purified by column chromatography on silica gel
hexane/EtOAc, 10:1) to give 5a as pale yellow crystals; yield: 1.90 g
fluorooctyl)benzylidene]ruthenium(V) Chloride (2e)
(
To a solution of 6a (45.0 mg, 0.07 mmol) in anhyd CH Cl2 (6.0 mL)
were added Grubbs II catalyst (53.4 mg, 0.06 mmol) and CuCl (13.9
mg, 0.14 mmol) under N and the mixture was stirred at 30 °C for 3 h.
The mixture was concentrated in vacuo and the residue was purified
by column chromatography on silica gel (hexane/CH Cl , 1:1) to give
2
(59%); mp 69.5–73.3 °C.
1
H NMR (270 MHz, CDCl ): δ = 3.98 (s, 3 H), 7.22 (s, 1 H), 7.47 (s, 1 H),
3
2
9.98 (s, 1 H), 11.43 (s, 1 H).
13
C NMR (68 MHz, CDCl ): δ = 56.6, 105–120 (m, C F17), 114.9, 120.1,
3
8
2
2
120.4, 123.5 149.0, 154.6, 195.9.
2e as green crystals; yield: 28.9 mg (37%); mp 135–137 °C.
1
9
F NMR (466 MHz, CDCl ): δ = –80.6 (3 F), –109.9 (2 F), –121.0 (2 F),
IR (FT-ATR): 3853, 3737, 3638, 2935, 2856, 2363, 2326, 1581, 1455,
1187, 1104, 898, 747 cm .
3
–1
–
122.5 (2 F), –125.9 (2 F), –127.7 (6 F).
1
HRMS (EI): m/z calcd for C16H7F17O : 570.0124; found: 570.0127.
H NMR (270 MHz, CDCl ): δ = 1.21 (d, J = 6.2 Hz, 10 H), 2.38–2.47 (m,
3
3
1
8 H), 3.79 (s, 3 H), 4.20 (s, 4 H), 5.80–5.75 (m, 1 H), 6.73 (s, 1 H), 7.06
(
1
s, 4 H), 16.32 (s, 1 H).
1-Isopropoxy-6-methoxy-4-(perfluorooctyl)-2-vinylbenzene (6a)
3
C NMR (68 MHz, CDCl ): δ = 21.9, 22.5, 26.1, 26.4, 29.7, 30.3, 51.4,
3
2-Isopropoxy-3-methoxy-5-(perfluorooctyl)benzaldehyde
56.0, 75.9, 76.2, 109.3, 116.8, 122.8, 123.8, 126.6, 127.6, 128.7, 132.8,
1
37.3, 139.1, 147.1, 149.6, 209.6, 295.0.
To a solution of 5a (300 mg, 0.52 mmol) and 2-iodopropane (894.4
1
9
mg, 5.26 mmol) in DMF (10 mL) was added K CO3 (581.7 mg, 4.20
F NMR (466 MHz, CDCl ): δ = –80.6 (3 F), –109.9 (2 F), –121.1 (4 F),
2
3
mmol) under N and the mixture was stirred at 60 °C for 2 h. After the
–121.7 (4 F), –122.5 (2 F), –125.9 (2 F).
2
addition of aq 1.0 M HCl and dilution with Et O, the organic layer was
+
2
HRMS (FAB): m/z [M + H] calcd for C40H40Cl2F17N O Ru: 1076.1239;
found: 1076.1250.
2
2
washed with H O and and brine, dried (Na SO ), filtered, and concen-
2
2
4
trated. The residue was purified by column chromatography on silica
©
Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–L

F
Synthesis
Y. Kobayashi et al.
Paper
13
Synthesis of Catalyst 2f
C NMR (68 MHz, CDCl ): δ = 21.9, 22.6, 71.3, 75.8, 106–119 (m,
3
C8F17), 112.8, 115.7, 116.7, 123.5, 125.6, 131.4, 135.8, 151.2.
1
9
1,2-Diisopropoxy-5-(perfluorooctyl)-3-vinylbenzene (6b)
F NMR (466 MHz, CDCl ): δ = –80.6 (3 F), –110.0 (2 F), –121.1 (2 F),
3
–121.7 (6 F), –122.5 (2 F), –125.9 (2 F).
2,3-Dihydroxy-5-(perfluorooctyl)benzaldehyde
HRMS (EI): m/z calcd for C22H19F17O : 638.1114; found: 638.1066.
2
To a mixture of 5a (250.0 mg, 0.43 mmol) in anhyd CH Cl2 (5.0 mL)
2
was added a solution of BBr (550 mg, 2.19 mmol) in CH Cl (5.0 mL)
3
2
2
[2,3-Diisopropoxy-5-(perfluorooctyl)benzylidene](1,3-dimesi-
tylimidazolidin-2-yl)ruthenium(V) Chloride (2f)
under N at 0 °C. The reaction temperature rose to r.t. and the mixture
2
was stirred for 20 h. H O was slowly added to the resulting mixture
2
To a solution of 6b (31.0 mg, 0.048 mmol) in anhyd CH Cl (5.0 mL)
2
2
and the stirring was continued for 30 min. After dilution with EtOAc,
the organic layer was washed with H O and brine, dried (Na SO ), fil-
were added Grubbs II catalyst (37.0 mg, 0.052 mmol) and CuCl (9.6
2
2
4
mg, 0.097 mmol) under N and the mixture was stirred at 30 °C for 1
2
tered, and concentrated. The residue was purified by column chroma-
tography on silica gel (hexane/EtOAc, 10:1) to give 2,3-dihydroxy-5-
h. The mixture was concentrated in vacuo and the residue was puri-
fied by column chromatography on silica gel (hexane/CH Cl , 1:1) to
2
2
(perfluorooctyl)benzaldehyde as a pale yellow powder; yield: 213.4
give 2f as green crystals; yield: 27.0 mg (50%); mp 125–127 °C.
mg (87%); mp 128.4–129.1 °C.
IR (FT-ATR): 3854, 3738, 3649, 2978, 2931, 2361, 2342, 1481, 1199,
1
H NMR (270 MHz, CDCl ): δ = 5.84 (s, 1 H), 7.40 (d, J = 11.8 Hz, 2 H),
–1
3
1107, 1072, 910, 729 cm
.
9.95 (s, 1 H), 11.45 (s, 1 H).
1
H NMR (270 MHz, CDCl ): δ = 1.21 (d, J = 6.4 Hz, 6 H), 1.27 (d, J = 5.6
3
13
C NMR (68 MHz, CDCl ): δ = 106–123 (m, C F17), 119.1, 119.9, 121.2,
3
8
Hz, 6 H), 2.37 (s, 6 H), 2.47 (br s, 12 H), 4.19 (s, 4 H), 4.51–4.45 (m, 1
H), 5.89–5.80 (m, 1 H), 6.70 (d, J = 1.3 Hz, 1 H), 7.06 (s, 4 H), 7.18 (d, J =
1.6 Hz, 1 H), 16.31 (s, 1 H).
123.1, 145.5, 151.1, 196.0.
1
9
F NMR (466 MHz, CDCl ): δ = –80.6 (3 F), –110.0 (2 F), –121.0 (2 F),
3
–121.7 (6 F), –122.5 (2 F), –125.9 (2 F).
13
C NMR (68 MHz, CDCl ): δ = 21.5, 21.9, 22.5, 51.3, 75.7, 76.0, 113.7,
3
HRMS (EI): m/z calcd for C15H5F17O : 555.9967; found: 555.9967.
114.5, 116.6, 123.5, 125.5, 126.6, 127.5, 129.4, 139.0, 143.5, 147.4,
3
151.2, 209.8, 296.5.
2
,3-Diisopropoxy-5-(perfluorooctyl)benzaldehyde
To solution of 2,3-dihydroxy-5-(perfluorooctyl)benzaldehyde
100.0 mg, 0.17 mmol) and 2-iodopropane (305.6 mg, 1.79 mmol) in
DMF (8 mL) was added K CO (198.8 mg, 1.43 mmol) under N2 and
19
F NMR (466 MHz, CDCl ): δ = –80.5 (3 F), –110.0 (2 F), –121.3 (4 F),
3
a
–121.7 (4 F), –122.5 (2 F), –125.9 (2 F).
