Functionalized 4-carboxy- and 4-keto-2,3-dihydropyrroles via Ni(II)-catalyzed nucleophilic amine ring-opening cyclizations of cyclopropanes

Article abstract of DOI:10.1021/jo5001059

A general synthetic approach to vinylogous 4-carboxy- and 4-keto-2,3-dihydropyrroles is reported using Ni(ClO₄) ₂6H₂O as a Lewis acid catalyst for nucleophilic amine ring-opening cyclizations of donor-acceptor (D-A) cyclopropanes. This methodology provided good to excellent yields of functionalized 2,3-dihydropyrroles under milder reaction conditions than previously reported and is amenable to a variety of D-A cyclopropanes and primary amines.

Full text of DOI:10.1021/jo5001059

Article
pubs.acs.org/joc
Functionalized 4‑Carboxy- and 4‑Keto-2,3-dihydropyrroles via Ni(II)-
Catalyzed Nucleophilic Amine Ring-Opening Cyclizations of
Cyclopropanes
M. Cynthia Martin, Dadasaheb V. Patil, and Stefan France*
School of Chemistry and Biochemistry, Georgia Institute of Technology, Atlanta, Georgia 30332, United States
S
* Supporting Information
ABSTRACT: A general synthetic approach to vinylogous 4-
carboxy- and 4-keto-2,3-dihydropyrroles is reported using
Ni(ClO4)2·6H2O as a Lewis acid catalyst for nucleophilic
amine ring-opening cyclizations of donor−acceptor (D−A)
cyclopropanes. This methodology provided good to excellent
yields of functionalized 2,3-dihydropyrroles under milder
reaction conditions than previously reported and is amenable
to a variety of D−A cyclopropanes and primary amines.
INTRODUCTION
■
Among nitrogen-containing five-membered heterocycles, 2,3-
dihydropyrroles1,2 (1) have garnered significant attention in the
literature because of their presence in various natural products
and pharmaceutically relevant compounds (Figure 1).3 They
Figure 2. Amine ring-opening cyclizations of cyclopropanes to form
2,3-dihydropyrroles.
Figure 1. Reactivity of 2,3-dihydropyrroles.
from β-ketoesters.12a The reactions gave 4-carboxy-dihydro-
pyrroles in modest to good yields but were performed in
are also extremely versatile synthetic building blocks for the
preparation of functionalized pyrrolidines4 (2, their fully
reduced counterparts) and pyrroles5 (3, their fully oxidized
refluxing methanol in sealed tubes for up to 24 h or using the
amine as solvent under reflux (>140 °C) for up to 8 h. Charette
counterparts). 2,3-Dihydropyrroles can be readily exploited for
further functionalization because of the presence of the
enamine moiety. Moreover, when an electron-withdrawing
group is substituted at the 4-position on the dihydropyrrole,
reported the use of D−A cyclopropanes derived from α-nitro
ketones and α-cyano ketones for the formation of 4-nitro- and
4-cyano-dihydropyrroles, respectively.12c
Over the past 5 years, our group has reported several
extended conjugation with the enamine is observed, and
examples of Lewis acid-catalyzed intramolecular ring-opening
vinylogous reactivity is possible.
cyclizations of doubly activated D−A cyclopropanes derived
Surprisingly, this type of reactivity has not been reported for
dihydropyrroles in the synthetic literature. Thus, at the start of
this project, we aimed to address this gap in knowledge by
studying the reactivity of vinylogous 2,3-dihydropyrroles.
from 1,3-dicarbonyl compounds.13 Lewis acids have recently
been shown to promote ring-opening reactions of D−A
cyclopropanes in the presence of amines under milder
conditions. In representative examples by Charette14 and
However, we were surprised to find that despite the numerous
Tang,15 Ni(ClO4)2·6H2O effectively promotes the ring-opening
reactions of secondary amines with malonate-derived D−A
cyclopropanes to give homoconjugate addition products. As an
expansion of our work, we envisaged a milder approach to 4-
carboxy-dihydropyrroles via primary amine ring-opening
reported synthetic efforts toward 2,3-dihydropyrroles6−11
general methods that access vinylogous dihydropyrroles are
limited to a handful of examples.9b,12
The most general approach to 2,3-dihydropyrroles bearing
electron-withdrawing groups in the 4-position involves ring-
opening cyclizations of cyclopropyl ketones in the presence of
primary amines (Figure 2). Lhommet first reported this
approach for donor−acceptor (D−A) cyclopropanes derived
Received: January 17, 2014
Published: March 6, 2014
© 2014 American Chemical Society
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a
Table 1. Reaction Optimization
b
entry
R
loading
amine
temp
time (h)
% yield
1
2-propenyl (4a)
2-propenyl (4a)
2-propenyl (4a)
2-propenyl (4a)
2-propenyl (4a)
2-propenyl (4a)
2-propenyl (4a)
2-propenyl (4a)
2-propenyl (4a)
2-propenyl (4a)
phenyl (4b)
30 mol %
30 mol %
30 mol %
20 mol %
15 mol %
15 mol %
15 mol %
15 mol %
5 mol %
250 mol %
200 mol %
120 mol %
250 mol %
250 mol %
250 mol %
200 mol %
120 mol %
250 mol %
200 mol %
250 mol %
200 mol %
200 mol %
120 mol %
rt
3
89
60
50
67
50
65
67
2
rt
3
3
rt
3
4
rt
6
5
rt
>16
1
c
c
c
6
reflux
reflux
reflux
reflux
reflux
rt
7
1
8
2
80
c
9
2
47
56
77
52
70
c
10
11
12
13
14
5 mol %
2
30 mol %
15 mol %
15 mol %
15 mol %
2
phenyl (4b)
rt
>16
11
2
phenyl (4b)
reflux
reflux
phenyl (4b)
83
a
b
Reactions run with cyclopropane (1 equiv), benzyl amine, and Ni(ClO4)2·6H2O in CH2Cl2 according to conditions indicated. Isolated yield after
c
column chromatography. Variable amounts of 5w were observed.
cyclizations of D−A cyclopropanes in the presence of a Lewis
acid catalyst. In this article, we report the results of our studies.
water can undergo a 1,6-addition18 into the extended π-system
(Scheme 1). Proton transfer and isomerization generates
Scheme 1. Proposed Mechanism for Formation of
Dihydropyrrole 5w
RESULTS AND DISCUSSION
■
Using our previous work as a starting point,13a our studies
began with alkenyl cyclopropyl ketone 4a as the model
substrate. Ni(ClO4)2·6H2O was selected as the Lewis acid to
initiate the reaction optimization because of its demonstrated
success in amine-mediated cyclopropane ring-openings.14,15
Upon treatment of cyclopropane 4a and benzyl amine (2.5
equiv) in CH2Cl2 with Ni(ClO4)2·6H2O (30 mol %) at room
temperature, dihydropyrrole 5a was obtained in 89% yield after
3 h (Table 1, entry 1). Next, the amount of amine was reduced
to improve atom economy and overall reaction efficiency. At
both 2.0 and 1.2 equiv of benzylamine, decreased product yields
were observed (entries 2 and 3). Upon lowering the catalyst
loading to 20 mol %, dihydropyrrole 5a was obtained in 67%
yield after 6 h (entry 4). At 15 mol % catalyst, the reaction gave
a 50% yield, although it failed to go to completion even after
more than 16 h (entry 5). To push the reaction to completion,
the reaction was heated at reflux. Within 1 h, the reaction was
complete. When the reaction with 15 mol % Ni(ClO4)2·6H2O
was set up in CH2Cl2 at reflux from the beginning, the reaction
was completed within 1 h to give 5a in 65% yield (entry 6).
