Efficiency Enhancement of a Photocatalytic Decarbonylation of an Aminocyclopropenone by Benzothiophene Substitution

Article abstract of DOI:10.1021/acs.joc.0c02997

To improve the efficiency of the photocatalytic decarbonylation of cyclopropenones, the effects of substituents on cyclopropenone were explored. A benzothiophene-substituted aminocyclopropenone exhibited significantly improved decarbonylation efficiency t

Full text of DOI:10.1021/acs.joc.0c02997

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Efficiency Enhancement of a Photocatalytic Decarbonylation of an
Aminocyclopropenone by Benzothiophene Substitution
Kenji Mishiro,* Mitsuki Nomura, Taniyuki Furuyama, and Munetaka Kunishima*
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ABSTRACT: To improve the efficiency of the photocatalytic decarbon-
ylation of cyclopropenones, the effects of substituents on cyclopropenone
were explored. A benzothiophene-substituted aminocyclopropenone ex-
hibited significantly improved decarbonylation efficiency to produce the
corresponding ynamine, which worked as a potent dehydration condensation
agent. The benzothiophene derivative was applicable to the photocatalytic
reaction in the presence of potential excited-state quenchers such as oxygen
and anilines. The high catalyst sensitivity would be attributed to the involvement of triplet energy transfer reaction pathway, which
was not observed in the reaction with previously reported aminocyclopropenones.
explored a photocatalytic method to generate alkynes and
achieved phototriggered uncaging of visible-light-stable cyclo-
propenones using a photocatalyst under visible-light con-
ditions.10 In the reactions, highly reactive ynamine and
cyclooctyne were generated from the corresponding cyclo-
propenones and the resulting active alkynes were used without
isolation in subsequent reactions, such as dehydration
condensation11 and alkyne−azide click chemistry.8 In our
previous report, we demonstrated that a UV-sensitive
tetrazole12 can tolerate the photocatalyst/visible-light con-
ditions for the photolysis of cyclopropenones. Compared with
the direct excitation method, the photocatalytic approach
offers a series of advantages, including the use of cheap and
safe visible light and applicability to UV-sensitive substrates
(Scheme 1).
INTRODUCTION
■
Photochemical transformations have been used widely for the
in situ generation of highly reactive species, such as carbene
and radicals, from stable precursors. In addition, photo-
chemical reactions play an important role in the in vivo
generation of bioactive compounds in a space- and time-
controlled manner.1 Photolabile precursors are generally called
“photocaged molecules”. In most cases, the photolysis of a
photocaged molecule occurs by direct photoexcitation. For the
photochemical uncaging reaction, long-wavelength light such
as visible light is desirable because it does not decompose
ultraviolet (UV)-sensitive molecules within the irradiated area.
In contrast, a photocaged molecule sensitive to visible light
could undergo undesired decomposition under ambient light
conditions.
Photocatalytic reactions can overcome the reactivity−
stability dilemma of the photocaged molecules. In some
photochemical reactions such as nitrene generation from
azide2 and ring-opening cycloaddition of azirine,3 direct
photoexcitation and photocatalysis conditions yield identical
products. In many cases, the photocatalytic reaction can be
performed under light irradiation with a longer wavelength
than that of direct substrate excitation conditions. Therefore,
using a visible-light-responsive photocatalyst, a visible-light
stable photocaged molecule could be uncaged under visible-
light conditions.
When a photocatalytic reaction is performed, undesired
quenching of the excited photocatalyst by coexisting redox-
sensitive molecules or oxygen could be a major problem.13
A
scheme of the previously developed photocatalytic dehydration
condensation is shown in Scheme 2a. First, aminocycloprope-
none 1a is photolyzed under photocatalyst/visible-light
conditions to give the corresponding ynamine 2a. The
ynamine reacts with carboxylic acid 3 to produce acyloxyen-
amine 4, which is aminolyzed with amine 5 to produce amide 6
and hydrated ynamine 7.14 The reaction proceeded efficiently
for monoalkyl amines such as 2-phenylethylamine and dialkyl
amines such as diethylamine. In contrast, the photolysis of
Cyclopropenone is a strained cyclic enone that releases the
ring strain on photoexcitation to produce an alkyne and one
molecule of carbon monoxide; hence, cyclopropenones are
regarded as photocaged alkynes.4 Owing to the unique
chemical reactivity of alkynes, such as ynamine,5 ynamide,6
ynol ether,7 and cyclooctyne,8 and the numerous reports on
bioactive alkynes,9 photochemical alkyne generation has a
versatile potential for chemical and biological applications. To
extend the versatility of photolytic alkyne generation, we
Received: December 22, 2020
Published: February 8, 2021
https://dx.doi.org/10.1021/acs.joc.0c02997
© 2021 American Chemical Society
J. Org. Chem. 2021, 86, 3625−3636
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Scheme 1. Phototriggered Active Alkyne Generation
Reactions
Table 1. Substituent Effect of the Aromatic Group
Scheme 2. Photocatalytic Dehydration Condensation
Reaction
aminocyclopropenone 1a was disturbed significantly when
aromatic amines such as aniline were employed. The
condensation reaction with aniline resulted in a low amide
yield (12%), and >70% of 1a remained intact after 24 h of
irradiation. According to the correlation of the reaction
outcome and the redox potential of the screened catalysts,
redox processes are probably involved in the photocatalytic
ynamine generation. Therefore, we hypothesized that the
efficiency of the photocatalytic reaction could be improved by
optimizing the aminocyclopropenone substituents, with an
influence on the redox properties of the aminocycloprope-
nones.15 In this paper, we examine the effect of amino-
cyclopropenone substituents on the efficiency of the photo-
catalytic decarbonylation and demonstrate the photocatalytic
uncaging of aminocyclopropenone in the presence of potential
excited-state quenchers (Scheme 2b).
a
b
NMR yield. Without thioxanthone (8).
related to the typical substituent parameters, such as the
Hammett constant. Then, other aromatic rings were explored.
Naphthyl cyclopropenone 1f exhibited a significantly lower
efficiency. The efficiency of thiophen-2-yl cyclopropenone 1g
was similar to that of 1a, whereas that of thiophene-3-yl
cyclopropenone 1h was slightly better. A remarkable difference
was observed for benzothiophene-substituted cyclopropenones
depending on the benzothiophene substitution position.
Benzothiophene-2-yl cyclopropenone 1i exhibited low effi-
ciency, whereas benzothiophene-3-yl cyclopropenone 1j
exhibited high efficiency. Among all of the screened cyclo-
propenones, 1j exhibited the fastest cyclopropenone con-
sumption and the highest yield of amide 6aa. As 1j was not
photolyzed in the absence of photocatalyst 8, the high reaction
efficiency with 1j is most likely because of its high sensitivity
toward the photocatalyst. In the reaction with 1j, ynamine-
derived product 7j was detected in 36% yield, suggesting the
dehydration condensation was caused by an ynamine
generated from 1j in situ.
RESULTS AND DISCUSSION
■
We explored the effect of aminocyclopropenone substituents
on our previously developed photocatalytic dehydration
condensation. A mixture of cyclopropenone 1, carboxylic
acid 3a, amine 5a, and thioxanthone (8) in CH2Cl2 was
irradiated with a household fluorescent lamp under a nitrogen
atmosphere. After 3 h, the yields of amide 6aa and recovered 1
1
were analyzed by H NMR (Table 1). First, the aromatic
substituents were investigated. Diisopropylamino group was
selected as the amino substituent because it afforded the best
results in the phototriggered dehydration condensation in our
previous study.14 The effect of substituents on the phenyl
group was studied with 2,4-disubstituted phenyl cyclo-
propenones 1b−e because of their synthetic accessibility.
Dimethyl-substituted 1c and difluoro-substituted 1d exhibited
slightly faster photolysis and a higher amide yield, although the
effect was not substantial. Overall, the result was not simply
Next, the substituent effect of the amino group was explored
(Table 2). The rate of the aminocyclopropenone decarbon-
ylation was not affected significantly by the substituents on the
amino group. In the reaction, the amide yields represent the
dehydration condensation reactivity of the ynamines generated
from the corresponding aminocyclopropenones.14 Acetamido-
substituted cyclopropenone 1m gave the corresponding
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having various substituents to give the corresponding anilides
in yields of 50−73% (Scheme 4). The result can be attributed
to the high photocatalyst sensitivity of 1j compared with that
of 1a.
Table 2. Substituent Effect of the Amino Group
Scheme 4. Photocatalytic Dehydration Condensation of
Carboxylic Acids and Aniline Derivatives
a
a
entry
NR1R2
6aa yield (%)
1 recovery (%)
1
2
3
NMePh (1k)
NPh2 (1l)
NiPrAc (1m)
13
9
0
51
65
71
a
NMR yield.
ynamide at a 17% yield; however, dehydration condensation
did not undergo with 1m because the ynamide was virtually
inactive under the reaction conditions. Considering the
photolysis efficiency and the reactivity of the produced
ynamine, it can be concluded that the dialkylamino group
would afford the best results in the photocatalytic dehydration
condensation reaction.
A screening of substrates for the phototriggered dehydration
condensation with 1j was then performed. A mixture of
cyclopropenone 1j, carboxylic acid 3, and amine 5 in CH2Cl2
was irradiated with visible light under a nitrogen atmosphere
until 1j disappeared, and the yield of amide 6 was analyzed.
From the comparison with the result reported previously for 1a
(Scheme 3), we found that 1j exhibited faster photolysis and
gave better yields for all of the substrates.
Cyclopropenone 1j was especially effective in the reaction
with aniline derivatives. The phototriggered dehydration
condensation with 1a was inefficient for the condensation of
a carboxylic acid and an aniline, presumably because aniline
quenched the excited photocatalyst.16 Meanwhile, the photo-
catalytic reactions with 1j proceeded effectively for anilines
a
b
c
From previous report.10 NMR yield. Isolated yield.
Remarkably, even under an oxygen atmosphere, the
photocatalytic dehydration condensation of 3a and 5a using
1j proceeded to give 6aa in 78% yield, while the reaction using
1a afforded the product 6aa only in 54% yield in the same
reaction time (Table 3). Although the reaction rate decreased
Table 3. Photocatalytic Dehydration Condensation under
Oxygen Atmosphere
Scheme 3. Substrate Scope of the Photocatalytic
Dehydration Condensation
a
a
entry
1
6aa yield (%)
7 yield (%)
1
2
1a
1j
54
78
37
69
a
Isolated yield.
compared with the reaction under a nitrogen atmosphere, this
result is indicative of the robustness of the reaction with 1j
against excited-state quenchers of the photocatalyst.
