Preference of Ruthenium-Based Metathesis Catalysts toward Z- and E-Alkenes as a Guide for Selective Reactions to Alkene Stereoisomers

Article abstract of DOI:10.1021/acs.joc.6b01276

As a guide for selective reactions toward either Z- or E-alkene in a metathesis reaction, the relative preference of metathesis Ru catalysts for each stereoisomer was determined by a method using time-dependent fluorescence quenching. We found that Ru-1 p

Full text of DOI:10.1021/acs.joc.6b01276

Article
pubs.acs.org/joc
Preference of Ruthenium-Based Metathesis Catalysts toward Z- and
E‑Alkenes as a Guide for Selective Reactions to Alkene Stereoisomers
Jihong Lee,† Kyung Hwan Kim,§ Ok Suk Lee,† Tae-Lim Choi,¶ Hee-Seung Lee,‡ Hyotcherl Ihee,*,§,‡
and Jeong-Hun Sohn*,†
†Department of Chemistry, Chungnam National University, Daejeon 305-764, Republic of Korea
§Center for Nanomaterials and Chemical Reactions, Institute for Basic Science (IBS), Daejeon 305-701, Republic of Korea
‡Department of Chemistry, KAIST, Daejeon 305-701, Republic of Korea
¶Department of Chemistry, Seoul National University, Seoul 151-747, Republic of Korea
S
* Supporting Information
ABSTRACT: As a guide for selective reactions toward either Z- or E-
alkene in a metathesis reaction, the relative preference of metathesis
Ru catalysts for each stereoisomer was determined by a method using
time-dependent fluorescence quenching. We found that Ru-1 prefers
the Z-isomer over the E-isomer, whereas Ru-2 prefers the E-isomer
over the Z-isomer. The Z/E-alkene preference of the catalysts precisely
predicted the Z/E isomeric selectivity in the metathesis reactions of
diene substrates possessing combinations of Z/E-alkenes. For the
diene substrates, the rate order of the reactions using Ru-1 was Z,Z-
1,6-diene > Z,E-1,6-diene > E,E-1,6-diene, while the completely
opposite order of E,E-1,6-diene > Z,E-1,6-diene > Z,Z-1,6-diene was
exhibited in the case of Ru-2.
these two catalysts, it has been reported that Ru-1 selectively
generates Z-alkene,7−10 while Ru-2 does not show clear
preference in the production of alkene stereoisomers in olefin
metathesis.9f,11 The catalysts Ru-1 and Ru-2 have absorbance
bands in the visible light range with no fluorescence emission
and thus are expected to be suitable for FRET studies as
fluorescence quenchers of dye-conjugated alkene substrates
when Ru-substrate complexes are formed. Measuring fluo-
rescence quenching as a function of time could determine the
relative kinetic and thermodynamic preferences, k and ΔG,
respectively, in the formation of an alkene-bound ruthenium
alkylidene intermediate from the corresponding catalyst
precursor and substrate pair.3a,c,d The higher sensitivity of the
FRET-based method over other spectroscopic methods such as
NMR measurements allows monitoring of small quantities of
catalyst−substrate complex formation and collect data over a
relatively short period of time.
INTRODUCTION
■
Selective catalytic transformation of coexisting E- and Z-alkene
stereoisomers is highly desirable in synthetic organic chemistry
and has become an important goal in many areas in the
chemical industry. For instance, the selective removal of trans
fats from food, which possess E-alkenes and are known to be
harmful to human health, has been an important issue in the
food industry.1 However, efficient methods enabling the
selective reaction for each stereoisomer have been scarcely
developed due to the lack of a guide regarding the selectivity of
catalysts toward each stereoisomer. Herein, we present the
preference of Ru-based metathesis catalysts for each stereo-
isomer, determined by a method using the principle of
fluorescence resonance energy transfer (FRET)2−4 as a guide
for the selective reaction to each stereoisomer (Figure 1). We
demonstrate that this guide is indeed consistent with the
selectivity of catalysts toward alkene stereoisomers in the olefin
metathesis reaction5 of diene substrates possessing combina-
tions of Z/E-alkenes.