When the amount of amine was reduced to 2.0 and 1.2 equiv
while employing the refluxing conditions, yields of 67 and 80%
were obtained within 1 to 2 h (entries 7 and 8).16 Any attempts
to reduce the catalyst loading below 15 mol % failed to provide
good product yields (entries 9 and 10). Similarly, changing the
solvent has a deleterious effect on overall reaction efficiency and
product yields.17 Thus, the optimum conditions were 15 mol %
of Ni(ClO4)2·6H2O with 1.2 equiv of benzylamine in refluxing
CH2Cl2 or 1,2-dichloroethane.
alcohol II, which undergoes loss of formaldehyde and
protonation to give side product 5w.19 To alleviate this side
product issue, the model substrate was changed to cyclopropyl
phenyl ketone 4b. At 30 mol % of Ni(ClO4)2·6H2O with 2.5
equiv of benzylamine, dihydropyrrole 5b was obtained in 77%
yield (Table 1, entry 11). Further experimentation determined
the optimal conditions to be 15 mol % of Ni(ClO4)2·6H2O and
1.2 equiv of benzylamine in CH2Cl2 at reflux. This gave desired
dihydropyrrole 5b in 83% yield after 2 h (entry 14).
Next, a variety of Lewis acids were screened to find the
optimal Lewis acid catalyst (Table 2). Anhydrous Ni(OTf)2
was employed to probe the importance of the water ligands. A
reduced yield of 58% was obtained (entry 2). This result
supports the catalytic role of the nickel but also suggests the
importance of the water for amine exchange. As with Ni(II)
hydrates, copper(II) hydrates are known to complex with
amines by displacing water molecules.20 However, when
Cu(ClO4)2·6H2O was used as the catalyst, a meager 31%
yield was obtained (entry 3). To rule out the possibility that the
Unfortunately, variable amounts of the unexpected side
product 5w were observed in all of the reactions at reflux, which
accounted for the reduced yields (entries 6−10). As 5a is an
extended Michael acceptor, it is plausible that a molecule of
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a
amine readily reacted with 4b to give dihydropyrroles 5c and
5d in 63 and 81%, respectively.22 However, no reaction to give
5e was observed with tert-butyl amine, which is presumably the
result of unfavorable steric interactions that preclude
nucleophilic attack. Other functionalized aliphatic amines
such as 2-methoxyethan-1-amine and 3-(triethoxysilyl)propan-
1-amine also provided their respective dihydropyrroles, 5f and
5g, in 83 and 42% yields. Similarly, unprotected tryptamine
provided 5h in 84% yield. Allylamine provided dihydropyrrole
5i in 96% yield, whereas propargylamine afforded only 30% of
5j along with a number of byproducts. The poor reaction
efficiency is most likely because of competing reactions
resulting from coordination of the alkyne π-system with the
Ni catalyst.23 This coordination can influence the electro-
philicity of the alkyne π-system as well as reduce the pKa of the
alkynyl hydrogen. Aniline proved to be amenable to the
transformation, although the reaction had to be performed at
higher temperatures for full conversion to give N-aryl
dihydropyrrole 5k in 74% yield. Amines bearing strong
electron-withdrawing groups (e.g., acetamide and tosamide)
failed to give any measurable dihydropyrrole products even at
elevated temperatures because of reduced nucleophilicity.
A chiral amine was also employed in hopes of imparting
some diastereocontrol. Disappointingly, when 4b was treated
with (S)-1-phenylethan-1-amine, dihydropyrrole 5n was
obtained as a 1:1 diastereomeric mixture in 90% yield. The
poor observed selectivity is most likely due to an SN1-like ring-
opening that generates a transient carbocation prior to unbiased
nucleophilic attack.
Table 2. Lewis Acid Screening
b
entry
Lewis acid
time (h)
% yield
1
2
3
4
5
6
7
8
9
Ni(ClO4)2·6H2O
Ni(OTf)2
2
83
58
31
14
27
17
8
3
Cu(ClO4)2·6H2O
Li(ClO4)·3H2O
Sc(OTf)3
3
>16
>16
>16
>16
>16
>16
In(OTf)3
Al(OTf)3
Mg(OTf)2
6
Zn(OTf)2
5
a
Reactions run with cyclopropane (1 equiv), benzylamine (1.2 equiv),
and Lewis acid (15 mol %) in CH2Cl2 under reflux. Isolated yields
b
after column chromatography.
ligand is responsible for the observed catalysis, Li(ClO4)·3H2O
was employed but only gave 14% yield of 5b (entry 4). All
other catalyst systems (Sc3+, In3+, Al3+, Mg2+, and Zn2+) proved
to be highly ineffective, most likely to catalyst deactivation upon
amine complexation (entries 5−9). Thus, Ni(ClO4)2·6H2O
remained the most effective Lewis acid catalyst for this
transformation.21
To explore reaction generality, other primary amines were
employed under the optimized conditions with cyclopropane
4b (Table 3). Alkyl amines such as ethylamine and isopropyl-
a b
,
Table 3. Primary Amine Screening
a
b
Reactions run with cyclopropane (1 equiv), amine (1.2 equiv), and Ni(ClO4)2·6H2O (15 mol %) in 1,2-dichloroethane at reflux. Numbers in
c
d
parentheses represent isolated yields after column chromatography. Reaction run in CH2Cl2 under reflux. Reaction run in toluene under reflux.
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a b
,
Table 4. Donor−Acceptor Cyclopropane Screening
a
b
Reactions run with cyclopropane (1 equiv), benzylamine (1.2 equiv), and Ni(ClO4)2·6H2O (15 mol %) in CH2Cl2 at reflux for 2 h. Numbers in
c
d
parentheses represent isolated yields after column chromatography. Reactions performed in toluene under reflux. No desired products observed.
Scheme 2. One-Pot Tandem Cyclopropanation/Amine Ring-Opening Cyclization
The methodology was also applied to the reactions of
different D−A cyclopropanes with benzylamine. (Table 4). In
the previous reactions, only D−A cyclopropanes bearing a 4-
methoxyphenyl substituent as the donor group were explored
to help facilitate formation of the dihydropyrroles. When a
phenyl substituent was employed instead, dihydropyrrole 5o
was obtained in 85% yield. Similar results were observed for 4p,
where 4-fluorophenyl was the donor and 5p was generated in
88% yield. When the aromatic substituent bears a strong
electron-withdrawing group, the reaction efficiency is reduced,
and a low yield of dihydropyrrole 5q is attained. When a
geminal methyl and phenyl group are the donors, the 2,2-
disubstituted dihydropyrrole 5r is observed in 79% yield. D−A
cyclopropanes bearing a single alkyl donor do not provide the
desired dihydropyrrole products. Cyclopropane 4t, with a
methylene silyl donor substituent, proved incompatible with
the reaction conditions because other major products were
observed. Cyclopropane 4u (derived from indene) reacted to
give 37% of 5u in toluene at reflux. No reaction was observed at
reduced temperatures. A similar result (44%) was achieved for
5v, which also contains substituents in both the 2- and 3-
positions. Both outcomes appear to be the result of steric
effects associated with the amine approaching the sterically
congested cyclopropanes.