To provide a comparison of the reactivity of amino-
cyclopropenone under photocatalyst and direct excitation
conditions, the phototriggered dehydration condensation
with 1j was performed under direct excitation conditions
with UV light (280−350 nm) (Table 4). Under direct
excitation conditions, phenyl-substituted 1a was photolyzed
in 3 h and the amide yield was 78%. Under the same UV
conditions, the reaction with 1j required 7 h to consume 1j
completely, and 6aa was obtained in an 84% yield. The
different extinction coefficients (ε) of the cyclopropenones
hinder precise comparisons of the photosensitivity under direct
irradiation conditions. Nevertheless, the results under the UV
a
b
c
From previous report.10 NMR yield. Isolated yield.
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condensation with 1j (entries 4 and 8). Because the recovery
of 1j was not quantitative in the reaction with 12, 12 might
decompose 1j to a nonynamine product.
Table 4. Phototriggered Dehydration Condensation with
Direct Excitation Conditions
The physical properties of the screened photocatalysts are
summarized in Table 6. Overall, 1j exhibited higher reactivity
a
Table 6. Physical Properties of the Photocatalyst 8−12
ET
Ered (C/C•−
)
Ered* (C*/C•−
)
a
a
entry
1
reaction time (h)
6aa yield (%)
1 recovery (%)
cat.
(kcal/mol)
(V)
(V)
ref
1
2
1a
1j
3
7
78
84
0
0
8
9
10
11
12
63.4
61.8
58.1
49.2
−1.62
−1.37
−2.19
−1.51
−0.57
+1.22
+1.21
+0.31
+0.66
+2.06
17 and 18
17 and 19
17 and 19
17 and 19
20
a
NMR Yield.
conditions suggest that the reactivity of cyclopropenones under
the photocatalyst conditions is totally different from that under
direct excitation conditions.
The reactivities of 1a and 1j were examined using other
photocatalysts (Table 5). Ir[dF(CF3)ppy]2(dtbbpy)PF6 (9)
a
Previously reported data in the literature. Ered and Ered* are versus
saturated calomel electrode (SCE). Measurements were performed in
MeCN. C: ground-state catalyst. C*: excited-state catalyst. C•−: one-
electron reduced catalyst.
against a catalyst with higher triplet energy (ET), whereas the
reactivity of 1a correlated with reduction potentials (Ered (C/
C•−) and Ered* (C*/C•−)) of the catalyst. These results
suggest triplet sensitization mechanism is dominant for 1j,
whereas the redox mechanism is dominant for 1a as we
reported previously. The plausible mechanisms are shown in
Scheme 5. Scheme 5a depicts redox-mediated mechanism.
Table 5. Phototriggered Dehydration Condensation with
Various Photocatalysts
Scheme 5. Proposed Mechanisms
First, an excited photocatalyst receives one electron from
cyclopropenone A to give cyclopropenium radical cation B.
After the oxidation, the three-membered ring of B is opened to
form intermediate C. In mechanism (I), C is reduced to obtain
D by the reduced-state photocatalyst and subsequent
decarbonylation gives ynamine E. In mechanism (II), the
decarbonylation of intermediate C gives a ketene iminium
radical cation F. The one-electron reduction of F by the
reduced-state photocatalyst gives the ynamine E. For efficient
photoredox process, the oxidizing activity of excited-state
catalyst (C*) and the reducing activity of one electron reduced
catalyst (C•−) need to be sufficiently high. In contrast, in the
triplet sensitization mechanism (Scheme 5b), cyclopropenone
is excited to a triplet excited state and subsequent decarbon-
ylation occurs to produce a corresponding ynamine.
catalyzed the reaction with 1j efficiently, and the efficiency was
much higher than that with 1a (entries 1 and 5). Ir(ppy)3 (10)
and Ir(ppy)2(dtbbpy)PF6 (11), which were virtually inactive
against 1a catalyzed the reaction of 1j, and 10 showed a higher
efficiency than 11 (entries 2, 3, 6, and 7). In contrast, (Mes-
Acr)ClO4, (12) which showed a moderate dehydration
condensation activity with 1a did not catalyze the dehydration
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To gain further mechanistic insight into the photocatalytic
reaction, a Stern−Volmer fluorescence-quenching experiment
and a cyclic voltammetry (CV) experiment were performed for
1a and 1j (Figure 1). In the fluorescence-quenching experi-
scope of the photocatalytic alkyne generation reactions in the
presence of potential photocatalyst quenchers. The mecha-
nistic switching phenomenon between triplet energy transfer
and electron transfer is reported previously;21 however, it has
not been commonly applied to organic reactions. As seen in
our reactions, switching of the mechanism could be an effective
strategy for the efficiency improvement of photocatalytic
reactions.
EXPERIMENTAL SECTION
■
General Information. All reactions were performed under air,
unless otherwise noted. A 20 W household fluorescent lamp
(Panasonic) was used for visible light (400−750 nm) conditions. A
6 W handheld UV lamp (FUNAKOSHI UVM-57) was used for UVB
(280−350 nm) conditions. A 1.656 W blue light-emitting diode
(LED) lamp (ASONE HL-24) was used for blue light (450−500 nm)
conditions. All solvents and commercial reagents were used as
provided. Aminocyclopropenones 1a, 1f, 1k, and 1m were synthesized
according to reported procedures.14,22 For aminocyclopropenone 1l,
previously synthesized material was used. SiO2 column chromatog-
raphy was performed employing Kanto Chemical Silica Gel 60 N
(spherical, neutral, 40−100 mesh). Thin-layer chromatography
(TLC) was performed on silica gel 60 F254 plates. 1H and 13C
NMR were recorded on JEOL JNM-ECS400 (400 MHz) and JNM-
Figure 1. Stern−Volmer plot with [Ir(dFCF3ppy)2dtbbpy]PF6 (9):
(a) 1a as a quencher and (b) 1j as a quencher.
ment, the quenching rate of catalyst 9 with 1j (Stern−Volmer
constant (KSV) = 0.813 mM−1) was much higher than that with
1a (KSV = 0.0049 mM−1). The higher KSV value could be
attributed to the higher reaction efficiency of 1j than that of 1a.
In the CV experiment, 1j showed irreversible oxidation peak
at 1.5 V, which is lower than that of 1a (1.68 V) (Figure 2).
1
ECS600 (600 MHz) spectrometers as noted. Data for H NMR are
reported as follows: chemical shift (δ ppm), multiplicity (s = singlet,
br s = broad singlet, d = doublet, t = triplet, q = quartet, qt = quintet,
sx = sextet, sep = septet, m = multiplet), coupling constant (Hz),
integration, and assignment. Data for 13C NMR are reported in terms
1
of chemical shift. For H NMR, chemical shifts were reported as δ
values relative to tetramethylsilane (0 ppm) as an internal standard.
For 13C NMR, chemical shifts were calibrated against solvent peaks in
CDCl3 (77.00 ppm). UV spectra were recorded on a Shimadzu UV-
2400PC spectrophotometer. Fluorescence spectra were recorded on a
JASCO FP-6500. Mass spectrometry was performed on a JEOL JMS-
T100TD (direct analysis in real time (DART)-time-of-flight (TOF)).
Synthesis of 1a. To a stirred solution of AlCl3 (2.2 g, 16.4 mmol)
in MeNO2 (2.5 mL), tetrachlorocyclopropene (0.5 mL, 4.10 mmol)
was added at 0 °C under N2 atmosphere. After 20 min, to the mixture,
a solution of benzene (360 μL, 4.02 mmol) in dichloromethane
(DCM) (4.0 mL) was added over 10 min. After stirring for 2 h at 0
°C, the mixture was quenched with ice-cooled water (12 mL). The
DCM phase was separated, and aqueous phase was extracted with
DCM (5 mL × 3). Combined DCM phase was dried over Na2SO4,
filtered, and concentrated in vacuo. The residue was dissolved in
acetone/water (7.5/2.5 mL) at 0 °C and stirred for 40 min. After
reaction completion, the mixture was diluted with DCM (20 mL).
The DCM phase was separated and aqueous phase was extracted with
DCM (10 mL × 3). Combined DCM phase was dried over Na2SO4,
filtered, and concentrated in vacuo to give 2-chloro-3-phenyl-
cycloprop-2-en-1-one (14a) as a yellow oil (652.6 mg). Purity of
14a was determined to be 68 wt % by quantitative NMR (qNMR)
with 1,3,5-trimethoxybenzene as an internal standard (chemical yield
of 14a = 40% over two steps). 14a was used in the next step without
further purification.
Figure 2. Cyclic voltammogram of 1a and 1j. Solvent = MeCN.
[analyte] = 10 mM. Supporting electrolyte = 0.1 M [nBu4N][PF6].
Scan rate = 100 mV/s. The potential was calibrated with ferrocene/
ferrocenium couple.
Considering the CV result, contribution of the redox process
cannot be completely excluded for the reaction with 1j,
although it would be much less compared to the reaction with
1a. To rationally explain the effect of the aminocycloprope-
none substituents on the efficiency of the redox and the triplet
sensitizing mechanism, further investigation such as spectro-
scopic analysis of reaction intermediates and quantum
chemical calculation of possible reaction pathways would be
required.