(
+
HRMS (FAB): m/z [M + H] calcd for C42H45Cl2F17N O Ru: 1104.1630;
found: 1104.1637.
2
2
2
3
the mixture was stirred at 60 °C for 2 h. After the addition of aq 1.0 M
HCl and dilution with EtOAc, the organic layer was washed with H O
2
Synthesis of Catalyst 2g
and brine, dried (Na SO ), filtered, and concentrated. The residue was
2
4
purified by column chromatography on silica gel (hexane/EtOAc,
0:1) to give 2,3-diisopropoxy-5-(perfluorooctyl)benzaldehyde as a
1-Isopropoxy-6-phenyl-4-(perfluorooctyl)-2-vinylbenzene (6c)
1
colorless oil; yield: 113.9 mg (99%).
2-Hydroxy-5-(perfluorooctyl)benzaldehyde (5b)22
1
H NMR (270 MHz, CDCl ): δ = 1.36 (d, J = 6.2 Hz, 6 H), 1.41 (d, J = 5.6
3
To a solution of salicylaldehyde (4b; 300 mg, 2.46 mmol), perfluo-
rooctyl iodide (2.0 g, 3.68 mmol), and V-70L (758.5 mg, 2.46 mmol) in
DMF (16.0 mL) was added Cs CO (6.41 g, 19.7 mmol) at r.t. The mix-
Hz, 6 H), 4.59–4.68 (m, 1 H), 4.77–4.86 (m, 1 H), 7.24 (sd, J = 2.9 Hz, 1
H), 7.67 (d, J = 2.4 Hz, 1 H), 10.46 (s, 1 H).
13
2
3
C NMR (68 MHz, CDCl ): δ = 21.7, 71.8, 106–119 (m, C F17), 118.0,
3
8
ture was stirred for 20 h at the same temperature. After the addition
of aq 1.0 M HCl and dilution with EtOAc, the organic layer was
washed with H O and brine, dried (Na SO ), filtered, and concentrat-
119.2, 123.9, 130.7, 151.5, 154.3, 189.6.
1
9
F NMR (466 MHz, CDCl ): δ = –80.6 (3 F), –110.2 (2 F), –121.1 (2 F),
3
2
2
4
–121.5 (2 F), –121.7 (4 F), –122.6 (2 F), –126.0 (2 F).
ed. The residue was purified by column chromatography on silica gel
HRMS (EI): m/z calcd for C21H17F17O : 640.0906; found: 640.0926.
(hexane/EtOAc, 10:1) to give 5b as pale yellow crystals; yield: 476.4
3
mg (36%); mp 57–58 °C.
1
6b
H NMR (270 MHz, CDCl ): δ = 7.13 (d, J = 8.9 Hz, 1 H), 7.72 (d, J = 8.9
3
Hz, 1 H), 9.97 (s, 1 H), 11.33 (s, 1 H).
To a solution of (Ph PMe)Br (252.8 mg, 0.70 mmol) in anhyd THF (7.0
mL) was added a 1.9 mol/L THF solution of sodium bis(trimethylsi-
3
1
9
F NMR (466 MHz, CDCl ): δ = –80.6 (3 F), –110.0 (2 F), –121.0 (2 F),
3
lyl)amide (259.3 mg, 0.7 mL, 1.41 mmol) under N at –78 °C and the
–121.7 (6 F), –122.5 (2 F), –125.9 (2 F).
2
mixture was stirred for 30 min. The reaction temperature rose to –10
°
5
(
C and was stirred for further 30 min. A solution of 2,3-diisopropoxy-
-(perfluorooctyl)benzaldehyde (117.0 mg, 0.17 mmol) in anhyd THF
7.0 mL) was then added and the stirring continued for 2 h at r.t. After
2
-Hydroxy-3-bromo-5-(perfluorooctyl)benzaldehyde
To a solution of 5b (1.8 g, 3.33 mmol) in AcOH (5.0 mL) was added a
solution of Br (5.0 g, 31.29 mmol) in AcOH (10.0 mL) at 50 °C and the
mixture was stirred for 16 h. After the addition of aq Na S O and di-
lution with EtOAc, the organic layer was washed with H O and brine,
2
the addition of aq 1.0 M HCl and dilution with EtOAc, the organic lay-
er was washed with H O and brine, dried (Na SO ), filtered, and con-
centrated. The residue was purified by column chromatography on
silica gel (hexane/EtOAc, 10:1) to give 6b as a colorless oil; yield: 86.3
mg (76%); 66% over 3 steps.
2
2
3
2
2
4
2
dried (Na SO ), filtered, and concentrated. The residue was purified
2
4
by column chromatography on silica gel (hexane/EtOAc, 10:1) to give
-hydroxy-3-bromo-5-(perfluorooctyl)benzaldehyde as pale yellow
2
1
H NMR (270 MHz, CDCl ): δ = 1.29 (d, J = 6.2 Hz, 6 H), 1.36 (d, J = 6.2
3
crystals; yield: 1.8 g (86%); mp 45–46 °C.
Hz, 6 H), 4.61–4.48 (m, 2 H), 5.32 (d, J = 11.3 Hz, 1 H), 5.74 (d, J = 17.8
Hz, 1 H), 6.95 (s, 1 H), 7.08 (q, J = 9.5 Hz, 1 H), 7.32 (s, 1 H).
1
H NMR (270 MHz, CDCl ): δ = 7.80 (d, J = 2.4 Hz, 1 H), 7.99 (d, J = 1.9
3
Hz, 1 H), 9.94 (s, 1 H), 11.95 (s, 1 H).
©
Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–L

G
Synthesis
Y. Kobayashi et al.
Paper
13
C NMR (68 MHz, CDCl ): δ = 106–123 (m, C F17), 112.4, 120.6, 121.7,
was stirred at 90 °C under N for 20 h. After the addition of aq 1.0 M
3
8
2
1
31.6, 137.7, 160.9, 195.4.
HCl, the catalyst was removed by filtration through a pad of Celite and
washed with EtOAc. The aqueous layer was extracted with EtOAc. The
1
9
F NMR (466 MHz, CDCl ): δ = –80.6 (3 F), –110.0 (2 F), –121.0 (2 F),
3
combined organic layers were washed with H O and brine, dried
–121.3 (2 F), –121.7 (4 F), –122.5 (2 F), –125.9 (2 F).
2
(
Na SO ), filtered, and concentrated. The residue was purified by col-
2 4
HRMS (EI): m/z calcd for C15H BrF O : 617.9123; found: 617.9135.
4
17
2
umn chromatography on silica gel (hexane/CHCl , 1:1) to give 6c as a
3
Anal. Calcd for C15H BrF O : C, 29.10; H, 0.65. Found: C, 29.15; H,
pale yellow oil; yield: 38.0 mg (76%); 57% over 4 steps.
4
17
2
0.93.
1
H NMR (270 MHz, CDCl ): δ = 0.99 (d, J = 6.2 Hz, 6 H), 3.83–3.92 (m, 1
3
H), 5.46 (dd, J = 0.5, 10.8 Hz, 1 H), 6.00 (dd, J = 0.8, 17.8 Hz, 1 H), 7.21
2-Isopropoxy-3-bromo-5-(perfluorooctyl)benzaldehyde
(dd, J = 11.3, 17.8 Hz, 1 H), 7.40–7.64 (m, 6 H), 7.89 (d, J = 2.2 Hz, 1 H).