In recent years, Schrock, Hoveyda, and Grubbs have
developed Mo- and Ru-based metathesis catalysts that show
highly selective reactions toward Z-alkene over E-alkene in the
metathesis reactions of ethenolysis and olefins between internal
and terminal alkenes.6 While we chose the Ru-1 catalyst for Z-
isomer selectivity, there have been no reports on a metathesis
catalyst suitable for E-isomer selectivity. We found through
FRET studies that the Ru-2 catalyst, which is the parent
complex of Ru-1, prefers E-alkene over Z-alkene. Regarding
RESULTS AND DISCUSSION
■
For the FRET studies, we prepared dapoxyl-conjugated Z- and
E-alkene substrates Z-ene and E-ene3d (Figure 1). The
fluorescence emission band of Z-ene and E-ene overlaps well
with the absorbance band of Ru-1 and Ru-2 in the solvents for
Ru-catalyzed metathesis reactions (see the Supporting In-
formation). The FRET studies were carried out with the
Received: May 27, 2016
© XXXX American Chemical Society
A
DOI: 10.1021/acs.joc.6b01276
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Figure 1. Determination of the preference of Ru-based metathesis
catalysts toward Z- and E-alkenes using the FRET-based method as a
guide to predict selective catalytic transformation of coexisting Z- and
E-alkenes. Ru-1 and Ru-2 have absorbance bands in the visible light
range with no fluorescence emission and thus can act as fluorescence
quenchers of dye-conjugated alkene substrates when Ru-substrate
complexes are formed. Measurement of fluorescence quenching as a
function of time can determine the kinetic and thermodynamic
preferences, k and ΔG, respectively, in the complex formation of a
catalyst−substrate pair.
Figure 2. Time-dependent fluorescence quenching of the dye-alkenes
Z-ene and E-ene due to the complex formation with (A) Ru-1 and
(B) Ru-2. Time-dependent fluorescence spectra (a−d for Ru-1 and e−
h for Ru-2) for each substrate−catalyst pair are shown above each
panel. Experimental data points are shown as black circles
(substrate:catalyst = 20:30 μM), and the theoretical curves from the
global fitting analysis are represented by red and green curves for Z-
ene and pink and blue curves for E-ene. The data points correspond to
the calibrated integrated values of the fluorescence spectra.
prepared dye-conjugated substrates and the catalysts. We
measured the time-dependent fluorescence quenching of pairs
of each of the two substrates (20 μM) and catalysts (30 μM)
over a period of 20 min. Because the solvent is an important
factor in both FRET studies and chemical reactions, pairs of
solvents CH2Cl2 and PhMe and PhMe and n-hexane for Ru-1
and Ru-2, respectively, were investigated. Note that we did not
consider that the altered Ru species, Ru ethylidene, plays any
particular role during measurement because the difference
between Ru benzylidene and ethylidene is not sufficiently
pronounced regarding the functionality preference of the
catalysts.3d Figure 2 shows the time-dependent fluorescence
spectra of each substrate for the two catalysts and the pairs of
solvents. The time-dependent fluorescence traces, representing
the integrated values of the corresponding fluorescence spectra,
calibrated for quenching via nonspecific complexation using the
control dapoxyl-conjugated alkane,3a are plotted in Figures 2A
and B. Both Figures 2A and B for Ru-1 and Ru-2, respectively,
clearly show the dependence of the fluorescence quenching rate
and amount on the substrate and solvent. While the
fluorescence quenching of Z-ene was more rapid and to a
higher degree than that of E-ene in the case of Ru-1, the
reverse was observed for Ru-2.
For a given substrate/catalyst pair, relative kinetic and
thermodynamic parameters k, k−1, and ΔG for the complex
formation between the catalyst and substrate were determined
by quantitatively analyzing the fluorescence quenching traces
with a set of parameters (Supporting Information). The results
are summarized in Table 1. The catalyst Ru-1 preferred Z-ene
over E-ene by 3.3-fold kinetically and 13-fold thermodynami-
cally in PhMe and 1.5-fold and 1.3-fold, respectively, in CH2Cl2.