To a stirred solution of 14a (68 wt %, 300.8 mg, 1.24 mmol) in
DCM (2.5 mL), a solution of diisopropylamine (420 μL, 2.97 mmol)
in DCM (1.0 mL) was added at 0 °C under N2 atmosphere. After 1.5
h, the mixture was diluted with AcOEt (15 mL); washed with 1 M
aqueous HCl (5 mL), water (10 mL × 2), and brine (5 mL); dried
over Na2SO4; filtered; and concentrated in vacuo. The residue was
purified by SiO2 column chromatography (eluent: AcOEt/hexane =
1/4−1/1) to give 1a as a colorless solid (164.8 mg, 58%). The
product 1a was characterized by 1H NMR spectrum that was identical
to previously reported data.14
CONCLUSIONS
■
In summary, the efficiency of the photocatalytic decarbon-
ylation of aminocyclopropenone was improved significantly by
optimizing the substituents on the cyclopropenone. According
to the catalyst screening, triplet sensitization mechanism,
which was not dominant in the reaction with amino-
cyclopropenone 1a, would be involved in the reaction with
benzothiophene-substituted aminocyclopropenone 1j. The
findings in this research would contribute to broaden substrate
2-(Diisopropylamino)-3-phenylcycloprop-2-en-1-one (1a). 1H
NMR (400 MHz, CDCl3) δ 7.60−7.57 (m, 2H), 7.43−7.37 (m,
2H), 7.37−7.33 (m, 1H), 4.19 (sept, J = 6.9 Hz, 1H), 3.62 (sept, J =
6.9 Hz, 1H), 1.386 (d, J = 6.9 Hz, 6H), 1.375 (d, J = 6.9 Hz, 6H).
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Synthesis of 1b. To a stirred solution of AlCl3 (299 mg, 2.24
mmol) in MeNO2 (0.8 mL), tetrachlorocyclopropene (0.2 mL, 1.64
mmol) was added at 0 °C under N2 atmosphere. After 30 min, to the
mixture, DCM (1.6 mL) was added and the mixture was cooled to
−78 °C. To the mixture, a solution of 1,3-dimethoxybenzene (206
mg, 1.49 mmol) in DCM (2.4 mL) was added. After stirring for 1 h at
−78 °C, the mixture was diluted with DCM (10 mL) and quenched
with ice-cooled water (5 mL). The mixture was warmed to 0 °C and
stirred for 30 min. Then, the DCM phase was separated and aqueous
phase was extracted with DCM (5 mL × 2). Combined DCM phase
mixture was quenched with ice-cooled water (5 mL). The DCM
phase was separated and aqueous phase was extracted with DCM (5
mL × 5). Combined DCM phase was dried over Na2SO4, filtered, and
concentrated in vacuo. The residue was dissolved in acetone/water
(3.5/15 mL) at 0 °C and stirred for 20 min. After reaction
completion, diisopropylamine (1.13 mL, 8.05 mmol) was added at 0
°C. After 30 min, the mixture was diluted with AcOEt (15 mL);
washed with 1 M aqueous HCl (8 mL), water (8 mL), and brine (8
mL); dried over Na2SO4; filtered; and concentrated in vacuo. The
residue was purified by SiO2 column chromatography (eluent:
AcOEt/hexane = 1/4−3/7). The purified material was washed
DCM/hexane to give 1d as a colorless solid (170.8 mg, 40% over
three steps).
2-(2,4-Difluorophenyl)-3-(diisopropylamino)cycloprop-2-en-1-
one (1d). 1H NMR (400 MHz, CDCl3) δ 7.64−7.56 (m, 1H), 6.97−
6.87 (m, 2H), 4.26 (sept, J = 6.6 Hz, 1H), 3.64 (sept, J = 6.9 Hz, 1H),
1.38 (d, J = 6.8 Hz, 6H), 1.34 (d, J = 6.9 Hz, 6H). 13C{1H} NMR
(100 MHz, CDCl3) δ 164.0, 163.9, 161.5, 161.4, 161.0, 160.9, 158.5,
158.4, 146.1, 140.4, 131.94, 131.90, 131.84, 131.80, 111.91, 111.88,
111.70, 111.66, 110.22, 110.18, 110.06, 110.02, 104.5, 104.2, 104.0,
102.4, 53.13, 53.06, 47.0, 23.3, 20.7. HRMS (DART) m/z: [M + H]+
calcd for C15H18F2NO 266.1357; found, 266.1364.
a
was dried over Na2SO4, filtered, and concentrated in vacuo. The
residue was purified by SiO2 column (eluent: AcOEt/hexane = 1:5−
1:2) to give a colorless solid. The solid was washed with AcOEt/
hexane (1/9) to give 2-chloro-3-(2,4-dimethoxyphenyl)cycloprop-2-
en-1-one (14b) as a colorless solid (168.6 mg, 50%).
2-Chloro-3-(2,4-dimethoxyphenyl)cycloprop-2-en-1-one (14b).
1H NMR (400 MHz, CDCl3) δ 7.72 (d, J = 8.7 Hz, 1H), 6.58 (dd,
J = 8.7, 2.3 Hz, 1H), 6.49 (d, J = 2.3 Hz, 4.2 Hz, 1H), 3.96 (s, 3H),
3.90 (s, 3H). 13C{1H} NMR (100 MHz, CDCl3) δ 166.1, 161.3,
153.1, 149.6, 135.1, 125.8, 105.7, 105.0, 98.2, 55.8, 55.7. High-
resolution mass spectrometry (HRMS) (DART) m/z: [M + H]+
calcd for C11H10ClO3 225.0319; found, 225.0316.
Synthesis of 1e. To a stirred solution of AlCl3 (858.7 mg, 6.44
mmol) in MeNO2 (1.0 mL), a solution of tetrachlorocyclopropene
(0.2 mL, 1.64 mmol) in DCE (0.9 mL) was added at 0 °C under N2
atmosphere. After 10 min, to the mixture, a solution of
dichlorobenzene (184 μL, 1.61 mmol) in 1,2-dichloroethane (DCE)
(0.8 mL) was added over 10 min. The solution was warmed to room
temperature. After stirring for 2 h at room temperature, the mixture
was warmed to 50 °C and stirred for 7 h. Then, the mixture was
quenched with ice-cooled water (5 mL). The organic phase was
separated and aqueous phase was extracted with DCM (5 mL × 5).
Combined organic phase was dried over Na2SO4, filtered, and
concentrated in vacuo. To the residue, acetone/water (2.8/1.2 mL)
was added at 0 °C and stirred for 10 min. The mixture in acetone/
water was extracted with DCM, dried over Na2SO4, filtered, and
concentrated in vacuo. Then, DCM (5.0 mL) was added to the
residue. To the mixture, oxalyl chloride (120 μL, 1.61 mmol) was
added at 0 °C. After stirring for 30 min at 0 °C, the mixture was
concentrated in vacuo to give a crude chlorocyclopropenone. The
material was dissolved in DCM (5.0 mL) and stirred at 0 °C. To the
solution, diisopropylamine (1.13 mL, 8.05 mmol) was added at 0 °C.
After 30 min, the mixture was diluted with AcOEt (20 mL); washed
with 1 M aqueous HCl (8 mL), water (8 mL), and brine (8 mL);
dried over Na2SO4; filtered; and concentrated in vacuo. The residue
was purified by SiO2 column chromatography (eluent: AcOEt/hexane
= 1/4−2/3) to give 1e as a colorless solid (123.2 mg, 26% over four
steps).
To a stirred solution of 14b (28 mg, 0.125 mmol) in DCM (0.1
mL), a solution of diisopropylamine (42 μL, 0.299 mmol) in DCM
(1.4 mL) was added at 0 °C under N2 atmosphere. After 1 h, the
mixture was diluted with AcOEt; washed with 0.1 M HCl, H2O, and
brine; dried over Na2SO4; filtered; and concentrated in vacuo. The
residue was purified by SiO2 column (eluent: AcOEt/hexane = 1:2−
1:0) to give a colorless solid. The solid was washed with hexane to
give 1b as a colorless solid (20.0 mg, 55%).
2-(Diisopropylamino)-3-(2,4-dimethoxyphenyl)cycloprop-2-en-
1-one (1b). 1H NMR (600 MHz, CDCl3) δ 7.50 (d, J = 8.6 Hz, 1H),
6.52 (dd, J = 8.6, 2.4 Hz, 1H), 6.47 (d, J = 2.4 Hz, 4.2 Hz, 1H), 4.46
(sept, J = 6.7 Hz, 1H), 3.88 (s, 3H), 3.84 (s, 3H), 3.57 (sept, J = 6.5
Hz, 1H), 1.36 (d, J = 6.9 Hz, 6H), 1.29 (d, J = 6.8 Hz, 6H). 13C{1H}
NMR (150 MHz, CDCl3) δ 161.7, 158.1, 146.6, 138.9, 132.4, 108.1,
107.2, 104.8, 98.5, 55.5, 52.6, 46.5, 23.6, 21.0. HRMS (DART) m/z:
[M + H]+ calcd for C17H24NO3 290.1756; found, 290.1759.
Synthesis of 1c. To a stirred solution of AlCl3 (858.7 mg, 6.44
mmol) in MeNO2 (1.0 mL), a solution of tetrachlorocyclopropene
(0.2 mL, 1.64 mmol) in DCM (0.9 mL) was added at 0 °C under N2
atmosphere. After 5 min, to the mixture, a solution of m-xylene (198
μL, 1.61 mmol) in DCM (0.8 mL) was added over 10 min. After
stirring for 2 h at 0 °C, the mixture was quenched with ice-cooled
water (5 mL). The DCM phase was separated, and aqueous phase was
extracted with DCM (5 mL × 3). Combined DCM phase was dried
over Na2SO4, filtered, and concentrated in vacuo. The residue was
dissolved in acetone/water (5.6/2.4 mL) at 0 °C and stirred for 1 h.
After reaction completion, diisopropylamine (1.13 mL, 8.05 mmol)
was added at 0 °C. After 30 min, the mixture was diluted with AcOEt
(15 mL); washed with 1 M aqueous HCl (8 mL), water (8 mL), and
brine (8 mL); dried over Na2SO4; filtered; and concentrated in vacuo.
The residue was purified by SiO2 column chromatography (eluent:
AcOEt/hexane = 1/4−3/7). The purified material was washed with
Et2O to give 1c as a colorless solid (217.9 mg, 53% over three steps).
2-(Diisopropylamino)-3-(2,4-dimethylphenyl)cycloprop-2-en-1-
2-(2,4-Dichlorophenyl)-3-(diisopropylamino)cycloprop-2-en-1-
1
one (1e). H NMR (400 MHz, CDCl3) δ 7.46 (d, J = 1.8 Hz, 1H),
7.34 (d, J = 8.2 Hz, 1H), 7.27 (dd, J = 8.2, 1.8 Hz, 1H), 4.13 (sept, J =
6.8 Hz, 1H), 3.63 (sept, J = 6.7 Hz, 1H), 1.38 (d, J = 6.4 Hz, 6H),
1.34 (d, J = 6.9 Hz, 6H). 13C{1H} NMR (100 MHz, CDCl3) δ 145.9,
142.7, 134.9, 134.8, 130.2, 129.8, 127.2, 124.0, 105.8, 54.7, 47.7, 23.5,
21.1. HRMS (DART) m/z: [M + H]+ calcd for C15H18Cl2NO
298.0765; found, 298.0759.