To a solution of 2-hydroxy-3-bromo-5-(perfluorooctyl)benzaldehyde
13
C NMR (68 MHz, CDCl ): δ = 21.9, 76.2, 106–119 (m, C F17), 123.8,
3
8
(
(
1.7 g, 2.67 mmol) and 2-iodopropane (4.5 g, 26.65 mmol) in DMF
25.0 mL) was added K CO (3.0 g, 21.32 mmol) under N and the mix-
124.1, 125.5, 127.7 128.3, 128.7, 129.1, 131.6 133.4, 136.4, 138.1,
2
3
2
155.6.
ture was stirred at 60 °C for 2 h. After the addition of aq 1.0 M HCl and
1
9
F NMR (466 MHz, CDCl ): δ = –80.6 (3 F), –110.0 (2 F), –121.1 (2 F),
3
dilution with EtOAc, the organic layer was washed with H O and
2
–121.3 (2 F), –121.7 (4 F), –122.5 (2 F), –125.9 (2 F).
brine, dried (Na SO ), filtered, and concentrated. The residue was pu-
2
4
rified by column chromatography on silica gel (hexane/EtOAc, 10:1)
to give 2-isopropoxy-3-bromo-5-(perfluorooctyl)benzaldehyde as
pale yellow crystals; yield: 1.7 g (96%); mp 75–76 °C.
1
HRMS (EI): m/z calcd for C25H F17O: 656.1008; found: 656.1004.
17
(1,3-Dimesitylimidazolidin-2-yl){[2-isopropoxy-5-(perfluorooc-
tyl)-[1,1′-biphenyl]-3-yl)methylene}ruthenium(V) Chloride (2g)
H NMR (270 MHz, CDCl ): δ = 1.43 (d, J = 6.2 Hz, 6 H), 4.65–4.74 (m, 1
3
H), 8.03 (dd, J = 8.9, 2.2 Hz, 2 H), 10.38 (s, 1 H).
To a solution of 6c (38.0 mg, 0.058 mmol) in anhyd CH Cl (6.0 mL)
2
2
1
3
were added Grubbs II catalyst (44.5 mg, 0.052 mmol) and CuCl (5.8
C NMR (68 MHz, CDCl ): δ = 22.0, 79.7, 106–120 (m, C F17), 119.3,
3
8
mg, 0.058 mmol) under N at 30 °C and the mixture was stirred for 2
1
1
25.9, 126.5, 131.8, 137.3, 160.7, 188.2.
9
2
h. The mixture was concentrated in vacuo, and the residue was puri-
fied by column chromatography on silica gel (hexane/CH Cl , 1:1) to
F NMR (466 MHz, CDCl ): δ = –80.6 (3 F), –110.3 (2 F), –121.1 (4 F),
3
2
2
–
121.7 (4 F), –122.5 (2 F), –125.9 (2 F).
give 2g as green crystals; yield: 16.4 mg (25%); mp 105–106 °C.
HRMS (EI): m/z calcd for C18H10BrF17O : 659.9593; found: 659.9561.
2
IR (FT-ATR): 3853, 3737, 3653, 3575, 2918, 2357, 1697, 1491, 1428,
1240, 1208, 1145, 909, 851, 715 cm .
–1
Anal. Calcd for C18H10BrF17O : C, 32.70; H, 1.52. Found: C, 32.63; H,
2
1.48.
1
H NMR (270 MHz, CDCl ): δ = 0.87 (d, J = 6.2 Hz, 6 H), 2.41–2.56 (m,
3
1
9 H), 4.23 (s, 4 H), 4.41–4.50 (s, 1 H), 7.08 (s, 4 H), 7.36 (s, 6 H), 7.53
1-Isopropoxy-6-bromo-4-(perfluorooctyl)-2-vinylbenzene
(d, J = 2.2 Hz, 1 H), 7.53 (s, 1 H).
To a solution of (Ph PMe)Br (432.2 mg, 0.12 mmol) in anhyd THF
13
3
C NMR (68 MHz, CDCl ): δ = 20.4, 20.8, 21.8, 78.7, 120.4, 123.8,
3
(10.0 mL) was added a 1.9 mol/L THF solution of sodium bis(trimeth-
128.3, 128.4, 128.6, 128.8, 129.2, 129.4, 131.0, 131.5, 136.7, 137.5,
ylsilyl)amide (443.7 mg, 1.2 mL, 2.42 mmol) under N2 at –78 °C and
stirred for 30 min. The reaction temperature rose to –10 °C and the
mixture was stirred for further 30 min. A solution of 2-isopropoxy-3-
bromo-5-(perfluorooctyl)benzaldehyde (200.0 mg, 0.30 mmol) in an-
hyd THF (10.0 mL) was then added and stirring continued for 2 h at
r.t. After the addition of aq 1.0 M HCl and dilution with EtOAc, the or-
ganic layer was washed with H O and brine, dried (Na SO ), filtered,
138.1, 139.1, 147.4, 151.3, 209.3, 296.5.
1
9
F NMR (466 MHz, CDCl ): δ = –80.6 (3 F), –109.4 (2 F), –121.1 (4 F),
3
–121.7 (4 F), –122.5 (2 F), –125.9 (2 F).
+
HRMS (FAB+): m/z [M + H] calcd for C45
H
42Cl
F
N
ORu: 1121.1446;
2
17
2
found: 1121.1476.
2
2
4
and concentrated. The residue was purified by column chromatogra-
phy on silica gel (hexane/EtOAc, 10:1) to give 1-isopropoxy-6-bromo-
Synthesis of Catalyst 2h
4
-(perfluorooctyl)-2-vinylbenzene as a pale yellow oil; yield: (183.0
1
-Isopropoxy-6-(1-naphthyl)-4-(perfluorooctyl)-2-vinylbenzene
mg, 91%).
(6d)
1
H NMR (270 MHz, CDCl ): δ = 1.35 (d, J = 6.5 Hz, 6 H), 4.50–4.61 (m, 1
3
A similar procedure used for the preparation of 6c was followed. A
mixture of 1-isopropoxy-6-bromo-4-(perfluorooctyl)-2-vinylben-
zene (155.0 mg, 0.2 mmol), 1-naphthylboronic acid (60.7 mg, 0.4
mmol), K
S-Phos (12.1 mg, 0.03 mmol) in anhyd 1,4-dioxane (14.0 mL) was
stirred at 90 °C under N for 6 h. After the addition of aq 1.0 M HCl,
the catalyst was removed by filtration through a pad of Celite and
washed with EtOAc. The aqueous layer was extracted with EtOAc. The
combined organic layers were washed with H O and brine, dried
H), 5.42 (d, J = 11.3 Hz, 1 H), 5.79 (d, J = 17.3 Hz, 1 H), 7.00 (dd, J = 17.6,
11.1 Hz, 1 H), 7.66 (d, J = 8.6 Hz, 2 H).
13
C NMR (68 MHz, CDCl ): δ = 22.3, 77.8, 106–120 (m, C F17), 117.2,
2
CO (97.5 mg, 0.7 mmol), Pd(OAc) (2.6 mg, 0.02 mmol), and
3
2
3
8
118.9, 124.3, 125.2, 131.0, 131.2, 134.4, 155.6.
1
9
2
F NMR (466 MHz, CDCl ): δ = –80.6 (3 F), –112.9 (2 F), –120.7 (2 F),
3
–121.6 (6 F), –122.5 (2 F), –125.9 (2 F).
HRMS (EI): m/z calcd for C19H12BrF17O: 657.9800; found: 657.9768.
2
(
Na SO ), filtered, and concentrated. The residue was purified by col-
2 4
6c
umn chromatography on silica gel (hexane/CHCl , 5:1) to give 6d as a
3
A mixture of 1-isopropoxy-6-bromo-4-(perfluorooctyl)-2-vinylben-
zene (50 mg, 0.076 mmol), phenylboronic acid (12.0 mg, 0.099
pale yellow oil; yield: 143.0 mg (86%); 65% over 4 steps.
1
H NMR (270 MHz, CDCl ): δ = 0.76 (dd, J = 49.4, 5.9 Hz, 6 H), 3.63–
3
mmol), K CO (31.5 mg, 0.23 mmol), Pd(OAc)2 (0.85 mg, 0.0038
2
3
3.72 (m, 1 H), 5.48 (d, J = 11.3 Hz, 1 H), 6.06 (d, J = 17.8 Hz, 1 H), 7.25
mmol), and S-Phos [dicyclohexyl(2′,6′-dimethoxy-[1,1′-biphenyl]-2-
yl)phosphine; 3.9 mg, 0.0095 mmol] in anhyd 1,4-dioxane (4.0 mL)
(dd, J = 10.5, 17.8 Hz, 1 H), 7.49–7.65 (m, 6 H), 8.00 (s, 3 H).