On the other hand, the kinetic and thermodynamic preferences
of Ru-2 for E-ene were 2-fold and 4-fold higher in PhMe and 4-
fold and 4-fold higher in n-hexane, respectively, than those for
Z-ene. These results indicate that the complex formation of Ru-
1 with Z-ene or Ru-2 with E-ene is more favorable both
kinetically and thermodynamically than that with the other
stereoisomer along with the solvent effect in complex
formation. Owing to the reversible nature of the alkene-
coordinated ruthenium alkylidene intermediate, the thermody-
namic preference of Ru for Z/E-alkenes is more important than
the kinetic preference. Unlike in the case of Ru-1, the complex
formation of Ru-2 with both substrates in PhMe was more
rapid and more favorable than that in n-hexane. With regard to
ΔG, the Z-alkene selectivity of Ru-1 is much higher in PhMe
than in CH2Cl2 (ΔΔG 6.3 vs 1.7), while that of Ru-2 is similar
in both PhMe and n-hexane (ΔΔG 4.4 vs 4.5) in complex
formation.
To examine whether the preference of the catalyst is valid as
a selectivity guide toward each stereoisomer, we investigated
the correlation between the preference and reactivity of the
catalyst toward each stereoisomer. We prepared tosylamide
substrates possessing Z,Z- (ZZ-ene), Z,E- (ZE-ene), and E,E-
1,6-diene (EE-ene) with identical tether lengths for intra-
molecular olefin metathesis (Supporting Information) and
evaluated the reaction rates for the three substrates with the
two Ru catalysts.
We carried out intramolecular olefin metathesis reactions of
the three substrates using Ru-1 in CH2Cl2 and PhMe and Ru-2
in PhMe and n-hexane. The reactivity of Ru-1 with the internal
alkene was much lower than that of Ru-2, and the reaction
using Ru-1 in CH2Cl2 at reflux did not produce P,12 instead
leading to the recovery of intact diene substrates. At 100 °C in
B
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Table 1. Relative Kinetic and Thermodynamic Parameters for the Complex Formation by the Reaction of Ru with E/Z-Alkene
a
Substrates
catalyst
solvent
PhMe
substrate
k (M−1 s−1
)
k−1 (s−1
)
ΔG (kJ/mol)
Ru-1
Z-ene
E-ene
Z-ene
E-ene
Z-ene
E-ene
Z-ene
E-ene
5.51 0.15 × 103
1.68 0.07 × 103
5.62 0.19 × 103
3.63 0.24 × 103
2.88 0.13 × 103
5.88 0.17 × 103
9.77 0.46 × 102
3.97 0.67 × 103
2.68 0.33 × 10−2
1.07 0.41 × 10−1
1.35 0.07 × 10−1
1.17 0.17 × 10−1
1.63 0.26 × 10−1
8.29 0.04 × 10−2
1.11 0.15 × 10−1
1.09 0.12 × 10−1
−29.8 0.30
−23.5 0.93
−26.9 0.15
−25.2 0.39
−23.8 0.40
−27.2 0.07
−22.1 0.34
−25.6 0.45
CH2Cl2
PhMe
Ru-2
n-hexane
a
k and k−1 are directly determined as fitting parameters and ΔG is calculated as −RTln(k/k−1). k and ΔG represent the kinetic and thermodynamic
preferences, respectively.
PhMe, the reaction of ZZ-ene using Ru-1 (20 mol %) for 1 h
under Ar produced P in 20% yield, which was unchanged for a
longer period of reaction time, most likely because of catalyst
decomposition.8d Thus, for Ru-1, the reactions occurred for 1 h
at 100 °C in PhMe; both consumption of the substrate and
formation of the product were monitored over time to avoid
misinterpretation of the data. Despite low yields, it was clear
that the reaction rate was dependent on the substrate. The rate
order was ZZ-ene > ZE-ene > EE-ene for both substrate
consumption and product formation, which is in accordance
with the preference of Ru-1 for Z/E isomers. In the case of EE-
ene, the reaction did not proceed at all under the reaction
conditions. The difference between the substrate consumption
and the product formation was marginal; thus, only the product
formation was measured over the given time period (Figure 3).
Because the reaction of the diene substrates using Ru-2 was
much more rapid than that using Ru-1, the reaction was carried
out using 2 mol % Ru-2 at 0 °C in PhMe and n-hexane and
monitored for 2−3 h to obtain the rate of product formation.