Synthesis of 1f. To a stirred solution of AlCl3 (596.0 mg, 4.47
mmol) in MeNO2 (0.8 mL), a solution of tetrachlorocyclopropene
(0.2 mL, 1.64 mmol) in DCM (2.2 mL) was added at 0 °C under N2
atmosphere. The solution was cooled to −78 °C. After 10 min, to the
mixture, a solution of naphthalene (191.0 mg, 1.49 mmol) in DCM
(2.0 mL) was added over 10 min. After stirring for 2 h at −78 °C, the
mixture was quenched with ice-cooled water (10 mL). The DCM
phase was separated and aqueous phase was extracted with DCM (5
mL × 3). Combined DCM phase was dried over Na2SO4, filtered, and
concentrated in vacuo. The residue was dissolved in acetone/water
(5.6/2.4 mL) at 0 °C and stirred for 30 min. After reaction
completion, the mixture was diluted with DCM (15 mL). The DCM
phase was separated and aqueous phase extracted with DCM (5 mL ×
3). Combined DCM phase was dried over Na2SO4, filtered, and
1
one (1c). H NMR (600 MHz, CDCl3) δ 7.22 (d, J = 7.9 Hz, 1H),
7.06 (s, 1H), 7.00 (d, J = 7.6 Hz, 1H), 4.21 (sept, J = 6.9 Hz, 1H),
3.60 (sept, J = 6.5 Hz, 1H), 1.37 (d, J = 6.5 Hz, 6H), 1.35 (d, J = 6.9
Hz, 6H). 13C{1H} NMR (150 MHz, CDCl3) δ 145.9, 140.6, 139.0,
138.8, 131.1, 127.6, 126.2, 122.4, 109.9, 54.6, 47.0, 23.3, 21.0, 20.9,
20.6. HRMS (DART) m/z: [M + H]+ calcd for C17H24NO 258.1858;
found, 258.1856.
Synthesis of 1d. To a stirred solution of AlCl3 (858.7 mg, 6.44
mmol) in MeNO2 (1.0 mL), a solution of tetrachlorocyclopropene
(0.2 mL, 1.64 mmol) in DCM (0.9 mL) was added at 0 °C under N2
atmosphere. After 10 min, to the mixture, a solution of
difluorobenzene (158 μL, 1.61 mmol) in DCM (0.8 mL) was
added over 10 min. After stirring for 3 h at 0 °C, the mixture was
warmed to room temperature (rt) and stirred for 5 h. Then, the
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concentrated in vacuo to give a crude chlorocyclopropenone as a
yellow oil. To a stirred solution of the crude chlorocyclopropenone in
DCM (8.0 mL), diisopropylamine (1.04 mL, 7.45 mmol) was added
at 0 °C. After 40 min, the mixture was diluted with DCM (15 mL);
washed with 1 M aqueous HCl (8 mL), water (8 mL), and brine (10
mL); dried over Na2SO4; filtered; and concentrated in vacuo. The
residue was purified by SiO2 column chromatography (eluent:
AcOEt/hexane = 3/2−1/0). The purified material was washed with
DCM/hexane to give 1f as a colorless solid (270.1 mg, 65% over three
Synthesis of 1i. To a stirred solution of AlCl3 (747.4 g, 5.96
mmol) in MeNO2 (0.8 mL), a solution of tetrachlorocyclopropene
(0.2 mL, 1.64 mmol) in DCM (2.2 mL) was added at 0 °C under N2
atmosphere. The solution was cooled to −78 °C. After 15 min, to the
mixture, a solution of 3-methylbenzo[b]thiophene (195.4 μL, 1.49
mmol) in DCM (2.0 mL) was added over 10 min. After stirring for 40
min at −78 °C, the mixture was quenched with ice-cooled water (5
mL). The DCM phase was separated and aqueous phase was
extracted with DCM (10 mL × 3). Combined DCM phase was dried
over Na2SO4, filtered, and concentrated in vacuo. The residue was
dissolved in acetone/water (4.2/1.8 mL) at 0 °C and stirred for 30
min. After reaction completion, diisopropylamine (1.13 mL, 8.05
mmol) was added at 0 °C. After 30 min, the mixture was diluted with
AcOEt (15 mL); washed with 1 M aqueous HCl (8 mL), water (8
mL), and brine (8 mL); dried over Na2SO4; filtered; and
concentrated in vacuo. The residue was purified by SiO2 column
chromatography (eluent: AcOEt/hexane = 1/4−3/7). The purified
material was washed with Et2O and DCM/hexane to give 1i as a
colorless solid (166.7 mg, 37% over three steps).
2-(Diisopropylamino)-3-(3-methylbenzo[b]thiophen-2-yl)-
cycloprop-2-en-1-one (1i). 1H NMR (600 MHz, CDCl3) δ 7.76 (d, J
= 7.9 Hz, 1H), 7.73 (d, J = 7.9 Hz, 1H), 7.41−7.35 (m, 2H), 4.29
(sept, J = 6.9 Hz, 1H), 3.62 (sept, J = 6.5 Hz, 1H), 2.75 (s, 3H), 1.40
(d, J = 6.8 Hz, 6H), 1.37 (d, J = 6.5 Hz, 6H). 13C{1H} NMR (150
MHz, CDCl3) δ 144.0, 139.7, 139.4, 137.6, 136.4, 125.6, 124.6, 122.7,
122.3, 120.7, 104.3, 54.4, 47.7, 23.5, 21.3, 13.2. HRMS (DART) m/z:
[M + H]+ calcd for C18H22NOS 300.1422; found, 300.1429.
Synthesis of 1j. To a stirred solution of AlCl3 (2.0 g, 14.9 mmol)
in MeNO2 (2.0 mL), a solution of tetrachlorocyclopropene (0.5 mL,
4.10 mmol) in DCM (5.0 mL) was added at 0 °C under N2
atmosphere. The solution was cooled to −78 °C. After 10 min, to
the mixture, a solution of 2-methylbenzo[b]thiophene (552.9 mg,
3.73 mmol) in DCM (6.5 mL) was added over 10 min. After stirring
for 1 h at −78 °C, the mixture was quenched with ice-cooled water (5
mL). The DCM phase was separated and aqueous phase was
extracted with DCM (5 mL × 3). Combined DCM phase was dried
over Na2SO4, filtered, and concentrated in vacuo. The residue was
dissolved in acetone/water (13.5/15 mL) at 0 °C and stirred for 30
min. After reaction completion, diisopropylamine (2.6 mL, 18.7
mmol) was added at 0 °C. After 1 h, the mixture was diluted with
AcOEt (15 mL); washed with 1 M aqueous HCl (16 mL), water (16
mL), and brine (16 mL); dried over Na2SO4; filtered; and
concentrated in vacuo. The residue was purified by SiO2 column
chromatography (eluent: AcOEt/hexane = 1/4−2/3). The purified
material was washed with DCM/hexane to give 1j as a colorless solid
(513.6 mg, 46% over three steps).
2-(Diisopropylamino)-3-(2-methylbenzo[b]thiophen-3-yl)-
cycloprop-2-en-1-one (1j). 1H NMR (600 MHz, CDCl3) δ 7.75 (d, J
= 8.2 Hz, 1H), 7.73 (d, J = 8.3 Hz, 1H), 7.37 (t, J = 7.9 Hz, 1H), 7.30
(t, J = 7.6 Hz, 1H), 4.09 (br s, 1H), 3.60 (br s, 1H), 2.69 (s, 3H), 1.39
(br s, 6H), 1.29 (br s, 6H). 13C{1H} NMR (150 MHz, CDCl3) δ
146.6, 142.1, 141.7, 138.5, 138.0, 124.4, 124.1, 122.0, 121.8, 119.1,
104.5, 53.3, 46.8, 23.4, 21.0, 15.4. HRMS (DART) m/z: [M + H]+
calcd for C18H22NOS 300.1422; found, 300.1435.
1
steps). The product 1f was characterized by H NMR spectrum that
was identical to the previously reported data.14
2-(Diisopropylamino)-3-(naphthalene-1-yl)cycloprop-2-en-1-
1
one (1f). H NMR (400 MHz, CDCl3) δ 8.77 (d, J = 8.2 Hz, 1H),
7.86 (d, J = 8.2 Hz, 2H), 7.71−7.67 (m, 1H), 7.58−7.54 (m, 2H),
7.50−7.46 (m, 1H), 4.36 (sept, J = 6.8 Hz, 1H), 3.68 (sept, J = 6.8
Hz, 1H), 1.44 (d, J = 6.4 Hz, 6H), 1.42 (d, J = 6.8 Hz, 6H).
Synthesis of 1g. To a stirred solution of AlCl3 (875 mg, 6.56
mmol) in MeNO2 (0.8 mL), a solution of tetrachlorocyclopropene
(0.2 mL, 1.64 mmol) in DCM (1.6 mL) was added at 0 °C under N2
atmosphere. After stirring for 10 min, the mixture was cooled to −78
°C. To the mixture, a solution of thiophene (119 μL, 1.49 mmol) in
DCM (1.6 mL) was added over 10 min. After stirring for 25 min at
−78°C, the mixture was diluted with DCM (10 mL) and quenched
with ice-cold water (5 mL). The DCM phase was separated, and the
aqueous phase was extracted with DCM (5 mL × 2). Combined
DCM phase was dried over Na2SO4, filtered, and concentrated in
vacuo. The residue was dissolved in acetone/water (4.0/1.0 mL) at 0
°C and stirred for 30 min. After completion of the hydrolysis, a
solution of diisopropylamine (1.26 mL, 8.96 mmol) in DCM (10 mL)
was added at 0 °C. After 20 min, the DCM phase was separated, and
the aqueous phase was extracted with DCM (5.0 mL × 2). The DCM
phases were combined, dried over Na2SO4, filtered, and concentrated
in vacuo. The residue was purified by SiO2 column chromatography
(eluent: AcOEt/hexane = 1/3−2/1). The purified material was
washed with hexane to give 1g as a brown solid (240.8 mg, 69% over
three steps).
2-(Diisopropylamino)-3-(thiophen-2-yl)cycloprop-2-en-1-one
1
(1g). H NMR (400 MHz, CDCl3) δ 7.43 (dd, J = 3.7, 0.9 Hz, 1H),
7.37 (dd, J = 5.0, 0.9 Hz, 1H), 7.09 (dd J = 5.0, 3.7 Hz, 1H), 4.17
(sept, J = 6.9 Hz, 1H), 3.62 (sept, J = 6.9 Hz, 1H), 1.39 (d, J = 6.9 Hz,
6H), 1.36 (d, J = 6.9 Hz, 6H). 13C{1H} NMR (100 MHz, CDCl3) δ
143.4, 136.8, 130.1, 128.0, 127.2, 126.1, 104.1, 54.0, 48.5, 23.4, 21.6.