©
Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–L

H
Synthesis
Y. Kobayashi et al.
Paper
1
3
C NMR (68 MHz, CDCl ): δ = 21.9, 22.1, 76.3, 106–119 (m, C F17),
(1,3-Dimesitylimidazolidin-2-yl){[2-isopropoxy-5-(perfluorooc-
tyl)-3-(naphthalen-2-yl)phenyl]methylene}ruthenium(V) Chlo-
ride (2i)
3
8
1
1
16.1, 125.2, 125.5, 125.9, 126.0, 126.0, 126.3, 127.7, 128.3, 128.4,
31.3, 131.7, 133.2, 133.7, 134.7, 135.8, 138.5, 156.5.
1
9
F NMR (466 MHz, CDCl ): δ = –80.6 (3 F), –110.0 (2 F), –121.1 (2 F),
To a solution of 6e (33.0 mg, 0.05 mmol) in anhyd CH
were added Grubbs II catalyst (39.7 mg, 0.05 mmol) and CuCl (4.6 mg,
.05 mmol) under N and the mixture was stirred at 30 °C for 3 h. The
2 2
Cl (6.0 mL)
3
–
121.4 (2 F), –121.7 (4 F), –122.6 (2 F), –126.0 (2 F).
0
2
HRMS (EI): m/z calcd for C29H19F17O: 706.1164; found: 706.1165.
reaction mixture was concentrated in vacuo and the residue was pu-
rified by column chromatography on silica gel (hexane/CH Cl , 1:1) to
2
2
(1,3-Dimesitylimidazolidin-2-yl){[2-isopropoxy-5-(perfluorooc-
give 2i as green crystals; yield: 25.2 mg (46%); mp 116.3–117.0 °C.
tyl)-3-(naphthalen-1-yl)phenyl]methylene}ruthenium(V) Chlo-
ride (2h)
IR (FT-ATR): 2919, 2360, 1605, 1481, 1398, 1242, 1207, 1145, 1109,
–1
1
094, 743 cm .
To a solution of 6d (57.9 mg, 0.08 mmol) in anhyd CH Cl (6.0 mL)
were added Grubbs II catalyst (74.4 mg, 0.09 mmol) and CuCl (17.3
mg, 0.2 mmol) under N and the mixture was stirred at 30 °C for 3 h.
The mixture was concentrated in vacuo and the residue was purified
by column chromatography on silica gel (hexane/CH Cl , 1:1) to give
2
2
1
H NMR (270 MHz, CDCl ): δ = 0.86 (d, J = 6.2 Hz, 6 H), 2.50 (br s, 18
3
H), 4.23 (s, 4 H), 4.45–4.54 (m, 1 H), 7.07–7.12 (m, 6 H), 7.26–7.54 (m,
2
3
H), 7.62 (d, J = 2.2 Hz, 1 H), 7.80–7.87 (m, 4 H), 16.51 (s, 1 H).
13
2
2
C NMR (68 MHz, CDCl ): δ = 15.3, 22.1, 22.7, 66.0, 77.3, 110.3–119.9
3
2
h as green crystals; yield: 39.8 mg (34%); mp 129.3–131.3 °C.
(m, C8F17), 123.9, 124.3, 124.7, 126.4, 127.3, 127.7, 127.9, 128.2, 129.1,
131.7, 132.8, 133.5, 133.7, 135.8, 136.3, 155.8.
IR (FT-ATR): 2924, 2363, 1649, 1460, 1235, 1203, 1140, 773 cm–1
.
1
9
1
F NMR (466 MHz, CDCl ): δ = –80.6 (3 F), 109.6 (2 F), –121.1 (4 F),
H NMR (270 MHz, CDCl ): δ = 0.75 (dd, J = 51.8, 6.2 Hz, 6 H), 2.46 (br
3
3
–121.7 (4 F), –122.5 (2 F), –125.9 (2 F).
s, 18 H), 4.13–4.22 (m, 5 H), 7.06–7.18 (m, 5 H), 7.42–7.49 (m, 5 H),
+
7.60–7.67 (m, 2 H), 7.85 (d, J = 7.8 Hz, 2 H), 16.53 (s, 1 H).
HRMS (FAB+): m/z [M + H] calcd for C49H44Cl2F17N ORu: 1172.1689;
2
13
found: 1172.1731.
C NMR (68 MHz, CDCl ): δ = 18.4, 20.8, 20.8, 51.4, 79.1, 110–119 (m,
3
C8F17), 120.9, 125.2, 125.9, 126.5, 127.5, 127.6, 128.2, 128.8, 129.0,
129.5, 131.7, 133.1, 135.6, 139.1, 147.2, 152.2, 209.5.
Synthesis of Catalyst 2j
1
9
F NMR (466 MHz, CDCl ): δ = –80.6 (3 F), –109.5 (2 F), –121.1 (2 F),
3
–121.3 (2 F), –121.7 (4 F), –122.5 (2 F), –125.9 (2 F).
2-Fluoro-4-isopropoxy-1-(perfluorooctyl)-3-vinylbenzene (9)
+
HRMS (FAB+): m/z [M + H] calcd for C49H44Cl2F17N ORu: 1172.1689;
2
3-Fluoro-4-(perfluorooctyl)phenol (8)
found: 1172.1677.
To a suspension of 4-bromo-3-fluorophenol (7; 750.0 mg, 3.92 mmol)
and Cu powder (6.3 g, 99.49 mmol) in anhyd DMF (15.0 mL) was add-
Synthesis of Catalyst 2i
ed perfluorooctyl iodide (4.2 g, 7.85 mmol) under N and the mixture
2
was stirred at 110 °C for 3 h. After the addition of H O, Cu powder was
2
1
-Isopropoxy-6-(2-naphthyl)-4-(perfluorooctyl)-2-vinylbenzene
removed by filtration through a pad of Celite and washed with EtOAc.
The aqueous layer was extracted with EtOAc. The combined organic
layers were washed with H O and brine, dried (Na SO ), filtered, and
(6e)
A similar procedure used for the preparation of 6c was followed. A
mixture of 1-isopropoxy-6-bromo-4-(perfluorooctyl)-2-vinylben-
zene (135.0 mg, 0.2 mmol), 2-naphthylboronic acid (46.0 mg, 0.3
mmol), K CO (85.5 mg, 0.6 mmol), Pd(OAc) (2.3 mg, 0.01 mmol), and
S-Phos (10.5 mg, 0.03 mmol) in anhyd 1,4-dioxane (11.0 mL) was
stirred at 90 °C under N2 for 3 h. After the addition of aq 1.0 M HCl,
the catalyst was removed by filtration through a pad of Celite and
washed with EtOAc. The aqueous phase was extracted with EtOAc.
2
2
4
concentrated. The residue was purified by column chromatography
on silica gel (hexane/EtOAc, 10:1) to give 8 as white crystals; yield:
2
3
2
1529 mg (73%); mp 58.3–58.8 °C.
1
H NMR (270 MHz, CDCl ): δ = 5.43 (br s, 1 H), 6.65–6.74 (m, 2 H),
3
7.40 (t, J = 5.6 Hz, 1 H).
13
C NMR (68 MHz, CDCl ): δ = 104.6, 107–120 (m, C F17), 111.6, 130.3,
3
8
The combined organic layers were washed with H O and brine, dried
159.7, 160.7, 163.5.
2
(
Na SO ), filtered, and concentrated. The residue was purified by col-
19
2
4
F NMR (466 MHz, CDCl ): δ = –80.7 (3 F), –108.2 (2 F), –109.5 (1 F),
3
umn chromatography on silica gel (hexane/CHCl , 5:1) to give 6e as a
pale yellow oil; yield: 57.3 mg (40%); 30% over 4 steps.
3
–121.4 (2 F), –121.7 (6 F), –122.6 (2 F), –126.0 (2 F).
HRMS (EI): m/z calcd for C14H4F18O: 529.9975; found: 529.9926.