Cyclopropanes derived from other β-ketoesters were also
subjected to the reaction conditions. Dihydropyrrole 5w was
successfully prepared in 85% yield from the corresponding
cyclopropyl ethyl ketone. Similarly, the cyclopropyl 2-thienyl
ketone afforded desired product 5x in 83% yield. Alternatively,
dimethyl malonate-derived cylopropane 4y gave pyrrolidin-2-
one 5y in 63% yield upon workup/purification. This result is
consistent with observations made by Yamagata.12b
1,3-Diketones have not previously been studied in the amine
ring-opening cyclizations. To examine their compatibility,
cyclopropanes 4z (from a symmetric 1,3-diketone) and 4aa
(from an unsymmetric 1,3-diketone) were synthesized and
treated with benzylamine under the reaction conditions.
Cyclopropane 4z provided its product 5z in 78% yield. In the
case of 4aa (from the unsymmetric 1,3-diketone), regioisomers
are possible. Fortunately, the only product observed is the one
that has the phenyl ring in conjugation with the enone π-system
(5aa).
Given that both the syntheses of the D−A cyclopropanes
(via Rh-catalyzed cyclopropanation of alkenes with α-diazo
carbonyls) and the dihydropyrroles take place in CH2Cl2, a
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resolution of 10 000 using PFK (perfluorokerosene) as an internal
calibrant. Uncorrected melting points were measured with a digital
melting-point apparatus.
tandem one-pot cyclopropanation/amine ring-opening cycliza-
tion was explored (Scheme 2). In a representative example,
methyl 2-diazo-3-oxo-3-phenylpropanoate 6b was first reacted
with 4-vinylanisole in the presence of 0.1 mol % Rh2esp2 to
form cyclopropane 4b. After 30 min, benzylamine (1.2 equiv)
and Ni(ClO4)2·6H2O (15 mol %) were added simultaneously,
and the reaction mixture was heated at reflux.24 Desired
dihydropyrrole 5b was obtained in 68% yield, which
corresponds to an average of ∼82% yield per step.
The 2,3-dihydropyrrole products could be smoothly
converted to the corresponding pyrroles in the presence of
1,2-dichloro-5,6-dicyanobenzoquinone (DDQ).12c,25 For in-
stance, when dihydropyrroles 5n and 5w were subjected to
DDQ in toluene at reflux, pyrroles 7n and 7w were formed in
65 and 62% yields, respectively (Scheme 3). Thus, highly
substituted pyrroles are readily accessible using the method-
ology.
Synthesis of Cyclopropanes 4. Cyclopropanes 4a,13a 4x,13b 4y,26
4z,27 and 4aa28 were prepared according to previously reported
methods. The remaining cyclopropanes were synthesized according to
one of the two following methods.
General Method A. The corresponding alkene (1.0 equiv) was
added to a solution Rh2esp2 (0.1 mol %) in DCM at 0 °C. After
stirring for 5 min, a solution of the α-diazo ester (1.0 equiv) was added
in one shot and allowed to stir for 10 min at 0 °C. The ice bath was
removed, and the reaction was allowed to warm to room temperature.
After 1 h the reaction was quenched with saturated aqueous thiourea
and allowed to stir for 30 min. The organic layer was collected, and the
aqueous layer was extracted with DCM three times. Then, the organic
layer was washed with brine, dried with Na2SO4, and concentrated,
and column chromatography afforded the desired products.
General Method B. A solution of Grignard reagent (1.5 equiv) was
added slowly to a stirred solution of Weinreb amide in THF (10 mL)
at 0 °C. The solution was stirred for 5 min at this temperature and
then allowed to warm gradually to room temperature. The reaction
was monitored by TLC. The solution was then quenched with
saturated aqueous ammonium chloride, extracted with Et2O (three
times), washed with brine, dried over MgSO4, and concentrated under
reduced pressure.
Scheme 3. DDQ-Mediated Conversion of Dihydropyrroles
to Pyrroles
Methyl 1-Benzoyl-2-(4-methoxyphenyl)cyclopropane-1-car-
boxylate (4b). According to general method B, a solution of
phenyllithium (6.89 mL, 12.4 mmol) was added slowly to a stirred
solution of methyl 1-(methoxy(methyl)carbamoyl)-2-(4-
methoxyphenyl)cyclopropane-1-carboxylate (2.80 g, 9.55 mmol) in
THF (35 mL) at 0 °C to afford 4b (1.68 g, 57% yield) after
purification via flash chromatography (25% EtOAc/hexane, Rf = 0.42)
1
as a yellow solid (mp 79−80 °C). H NMR (300 MHz, CDCl3): δ
7.95−7.89 (m, 2H), 7.55−7.49 (m, 1H), 7.46−7.39 (m, 2H), 7.25−
7.21 (m, 1H), 6.85−6.80 (m, 2H), 3.73 (s, 3H), 3.52 (t, J = 8.6 Hz,
1H), 3.22 (s, 3H), 2.40 (dd, J = 4.8, 8.1 Hz, 1H), 1.66 (dd, J = 4.8, 9.1
Hz, 1H). 13C NMR (75 MHz, CDCl3): δ 194.2, 168.7, 158.5, 136.9,
132.7, 129.8, 128.3, 127.9, 126.4, 113.2, 54.8, 51.9, 42.0, 30.0, 20.0. IR:
2951 (s), 2836 (s), 1731 (s), 1674 (s), 1611 (s), 1597 (s), 1580 (s),
1515 (s) cm−1. HRMS (EI) m/z: [M]+ calcd for C19H18O4, 310.1205;
found, 310.1202.
In summary, we have developed an efficient and general
Ni(II)-catalyzed approach to 4-keto- and 4-carboxy-2,3-
dihydropyrroles using activated D−A cyclopropanes under
milder conditions than previously reported. The method is
amenable to a variety of primary amine nucleophiles as well as
substituted D−A cyclopropanes to provide highly substituted
dihydropyrroles. Furthermore, the dihydropyrrole products can
readily undergo derivatization to serve as building blocks for
chemical synthesis. Future work will examine the vinylogous
reactivity of these substrates for the efficient synthesis of
complex, bioactive molecules.
Methyl 1-Benzoyl-2-phenylcyclopropane-1-carboxylate
(4o). According to general method B, a solution of phenyllithium
(1.12 mL, 2.02 mmol) was added slowly to a stirred solution of methyl
1-(methoxy(methyl)carbamoyl)-2-phenylcyclopropane-1-carboxylate
(408 mg, 1.55 mmol) in THF (35 mL) at 0 °C to afford 4o (95.8 mg,
22% yield) after purification via flash chromatography (25% EtOAc/
1
hexane, Rf = 0.64) as a yellow solid (mp 91−92 °C). H NMR (300
MHz, CDCl3): δ 7.95−7.90 (m, 2H), 7.59−7.53 (m, 1H), 7.49−7.43
(m, 2H), 7.33−7.29 (m, 3H), 7.28−7.23 (m, 2H), 3.57 (t, J = 8.6 Hz,
1H), 3.24 (s, 3H), 2.45 (dd, J = 4.8, 8.1 Hz, 1H), 1.69 (dd, J = 4.9, 9.1
Hz, 1H). 13C NMR (75 MHz, CDCl3): δ 194.4, 168.8, 136.9, 134.7,
132.9, 129.0, 128.5, 128.1, 127.2, 52.1, 42.2, 30.6, 20.0. IR: 3058 (s),
3002 (s), 2952 (s), 1728 (m), 1677 (w), 1596 (s) cm−1. HRMS (EI)
m/z: [M]+ calcd for C18H16O3, 280.1099; found, 280.1104.