The results indicated that the reaction with Ru-2 in PhMe was
more rapid than that in n-hexane; all of the three diene
substrates underwent P production with the rate order of EE-
ene > ZE-ene > ZZ-ene in both solvents. The higher reaction
rate in PhMe compared with that in n-hexane and the rate
order were also in agreement with the preference of Ru-2 for E-
alkene over Z-alkene, as shown in Table 1. For the catalyst/
substrate pairs, we obtained log plots of product versus time, all
of which were found to be linear (Figure 3).
From the slopes of these plots, the rate constants for the
catalyst/substrate pairs were determined, the results of which
are summarized in Table 2. The rate constants in Table 2
Table 2. Rate Constants for the Metathesis Reactions of the
a
Three Diene Substrates with Ru Catalysts
catalyst
solvent, T
substrate
k
Ru-1
PhMe, 100 °C
ZZ-1
ZE-1
EE-1
ZZ-1
ZE-1
EE-1
ZZ-1
ZE-1
EE-1
4.51 0.42 × 10−5
1.99 0.16 × 10−5
no reaction
9.49 0.45 × 10−5
1.47 0.05 × 10−4
2.24 0.16 × 10−4
6.14 0.57 × 10−5
8.54 1.06 × 10−5
1.28 0.15 × 10−4
Ru-2
PhMe, 0 °C
n-hexane, 0 °C
a
Rate constants were obtained from the slopes of log plots of product
concentration versus time.
indicate that Ru-1 is 2.3-fold more reactive toward ZZ-ene over
ZE-ene, and this k ratio is higher than that for Ru-2, which is
1.5-fold more reactive toward ZE-ene than ZZ-ene. The greater
k ratio for Ru-1 over Ru-2 (Table 2) is in accordance with the
higher preference of Ru-1 for Z-alkene over E-alkene than that
of Ru-2 for E-alkene over Z-alkene (Table 1). In the case of
Ru-2, the higher reaction rate in PhMe than that in n-hexane
correlates well with the more favorable complex formation of
Ru-2 in PhMe than in n-hexane. In these two solvents, all k
ratios between the three diene substrates are similar (k ratios =
∼1.5), which would be attributable to almost the same ΔΔG
between the Z/E-alkenes in both solvents (ΔΔG = ∼4). These
results are in agreement with previously reported computa-
Figure 3. Log plots of product concentration versus time for
metathesis reactions of ZZ-ene, ZE-ene, and EE-ene with Ru-1 and
Ru-2. Reactions with Ru-1 in CH2Cl2 (A) and PhMe (B). Reactions
with Ru-2 in PhMe (C) and in n-hexane (D). Symbols represent ZZ-
ene ( ), ZE-ene ( ), and EE-ene ( ). Reaction conditions:
substrate (150 mg, 0.535 mmol) and Ru-1 (20 mol %) in CH2Cl2
(5.35 mL) at reflux (A) and PhMe at 100 °C (B). Substrate (150 mg,
0.535 mmol) and Ru-2 (2 mol %) in PhMe (5.35 mL) at 0 °C (C)
and n-hexane (5.35 mL) at 0 °C (D). All reactions were carried out
under Ar, and the product concentrations were obtained based on the
isolated product.
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slowly added LiHMDS (1.0 M in THF, 1.20 mL, 1.20 mmol) at −78
°C, and the mixture was stirred for 30 min. After addition of MeI
(0.080 mL, 1.28 mmol) at 0 °C, the resulting mixture was allowed to
warm to room temperature and stirred for 3 h. Saturated aqueous
NH4Cl (10 mL) was added, and the mixture was extracted with Et2O
(10 mL × 3). The combined organic layer was washed with brine (5
mL), dried over MgSO4, filtered, and concentrated under reduced
pressure. The crude product was purified by silica gel column
chromatography (n-hexane:EtOAc = 3:1 v/v) to give N,N-di(but-2-yn-
tional studies describing that the energy of the rate-determining
transition state for trisubstituted ruthenacyclobutane formation
is higher for the Ru-1/E-alkene pair than that for the Ru-1/Z-
alkene pair due to the steric repulsion between the N-mesityl
group and at least one substituent in the transition state for the
Ru-1/E-alkene pair.6b This steric interaction in the side-bound
mechanism9e,13 could confer more differentiation in the
preference of Ru-1 between Z/E-isomers than that of Ru-2,
catalyzing via the bottom-bound mechanism.14 Overall, our
results indicate that the preference of a metathesis Ru catalyst
for an alkene stereoisomer over the other stereoisomer,
determined by the FRET-based method, dictates the Z/E
isomeric selectivity in the olefin metathesis reactions of diene
substrates possessing combinations of Z/E-alkenes.