1
H NMR (270 MHz, CDCl ): δ = 0.96 (d, J = 5.9 Hz, 6 H), 3.79–3.88 (m, 1
3
H), 5.42 (d, J = 11.3 Hz, 1 H), 5.84 (d, J = 17.8 Hz, 1 H), 7.17 (dd, J = 10.5,
2
-Bromo-3-fluoro-4-(perfluorooctyl)phenol
17.6 Hz, 1 H), 7.50–7.56 (m, 3 H), 7.71–7.74 (m, 2 H), 7.87–7.92 (m, 3
To a solution of 8 (500.0 mg, 0.94 mmol) in AcOH (5.0 mL) was added
a solution of Br2 (165.7 mg, 1.03 mmol) in AcOH (5.0 mL) and the
mixture was stirred at 50 °C for 5 h. After the addition of aq Na S O
and dilution with EtOAc, the organic layer was washed with H O and
brine, dried (Na SO ), filtered, and concentrated. The residue was pu-
rified by column chromatography on silica gel (hexane/EtOAc, 5:1) to
give 2-bromo-3-fluoro-4-(perfluorooctyl)phenol as white crystals;
yield: 535.3 mg (93%); mp 57–58 °C.
H), 8.02 (s, 1 H).
13
C NMR (68 MHz, CDCl ): δ = 22.1, 76.4, 106–119 (m, C F17), 119.9,
3
8
2
2
3
1
1
23.9, 124.3, 124.7, 126.4, 127.3, 127.8, 127.9, 127.9, 128.2, 129.1,
31.7, 132.8, 133.5, 133.7, 135.8, 136.4, 155.9.
2
2
4
1
9
F NMR (466 MHz, CDCl ): δ = –80.7 (3 F), –110.0 (2 F), –121.1 (4 F),
3
–121.7 (4 F), –122.6 (2 F), –126.0 (2 F).
HRMS (EI): m/z calcd for C29H19F17O: 706.1164; found: 706.1168.
1
H NMR (270 MHz, CDCl ): δ = 6.01 (br s, 1 H), 6.88 (d, J = 11.6 Hz, 1
3
H), 7.64 (d, J = 7.02 Hz, 1 H).
13
C NMR (68 MHz, CDCl ): δ = 105.1, 105.2, 109–120 (m, C F17), 131.8,
3
8
156.8, 158.9, 162.7.
©
Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–L

I
Synthesis
Y. Kobayashi et al.
Paper
1
9
13
F NMR (466 MHz, CDCl ): δ = –80.6 (3 F), –108.3 (2 F), –109.5 (1 F),
C NMR (68 MHz, CDCl ): δ = 19.4, 20.9, 51.4, 77.5, 102.8, 103.2,
3
3
–121.4 (2 F), –121.7 (6 F), –122.5 (2 F), –125.9 (2 F).
122.3, 129.4, 139.1, 141.8, 155.8, 155.9, 158.3, 162.1, 209.2, 291.7.
1
9
HRMS (EI): m/z calcd for C14H BrF18O: 607.9080; found: 607.9066.
F NMR (466 MHz, CDCl ): δ = –80.6 (3 F), –106.3 (1 F), –108.5 (2 F),
3
3
–121.4 (2 F), –121.5 (2 F), –122.6 (4 F), –125.9 (2 F).
HRMS (FAB): m/z [M + H]+ calcd for C39H37Cl2F18N ORu: 1064.1039;
2-Bromo-3-fluoro-1-isopropoxy-4-(perfluorooctyl)benzene
2
To a solution of 2-bromo-3-fluoro-4-(perfluorooctyl)phenol (360.0
mg, 0.59 mmol) and 2-iodopropane (1.0 g, 5.91 mmol) in DMF (25.0
mL) was added K CO (654.0 mg, 21.32 mmol) under N and the mix-
found: 1064.1049.
2
3
2
Synthesis of Catalyst 3a
ture was stirred at 60 °C for 2 h. After the addition of aq 1.0 M HCl and
dilution with EtOAc, the organic layer was washed with H O and
2
6-(Perfluorooctyl)-8-vinylchroman (13a)
brine, dried (Na SO ), filtered, and concentrated. The residue was pu-
2
4
rified by column chromatography on silica gel (hexane/EtOAc, 10:1)
to give 2-bromo-3-fluoro-1-isopropoxy-4-(perfluorooctyl)benzene
as a colorless oil; yield: 306.7 mg (79%).
4
-(Perfluorooctyl)phenol (11a)22
To a suspension of 4-bromophenol (10; 1.0 g, 5.78 mmol) and Cu
powder (7.3 g, 114.87 mmol) in anhyd DMF (10.0 mL) was added per-
fluorooctyl iodide (6.3 g, 11.56 mmol) under N and the mixture was
stirred at 120 °C for 3 h. After the addition of H O, Cu powder was
removed by filtration through a pad of Celite and washed with EtOAc.
The aqueous layer was extracted with EtOAc. The combined layers
1
H NMR (270 MHz, CDCl ): δ = 1.43 (d, J = 5.9 Hz, 6 H), 4.54–4.63 (m, 1
3
2
H), 6.69 (d, J = 12.4 Hz, 1 H), 7.67 (d, J = 7.5 Hz, 1 H).
2
13
C NMR (68 MHz, CDCl ): δ = 21.6, 72.8, 102.7, 107.6, 109–120 (m,
3
C8F17), 132.7, 158.6, 158.8, 162.4.
1
9
were washed with H O and brine, dried (Na SO ), filtered, and con-
centrated. The residue was purified by column chromatography on
silica gel (hexane/EtOAc, 10:1) to give 11a as white crystals; yield: 1.8
g (61%); mp 72.1–73.4 °C.
F NMR (466 MHz, CDCl ): δ = –80.6 (3 F), –108.3 (2 F), –109.7 (1 F),
2
2
4
3
–
121.4 (2 F), –121.7 (6 F), –122.5 (2 F), –125.9 (2 F).
HRMS (EI): m/z calcd for C17H BrF18O: 649.9549; found: 649.9520.
9
1
H NMR (270 MHz, CDCl ): δ = 5.69 (s, 1 H), 6.94 (d, J = 8.6 Hz, 2 H),
3
9
8
.04 (d, J = 9.4 Hz, 2 H).
2-Bromo-3-fluoro-1-isopropoxy-4-(perfluorooctyl)benzene (100.0
1
9
F NMR (466 MHz, CDCl ): δ = –80.6 (3 F), –112.3 (2 F), –120.7 (4 F),
mg, 0.153 mmol), potassium vinyltrifluoroborate (22.5 mg, 0.16
mmol), Pd(PPh3)4 (8.84 mg, 0.0076 mmol), and Cs CO (149.5 mg,
3
–121.3 (2 F), –121.8 (2 F), –122.5 (2 F), –125.9 (2 F).
2
3
0
.45 mmol) were added to THF/H O (9:1, 4.0 mL) under N and the
2
2
mixture was stirred at 85 °C for 22 h. After the addition of aq 1.0 M
HCl, the catalyst was removed by filtration through a pad of Celite and
washed with EtOAc. The aqueous phase was extracted with EtOAc.
2,6-Dibromo-4-(perfluorooctyl)phenol
To a solution of 11a (1.8 g, 3.33 mmol) in AcOH (10.0 mL) was added a
solution of Br (2.8 g, 17.55 mmol) in AcOH (5.0 mL) and the mixture
2
The combined organic layers were washed with H O and brine, dried
was stirred at 50 °C for 5 h. After the addition of aq Na S O and dilu-
2
2
2
3
(
Na SO ), filtered, and concentrated. The residue was purified by col-
tion with EtOAc, the organic layer was washed with H O and brine,
2
4
2
umn chromatography on silica gel (hexane/CHCl , 10:1) to give 9 as
dried (Na SO ), filtered, and concentrated. The residue was purified
3
2
4
white crystals; yield: 61.4 mg (67%); 49% over 3 steps; mp 43–44 °C.
by column chromatography on silica gel (hexane/EtOAc, 10:1) to give
2,6-dibromo-4-(perfluorooctyl)phenol as white crystals; yield: 2.3 g
1
H NMR (270 MHz, CDCl ): δ = 1.40 (d, J = 5.9 Hz, 6 H), 4.53–4.62 (m, 1
3
(98%); mp 88.9–89.9 °C.