EXPERIMENTAL SECTION
■
General Information. Chromatographic purification was per-
formed as flash chromatography with Dynamic Adsorbents silica gel
(32−65 μm) and solvents indicated as eluent with 0.1−0.5 bar
pressure. For quantitative flash chromatography, technical grades
solvents were utilized. Analytical thin-layer chromatography (TLC)
was performed on EMD silica gel 60 F254 TLC glass plates.
Visualization was accomplished with UV light. Infrared (IR) spectra
were obtained using a FTIR with an ATR attachment and by
attenuated total reflection (ATR) through a diamond plate. The IR
bands are characterized as weak (w), medium (m), and strong (s).
Proton and carbon nuclear magnetic resonance spectra (1H and 13C
NMR) were recorded on a 300 or 500 MHz spectrometer with solvent
resonances as the internal standard (1H NMR: CDCl3 at 7.26 ppm;
13C NMR: CDCl3 at 77.0 ppm). 1H NMR data are reported as follows:
chemical shift (ppm), multiplicity (s = singlet, d = doublet, dd =
doublet of doublets, dt = doublet of triplets, ddd = doublet of doublet
of doublets, t = triplet, m = multiplet, and br = broad), coupling
constants (Hz), and integration. The accurate mass analyses were run
in EI mode using a double-focusing magnetic analyzer at a mass
Methyl 1-Benzoyl-2-(4-fluorophenyl)cyclopropane-1-car-
boxylate (4p). According to general method B, a solution of
phenyllithium (1.13 mL, 2.04 mmol) was added slowly to a stirred
solution of methyl 2-(4-fluorophenyl)-1-(methoxy(methyl)-
carbamoyl)cyclopropane-1-carboxylate (478 mg, 1.70 mmol) in THF
(35 mL) at 0 °C to afford 4p (100 mg, 20% yield) after purification via
flash chromatography (25% EtOAc/hexane, Rf = 0.54) as a pale yellow
solid (mp 93−94 °C). 1H NMR (300 MHz, CDCl3): δ 7.94−7.89 (m,
2H), 7.59−7.52 (m, 1H), 7.49−7.42 (m, 1H), 7.32−7.24 (m, 2H),
7.02−6.94 (m, 2H), 3.53 (t, J = 8.6 Hz, 1H), 3.25 (s, 3H), 2.41 (dd, J
= 5.0, 8.1 Hz, 1H), 1.68 (dd, J = 4.9, 9.1 Hz, 1H). 13C NMR (75 MHz,
CDCl3): δ 194.1, 168.7, 163.5, 160.3, 136.8, 132.9, 130.5, 128.5, 128.1,
114.9, 52.1, 42.1, 29.7, 20.0. IR: 3003 (s), 2952 (s), 1725 (m), 1684
(m), 1597 (s), 1580 (s), 1510 (m) cm−1. HRMS (EI) m/z: [M]+ calcd
for C18H15FO3, 298.1005; found, 298.1011.
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Methyl 1-Benzoyl-2-(4-nitrophenyl)cyclopropane-1-carbox-
ylate (4q). According to general method A, to a solution of Rh2esp2
(1.90 mg, 2.45 μmol) in DCM was added 4-nitrostyrene (0.31 mL,
2.45 mmol) followed by a solution of methyl 2-diazo-3-oxo-3-
phenylpropanoate (500 mg, 2.45 mmol). The reaction was quenched,
and column chromatography afforded 4q (25% EtOAc/hexane, Rf =
quenched, and column chromatography afforded 4u (25% EtOAc/
hexane, Rf = 0.58) as a white solid (mp 96−97 °C) (323 mg, 45%
yield). 1H NMR (300 MHz, CDCl3): δ 7.96−7.91 (m, 2H), 7.57−7.51
(m, 1H), 7.48−7.40 (m, 3H), 7.25−7.17 (m, 3H), 3.77−3.73 (m, 1H),
3.68 (s, 1H), 3.41−3.31 (m, 1H), 3.13 (s, 3H), 2.70 (dt, J = 0.9, 6.6
Hz, 1H). 13C NMR (75 MHz, CDCl3): δ 194.7, 167.8, 144.0, 138.7,
137.4, 132.5, 128.3, 127.8, 126.9, 126.3, 124.9, 124.0, 51.6, 44.0, 39.2,
33.4. IR: 3056 (s), 2946 (s), 1728 (m), 1669 (w), 1596 (s), 1579 (s)
cm−1. HRMS (EI) m/z: [M]+ calcd for C19H16O3, 292.1099, Obs.
292.1105.
1
0.54) as a white solid (mp 121−122 °C) (47 mg, 6.0% yield). H
NMR (300 MHz, CDCl3): δ 8.16 (d, J = 8.9 Hz, 1H), 7.91 (d, J = 7.1
Hz, 1H), 7.64−7.55 (m, 1H), 7.53−7.43 (m, 4H), 3.60 (t, J = 8.5 Hz,
1H), 3.27 (s, 3H), 2.49 (dd, J = 5.0, 8.1 Hz, 1H), 1.77 (dd, J = 5.1, 9.0
Hz, 1H). 13C NMR (75 MHz, CDCl3): δ 193.3, 168.4, 147.1, 142.7,
136.3, 133.3, 129.9, 128.8, 128.2, 123.3, 52.5, 42.6, 29.7, 19.9. IR: 2952
(s), 2848 (s), 1733 (m), 1676 (m), 1596 (s), 1515 (m) cm−1. HRMS
(EI) m/z: [M]+ calcd for C18H15NO5, 325.0950; found, 325.0951.
Methyl 1-Benzoyl-2-methyl-2-phenylcyclopropane-1-car-
boxylate (4r). According to general method A, to a solution of
Rh2esp2 (2.60 mg, 3.43 μmol) in DCM was added α-methylstyrene
(0.45 mL, 3.43 mmol) followed by a solution of methyl 2-diazo-3-oxo-
3-phenylpropanoate (700 mg, 3.43 mmol). The reaction was
quenched, and column chromatography afforded 4r (25% EtOAc/
hexane, Rf = 0.57) as a white solid (mp 86−87 °C) (595 mg, 59%
yield). Diastereomeric ratio: 10:1. Major diastereomer: 1H NMR (300
MHz, CDCl3): δ 8.12−8.06 (m, 2H), 7.57−7.38 (m, 5H), 7.35−7.27
(m, 2H), 7.26−7.18 (m, 1H), 3.25 (s, 3H), 2.34 (d, J = 4.9 Hz, 1H),
1.75 (d, J = 5.0 Hz, 1H), 1.35 (s, 3H). 13C NMR (75 MHz, CDCl3): δ
193.4, 168.9, 141.2, 136.8, 132.9, 132.2, 128.8, 127.9, 126.7, 51.8, 42.9,
37.6, 25.1, 24.9. IR: 3060 (s), 2997 (s), 2949 (s), 2923 (s), 1724 (m),
1681 (w), 1595 (s), 1578 (s) cm−1. HRMS (EI) m/z: [M]+ calcd for
C19H18O3, 294.1256; found, 294.1253.
Methyl 1-Benzoyl-2-methyl-3-phenylcyclopropane-1-car-
boxylate (4v). According to general method A, to a solution of
Rh2esp2 (1.90 mg, 2.45 μmol) in DCM was added β-methylstyrene
(0.32 mL, 2.45 mmol) followed by a solution of methyl 2-diazo-3-oxo-
3-phenylpropanoate (500 mg, 2.45 mmol). The reaction was
quenched, and column chromatography afforded 4v (25% EtOAc/
hexane, Rf = 0.68) as a colorless oil (143 mg, 20% yield).