1-yl)-4-methylbenzenesulfonamide16 (134 mg, 84%): H NMR (300
1
MHz, CDCl3) δ 7.71 (d, J = 8.0 Hz, 2H), 7.28 (d, J = 8.2 Hz, 2H),
4.06 (m, 4H), 2.40 (s, 3H), 1.63 (s, 6H); 13C NMR (150 MHz,
CDCl3): δ 150.4, 144.0, 129.1, 128.1, 81.7, 74.2, 36.2, 21.5, 3.41. To a
solution of N,N-di(but-2-yn-1-yl)-4-methylbenzenesulfonamide (100
mg, 0.363 mmol) in EtOAc (10 mL) was added 5% Pd on CaCO3 (50
mg), and the resulting suspension was stirred overnight under H2 at
room temperature. The mixture was filtered through Celite and
concentrated under reduced pressure. The residue was purified by
silica gel column chromatography (n-hexane:EtOAc = 20:1 v/v) to
give ZZ-ene (75 mg, 76%): 1H NMR (300 MHz, CDCl3): δ 7.72 (d, J
= 7.8 Hz, 2H), 7.31 (d, J = 7.8 Hz, 2H), 5.59 (m, 2H), 5.28 (m, 2H,),
3.86 (, d, J = 6.7 Hz, 4H), 2.45 (s, 3H), 1.61 (d, J = 6.8 Hz, 6H,); 13C
NMR (150 MHz, CDCl3): δ 143.4, 137.7, 129.9, 128.6, 127.4, 125.2,
43.4, 21.7, 13.0; IR (film): cm−1 3027, 2966, 2931, 2873, 1597, 1458,
1030, 891, 771, 690, 451; HRMS (ESI) (m/z): calcd for
C15H21NNaO2S [M + Na]+ 302.1191, found 302.1189.
CONCLUSION
■
In summary, we determined the relative Z/E-alkene preference
of metathesis Ru catalysts using time-dependent fluorescence
quenching as a guide for a selective reaction toward either Z- or
E-alkene in Ru alkylidene-catalyzed metathesis. We found that
Ru-1 prefers the Z-isomer over the E-isomer, whereas Ru-2
prefers the E-isomer over the Z-isomer. The Z/E-alkene
preference of the catalysts correlated well with the Z/E isomeric
selectivity in the olefin metathesis reactions of the diene
substrates possessing combinations of Z/E-alkenes. The
correlation indicates that the preference of a Ru catalyst for
an internal alkene over the other stereoisomer would direct the
Z/E isomeric selectivity in the olefin metathesis reactions of
diene substrates. The results demonstrate that a guide for the
selectivity of Ru alkylidene-catalyzed metathesis toward either
Z- or E-alkene can be obtained using time-dependent
fluorescence quenching.
Synthesis of EE-ene. To a solution of TsNH2 (250 mg, 1.45
mmol) in DMF (5 mL) was added NaH (60% in mineral oil, 132 mg,
3.19 mmol) at 0 °C, and the mixture was stirred for 10 min. To the
mixture was added trans-crotyl bromide (85%, 0.33 mL, 3.19 mmol),
and the resulting mixture was allowed to warm to room temperature
and stirred for 4 h. Saturated aqueous NH4Cl (15 mL) was added, and
the mixture was extracted with Et2O (20 mL × 3). The combined
organic layer was washed with brine (10 mL), dried over MgSO4,
filtered, and concentrated under reduced pressure. The crude product
was purified by silica gel column chromatography (n-hexane:EtOAc =
1
20:1 v/v) to afford EE-ene (240 mg, 60%): H NMR (300 MHz,
EXPERIMENTAL SECTION
CDCl3): δ 7.69 (d, J = 8.0 Hz, 2H), 7.29 (d, J = 8.0 Hz, 2H), 5.56 (m,
2H,), 5.24 (m, 2H,), 3.73 (d, J = 6.6 Hz, 4H), 2.43 (s, 3H), 1.63 (d, J =
6.5 Hz, 6H); 13C NMR (150 MHz, CDCl3): δ 142.9, 137.8, 130.2,
129.5, 127.2, 125.5, 48.4,21.5, 17.6; IR (film): cm−1 3024, 2924, 2862,
1666, 1442, 1338, 1249, 1157, 1092, 1045, 879, 702; HRMS (ESI)
(m/z): calcd for C15H21NNaO2S [M + Na]+ 302.1191, found
302.1181.