HRMS (DART) m/z: [M + H]+ calcd for C13H18NOS 236.1109;
found, 236.1102.
Synthesis of 1h. To a stirred solution of AlCl3 (596.0 mg, 4.47
mmol) in MeNO2 (0.8 mL), a solution of tetrachlorocyclopropene
(0.2 mL, 1.64 mmol) in DCM (2.2 mL) was added at 0 °C under N2
atmosphere. The solution was cooled to −78 °C. After 10 min, to the
mixture, a solution of 2,5-dimethylthiophene (169 μL, 1.49 mmol) in
DCM (2.0 mL) was added over 10 min. After stirring for 1.5 h at −78
°C, the mixture was quenched with ice-cooled water (5 mL). The
DCM phase was separated and aqueous phase was extracted with
DCM (5 mL × 3). Combined DCM phase was dried over Na2SO4,
filtered, and concentrated in vacuo. The residue was dissolved in
acetone/water (7.2/1.8 mL) at 0 °C and stirred for 40 min. After
reaction completion, diisopropylamine (1.04 mL, 7.45 mmol) was
added at 0 °C. After 1 h, the mixture was diluted with AcOEt (15
mL); washed with 1 M aqueous HCl (8 mL), water (8 mL), and brine
(8 mL); dried over Na2SO4; filtered; and concentrated in vacuo. The
residue was purified by SiO2 column chromatography (eluent:
AcOEt/hexane = 1/4−3/7). The purified material was washed with
DCM/hexane to give 1h as a pale yellow solid (216.3 mg, 55% over
three steps).
Synthesis of 1k. To a stirred solution of 14a (68 wt %, 147.7 mg,
0.61 mmol) in DCM (1.4 mL), N-methylaniline (163 μL, 1.50 mmol)
was added at 0 °C under N2 atmosphere. After 1 h, the mixture was
diluted with DCM (15 mL); washed with 1 M aqueous HCl (5 mL),
water (10 mL), and brine (5 mL); dried over Na2SO4; filtered; and
concentrated in vacuo. The residue was purified by SiO2 column
chromatography (eluent: AcOEt/hexane = 1/4−0/1) to give 1k as a
colorless solid (139.2 mg, 97%). The product 1k was characterized by
1H NMR spectrum that was identical to previously reported data.14
1
2-(Methyl(phenyl)amino)3-phenylcycloprop-2-en-1-one (1k). H
2-(Diisopropylamino)-3-(2,5-dimethylthiophen-3-yl)cycloprop-
2-en-1-one (1h). 1H NMR (600 MHz, CDCl3) δ 6.59−6.58 (m, 1H),
4.08 (sept, J = 6.8 Hz, 1H), 3.58 (sept, J = 6.8 Hz, 1H), 2.72 (s, 3H),
2.42 (s, 3H), 1.35 (s, 6H), 1.34 (s, 6H). 13C{1H} NMR (150 MHz,
CDCl3) δ 144.1, 141.3, 136.9, 136.8, 123.3, 122.4, 105.7, 53.4, 47.2,
23.0, 20.7, 14.7, 14.1. HRMS (DART) m/z: [M + H]+ calcd for
C15H22NOS 264.1422; found, 264.1420.
NMR (400 MHz, CDCl3) δ 7.72 (br s, 2H), 7.45−7.16 (m, 8H), 3.75
(s, 3H).
Synthesis of 1m. To a stirred solution of isopropylacetamide
(227 mg, 2.24 mmol) in tetrahydrofuran (THF) (4.0 mL), nBuLi (1.6
M in hexane, 1.3 mL, 2.10 mmol) was added at −78 °C under N2
atmosphere. After stirring for 15 min, the mixture was transferred to a
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solution of 14a (73 wt %, 314 mg, 1.40 mmol) in THF (6.0 mL)
under N2 atmosphere. After 1 h, 1 M aqueous HCl (5.0 mL) was
added to the solution and the mixture was warmed to rt. The mixture
was extracted with DCM (10 mL × 3), dried over Na2SO4, filtered,
and concentrated in vacuo. The residue was purified by SiO2 column
chromatography (eluent: AcOEt/hexane = 1/3−1/1) to give 1m as a
pale yellow solid (210 mg, 65%). The product 1m was characterized
by 1H NMR spectrum that was identical to previously reported data.14
N-Isopropyl-N-(3-oxo-2-phenylcycloprop-1-en-1-yl)acetamide
(1m). 1H NMR (600 MHz, CDCl3) δ 7.81 (d, J = 3.8 Hz, 2H), 7.53−
7.49 (m, 3H), 4.68 (br s, 1H), 2.54 (s, 3H), 1.51 (d, J = 7.2 Hz, 6H).
Procedure for Tables 1 and 2. Aminocyclopropenone 1 (50
μmol), 3-phenylpropionic acid 3a (7.5 mg, 50 μmol), 2-phenylethyl-
amine 5a (6.4 μL, 50 μmol), thioxanthone (2.1 mg, 10 μmol), and
DCM (5.0 mL) were added into a screw-capped test tube filled with
N2 gas equipped with a magnetic stir bar. The mixture was irradiated
with a household fluorescent lamp (400−750 nm) that was placed 4.0
cm from the reaction vessel. The temperature was kept at 20 °C using
a temperature-controlled water bath. After 3 h irradiation, the mixture
was diluted in DCM; washed with aqueous 1 M KHSO4, aqueous
NaHCO3, and brine; dried over Na2SO4; filtered; and concentrated in
vacuo. The product yield was determined by qNMR using 1,3,5-
trimethoxybenzene as an internal standard.
Procedure for Scheme 3. Aminocyclopropenone 1 (50 μmol),
carboxylic acid 3 (50 μmol), amine 5 (50 μmol), thioxanthone (2.1
mg, 10 μmol), and DCM (5.0 mL) were added into a screw-capped
test tube filled with N2 gas equipped with a magnetic stir bar. The
mixture was irradiated with a household fluorescent lamp (400−750
nm) that was placed 4.0 cm from the reaction vessel. The temperature
was kept at 20 °C using a temperature-controlled water bath. The
reaction progress was monitored by preparative TLC (PTLC). After 1
disappeared, the mixture was diluted in DCM; washed with aqueous 1
M KHSO4, aqueous NaHCO3, and brine; dried over Na2SO4; filtered;
and concentrated in vacuo. The NMR yield of the dehydration
condensation product was determined by qNMR using 1,3,5-
trimethoxybenzene as an internal standard. The isolated yield was
determined after purification by PTLC.
(AcOEt/hexane = 3/7) to give 6ab as a colorless solid (10.1 mg,
86%). The product 6ab was characterized by 1H NMR spectrum that
was identical to previously reported data.24
N-Hexyl-3-phenylpropanamide (6ab). 1H NMR (400 MHz,
CDCl3) δ 7.29 (d, J = 7.8 Hz, 2H), 7.21−7.19 (m, 3H), 5.26 (br s,
1H), 3.20 (dt, J = 6.9, 6.4 Hz, 2H), 2.97 (t, J = 7.3 Hz, 2H), 2.46 (t, J
= 7.4 Hz, 2H), 1.44−1.37 (m, 2H), 1.29−1.23 (m, 6H), 0.88 (t, J =
6.9 Hz, 3H).
Condensation of 3a and 5c. 1j (15.0 mg, 50 μmol), 3-
phenylpropionic acid (3a) (7.5 mg, 50 μmol), tert-butylamine (5c)
(5.3 μL, 50 μmol), thioxanthone (2.12 mg, 10 μmol), and DCM (5.0
mL) were added into a screw-capped test tube filled with N2 gas
equipped with a magnetic stir bar. The mixture was stirred and
irradiated with a household fluorescent lamp that was placed 4.0 cm
from the reaction vessel. Temperature was kept at 20 °C using a
temperature-controlled water bath. After 9 h, the mixture was diluted
with DCM; washed with 1 M aqueous KHSO4, saturated aqueous
NaHCO3, and brine successively; dried over Na2SO4; filtered; and
concentrated in vacuo. NMR yield was determined to be 82% by
qNMR using 1,3,5-trimethoxybenzene as an internal standard.
Isolation yield was determined after purification with PTLC
(AcOEt/hexane = 2/3) to give 6ac as a colorless solid (7.6 mg,
74%). The product 6ac was characterized by 1H NMR spectrum that
was identical to previously reported data.25
1
N-(tert-Butyl)-3-phenylpropanamide (6ac). H NMR (400 MHz,
CDCl3) δ 7.30−7.26 (m, 2H), 7.21−7.19 (m, 3H) 5.09 (br s, 1H),
2.94 (t, J = 7.8 Hz, 2H), 2.38 (t, J = 7.8 Hz, 2H), 1.28 (s, 9H).
Condensation of 3a and 5d. 1j (15.0 mg, 50 μmol), 3-
phenylpropionic acid (3a) (7.5 mg, 50 μmol), diethylamine (5d)
(5.2 μL, 50 μmol), thioxanthone (2.12 mg, 10 μmol), and DCM (5.0
mL) were added into a screw-capped test tube filled with N2 gas
equipped with a magnetic stir bar. The mixture was stirred and
irradiated with a household fluorescent lamp that was placed 4.0 cm
from the reaction vessel. Temperature was kept at 20 °C using a
temperature-controlled water bath. After 10 h, the mixture was diluted
with DCM; washed with 1 M aqueous KHSO4, saturated aqueous
NaHCO3, and brine successively; dried over Na2SO4; filtered; and
concentrated in vacuo. NMR yield was determined to be 83% by
qNMR using 1,3,5-trimethoxybenzene as an internal standard.
Isolation yield was determined after purification with PTLC
(AcOEt/hexane = 1/1) to give 6ad as a colorless solid (8.2 mg,
80%). The product 6ad was characterized by 1H NMR spectrum that
was identical to previously reported data.26
Condensation of 3a and 5a. 1j (15.0 mg, 50 μmol), 3-
phenylpropionic acid (3a) (7.5 mg, 50 μmol), 2-phenylethylamine
(5a) (6.3 μL, 50 μmol), thioxanthone (2.12 mg, 10 μmol), and DCM
(5.0 mL) were added into a screw-capped test tube filled with N2 gas
equipped with a magnetic stir bar. The mixture was stirred and
irradiated with a household fluorescent lamp that was placed 4.0 cm
from the reaction vessel. Temperature was kept at 20 °C using a
temperature-controlled water bath. After 10 h, the mixture was diluted
with DCM; washed with 1 M aqueous KHSO4, saturated aqueous
NaHCO3, and brine successively; dried over Na2SO4; filtered; and
concentrated in vacuo. NMR yield was determined to be 86% by
qNMR using 1,3,5-trimethoxybenzene as an internal standard.