1
Diastereomeric ratio: 11:1. H NMR (300 MHz, CDCl3): δ 8.00−
7.94 (m, 2H), 7.59−7.53 (m, 1H), 7.52−7.23 (m, 8H), 3.50 (d, J = 9.7
Hz, 1H), 3.41 (s, 3H), 2.11−1.99 (m, 1H), 1.63 (d, J = 6.7 Hz, 3H).
13C NMR (75 MHz, CDCl3): δ 194.6, 169.1, 136.8, 133.8, 132.6,
130.1, 129.7, 128.1, 127.3, 126.8, 51.6, 42.3, 33.5, 28.2, 9.7. IR: 3027
(s), 2949 (s), 1737 (s), 1677 (s), 1597 (s), 1580 (s) cm−1. HRMS (EI)
m/z: [M]+ calcd for C19H18O3, 294.1256; found, 294.1247.
Methyl 2-(4-Methoxyphenyl)-1-propionylcyclopropane-1-
carboxylate (4w). According to general method B, a solution of
ethyl-magnesium bromide (6.20 mL, 6.14 mmol) was added slowly to
a stirred solution of methyl 1-(methoxy(methyl)carbamoyl)-2-(4-
methoxyphenyl)cyclopropane-1-carboxylate (1.20 g, 4.09 mmol) in
THF (35 mL) at 0 °C to afford 4w (300 mg, 28% yield) after
purification via flash chromatography (25% EtOAc/hexane, Rf = 0.58)
as a colorless oil. 1H NMR (300 MHz, CDCl3): δ 7.11−7.05 (m, 2H),
6.82−6.74 (m, 2H), 3.75 (s, 3H), 3.36 (s, 3H), 3.21 (t, J = 8.6 Hz,
1H), 3.06−2.92 (m, 1H), 2.70−2.56 (m, 1H), 2.16 (dd, J = 4.6, 8.0
Hz, 1H), 1.67 (dd, J = 4.6, 9.1 Hz, 1H), 1.08 (t, J = 7.2 Hz, 2H). 13C
NMR (75 MHz, CDCl3): δ 204.9, 168.8, 158.7, 129.7, 126.8, 113.4,
55.1, 51.9, 44.2, 35.0, 34.6, 21.5, 8.0. IR: 2938 (s), 2837 (s), 1704 (m),
1612 (s), 1582 (s) cm−1. HRMS (EI) m/z: [M]+ calcd for C15H18O4,
262.1205; found, 262.1204.
Reaction Optimization Procedures. Procedure for Catalyst
and Amine Loading at Varying Temperatures. To a flask containing
the nickel catalyst with the appropriate loading (5, 15, 20, or 30 mol
%) and benzylamine with the appropriate loading (120, 200, or 250
mol %) in anhydrous DCM was added either cyclopropane 4a or 4b,
and the reaction was allowed to go at room temperature or under
reflux. The reaction was monitored via TLC, and upon complete
disappearance of the starting material, the reaction was dried over
MgSO4 and filtered. Column chromatography provided pure desired
product 5a or 5b.
Procedure for Catalyst Screening. To a flask containing the
appropriate catalyst (15 mol %) and benzylamine (120 mol %) in
anhydrous DCM was added cyclopropane 4b, and the reaction was
allowed to go under reflux. The reaction was monitored via TLC, and
upon complete disappearance of the starting material, the reaction was
dried over MgSO4 and filtered. Column chromatrography provided
pure product 5b.
Procedure for Solvent Screening. To a flask containing the nickel
catalyst (15 mol %) and benzylamine (200 mol %) in the appropriate
solvent (THF, Et2O, toluene, DCE, acetone, or MeCN) was added
cyclopropane 4a, and the reaction was allowed to go under reflux. The
reaction was monitored via TLC, and upon complete disappearance of
the starting material, the reaction was dried over MgSO4 and filtered.
Column chromatography provided pure product 5a.
Methyl 1-Benzoyl-2-butylcyclopropane-1-carboxylate (4s).
According to general method A, to a solution of Rh2esp2 (0.90 mg,
1.22 μmol) in DCM was added n-hexene (0.15 mL, 1.22 mmol)
followed by a solution of methyl 2-diazo-3-oxo-3-phenylpropanoate
(250 mg, 1.22 mmol). The reaction was quenched, and column
chromatography afforded 4s (25% EtOAc/hexane, Rf = 0.72) as a
1
colorless liquid (124 mg, 39% yield). Diastereomeric ratio: 3:1. H
NMR (300 MHz, CDCl3): δ 7.91−7.81 (m, 3.00), 7.57−7.49 (m,
1.37), 7.47−7.37 (m, 3.09), 3.53 (s, 0.83), 3.51 (s, 2.43), 2.23−2.11
(m, 1.22), 1.67 (dd, J = 4.4, 7.7 Hz, 1.10), 1.60−1.48 (m, 2.83), 1.43−
1.29 (m, 5.70), 0.92−0.86 (m, 2.76), 0.84−0.76 (m, 0.91). 13C NMR
(75 MHz, CDCl3): δ 194.9, 170.6, 137.3, 137.0, 132.7, 132.5, 130.1,
128.4, 128.3, 127.9, 127.3, 77.4, 77.0, 76.6, 52.1, 52.1, 52.0, 38.6, 37.5,
31.1, 29.4, 27.9, 27.0, 26.7, 22.1, 22.1, 22.0, 20.4, 13.8, 13.7. IR: 2955
(s), 2929 (s), 2861 (s), 1730 (m), 1678 (w), 1598 (s), 1581 (s) cm−1.
HRMS (EI) m/z: [M]+ calcd for C16H20O3, 260.1412; found,
260.1413.
Methyl 1-Benzoyl-2-((trimethylsilyl)methyl)cyclopropane-1-
carboxylate (4t). According to general method A, to a solution of
Rh2esp2 (1.90 mg, 2.45 μmol) in DCM was added allyltrimethylsilane
(0.39 mL, 2.45 mmol) followed by a solution of methyl 2-diazo-3-oxo-
3-phenylpropanoate (500 mg, 2.45 mmol). The reaction was
quenched, and column chromatography afforded 4t (25% EtOAc/
hexane, Rf = 0.72) as a colorless oil (431 mg, 61% yield).
Diastereomeric ratio: 3:1. 1H NMR (500 MHz, CDCl3): δ 7.89−
7.83 (m, 3.00), 7.55−7.50 (m, 1.30), 7.48−7.40 (m, 2.99), 3.53 (s,
1.13), 3.52 (s, 2.94), 2.23−2.16 (m, 1.06), 1.61 (dd, J = 4.3, 7.9 Hz,
1.04), 1.56 (dd, J = 4.3, 7.6 Hz, 0.38), 1.50 (dd, J = 4.5, 9.1 Hz, 0.38),
1.45 (dd, J = 4.4, 9.0 Hz, 1.02), 0.89 (dd, J = 4.4, 14.4 Hz, 1.01), 0.80
(dd, J = 2.7, 14.2 Hz, 0.39), 0.67 (dd, J = 10.7, 14.5 Hz, 1.00), 0.09 (s,
0.90), 0.07 (s, 8.85), 0.03 (s, 3.30). 13C NMR (126 MHz, CDCl3): δ
195.0, 170.7, 172.0, 137.5, 132.8, 132.6, 130.2, 129.2, 128.5, 128.5,
128.5, 128.4, 128.0, 127.6, 127.5, 77.3, 77.0, 76.8, 52.2, 52.1, 39.5, 38.1,
26.9, 24.5, 24.4, 23.8, 21.7, 15.6, 14.3. IR: 2953 (s), 2898 (s), 1727
(m), 1676 (w), 1597 (s), 1581 (s) cm−1. HRMS (EI) m/z: [M]+ calcd
for C16H22O3Si, 290.1338; found, 290.1333.