■
General. Common solvents were purified before use. Tetrahy-
drofuran and dichloromethane were purified by distillation from
sodium-benzophenone and calcium hydride, respectively. Anhydrous
acetone, N,N-dimethylformamide, acetonitrile, ethyl acetate, and
triethylamine were used as received. All reagents were reagent grade
and purified where necessary. “Water” refers to distilled water.
Reactions were monitored by thin layer chromatography (TLC) using
silica gel plates. Flash column chromatography was performed over
Synthesis of ZE-ene. To a solution of p-toluenesulfonamide (500
mg, 2.92 mmol), DMAP (70 mg, 0.58 mmol), and (Boc)2O (703 mg,
3.21 mmol) in CH2Cl2 (6 mL) was added Et3N (0. 485 mL, 3.50
mmol), and the mixture was stirred overnight at room temperature. At
0 °C, 1.0 M aqueous HCl (5 mL) was added, and the mixture was
extracted with EtOAc (10 mL × 3). The combined organic layer was
washed with saturated aqueous NaHCO3 (5 mL), brine (5 mL), dried
over MgSO4, filtered, and concentrated under reduced pressure. The
crude product was purified by silica gel column chromatography (n-
hexane:EtOAc = 1:1 v/v) to afford tert-butyl prop-2-yn-1-ylcarba-
ultrapure silica gel (230−400 mesh). H NMR and 13C NMR spectra
1
were recorded on a 300 or 600 MHz spectrometer using residual
solvent peaks as an internal standard (CHCl3: δ 7.24 ppm for proton
and δ 77.0 ppm for carbon). Multiplicities for 1H NMR are designated
as s = singlet, d = doublet, dd = doublet of doublets, t = triplet, q =
quartet, m = multiplet, and bs = broad singlet. Infrared spectra (IR)
were recorded on an FT-IR spectrometer and are reported in
reciprocal centimeters (cm−1). UV−visible spectra were recorded on a
UV−visible spectrophotometer. High-resolution mass spectra
(HRMS) were obtained on a TOF-Q instrument.
mate17 (825 mg, 98%): H NMR (300 MHz, CDCl3): δ 7.95 (d, J =
1
8.0 Hz, 2 H), 7.34 (d, J = 8.0 Hz, 2 H), 2.45 (s, 3 H), 1.40 (s, 9 H);
13C NMR (75 MHz, CDCl3): δ 149.2, 144.8, 136.0, 129.6, 128.3, 84.2,
28.0, 21.8. To a mixture of tert-butyl prop-2-yn-1-ylcarbamate (500
mg, 1.84 mmol), PPh3 (483 mg, 1.84 mmol), and propargyl alcohol
(0.112 mL, 1.84 mmol) in THF (18 mL) was slowly added DEAD (40
w% in PhMe, 0.84 mL, 1.84 mmol) at 0 °C, and the reaction mixture
was stirred for 3 h at room temperature. Water (10 mL) was added,
and the mixture was extracted with EtOAc (15 mL × 3). The
combined organic layer was washed with brine (5 mL), dried over
MgSO4, filtered, and concentrated. The crude product was purified by
silica gel column chromatography (n-hexane:EtOAc = 10:1 v/v) to
Synthesis of ZZ-ene. To a mixture of p-toluenesulfonamide (100
mg, 0.582 mmol) and K2CO3 (241 mg, 1.75 mmol) in acetone (6 mL)
was added propargyl bromide (0.125 mL, 1.46 mmol), and the
reaction mixture was refluxed overnight. The mixture was concen-