Isolation yield was determined after purification with PTLC
(AcOEt/hexane = 2/3) to give 6aa as a colorless solid (11.4 mg,
90%). The product 6aa was characterized by 1H NMR spectrum that
was identical to previously reported data.23
1
N,N-Diethyl-3-phenylpropanamide (6ad). H NMR (400 MHz,
CDCl3) δ 7.31−7.18 (m, 5H), 3.38 (q, J = 7.2 Hz, 2H), 3.22 (q, J =
7.2 Hz, 2H), 2.98 (t, J = 8.2 Hz, 2H), 2.61−2.57 (m, 2H), 1.13−1.08
(m, 6H).
Condensation of 3a and 5e. 1j (15.0 mg, 50 μmol), 3-
phenylpropionic acid (3a) (7.5 mg, 50 μmol), pyrrolidine (5e) (4.1
μL, 50 μmol), thioxanthone (2.12 mg, 10 μmol), and DCM (5.0 mL)
were added into a screw-capped test tube filled with N2 gas equipped
with a magnetic stir bar. The mixture was stirred and irradiated with a
household fluorescent lamp that was placed 4.0 cm from the reaction
vessel. Temperature was kept at 20 °C using a temperature-controlled
water bath. After 11 h, the mixture was diluted with DCM; washed
with 1 M aqueous KHSO4, saturated aqueous NaHCO3, and brine
successively; dried over Na2SO4; filtered; and concentrated in vacuo.
NMR yield was determined to be 87% by qNMR using 1,3,5-
trimethoxybenzene as an internal standard. Isolation yield was
determined after purification with PTLC (AcOEt/hexane = 7/3) to
give 6ae as a colorless solid (9.6 mg, 94%). The product 6ae was
1
N-Phenethyl-3-phenylpropanamide (6aa). H NMR (600 MHz,
CDCl3) δ 7.30−7.18 (m, 8H), 7.10−7.08 (m, 2H), 5.31 (br s, 1H),
3.48 (td, J = 6.9, 6.5 Hz, 2H), 2.94 (t, J = 7.9 Hz, 2H), 2.74 (t, J = 6.9
Hz, 2H), 2.42 (t, J = 7.9 Hz, 2H).
Condensation of 3a and 5b. 1j (15.0 mg, 50 μmol), 3-
phenylpropionic acid (3a) (7.5 mg, 50 μmol), n-hexylamine (5b)
(6.6 μL, 50 μmol), thioxanthone (2.12 mg, 10 μmol), and DCM (5.0
mL) were added into a screw-capped test tube filled with N2 gas
equipped with a magnetic stir bar. The mixture was stirred and
irradiated with a household fluorescent lamp that was placed 4.0 cm
from the reaction vessel. Temperature was kept at 20 °C using a
temperature-controlled water bath. After 10 h, the mixture was diluted
with DCM; washed with 1 M aqueous KHSO4, saturated aqueous
NaHCO3, and brine successively; dried over Na2SO4; filtered; and
concentrated in vacuo. NMR yield was determined to be 82% by
qNMR using 1,3,5-trimethoxybenzene as an internal standard.
Isolation yield was determined after purification with PTLC
1
characterized by H NMR spectrum that was identical to previously
reported data.27
1
3-Phenyl-1-(pyrrolidin-1-yl)propan-1-one (6ae). H NMR (400
MHz, CDCl3) δ 7.30−7.18 (m, 5H), 3.46 (t, J = 6.8 Hz, 2H), 3.29 (t,
J = 6.9 Hz, 2H), 2.99 (t, J = 7.8 Hz, 2H), 2.56 (t, J = 8.2 Hz, 2H),
1.92−1.78 (m, 4H).
Condensation of 3b and 5a. 1j (15.0 mg, 50 μmol), isobutyric
acid (3b) (4.6 μL, 50 μmol), 2-phenylethylamine (5a) (6.3 μL, 50
μmol), thioxanthone (2.12 mg, 10 μmol), and DCM (5.0 mL) were
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added into a screw-capped test tube filled with N2 gas equipped with a
magnetic stir bar. The mixture was stirred and irradiated with a
household fluorescent lamp that was placed 4.0 cm from the reaction
vessel. Temperature was kept at 20 °C using a temperature-controlled
water bath. After 9 h, the mixture was diluted with DCM; washed
with 1 M aqueous KHSO4, saturated aqueous NaHCO3, and brine
successively; dried over Na2SO4; filtered; and concentrated in vacuo.
NMR yield was determined to be 91% by qNMR using 1,3,5-
trimethoxybenzene as an internal standard. Isolation yield was
determined after purification with PTLC (AcOEt/hexane = 1/1) to
give 6ba as a colorless solid (8.0 mg, 84%). The product 6ba was
84%). The product 6ea was characterized by 1H NMR spectrum that
was identical to previously reported data.23
(3r,5r,7r)-N-Phenethyladamantane-1-carboxamide (6ea). 1H
NMR (600 MHz, CDCl3) δ 7.32 (t, J = 7.6 Hz, 2H), 7.25−7.22
(m, 1H), 7.19 (d, J = 6.8 Hz, 2H), 5.57 (br s, 1H), 3.50 (dt, J = 6.8,
6.4 Hz, 2H), 2.80 (t, J = 6.9 Hz, 2H), 2.01 (s, 3H), 1.78 (d, J = 2.8
Hz, 6H), 1.70 (dd, J = 17.1, 12.4 Hz, 6H).
1.0 mmol Scale Reaction of the Photocatalyst Promoted
Dehydration Condensation of 3a and 5a Using 1j. 1j (299.4
mg, 1.0 mmol), 3a (150.2 mg, 1.0 mmol), 5a (126 μL, 1.0 mmol),
thioxanthone (42.5 mg, 0.20 mmol), and DCM (100 mL) were added
into a Pyrex flask equipped with a magnetic stir bar and N2 balloon.
The mixture was stirred and irradiated with a household fluorescent
lamp that was placed 5.0 cm from the reaction vessel. Temperature
was kept at 20 °C using a temperature-controlled water bath. After 33
h, the mixture was washed with 1 M aqueous KHSO4, saturated
aqueous NaHCO3, and brine successively; dried over Na2SO4;
filtered; and concentrated in vacuo. The residue was purified by SiO2
column chromatography (eluent: AcOEt/hexane = 1/9−3/7) to give
6aa as a colorless solid (207.7 mg, 82%) and 7j as a colorless solid
(214.6 mg, 74%). The 1.0 mmol scale reaction in flask was much less
efficient than the 0.05 mmol scale reaction in test tube due to the
lower irradiation efficiency.
N,N-Diisopropyl-2-(2-methylbenzo[b]thiophen-3-yl)acetamide
(7j). 1H NMR (400 MHz, CDCl3) δ 7.73 (d, J = 7.4 Hz, 1H), 7.71 (d,
J = 7.8 Hz, 1H), 7.31 (td, J = 7.6, 0.9 Hz, 1H), 7.25 (td, J = 7.6, 0.9
Hz, 1H), 3.96 (sept, J = 6.9 Hz, 1H), 3.79 (s, 2H), 3.34 (sept, J = 6.4
Hz, 1H), 2.51 (s, 3H), 2.77 (d, J = 6.9 Hz, 6H), 0.99 (d, J = 6.4 Hz).
13C{1H} NMR (100 MHz, CDCl3) δ 168.9, 140.1, 138.0, 135.9,
125.3, 124.0, 123.5, 121.9, 121.4, 49.1, 46.1, 35.2, 20.55, 20.48, 14.1.
HRMS (DART+) calcd for C17H24NOS ([M + H+]+): 290.1579,
found: 290.1565.
Phototriggered Dehydration Condensation under Oxygen
Atmosphere (Table 3). Aminocyclopropenone 1 (50 μmol),
carboxylic acid 3a (7.5 mg, 50 μmol), amine 5a (6.3 μL, 50 μmol),
thioxanthone (2.1 mg, 10 μmol), and DCM (5.0 mL) were added into
a test tube equipped with a magnetic stir bar and an oxygen-filled
balloon. The mixture was irradiated with a household fluorescent
lamp (400−750 nm) that was placed 4.0 cm from the reaction vessel.
The temperature was kept at 20 °C using a temperature-controlled
water bath. The reaction progress was monitored by TLC. After 24 h
irradiation, the mixture was diluted in DCM; washed with aqueous 1
M KHSO4, aqueous NaHCO3, and brine; dried over Na2SO4; filtered;
and concentrated in vacuo. The isolated yields of condensation
product 6aa, hydrated ynamine 7, and recovery of 1 were determined
after purification by PTLC.
1
characterized by H NMR spectrum that was identical to previously
reported data.14
N-Phenethylisobutyramide (6ba). 1H NMR (400 MHz, CDCl3) δ
7.33−7.29 (m, 2H), 7.23−7.18 (m, 3H), 5.38 (br s, 1H), 3.52 (dt, J =
6.9, 6.1 Hz, 2H), 2.82 (t, J = 6.9 Hz, 2H), 2.27 (sept, J = 6.9 Hz, 1H),
1.11 (d, J = 6.9 Hz, 6H).
Condensation of 3c and 5a. 1j (15.0 mg, 50 μmol), cyclo-
hexanecarboxylic acid (3c) (6.4 mg, 50 μmol), 2-phenylethylamine
(5a) (6.3 μL, 50 μmol), thioxanthone (2.12 mg, 10 μmol), and DCM
(5.0 mL) were added into a screw-capped test tube filled with N2 gas
equipped with a magnetic stir bar. The mixture was stirred and
irradiated with a household fluorescent lamp that was placed 4.0 cm
from the reaction vessel. Temperature was kept at 20 °C using a
temperature-controlled water bath. After 12 h, the mixture was diluted
with DCM; washed with 1 M aqueous KHSO4, saturated aqueous
NaHCO3, and brine successively; dried over Na2SO4; filtered; and
concentrated in vacuo. NMR yield was determined to be 82% by
qNMR using 1,3,5-trimethoxybenzene as an internal standard.