Synthesis of Dihydropyrroles. General Procedure. The
corresponding cyclopropane (1.0 equiv) was added to a stirring
solution of Ni(ClO4)2·6H2O (15 mol %) and amine (1.2 equiv) in
DCM (4−5 mL) or DCE (4−5 mL) or toluene (4−5 mL) at room
temperature. The reaction was allowed to go under reflux. After 2 h,
the reaction was dried over MgSO4 and filtered. The organic filtrate
Methyl 1-Benzoyl-1,1a,6,6a-tetrahydrocyclopropa[a]-
indene-1-carboxylate (4u). According to general method A, to a
solution of Rh2esp2 (1.90 mg, 2.45 μmol) in DCM was added indene
(285 mg, 2.45 mmol) followed by a solution of methyl 2-diazo-3-oxo-
3-phenylpropanoate (500 mg, 2.45 mmol). The reaction was
3035
dx.doi.org/10.1021/jo5001059 | J. Org. Chem. 2014, 79, 3030−3039

The Journal of Organic Chemistry
Article
was concentrated using a rotary evaporator, and column chromatog-
raphy provided the pure desired products.
(dd, J = 11.9, 15.2 Hz, 1H), 3.15 (s, 2H), 3.11−3.01 (m, 1H), 2.90−
2.80 (m, 2H). 13C NMR (75 MHz, CDCl3): δ 166.4, 162.2, 159.1,
135.1, 132.2, 128.7, 128.0, 114.0, 96.3, 70.3, 65.3, 58.6, 55.2, 50.0, 44.4,
38.5. IR: 2949 (s), 1681 (s), 1611 (s), 1575 (s), 1512 (s) cm−1. HRMS
(EI) m/z: [M]+ calcd for C22H25NO4, 367.1627; found, 367.1624.
Methyl 5-(4-Methoxyphenyl)-2-phenyl-1-(3-(triethoxysilyl)-
propyl)-4,5-dihydro-1H-pyrrole-3-carboxylate (5g). According to
the general procedure, cyclopropane 4b (75 mg, 0.242 mmol) was
added to a stirring solution of Ni(ClO4)2·6H2O (13.3 mg, 0.0363
mmol) and 3-(triethoxysilyl)propan-1-amine (0.05 mL, 0.290 mmol)
in DCE (5 mL) to afford 5g (53.2 mg, 42% yield) after purification via
flash chromatography (25% EtOAc/hexane, Rf = 0.38) as a colorless
Methyl 1-Benzyl-5-(4-methoxyphenyl)-2-(prop-1-en-2-yl)-4,5-di-
hydro-1H-pyrrole-3-carboxylate (5a). According to the general
procedure, cyclopropane 4a (75 mg, 0.273 mmol) was added to a
stirring solution of Ni(ClO4)2·6H2O (15.0 mg, 0.041 mmol) and
benzylamine (0.04 mL, 0.328 mmol) in DCM (4 mL) to afford 5a
(79.1 mg, 80% yield) after purification via flash chromatography (25%
1
EtOAc/hexane, Rf = 0.40) as a colorless oil. H NMR (300 MHz,
CDCl3): δ 7.36−7.25 (m, 3H), 7.15−7.05 (m, 4H), 6.87 (d, J = 8.4
Hz, 2H), 5.37 (s, 1H), 5.12 (s, 1H), 4.61−4.49 (m, 2H), 3.81 (s, 3H),
3.74 (d, J = 15.8 Hz, 1H), 3.65 (s, 3H), 3.30 (dd, J = 12.5, 14.9 Hz,
1H), 2.77 (dd, J = 7.1, 15.1 Hz, 1H), 2.08 (s, 3H). 13C NMR (75
MHz, CDCl3): δ 166.3, 163.7, 159.1, 137.3, 134.5, 128.5, 127.9, 127.3,
117.2, 114.1, 104.9, 93.5, 63.1, 55.2, 50.1, 47.6, 37.5, 22.3. IR: 2946 (s),
1670 (s), 1611 (s), 1567 (s), 1511 (s) cm−1. HRMS (EI) m/z: [M]+
calcd for C23H25NO3, 363.1834; found, 363.1831.
1
oil. H NMR (300 MHz, CDCl3): δ 7.45−7.28 (m, 8H), 6.94−6.87
(m, 2H), 4.76 (dd, J = 8.4, 12.0 Hz, 1H), 3.81 (s, 3H), 3.69 (q, J = 7.0
Hz, 6H), 3.47 (s, 3H), 3.39 (dd, J = 12.1, 15.1 Hz, 1H), 2.87−2.77 (m,
2H), 2.69−2.59 (m, 1H), 1.15 (t, J = 7.0 Hz, 9H). 13C NMR (75
MHz, CDCl3): δ 166.5, 162.4, 159.1, 135.1, 132.5, 128.7, 128.0, 128.0,
128.0, 114.1, 95.8, 64.5, 58.3, 55.3, 50.1, 47.8, 38.5, 20.9, 18.2, 7.4. IR:
2972 (s), 2926 (s), 1682 (s), 1611 (s), 1573 (s), 1511 (s) cm−1.
HRMS (EI) m/z: [M]+ calcd for C28H39NO6Si, 513.2359; found,
513.2379.
Methyl 1-Benzyl-5-(4-methoxyphenyl)-2-phenyl-4,5-dihydro-1H-
pyrrole-3-carboxylate (5b). According to the general procedure,
cyclopropane 4b (50 mg, 0.161 mmol) was added to a stirring solution
of Ni(ClO4)2·6H2O (8.80 mg, 0.0241 mmol) and benzylamine (0.02
mL, 0.193 mmol) in DCM (4 mL) to afford 5b (53.6 mg, 83% yield)
after purification via flash chromatography (25% EtOAc/hexane, Rf =
0.44) as a colorless oil. 1H NMR (300 MHz, CDCl3): δ 7.50−7.43 (m,
5H), 7.31−7.25 (m, 5H), 7.03−6.99 (m, 2H), 6.94 (d, J = 8.8 Hz,
2H), 4.63 (dd, J = 8.1, 12.3 Hz, 1H), 4.30 (d, J = 15.7 Hz, 1H), 3.86 (s,
3H), 3.69 (d, J = 15.7 Hz, 1H), 3.53 (s, 3H), 3.41 (dd, J = 12.3, 15.2
Hz, 1H), 2.90 (dd, J = 8.1, 15.3 Hz, 1H). 13C NMR (75 MHz,
CDCl3): δ 166.5, 161.8, 159.1, 137.0, 134.6, 132.0, 128.9, 128.4, 128.1,
127.7, 127.3, 114.1, 96.3, 63.1, 55.2, 50.1, 48.3, 38.2. IR: 2946 (s),
2836 (s), 1662 (s), 1610 (s), 1575 (s), 1511 (m) cm−1. HRMS (EI)
m/z: [M]+ calcd for C26H25NO3, 399.1834; found, 399.1832.