trated under reduced pressure, diluted with Et2O (30 mL), washed
with brine (5 mL), dried over MgSO4, filtered, and concentrated under
reduced pressure. The crude product was purified by silica gel column
chromatography (n-hexane:EtOAc = 3:1 v/v) to give 4-methyl-N,N-
di(prop-2-yn-1-yl)benzenesulfonamide15 (142.9 mg, 99%): H NMR
1
(300 MHz, CDCl3): δ 7.71 (d, J = 7.8 Hz, 2H), 7.30 (d, J = 7.8 Hz,
2H), 4.16 (d, J = 2.7 Hz, 4H), 2.42 (s, 3H), 2.14 (t, J = 2.7 Hz, 2H);
13C NMR (CDCl3, 150 MHz): δ 21.6, 36.2, 74.4 76.2, 128.2, 129.2,
136.9, 144.2. To a solution of 4-methyl-N,N-di(prop-2-yn-1-yl)-
benzenesulfonamide (142.9 mg, 0.578 mmol) in THF (6 mL) was
afford tert-butyl prop-2-yn-1-yl(tosyl)carbamate18 (430 mg, 76%): H
1
NMR (300 MHz, CDCl3): δ 1.34 (s, 9H), 2.31 (t, J = 2.3 Hz, 1H),
2.44 (s, 3H), 4.62 (d, J = 2.3 Hz, 2H), 7.31 (d, J = 8.0 Hz, 2H) and
7.91 (d, J = 8.0 Hz, 2H); 13C NMR (75 MHz, CDCl3): δ 150.3, 144.3,
D
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136.7, 129.0, 128.2, 84.7, 79.0, 74.0, 36.0, 27.8, 21.6. To a solution of
tert-butyl prop-2-yn-1-yl(tosyl)carbamate (400 mg, 1.30 mmol) in
THF (2.5 mL) was added LiHMDS (1.0 M in THF, 1.3 mL, 1.3
mmol), and the mixture was stirred for 30 min at −78 °C. After
addition of MeI (0.81 mL, 1.3 mmol), the reaction mixture was
allowed to warm to room temperature and stirred for 3 h. Saturated
aqueous NH4Cl (10 mL) was added, and the mixture was extracted
with Et2O (15 mL × 3). The combined organic layer was washed with
brine (10 mL), dried over MgSO4, filtered, and concentrated under the
reduced pressure. The crude product was purified by silica gel column
chromatography (n-hexane:EtOAc = 3:1 v/v) to give tert-butyl but-2-
yn-1-yl(tosyl)carbamate19 (394 mg, 94%): 1H NMR (300 MHz,
CDCl3): δ 7.92 (d, J = 8.3 Hz, 2H), 7.32 (d, J = 8.2 Hz, 2H), 4.58 (q, J
= 2.2 Hz, 2H), 2.45 (s, 3H), 1.84 (t, J = 2.3 Hz, 3H), 1.35 (s, 9H). 13C
NMR (150 MHz, CDCl3): 150.4, 144.2, 136.9, 129.1, 128.2, 84.6,
79.9, 74.3, 36.3, 27.8, 21.6. To a solution of tert-butyl but-2-yn-1-
yl(tosyl)carbamate (394 mg, 1.22 mmol) in EtOAc (15 mL) was
added 5% Pd on CaCO3 (118 mg), and the resulting suspension was
stirred overnight under H2 at room temperature. The mixture was
filtered through Celite and concentrated under reduced pressure. The
residue was purified by silica gel column chromatography (n-
hexane:EtOAc = 20:1 v/v) to give (Z)-tert-butyl but-2-en-1-yl(tosyl)-
carbamate19 (237 mg 60%): 1H NMR (300 MHz, CDCl3): δ 7.80 (d, J
= 8.0 Hz, 2H), 7.29 (d, J = 8.0 Hz, 2H), 5.68 (m, 1H), 5.53 (m, 1H),
4.51 (d, J = 6.7 Hz, 2H), 2.43 (s, 3H), 1.77 (d, J = 6.8 Hz, 3H), 1.34
(s, 9H); 13C NMR (150 MHz, CDCl3): δ 150.7, 144.0, 137.2, 129.2,
128.1, 127.0, 125.6, 84.2, 43.5, 27.7, 21.5, 13.3. To a solution of (Z)-
tert-butyl but-2-en-1-yl(tosyl)carbamate (237 mg, 0.732 mmol) in