Isolation yield was determined after purification with PTLC
(AcOEt/hexane = 2/3) to give 6ca as a colorless solid (9.2 mg,
79%). The product 6ca was characterized by 1H NMR spectrum that
was identical to previously reported data.23
N-Phenethylcyclohexanecarboxamide (6ca). 1H NMR (400
MHz, CDCl3) δ 7.33−7.18 (m, 5H), 5.44 (br s, 1H), 3.51 (dt, J =
6.9, 6.4 Hz, 2H), 2.81 (t, J = 6.4 Hz, 2H), 2.00 (tt, J = 11.9, 3.2 Hz,
1H), 1.82−1.64 (m, 5H), 1.48−1.11 (m, 5H).
Condensation of 3d and 5a. 1j (15.0 mg, 50 μmol), pivalic acid
(3d) (5.1 mg, 50 μmol), 2-phenylethylamine (5a) (6.3 μL, 50 μmol),
thioxanthone (2.12 mg, 10 μmol), and DCM (5.0 mL) were added
into a screw-capped test tube filled with N2 gas equipped with a
magnetic stir bar. The mixture was stirred and irradiated with a
household fluorescent lamp that was placed 4.0 cm from the reaction
vessel. Temperature was kept at 20 °C using a temperature-controlled
water bath. After 13 h, the mixture was diluted with DCM; washed
with 1 M aqueous KHSO4, saturated aqueous NaHCO3, and brine
successively; dried over Na2SO4; filtered; and concentrated in vacuo.
NMR yield was determined to be 81% by qNMR using 1,3,5-
trimethoxybenzene as an internal standard. Isolation yield was
determined after purification with PTLC (AcOEt/hexane = 3/7) to
give 6da as a colorless solid (8.1 mg, 79%). The product 6da was
With aminocyclopropenone 1a, amide 6aa and ynamine-derived
product 7a were obtained in 54 and 37% yields, respectively. With
aminocyclopropenone 1j, amide 6aa and ynamine-derived product 7j
were obtained in 78 and 69% yields, respectively.
Procedure for Scheme 4. Aminocyclopropenone 1 (50 μmol),
3-phenylpropionic acid 3a (7.5 mg, 50 μmol), aniline 5 (50 μmol),
thioxanthone (2.1 mg, 10 μmol), and DCM (5.0 mL) were added into
a screw-capped test tube filled with N2 gas equipped with a magnetic
stir bar. The mixture was irradiated with a household fluorescent lamp
(400−750 nm) that was placed 4.0 cm from the reaction vessel. The
temperature was kept at 20 °C using a temperature-controlled water
bath. After 24 h irradiation, the mixture was diluted in DCM; washed
with aqueous 1 M KHSO4, aqueous NaHCO3, and brine; dried over
Na2SO4; filtered; and concentrated in vacuo. The NMR yield of the
dehydration condensation product was determined by qNMR using
1,3,5-trimethoxybenzene as an internal standard. The isolated yield
was determined after purification by PTLC.
Condensation of 3a and 5f. 1j (15.0 mg, 50 μmol), 3-
phenylpropionic acid (3a) (7.5 mg, 50 μmol), aniline (5f) (4.6 μL,
50 μmol), thioxanthone (2.12 mg, 10 μmol), and DCM (5.0 mL)
were added into a screw-capped test tube filled with N2 gas equipped
with a magnetic stir bar. The mixture was stirred and irradiated with a
household fluorescent lamp that was placed 4.0 cm from the reaction
vessel. Temperature was kept at 20 °C using a temperature-controlled
1
characterized by H NMR spectrum that was identical to previously
reported data.26
1
N-Phenethylpivalamide (6da). H NMR (600 MHz, CDCl3) δ
7.33−7.30 (m, 2H), 7.25−7.18 (m, 3H), 5.60 (br s, 1H), 3.50 (dt, J =
6.9, 6.4 Hz, 2H), 2.82 (t, J = 6.9 Hz, 2H), 1.14 (s, 9H).
Condensation of 3e and 5a. 1j (15.0 mg, 50 μmol), 1-
adamanthancarboxylic acid (3e) (5.1 mg, 50 μmol), 2-phenylethyl-
amine (5a) (6.3 μL, 50 μmol), thioxanthone (2.12 mg, 10 μmol), and
DCM (5.0 mL) were added into a screw-capped test tube filled with
N2 gas equipped with a magnetic stir bar. The mixture was stirred and
irradiated with a household fluorescent lamp that was placed 4.0 cm
from the reaction vessel. Temperature was kept at 20 °C using a
temperature-controlled water bath. After 13 h, the mixture was diluted
with DCM; washed with 1 M aqueous KHSO4, saturated aqueous
NaHCO3, and brine successively; dried over Na2SO4; filtered; and
concentrated in vacuo. NMR yield was determined to be 83% by
qNMR using 1,3,5-trimethoxybenzene as an internal standard.
Isolation yield was determined after purification with PTLC
(AcOEt/hexane = 1/4) to give 6ea as a colorless solid (11.9 mg,
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1
water bath. After 24 h, the mixture was diluted with DCM; washed
with 1 M aqueous KHSO4, saturated aqueous NaHCO3, and brine
successively; dried over Na2SO4; filtered; and concentrated in vacuo.
NMR yield was determined to be 67% by qNMR using 1,3,5-
trimethoxybenzene as an internal standard. Isolation yield was
determined after purification with PTLC (AcOEt/hexane = 1/4) to
give 6af as a colorless solid (8.2 mg, 73%). The product 6af was
N-(4-Bromophenyl)-3-phenylpropanamide (6ai). H NMR (400
MHz, CDCl3) δ 7.39 (d, J = 9.2 Hz, 2H), 7.32−7.28 (m, 4H), 7.24−
7.21 (m, 3H), 7.04 (br s, 1H), 3.04 (t, J = 7.8 Hz, 2H), 2.65 (t, J = 7.8
Hz, 2H). 13C{1H} NMR (100 MHz, CDCl3) δ 170.3, 140.4, 136.7,
131.9, 128.7, 128.4, 126.5, 121.4, 116.8, 39.5, 31.5. HRMS (DART)
m/z: [M + H]+ calcd for C15H15BrNO 304.0337; found, 304.0337.
Condensation of 3a and 5j. 1j (15.0 mg, 50 μmol), 3-
phenylpropionic acid (3a) (7.5 mg, 50 μmol), 4-iodoaniline (5j)
(11.0 mg, 50 μmol), thioxanthone (2.12 mg, 10 μmol), and DCM
(5.0 mL) were added into a screw-capped test tube filled with N2 gas
equipped with a magnetic stir bar. The mixture was stirred and
irradiated with a household fluorescent lamp that was placed 4.0 cm
from the reaction vessel. Temperature was kept at 20 °C using a
temperature-controlled water bath. After 24 h, the mixture was diluted
with DCM; washed with 1 M aqueous KHSO4, saturated aqueous
NaHCO3, and brine successively; dried over Na2SO4; filtered; and
concentrated in vacuo. NMR yield was determined to be 60% by
qNMR using 1,3,5-trimethoxybenzene as an internal standard.
Isolation yield was determined after purification with PTLC (DCM
100%) to give 6aj as a colorless solid (10.9 mg, 62%).
1
characterized by H NMR spectrum that was identical to previously
reported data.23
1
N,3-Diphenylpropnamide (6af). H NMR (600 MHz, CDCl3) δ
7.42 (d, J = 7.9 Hz, 2H), 7.31−7.28 (m, 4H), 7.26−7.21 (m, 3H),
7.09 (t, J = 7.2 Hz, 1H), 7.05 (br s, 1H), 3.05 (t, J = 7.6 Hz, 2H), 2.66
(t, J = 7.6 Hz, 2H).
Condensation of 3a and 5g. 1j (15.0 mg, 50 μmol), 3-
phenylpropionic acid (3a) (7.5 mg, 50 μmol), 4-methoxyaniline
(5g) (6.2 mg, 50 μmol), thioxanthone (2.12 mg, 10 μmol), and DCM
(5.0 mL) were added into a screw-capped test tube filled with N2 gas
equipped with a magnetic stir bar. The mixture was stirred and
irradiated with a household fluorescent lamp that was placed 4.0 cm
from the reaction vessel. Temperature was kept at 20 °C using a
temperature-controlled water bath. After 24 h, the mixture was diluted
with DCM; washed with 1 M aqueous KHSO4, saturated aqueous
NaHCO3, and brine successively; dried over Na2SO4; filtered; and
concentrated in vacuo. NMR yield was determined to be 46% by
qNMR using 1,3,5-trimethoxybenzene as an internal standard.
Isolation yield was determined after purification with PTLC
(AcOEt/DCM = 1/19) to give 6ag as a colorless solid (6.4 mg, 50%).
N-(4-Methoxyphenyl)-3-phenylpropanamide (6ag). 1H NMR
(600 MHz, CDCl3) δ 7.32−7.29 (m, 4H), 7.26−7.21 (m, 3H),
6.96 (br s, 1H), 6.84−6.82 (m, 2H), 3.78 (s, 3H), 3.05 (t, J = 7.6 Hz,
2H), 2.63 (t, J = 7.6 Hz, 2H). 13C{1H} NMR (150 MHz, CDCl3) δ
170.2, 156.4, 140.7, 130.8, 128.6, 128.4, 126.4, 121.9, 114.1, 55.5,
55.4, 39.3, 31.7. HRMS (DART) m/z: [M + H]+ calcd for
C16H18NO2 256.1338; found, 256.1350.
Condensation of 3a and 5h. 1j (15.0 mg, 50 μmol), 3-
phenylpropionic acid (3a) (7.5 mg, 50 μmol), 4-chloroaniline (5h)
(6.4 mg, 50 μmol), thioxanthone (2.12 mg, 10 μmol), and DCM (5.0
mL) were added into a screw-capped test tube filled with N2 gas
equipped with a magnetic stir bar. The mixture was stirred and
irradiated with a household fluorescent lamp that was placed 4.0 cm
from the reaction vessel. Temperature was kept at 20 °C using a
temperature-controlled water bath. After 24 h, the mixture was diluted
with DCM; washed with 1 M aqueous KHSO4, saturated aqueous
NaHCO3, and brine successively; dried over Na2SO4; filtered; and
concentrated in vacuo. NMR yield was determined to be 59% by
qNMR using 1,3,5-trimethoxybenzene as an internal standard.
Isolation yield was determined after purification with PTLC (DCM
100%) to give 6ah as a colorless solid (7.1 mg, 55%).