Methyl 1-Ethyl-5-(4-methoxyphenyl)-2-phenyl-4,5-dihydro-1H-
pyrrole-3-carboxylate (5c). According to the general procedure,
cyclopropane 4b (81 mg, 0.261 mmol) was added to a stirring solution
of Ni(ClO4)2·6H2O (14.3 mg, 0.0391 mmol) and ethylamine (0.16
mL, 0.313 mmol) in DCE (4 mL) to afford 5c (55.8 mg, 63% yield)
after purification via flash chromatography (25% EtOAc/hexane, Rf =
0.42) as a colorless oil. 1H NMR (300 MHz, CDCl3): δ 7.48−7.30 (m,
7H), 6.92 (d, J = 8.5 Hz, 2H), 4.78 (dd, J = 9.1, 12.0 Hz, 1H), 3.82 (s,
3H), 3.48 (s, 3H), 3.39 (dd, J = 12.1, 14.9 Hz, 1H), 2.95 (qd, J = 7.2,
14.4 Hz, 1H), 2.83 (dd, J = 9.4, 15.4 Hz, 1H), 2.69 (qd, J = 7.0, 14.4
Hz, 1H), 0.81 (t, J = 7.1 Hz, 2H). 13C NMR (75 MHz, CDCl3): δ
166.4, 162.3, 159.1, 135.0, 132.5, 128.6, 128.0, 114.0, 96.3, 64.2, 55.2,
50.0, 39.7, 38.5, 12.7. IR: 2947 (s), 1677 (s), 1612 (s), 1572 (s), 1511
(s) cm−1. HRMS (EI) m/z: [M]+ calcd for C21H23NO3, 337.1678;
found, 337.1668.
Methyl 1-(2-(1H-Indol-3-yl)ethyl)-5-(4-methoxyphenyl)-2-phenyl-
4,5-dihydro-1H-pyrrole-3-carboxylate (5h). According to the general
procedure, cyclopropane 4b (100 mg, 0.322 mmol) was added to a
stirring solution of Ni(ClO4)2·6H2O (17.7 mg, 0.0484 mmol) and
tryptamine (62.0 mg, 0.387 mmol) in DCE (5 mL) to afford 5h (122
mg, 84% yield) after purification via flash chromatography (25%
1
EtOAc/hexane, Rf = 0.083) as a colorless oil. H NMR (300 MHz,
CDCl3): δ 7.94 (br s, 1H), 7.42−7.24 (m, 7H), 7.11 (t, J = 7.6 Hz,
1H), 6.96−6.89 (m, 3H), 6.86−6.81 (m, 1H), 6.72 (d, J = 2.3 Hz,
1H), 4.84 (dd, J = 8.7, 12.0 Hz, 1H), 3.83 (s, 3H), 3.49 (s, 3H), 3.41
(dd, J = 12.1, 15.0 Hz, 1H), 3.27−3.16 (m, 1H), 2.99−2.74 (m, 3H),
2.62−2.51 (m, 1H). 13C NMR (75 MHz, CDCl3): δ 166.6, 162.3,
159.2, 136.0, 135.0, 132.3, 128.7, 128.1, 128.1, 128.1, 127.0, 121.9,
119.1, 118.4, 118.4, 114.1, 112.6, 111.0, 96.0, 77.4, 77.0, 76.6, 64.9,
55.3, 50.1, 45.8, 38.5, 23.9. IR: 3273 (s), 2918 (s), 2851 (s), 1658 (m),
1622 (m), 1608 (s), 1567 (s), 1540 (m), 1533 (m) cm−1. HRMS (EI)
m/z: [M]+ calcd for C29H28N2O3, 452.2100; found, 452.2104.
Methyl 1-Allyl-5-(4-methoxyphenyl)-2-phenyl-4,5-dihydro-1H-
pyrrole-3-carboxylate (5i). According to the general procedure,
cyclopropane 4b (100 mg, 0.322 mmol) was added to a stirring
solution of Ni(ClO4)2·6H2O (17.7 mg, 0.0484 mmol) and allylamine
(0.03 mL, 0.387 mmol) in DCM (5 mL) to afford 5i (109 mg, 96%
yield) after purification via flash chromatography (25% EtOAc/hexane,
1
Rf = 0.38) as a yellow oil. H NMR (300 MHz, CDCl3): δ 7.47−7.34
(m, 5H), 7.32 (d, J = 8.8 Hz, 2H), 6.92 (d, J = 8.6 Hz, 2H), 5.57−5.43
(m, 1H), 5.09 (dd, J = 1.0, 10.2 Hz, 1H), 4.95 (dd, J = 1.6, 17.1 Hz,
1H), 4.78 (dd, J = 9.1, 12.0 Hz, 1H), 3.82 (s, 3H), 3.60−3.51 (m, 1H),
3.50 (s, 3H), 3.41 (dd, J = 12.0, 15.2 Hz, 1H), 3.12 (dd, J = 7.5, 16.0
Hz, 2H), 2.87 (dd, J = 9.2, 15.2 Hz, 2H). 13C NMR (75 MHz,
CDCl3): δ 166.3, 161.9, 159.1, 134.5, 133.1, 132.1, 128.7, 128.1, 127.9,
117.7, 114.0, 96.8, 77.4, 77.0, 76.6, 64.0, 55.1, 50.1, 47.5, 38.3. IR: 2944
(s), 2836 (s), 1663 (m), 1611 (m), 1582 (s), 1510 (m) cm−1. HRMS
(EI) m/z: [M]+ calcd for C22H23NO3, 349.1678; found, 349.1682.
Methyl 5-(4-Methoxyphenyl)-2-phenyl-1-(prop-2-yn-1-yl)-4,5-di-
hydro-1H-pyrrole-3-carboxylate (5j). According to the general
procedure, cyclopropane 4b (100 mg, 0.322 mmol) was added to a
stirring solution of Ni(ClO4)2·6H2O (17.7 mg, 0.0484 mmol) and
propargylamine (0.02 mL, 0.387 mmol) in DCE (5 mL) to afford 5j
(34.1 mg, 30% yield) after purification via flash chromatography (25%
Methyl 1-Isopropyl-5-(4-methoxyphenyl)-2-phenyl-4,5-dihydro-
1H-pyrrole-3-carboxylate (5d). According to the general procedure,
cyclopropane 4b (100 mg, 0.322 mmol) was added to a stirring
solution of Ni(ClO4)2·6H2O (17.7 mg, 0.0484 mmol) and isopropyl-
amine (0.03 mL, 0.387 mmol) in DCE (5 mL) to afford 5d (91.7 mg,
81% yield) after purification via flash chromatography (25% EtOAc/
1
hexane, Rf = 0.38) as a colorless oil. H NMR (300 MHz, CDCl3): δ
7.48−7.39 (m, 5H), 7.36−7.30 (m, 2H), 6.89 (d, J = 8.5 Hz, 2H), 4.79
(dd, J = 6.3, 12.2 Hz, 1H), 3.81 (s, 3H), 3.54−3.43 (m, 5H), 2.71 (dd,
J = 6.3, 15.2 Hz, 1H), 1.03 (d, J = 6.6 Hz, 3H), 0.70 (d, J = 7.0 Hz,
3H). 13C NMR (75 MHz, CDCl3): δ 166.4, 162.4, 158.6, 138.7, 132.9,
128.8, 128.4, 128.0, 127.1, 113.9, 96.4, 59.7, 55.2, 50.0, 48.2, 40.0, 22.4,
19.7. IR: 2971 (s), 1678 (s), 1612 (s), 1583 (s), 1510 (s) cm−1. HRMS
(EI) m/z: [M]+ calcd for C22H25NO3, 351.1834; found, 351.1832.