H), 5.30 (d, J = 11.3 Hz, 1 H), 5.73 (d, J = 17.0 Hz, 1 H), 6.65 (d, J = 13.2
Hz, 1 H), 6.92 (q, J = 9.6 Hz, 1 H), 7.55 (d, J = 8.6 Hz, 1 H).
1
H NMR (270 MHz, CDCl ): δ = 6.37 (br s, 1 H), 7.68 (s, 2 H).
3
13
13
C NMR (68 MHz, CDCl ): δ = 21.7, 71.4, 101.5, 104–119 (m, C F17),
C NMR (68 MHz, CDCl ): δ = 106–120 (m, C F17), 110.2, 123.3, 130.9,
3 8
3
8
115.4, 124.0, 125.5, 126.6, 130.0, 159.0, 162.5.
152.6.
1
9
19
F NMR (466 MHz, CDCl ): δ = –80.6 (3 F), –108.3 (2 F), –110.4 (1 F),
F NMR (466 MHz, CDCl ): δ = –80.6 (3 F), –109.8 (2 F), –121.0 (2 F),
3
3
–121.4 (2 F), –121.8 (6 F), –122.6 (2 F), –126.0 (2 F).
–121.3 (2 F), –121.7 (4 F), –122.5 (2 F), –125.9 (2 F).
HRMS (EI): m/z calcd for C19H12F18O: 598.0601; found: 598.0594.
HRMS (EI): m/z calcd for C14H Br F17O: 667.8279; found: 667.8267.
3
2
(
1,3-Dimesitylimidazolidin-2-yl)[2-fluoro-6-isopropoxy-3-(per-
1,3-Dibromo-2-(3-chloropropoxy)-5-(perfluorooctyl)benzene
(12a)
fluorooctyl)benzylidene]ruthenium(V) Chloride (2j)
To a solution of 9 (59.7 mg, 0.098 mmol) in anhyd CH Cl (6.0 mL)
were added Grubbs II catalyst (75.3 mg, 0.088 mmol) and CuCl (19.8
To a solution of 2,6-dibromo-4-(perfluorooctyl)phenol (400.0 mg,
0.59 mmol), 3-bromopropyl chloride (939.9 mg, 5.97 mmol), and
Bu NHSO (202.6 mg, 0.59 mmol) in anhyd MeCN (25.0 mL) was add-
2
2
mg, 0.20 mmol) under N and the mixture was stirred at 30 °C for 3 h.
2
4
4
The mixture was concentrated in vacuo and the residue was purified
by column chromatography on silica gel (hexane/CH Cl , 1:1) to give
ed K CO (660.0 mg, 4.77 mmol) under N at 45 °C and stirred for 20
2
3
2
2
2
h. After the addition of aq 1.0 M HCl and dilution with EtOAc, the or-
ganic layer was washed with H O and brine, dried (Na SO ), filtered,
2j as green crystals; yield: 43.2 mg (41%); mp 153–157 °C.
2
2
4
and concentrated. The residue was purified by column chromatogra-
phy on silica gel (hexane/EtOAc, 10:1) to give 12a as white crystals;
yield: 378.8 mg (84%); 82% over two steps; mp 55.6–56.6 °C.
1
IR (FT-ATR): 3905, 3857, 3747, 3642, 3569, 2971, 2918, 2363, 2342,
1
837, 1723, 1691, 1612, 1586, 1486, 1424, 1293, 1213, 1156, 1104,
–1
1029, 915, 846 cm
.
1
H NMR (270 MHz, CDCl ): δ = 2.30–2.39 (m, 2 H), 3.88 (t, J = 6.3 Hz, 2
H NMR (270 MHz, CDCl ): δ = 2.38 (s, 6 H), 2.45 (s, 12 H), 4.21 (s, 1
3
3
H), 4.23 (t, J = 5.8 Hz, 2 H), 7.74 (s, 2 H).
H), 4.90–4.82 (m, 1 H), 6.62 (d, J = 12.4 Hz, 1 H), 7.07 (s, 5 H), 16.22 (s,
H).
13
1
C NMR (68 MHz, CDCl ): δ = 33.2, 41.3, 70.1, 106–119 (m, C F17),
3
8
119.0, 127.2, 131.5, 156.3.
©
Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–L

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Synthesis
Y. Kobayashi et al.
Paper
1
9
F NMR (466 MHz, CDCl ): δ = –80.5 (3 F), –110.2 (2 F), –121.1 (4 F),
IR (FT-ATR): 3979, 3857, 3747, 3685, 3417, 2956, 2918, 2363, 2336,
1596, 1481, 1413, 1240, 1208, 1140, 1046, 988, 904, 857, 809, 741,
3
–
121.7 (4 F), –122.5 (2 F), –125.9 (2 F).
–1
720 cm .
HRMS (EI): m/z calcd for C17H Br ClF17O: 743.8359; found: 743.8380.
8
2
1
H NMR (270 MHz, CDCl ): δ = 2.09–2.00 (m, 2 H), 2.43 (d, J = 14.0 Hz,
3
1
6
8 H), 2.86 (t, J = 12.1 Hz, 2 H), 4.17 (s, 4 H), 4.27 (t, J = 10.2 Hz, 2 H),
.91 (s, 1 H), 7.08 (s, 4 H), 7.43 (s, 1 H), 16.32 (s, 1 H).
6
-(Perfluorooctyl)chroman-8-carbaldehyde
Anhyd THF (8.0 mL) was added to a 1.6 mol/L solution of n-BuLi in
hexane (2.4 mL, 3.8 mmol) under N2 at –78 °C and the mixture was
stirred for 10 min. A solution of 12a (410.0 mg, 0.54 mmol) in anhyd
THF (4.0 mL) was then added and the stirring continued for 40 min at
the same temperature. Anhyd DMF (6.0 mL) was then added and the
stirring continued for 1 h at –45 °C. After the addition of aq 1.0 M HCl
and dilution with EtOAc, the organic layer was washed with H O and
brine, dried (Na SO ), filtered, and concentrated. The residue was pu-
rified by column chromatography on silica gel (hexane/EtOAc, 10:1)
to give 6-(perfluorooctyl)chroman-8-carbaldehyde as white crystals;
yield: 203.4 mg (63%); mp 108–109 °C.
13C NMR (68 MHz, CDCl
123.3, 124.2, 127.1, 129.6, 136.1, 138.7, 139.0, 142.8, 143.2, 151.8,
209.2, 288.5.
19
): δ = 19.2, 21.0, 22.1, 23.6, 51.7, 70.2, 118.0,
3
F NMR (466 MHz, CDCl ): δ = –80.5 (3 F), –109.2 (2 F), –121.0 (2 F),
3
–121.3 (2 F), –121.7 (4 F), –122.5 (2 F), –126.0 (2 F).
2
HRMS (FAB): m/z [M + H]+ calcd for C39H36Cl2F17N ORu: 1044.0977;
found: 1044.0991.
2
2
4
Synthesis of Catalyst 3b
1
H NMR (495 MHz, CDCl ): δ = 2.03–2.08 (m, 2 H), 2.84 (t, J = 3.5 Hz, 2
3
4
-(3,3,4,4,5,5,6,6,7,7,8,8,9,9,10,10,11,11,11-Nonadecafluoroundec-
H), 4.33 (t, J = 2.9 Hz, 2 H), 7.39 (s, 1 H), 7.82 (s, 1 H), 10.35 (s, 1 H).
5
yl)phenol (11b)
13
C NMR (68 MHz, CDCl ): δ = 21.2, 24.7, 67.5, 104–120 (m, C F17),
3
8
To a suspension of 4-bromophenol (10; 376.0 mg, 2.17 mmol) and Cu
powder (6.3 g, 99.49 mmol) in anhyd DMF (15.0 mL) was added
1H,1H,2H,2H-perfluorooctyl iodide (2.5 g, 4.35 mmol) under N2 and
120.4, 124.1, 124.5, 125.6, 133.6, 160.0, 188.7.