CH2Cl2 (3 mL) was added CF3CO2H (1 mL) at 0 °C, and the
reaction mixture was allowed to warm to room temperature and stirred
for 2 h. The mixture was concentrated under reduced pressure and
dissolved in CH2Cl2 (20 mL). The solution was washed with saturated
aqueous NaHCO3 (5 mL) and brine (5 mL), dried over MgSO4,
filtered, and concentrated. The residue was purified by silica gel
column chromatography (n-hexane:EtOAc = 1:1 v/v) to afford (Z)-N-
(but-2-en-1-yl)-4-methylbenzenesulfonamide19 (159 mg, 97%): 1H
NMR (300 MHz, CDCl3): δ 7.75 (d, J = 8.0 Hz, 2H), 7.29 (d, J = 8.0
Hz, 2H), 5.52 (m, 1H), 5.29 (m, 1H), 5.13 (bs, 1H), 3.60 (m, 2H),
2.43 (s, 3H), 1.54 (d, J = 6.8 Hz, 3H); 13C NMR (150 MHz, CDCl3):
δ 143.2, 136.4, 128.7, 127.8, 126.7, 124.6, 39.5, 20.5, 12.6. To a
suspension of NaH (60% in mineral oil, 32 mg, 0.78 mmol) in DMF
(0.5 mL) was added a solution of the Boc-deprotected compound
(159 mg, 0.71 mmol) in DMF (1.5 mL) at 0 °C, and the mixture was
stirred for 10 min. To the mixture was added trans-crotyl bromide
(85%, 0.105 mL, 0.78 mmol), and the resulting mixture was allowed to
warm to room temperature and stirred for 4 h. After addition of
saturated aqueous NH4Cl (5 mL) at 0 °C, the mixture was extracted
with Et2O (10 mL × 3). The combined organic layer was washed with
brine (5 mL), dried over MgSO4, filtered, and concentrated. The
residue was purified by silica gel column chromatography (n-
hexane:EtOAc = 10:1 v/v) to give ZE-ene (188 mg, 95%): 1H
NMR (300 MHz, CDCl3): δ 7.72 (d, J = 8.1 Hz, 2H), 7.31 (d, J = 8.0
Hz, 2H), 5.56 (m, 2H,), 5.28 (m, 2H,), 3.85 (d, J = 6.4 Hz, 2H), 3.74
(d, J = 6.5 Hz, 2H), 2.43 (s, 3H), 1.65 (d, J = 6.4 Hz, 3H), 1.60 (d, J =
6.6 Hz, 3H); 13C NMR (150 MHz, CDCl3): δ 143.3, 137.9, 130.6,
129.9, 128.6, 128.4, 127.5, 125.8, 125.3, 125.2, 49.1, 43.1, 21.8, 18.0,
13.1; IR (film): cm−1 3023, 2923, 2861, 1728, 1662, 1596, 1492, 1342,
933, 821, 724; HRMS (ESI) (m/z): calcd for C15H21NNaO2S [M +
Na]+ 302.1191, found 302.1185.
were obtained as a function of time. The area of the fluorescence
curve, designated the fluorescence intensity, was calculated.
ASSOCIATED CONTENT
* Supporting Information
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.joc.6b01276.
■
S
UV−vis spectra of Ru catalysts, and fluorescence spectra
of substrates, global fitting analysis of FRET data, and 1H
and 13C NMR spectra of new compounds and their
intermediates (PDF)
AUTHOR INFORMATION
Corresponding Authors
*E-mail: sohnjh@cnu.ac.kr.
*E-mail: hyotcherl.ihee@kaist.ac.kr.
■
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
This work was supported by the NRF (Grants
2 0 1 4 R 1 A 1 A 4 A 0 1 0 0 7 9 3 3 , 2 0 1 1 0 0 2 9 1 9 4 , a n d
2016R1A2A1A05005509), the research fund of Chungnam
National University, and IBS-R004-G2.
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