N-(4-Iodophenyl)-3-phenylpropanamide (6aj). 1H NMR (600
MHz, CDCl3) δ 7.58 (d, J = 8.6 Hz, 2H), 7.30 (t, J = 7.6 Hz, 2H),
7.23−7.19 (m, 5H), 7.06 (br s, 1H), 3.03 (t, J = 7.6 Hz, 2H), 2.64 (t,
J = 7.6 Hz). 13C{1H} NMR (150 MHz, CDCl3) δ 170.3, 140.4, 137.9,
137.4, 128.7, 128.4, 126.5, 121.6, 87.4, 39.5, 31.4. HRMS (DART) m/
z: [M + H]+ calcd for C15H15BrNO 352.0198; found, 352.0193.
Condensation of 3a and 5k. 1j (15.0 mg, 50 μmol), 3-
phenylpropionic acid (3a) (7.5 mg, 50 μmol), N-methylaniline (5k)
(5.5 μL, 50 μmol), thioxanthone (2.12 mg, 10 μmol), and DCM (5.0
mL) were added into a screw-capped test tube filled with N2 gas
equipped with a magnetic stir bar. The mixture was stirred and
irradiated with a household fluorescent lamp that was placed 4.0 cm
from the reaction vessel. Temperature was kept at 20 °C using a
temperature-controlled water bath. After 24 h, the mixture was diluted
with DCM; washed with 1 M aqueous KHSO4, saturated aqueous
NaHCO3, and brine successively; dried over Na2SO4; filtered; and
concentrated in vacuo. NMR yield was determined to be 60% by
qNMR using 1,3,5-trimethoxybenzene as an internal standard.
Isolation yield was determined after purification with PTLC
(AcOEt/DCM = 1/99) to give 6ak as a colorless solid (7.3 mg, 61%).
1
N-Methyl-N,3-phenylpropanamide (6ak). H NMR (600 MHz,
CDCl3) δ 7.37−7.35 (m, 2H), 7.32−7.29 (m, 1H), 7.23−7.21 (m,
2H), 7.16 (t, J = 7.2 Hz, 1H), 7.05 (d, J = 7.2 Hz, 2H), 7.02 (d, J = 7.2
Hz, 2H), 3.25 (s, 3H), 2.91 (t, J = 7.9 Hz, 2H), 2.37 (t, J = 7.9 Hz,
2H). 13C{1H} NMR (150 MHz, CDCl3) δ 172.2, 144.0, 141.3, 129.7,
128.4, 128.3, 127.7, 127.3, 126.0, 37.3, 36.0, 31.8. HRMS (DART) m/
z: [M + H]+ calcd for C16H18NO 240.1388; found, 240.1380.
Procedure for Table 4. Aminocyclopropenone 1 (50 μmol), 3-
phenylpropionic acid 3a (7.5 mg, 50 μmol), 2-phenylethylamine 5a
(6.4 μL, 50 μmol), and DCM (5.0 mL) were added into a screw-
capped test tube filled with N2 gas equipped with a magnetic stir bar.
The mixture was irradiated with a UVB lamp (280−350 nm) that was
placed 8.0 cm from the reaction vessel. The temperature was kept at
20 °C using a temperature-controlled water bath. The reaction
progress was monitored by TLC. After 1 disappeared, the mixture was
diluted in DCM; washed with aqueous 1 M KHSO4, aqueous
NaHCO3, and brine; dried over Na2SO4; filtered; and concentrated in
vacuo. The product yield was determined by qNMR using 1,3,5-
trimethoxybenzene as an internal standard.
N-(4-Chlorophenyl)-3-phenylpropanamide (6ah). 1H NMR (600
MHz, CDCl3) δ 7.37 (d, J = 8.6 Hz, 2H), 7.30 (t, J = 7.4 Hz, 2H),
7.26−7.23 (m, 5H), 7.03 (br s, 1H), 3.05 (t, J = 7.6 Hz, 2H), 2.65 (t,
J = 7.6 Hz, 2H). 13C{1H} NMR (150 MHz, CDCl3) δ 170.3, 140.4,
136.2, 129.3, 129.0, 128.7, 128.4, 126.5, 121.1, 39.4, 31.5. HRMS
(DART) m/z: [M + H]+ calcd for C15H15ClNO 260.0842; found,
260.0852.
Condensation of 3a and 5i. 1j (15.0 mg, 50 μmol), 3-
phenylpropionic acid (3a) (7.5 mg, 50 μmol), 4-bromoaniline (5i)
(8.6 mg, 50 μmol), thioxanthone (2.12 mg, 10 μmol), and DCM (5.0
mL) were added into a screw-capped test tube filled with N2 gas
equipped with a magnetic stir bar. The mixture was stirred and
irradiated with a household fluorescent lamp that was placed 4.0 cm
from the reaction vessel. Temperature was kept at 20 °C using a
temperature-controlled water bath. After 24 h, the mixture was diluted
with DCM; washed with 1 M aqueous KHSO4, saturated aqueous
NaHCO3, and brine successively; dried over Na2SO4; filtered; and
concentrated in vacuo. NMR yield was determined to be 59% by
qNMR using 1,3,5-trimethoxybenzene as an internal standard.
Isolation yield was determined after purification with PTLC
(DCM/hexane = 19/1) to give 6ai as a colorless solid (9.3 mg, 61%).
Procedure for Table 5. Aminocyclopropenone 1 (50 μmol), 3-
phenylpropionic acid 3a (7.5 mg, 50 μmol), 2-phenylethylamine 5a
(6.4 μL, 50 μmol), photocatalyst (10 μmol), and DCM (5.0 mL)
were added into a screw-capped test tube filled with N2 gas equipped
with a magnetic stir bar. The mixture was irradiated with a blue LED
(450−500 nm) that was placed 4.0 cm from the reaction vessel. The
temperature was kept at 20 °C using a temperature-controlled water
b
bath. The reaction progress was monitored by TLC. After 24 h, the
mixture was diluted in DCM; washed with aqueous 1 M KHSO4,
aqueous NaHCO3, and brine; dried over Na2SO4; filtered; and
concentrated in vacuo. The yields of the condensation product and
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Article
recovered aminocyclopropenone were determined by qNMR using
1,3,5-trimethoxybenzene as an internal standard.
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Azides by Transition-Metal Photocatalysis. Angew. Chem., Int. Ed.
ASSOCIATED CONTENT
* Supporting Information
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.joc.0c02997.
■
sı
̈
2014, 53, 793−797. (b) Brachet, E.; Ghosh, T.; Ghosh, I.; Konig, B.
Visible light C−H amidation of heteroarenes with benzoyl azides.
Chem. Sci. 2015, 6, 987−992. (c) Scholz, S. O.; Farney, E. P.; Kim, S.;
Bates, D. M.; Yoon, T. P. Spin-Selective Generation of Triplet
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Detailed experimental procedure for the synthesis of
aminocyclopropenones (1a−m), UV−vis spectra of
aminocyclopropenones (1a−m) and photocatalysts
(8−12), cyclic voltammogram of 1a and 1j, and
fluorescence spectra for the Stern−Volmer fluores-
cence-quenching experiment (PDF)
AUTHOR INFORMATION
Corresponding Authors
■
Kenji Mishiro − Institute for Frontier Science Initiative,
Kanazawa University, Kanazawa 920-1192, Japan;
orcid.org/0000-0002-5071-7574; Email: mishiro@
p.kanazawa-u.ac.jp
(4) Poloukhtine, A.; Popik, V. V. Highly Efficient Photochemical
Generation of a Triple Bond: Synthesis, Properties, and Photo-
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Munetaka Kunishima − Faculty of Pharmaceutical Sciences,
Institute of Medical, Pharmaceutical, and Health Sciences,
Kanazawa University, Kanazawa 920-1192, Japan;
orcid.org/0000-0002-3296-490X; Email: kunisima@
p.kanazawa-u.ac.jp
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Authors
Mitsuki Nomura − Faculty of Pharmaceutical Sciences,
Institute of Medical, Pharmaceutical, and Health Sciences,
Kanazawa University, Kanazawa 920-1192, Japan
Taniyuki Furuyama − Graduate School of Natural Science
and Technology, Kanazawa University, Kanazawa 920-
1192, Japan; Japan Science and Technology Agency (JST)
PRESTO, Kawaguchi, Saitama 332-0012, Japan;
orcid.org/0000-0002-5435-1581
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Cycloalkine, I. Chem. Ber. 1961, 94, 3260−3275. (b) Agard, N. J.;
Prescher, J. A.; Bertozzi, C. R. A Strain-Promoted [3 + 2] Azide−
Alkyne Cycloaddition for Covalent Modification of Biomolecules in
Living Systems. J. Am. Chem. Soc. 2004, 126, 15046−15047.
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Med. Chem. 1996, 39, 2103−2117. (b) Talele, T. T. Acetylene Group,
Friend or Foe in Medicinal Chemistry. J. Med. Chem. 2020, 63, 5625−
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Complete contact information is available at:
https://pubs.acs.org/10.1021/acs.joc.0c02997
(10) Mishiro, K.; Kimura, T.; Furuyama, T.; Kunishima, M.
Phototriggered Active Alkyne Generation from Cyclopropenones
with Visible Light-Responsive Photocatalysts. Org. Lett. 2019, 21,
4101−4105.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
(11) (a) Viehe, H. G. Synthesis and Reactions of the Alkynylamines.
■
̈
Angew. Chem., Int. Ed. 1967, 6, 767. (b) Steglich, W.; Hofle, G.;
This research was supported by MEXT KAKENHI, Grant in
Aid for Early Career Scientists (20K15953), The Tokyo
Biochemical Research Foundation, and Kanazawa University
SAKIGAKE project 2020. K.M. acknowledges the support
from the Program to Disseminate Tenure Tracking System,
MEXT.
̈
̈
Konig, W.; Weygand, F. Reaktionen von Inaminen mit Carbonsaure-
̈
und N-Acyl-aminosaureanhydriden sowie Anlagerung an Oxazolone-
(5) und Pseudooxazolone-(5). Chem. Ber. 1968, 101, 308.
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(b) Li, Z.; Qian, L.; Li, L.; Bernhammer, J. C.; Huynh, H. V.; Lee, J.-
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Operationally simple hydrotrifluoromethylation of alkenes with
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ADDITIONAL NOTES
■
a
1H NMR was recorded at 45 °C (above the coalescence
temperature of the rotamers).
For entry 4, the reaction was stopped after 12 h because
b
multiple byproduct started to appear and the reaction rate
significantly decreased. For entry 5, aminocyclopropenone 1j
disappeared after 4 h; therefore, the reaction was stopped after
4 h irradiation.
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