1
9
F NMR (466 MHz, CDCl ): δ = –80.6 (3 F), –110.0 (2 F), –121.1 (2 F),
3
–121.4 (2 F), –121.7 (4 F), –122.5 (2 F), –125.9 (2 F).
the mixture was stirred at 120 °C for 3 h. After the addition of H O, Cu
2
HRMS (FAB): m/z [M + H]+ calcd for C18H9F17O : 581.0331; found:
powder was removed by filtration through a pad of Celite and washed
with EtOAc. The aqueous phase was extracted with EtOAc. The com-
bined organic layers were washed with H O and brine, dried (Na SO ),
2
581.0382.
2
2
4
filtered, and concentrated. The residue was purified by column chro-
matography on silica gel (hexane/EtOAc, 10:1) to give 11b as white
crystals; yield: 334.9 mg (28%); mp 82.8–83.3 °C.
1
6
-(Perfluorooctyl)-8-vinylchroman (13a)
To a solution of (Ph PMe)Br (246.2 mg, 0.68 mmol) in anhyd THF
3
(10.0 mL) was added a 1.9 mol/L THF solution of sodium bis(trimeth-
H NMR (495 MHz, CDCl ): δ = 2.37–2.28 (m, 2 H), 2.85–2.82 (m, 2 H),
ylsilyl)amide in THF (252.7 mg, 0.68 mL, 1.37 mmol) under N at –78
3
2
4
.66 (s, 1 H), 7.79–7.76 (m, 1 H), 7.08–7.06 (m, 2 H).
°
C and the mixture was stirred for 30 min. The reaction temperature
1
9
rose to –10 °C and the mixture was stirred for an additional 30 min. A
solution of 6-(perfluorooctyl)chroman-8-carbaldehyde (100 mg, 0.17
mmol) in anhyd THF (8.0 mL) was then added and the stirring contin-
ued for 2 h at r.t. After the addition of aq 1.0 M HCl and dilution with
F NMR (466 MHz, CDCl ): δ = –80.6 (3 F), –114.5 (2 F), –121.5 (2 F),
3
–121.7 (4 F), –122.5 (2 F), –123.3 (2 F), –125.9 (2 F).
1,3-Dibromo-2-(3-chloropropoxy)-5-
EtOAc, the organic layer was washed with H O and brine, dried
2
(3,3,4,4,5,5,6,6,7,7,8,8,9,9,10,10,11,11,11-nonadecafluoroundec-
yl)benzene (12b)
(Na SO ), filtered, and concentrated. The residue was purified by col-
2 4
umn chromatography on silica gel (hexane/EtOAc, 10:1) to give 13a as
a colorless oil; yield: 23.4 mg (23%); 15% over two steps.
2
,6-Dibromo-4-(3,3,4,4,5,5,6,6,7,7,8,8,9,9,10,10,11,11,11-nonadeca-
1
H NMR (270 MHz, CDCl ): δ = 1.89–1.98 (m, 2 H), 2.74 (t, J = 6.6 Hz, 2
3
fluoroundecyl)phenol
H), 4.19 (t, J = 5.2 Hz, 2 H), 5.23 (dd, J = 0.8, 11.0 Hz, 1 H), 5.23 (dd, J =
To a solution of 11b (385.0 mg, 0.71 mmol) in AcOH (3.0 mL) was add-
ed a solution of Br (1.1 g, 7.12 mmol) in AcOH (3.0 mL) at r.t. and the
mixture was stirred for 20 h. After the addition of aq Na S O and di-
lution with EtOAc, the organic layer was washed with H O and brine,
0.8, 11.0 Hz, 1 H), 5.66 (dd, J = 1.3, 18.0 Hz, 1 H), 6.88 (q, J = 9.5 Hz, 1
2
H), 7.06 (s, 1 H), 7.36 (s, 1 H).
2
2
3
13
C NMR (68 MHz, CDCl ): δ = 21.7, 25.0, 66.8, 115.8, 117.0, 119.9,
3
2
122.5, 127.5, 130.7, 135.7, 154.8.
dried (Na SO ), filtered, and concentrated. The residue was purified
2
4
1
9
by column chromatography on silica gel (hexane/EtOAc, 10:1) to give
,6-dibromo-4-(3,3,4,4,5,5,6,6,7,7,8,8,9,9,10,10,11,11,11-nonadecafluo-
roundecyl)phenol as white crystals; yield: 492.0 mg (99%); mp 56.2–
F NMR (466 MHz, CDCl ): δ = –80.6 (3 F), –109.6 (2 F), –121.1 (2 F),
3
2
–
121.5 (2 F), –121.7 (4 F), –122.5 (2 F), –125.9 (2 F).
HRMS (EI): m/z calcd for C19H11F17O: 578.0538; found: 578.0564.
56.7 °C.
1
H NMR (270 MHz, CDCl ): δ = 2.23–2.42 (m, 2 H), 2.79–2.85 (m, 2 H),
3
(
1,3-Dimesitylimidazolidin-2-yl){[6-(perfluorooctyl)chroman-8-
5
.81 (s, 1 H), 7.31 (s, 1 H).
yl]methylene}ruthenium(V) Chloride (3a)
13
C NMR (68 MHz, CDCl ): δ = 25.2, 32.8, 107–121 (m, C F17), 110.8,
To a solution of 13a (22.0 mg, 0.038 mmol) in anhyd CH Cl (5.0 mL)
were added Grubbs II catalyst (29.0 mg, 0.034 mmol) and CuCl (7.5
mg, 0.075 mmol) under N and the mixture was stirred at 30 °C for 3
3
8
2
2
131.8, 133.6, 148.3.
1
9
F NMR (466 MHz, CDCl ): δ = –80.6 (3 F), –114.5 (2 F), –121.4 (2 F),
3
2
h. The mixture was concentrated in vacuo and the residue was puri-
fied by column chromatography on silica gel (hexane/CH Cl , 1:1) to
give 3a as green crystals; yield: 14.0 mg (35%); mp 178–183 °C (dec.).
–121.7 (4 F), –122.5 (2 F), –123.3 (2 F), –125.9 (2 F).
2
2
Anal. Calcd for C16H Br F17O: C, 27.53; H, 1.01. Found: C, 27.39; H,
7
2
1.13.
©
Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–L

K
Synthesis
Y. Kobayashi et al.
Paper
12b
and concentrated. The residue was purified by column chromatogra-
phy on silica gel (hexane/CHCl , 10:1) to give 13b as a white powder;
yield: 68.9 mg (34%); 29% over two steps; mp 33–34 °C.
To a solution of 2,6-dibromo-4-(3,3,4,4,5,5,6,6,7,7,8,8,9,9,10,10,11,11,11-
nonadecafluoroundecyl)phenol (490.0 mg, 0.70 mmol), 3-bromopro-
pyl chloride (1.1 g, 7.01 mmol), and Bu NHSO (238.0 mg, 0.70 mmol)
3
1
4
4
H NMR (270 MHz, CDCl ): δ = 1.95–2.04 (m, 2 H), 2.23–2.43 (m, 2 H),
3
in anhyd MeCN (20.0 mL) was added K CO (775.0 mg, 5.60 mmol)
2.74–2.83 (m, 4 H), 4.21 (t, J = 5.2 Hz, 2 H), 5.26 (dd, J = 1.35, 11.0 Hz,
2
3
under N and the mixture was stirred at 40 °C for 20 h. After the addi-
1 H), 5.71 (t, J = 1.3, 17.8 Hz, 1 H), 6.80 (s, 1 H), 6.97 (q, J = 9.7 Hz, 1 H),
2
tion of aq 1.0 M HCl and dilution with EtOAc, the organic layer was
washed with H O and brine, dried (Na SO ), filtered, and concentrat-
7.11 (s, 1 H).
2
2
4
13
C NMR (68 MHz, CDCl ): δ = 22.1, 25.0, 25.6, 33.3, 66.5, 104–119 (m,
3
ed. The residue was purified by column chromatography on silica gel
hexane/EtOAc, 10:1) to give 12b as white crystals; yield: 477.7 mg
C8F17), 114.7, 122.6, 124.1, 126.2, 129.0, 130.1, 131.4, 150.9.
(
1
9
F NMR (466 MHz, CDCl ): δ = –80.6 (3 F), –114.5 (2 F), –121.5 (2 F),
(88%); 87% over two steps; mp 55.5–56.4 °C.
3
–121.7 (4 F), –122.5 (2 F), –123.3 (2 F), –126.0 (2 F).
1
H NMR (270 MHz, CDCl ): δ = 2.26–2.38 (m, 2 H), 2.81–2.87 (m, 2 H),
3
HRMS (EI): m/z calcd for C21H15F17O: 606.0851; found: 606.0822.
3.86 (t, J = 6.6 Hz, 2 H), 4.13 (t, J = 5.66 Hz, 2 H), 7.37 (s, 1 H).
13
C NMR (68 MHz, CDCl ): δ = 25.4, 32.7, 33.3, 41.5, 69.8, 106–122 (m,
3
(
1,3-Dimesitylimidazolidin-2-yl){[6-
C8F17), 118.5, 132.6, 137.8, 151.8.
(3,3,4,4,5,5,6,6,7,7,8,8,9,9,10,10,10-heptadecafluorodecyl)chro-
1
9
F NMR (466 MHz, CDCl ): δ = –80.6 (3 F), –114.4 (2 F), –121.4 (2 F),
3
man-8-yl]methylene}ruthenium(V) Chloride (3b)
–121.7 (4 F), –122.5 (2 F), –123.2 (2 F), –125.9 (2 F).
To a solution of 13b (40.0 mg, 0.065 mmol) in anhyd CH Cl (6.0 mL)
were added Grubbs II catalyst (50.3 mg, 0.059 mmol) and CuCl (13.0
mg, 0.13 mmol) under N and the mixture was stirred at 30 °C for 3 h.
2
2
Anal. Calcd for C19H12Br ClF17O: C, 29.46; H, 1.56. Found: C, 29.25; H,
2
1.71.
2
The mixture was concentrated in vacuo and the residue was purified
by column chromatography on silica gel (hexane/EtOAc, 2:1) to give
3b as green crystals; yield: 55.5 mg (78%); mp 160–165 °C (dec.).
6
-(3,3,4,4,5,5,6,6,7,7,8,8,9,9,10,10,11,11,11-Nonadecafluoroundec-
yl)-8-vinylchroman (13b)
IR (FT-ATR): 3905, 3857, 3816, 3743, 3700, 3642, 3616, 3569, 3013,
2945, 2913, 2856, 2363, 2331, 1738, 1691, 1596, 1555, 1476, 1455,
6
-(3,3,4,4,5,5,6,6,7,7,8,8,9,9,10,10,11,11,11-Nonadecafluoroundec-
1413, 1245, 1203, 1140, 1108, 1035, 993, 915, 857, 814, 730 cm–1
.
yl)chroman-8-carbaldehyde
Anhyd THF (6.0 mL) was added to a 1.6 mol/L solution of n-BuLi in
hexane (1.8 mL, 2.8 mmol) under N2 at –78 °C and the mixture was
stirred for 10 min. A solution of 12b (200.0 mg, 0.25 mmol) in anhyd
THF (5.0 mL) was then added and the stirring continued for 40 min at
the same temperature. Anhyd DMF (4.0 mL) was then added and the
stirring continued for 1 h at –45 °C. After the addition of aq 1.0 M HCl
1
H NMR (270 MHz, CDCl ): δ = 2.01–2.04 (m, 2 H), 2.22–2.31 (m, 2 H),
3
2.43 (d, J = 14.8 Hz, 18 H), 2.77–2.87 (m, 4 H), 4.10–4.21 (m, 6 H), 6.51
(s, 1 H), 7.08 (s, 5 H), 16.43 (s, 1 H).
13
C NMR (68 MHz, CDCl ): δ = 19.2, 21.0, 22.5, 23.5, 51.7, 69.5, 77.5,
3
1
2
18.9, 124.1, 128.9, 129.5, 133.2, 136.3, 138.7, 143.7, 148.5, 210.7,
91.4.
and dilution with EtOAc, the organic layer was washed with H O and
2
1
9
F NMR (466 MHz, CDCl ): δ = –80.5 (3 F), –114.4 (2 F), –121.5 (2 F),
brine, dried (Na SO ), filtered, and concentrated. The residue was pu-
3
2
4
–
121.8 (4 F), –122.5 (2 F), –123.3 (2 F), –126.0 (2 F).
rified by column chromatography on silica gel (hexane/EtOAc, 10:1)
to give 6-(3,3,4,4,5,5,6,6,7,7,8,8,9,9,10,10,11,11,11-nonadecafluo-
roundecyl)chroman-8-carbaldehyde as white crystals; yield: 136.3
mg (86%); mp 80.6–80.9 °C.
HRMS (FAB): m/z [M + H]+ calcd for C41H40Cl2F17N ORu: 1072.1290;
found: 1072.1320.
2
1
H NMR (270 MHz, CDCl ): δ = 2.01–2.10 (m, 2 H), 2.29–2.36 (m, 2 H),
.80–2.87 (m, 4 H), 4.30 (t, J = 5.2 Hz, 2 H), 7.12 (s, 1 H), 7.48 (s, 1 H),
Ring-Closing Metathesis Reaction of 14 in CDCl ; Diethyl 3-Methyl-
cyclopent-3-ene-1,1-dicarboxylate (15); Typical Procedure
3
3
19
2
1
0.39 (s, 1 H).
Diethyl 2-allyl-2-(2-methylallyl)malonate (14; 13.4–40.5 mg, 0.053–
13
C NMR (68 MHz, CDCl ): δ = 21.7, 24.7, 25.4, 32.9, 66.9, 105–121 (m,
0.159 mmol) and catalyst 2e (5.0 mol%) were dissolved in CDCl (0.03
3
3
M) in an NMR tube at 23 °C. The mixture was analyzed by 1H NMR
C8F17), 124.0, 124.3, 125.6, 130.4, 136.0, 156.5, 189.8.
1
1
9
spectroscopy. Conversion was evaluated from the H NMR spectra by
F NMR (466 MHz, CDCl ): δ = –80.6 (3 F), –114.4 (2 F), –121.4 (2 F),
3
integration of 14 and RCM product 15 signals; colorless oil.
–121.7 (4 F), –122.5 (2 F), –123.3 (2 F), –125.9 (2 F).
1
H NMR (270 MHz, CDCl ): δ = 1.18 (t, J = 7.3 Hz, 6 H), 1.64 (s, 3 H),
3
Anal. Calcd for C20H13F17O : C, 39.49; H, 2.15. Found: C, 39.17; H, 2.04.
2
2.83–2.90 (m, 4 H), 4.12 (q, J = 7.0, 14.3 Hz, 4 H), 5.12 (s, 1 H).
13b
To a solution of (Ph PMe)Br (465.8 mg, 1.304 mmol) in anhyd THF
3
Acknowledgment
(13.0 mL) was added a 1.9 mol/L THF solution of sodium bis(trimeth-
ylsilyl)amide (477.3 mg, 1.29 mL, 2.603 mmol) under N at –78 °C and
the mixture was stirred for 30 min. The reaction temperature rose to
2
This work was supported by JSPS KAKENHI Grant Number 26450145,
and Professor Uozumi’s JST-ACCEL program.
–10 °C and the mixture was stirred for an additional 20 min. A solu-
tion of 6-(3,3,4,4,5,5,6,6,7,7,8,8,9,9,10,10,11,11,11-nonadecafluoro-
undecyl)chroman-8-carbaldehyde (198 mg, 0.326 mmol) in anhyd
THF (7.0 mL) was then added and the stirring was continued for 3 h at
r.t. After the addition of aq 1.0 M HCl and dilution with EtOAc, the or-
ganic layer was washed with H O and brine, dried (Na SO ), filtered,
Supporting Information
Supporting information for this article is available online at
http://dx.doi.org/10.1055/s-0036-1588686.
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Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–L

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Synthesis
Y. Kobayashi et al.
Paper
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©
Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–L