Methyl 1-(2-Methoxyethyl)-5-(4-methoxyphenyl)-2-phenyl-4,5-
dihydro-1H-pyrrole-3-carboxylate (5f). According to the general
procedure, cyclopropane 4b (75 mg, 0.242 mmol) was added to a
stirring solution of Ni(ClO4)2·6H2O (13.3 mg, 0.0363 mmol) and 2-
methoxyethan-1-amine (0.03 mL, 0.290 mmol) in DCM (5 mL) to
afford 5f (74.1 mg, 83% yield) after purification via flash
chromatography (25% EtOAc/hexane, Rf = 0.21) as a colorless oil.
1H NMR (300 MHz, CDCl3): δ 7.48−7.31 (m, 7H), 6.95−6.89 (m,
1
EtOAc/hexane, Rf = 0.42) as a colorless oil. H NMR (300 MHz,
CDCl3): δ 7.49−7.35 (m, 7H), 6.93 (d, J = 8.7 Hz, 1H), 4.86 (t, J =
11.5 Hz, 1H), 3.83 (s, 3H), 3.60 (dd, J = 2.4, 17.9 Hz, 1H), 3.51 (s,
3H), 3.34 (dd, J = 11.3, 15.2 Hz, 1H), 3.22 (dd, J = 2.4, 17.9 Hz, 1H),
2.85 (dd, J = 11.6, 15.2 Hz, 1H), 2.20 (t, J = 2.3 Hz, 1H). 13C NMR
(75 MHz, CDCl3): δ 166.1, 161.0, 159.3, 133.2, 131.9, 128.9, 128.6,
128.1, 114.1, 101.4, 78.3, 72.7, 64.8, 55.3, 50.4, 38.3, 35.7. IR: 3293 (s),
2948 (s), 2836 (s), 1729 (m), 1674 (m), 1612 (m), 1587 (s), 1512
(m) cm−1. HRMS (EI) m/z: [M]+ calcd for C22H21NO3, 347.1521;
found, 347.1531.
2H), 4.88 (dd, J = 8.4, 12.1 Hz, 1H), 3.82 (s, 3H), 3.48 (s, 3H), 3.42
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Article
Methyl 5-(4-Methoxyphenyl)-1,2-diphenyl-4,5-dihydro-1H-pyr-
role-3-carboxylate (5k). According to the general procedure,
cyclopropane 4b (75 mg, 0.242 mmol) was added to a stirring
solution of Ni(ClO4)2·6H2O (13.3 mg, 0.0363 mmol) and aniline
(0.03 mL, 0.290 mmol) in toluene (5 mL) to afford 5k (69.1 mg, 74%
yield) after purification via flash chromatography (25% EtOAc/hexane,
Rf = 0.32) as a yellow oil. 1H NMR (300 MHz, CDCl3): δ 8.24 (d, J =
8.6 Hz, 2H), 7.51−7.45 (m, 7H), 7.28−7.23 (m, 3H), 6.98−6.93 (m,
2H), 4.72 (dd, J = 8.1, 12.3 Hz, 1H), 4.33 (d, J = 15.6 Hz, 1H), 3.65
(d, J = 15.4 Hz, 1H), 3.51 (s, 3H), 3.48−3.41 (m, 1H), 2.81 (dd, J =
8.1, 15.4 Hz, 1H). 13C NMR (75 MHz, CDCl3): δ 166.0, 161.8, 150.0,
147.5, 136.3, 131.4, 129.4, 128.7, 128.6, 128.4, 127.7, 127.7, 124.2,
97.2, 63.1, 50.4, 49.3, 38.5. IR: 3028 (s), 2923 (s), 2853 (s), 1664 (s),
1584 (s), 1518 (m) cm−1. HRMS (EI) m/z: [M]+ calcd for
C25H22N2O4, 414.1580; found, 414.1576.
Methyl 1-Benzyl-5-methyl-2,5-diphenyl-4,5-dihydro-1H-pyrrole-
3-carboxylate (5r). According to the general procedure, cyclopropane
4r (75 mg, 0.255 mmol) was added to a stirring solution of Ni(ClO4)2·
6H2O (14.0 mg, 0.0382 mmol) and benzylamine (0.03 mL, 0.306
mmol) in DCM (5 mL) to afford 5r (77.3 mg, 79% yield) after
purification via flash chromatography (25% EtOAc/hexane, Rf = 0.44)
as a colorless oil. 1H NMR (300 MHz, CDCl3): δ 7.54−7.47 (m, 2H),
7.44−7.28 (m, 8H), 7.19−7.12 (m, 3H), 6.97−6.90 (m, 2H), 4.23 (d, J
= 16.5 Hz, 1H), 3.83 (d, J = 16.7 Hz, 1H), 3.49 (s, 3H), 3.22 (q, J =
15.0 Hz, 2H), 1.64 (s, 3H). 13C NMR (75 MHz, CDCl3): δ 166.5,
161.6, 145.7, 139.5, 132.5, 128.5, 128.4, 128.2, 128.0, 128.0, 127.3,
126.9, 126.6, 125.6, 95.4, 77.4, 77.0, 76.6, 69.4, 50.1, 47.2, 47.0, 25.8.
IR: 3028 (s), 2945 (s), 1732 (s), 1661 (s), 1614 (m), 1580 (m) cm−1.
HRMS (EI) m/z: [M]+ calcd for C26H25NO2, 383.1885; found,.
383.1877.
Methyl 1-Benzyl-2-phenyl-1,3a,4,8b-tetrahydroindeno[1,2-b]-
pyrrole-3-carboxylate (5u). According to the general procedure,
cyclopropane 4u (75 mg, 0.257 mmol) was added to a stirring solution
of Ni(ClO4)2·6H2O (14.1 mg, 0.0385 mmol) and benzylamine (0.03
mL, 0.308 mmol) in toluene (5 mL) to afford 5u (26.9 mg, 37% yield)
after purification via flash chromatography (25% EtOAc/hexane, Rf =
0.20) as a colorless oil. Diastereomeric ratio: 1:1. 1H NMR (300 MHz,
CDCl3): δ 8.05−7.95 (m, 5.25), 7.63−7.55 (m, 2.44), 7.51−7.42 (m,
5.91), 7.41−7.14 (m, 26.79), 4.50 (dd, J = 8.8, 18.1 Hz, 2.00), 4.29 (d,
J = 5.0 Hz, 0.99), 4.10 (d, J = 5.5 Hz, 0.90), 3.97−3.76 (m, 4.81), 3.66
(s, 3.42), 3.61 (s, 3.50), 3.43−3.23 (m, 5.30), 2.80 (dd, J = 5.2, 15.2
Hz, 1.12), 2.56−2.44 (m, 1.35). 13C NMR (75 MHz, CDCl3): δ 169.6,
143.7, 142.0, 141.8, 140.8, 136.8, 133.5, 128.7, 128.3, 127.8, 126.7,
125.0, 124.4, 66.6, 66.4, 57.4, 56.5, 52.4, 50.2, 45.6, 44.9, 35.4, 34.3. IR:
2950 (s), 1734 (s), 1682 (s), 1568 (s), 1512 (s) cm−1. HRMS (EI) m/
z: [M]+ calcd for C26H23NO2, 381.1729; found, 381.1714.
1
Rf = 0.38) as a colorless oil. H NMR (300 MHz, CDCl3): δ 7.46−
7.41 (m, 2H), 7.39−7.33 (m, 2H), 7.33−7.27 (m, 3H), 7.00−6.81 (m,
5H), 6.62−6.57 (m, 2H), 5.07 (dd, J = 6.2, 11.4 Hz, 1H), 3.81 (s, 3H),
3.65 (dd, J = 11.4, 15.3 Hz, 1H), 3.58 (s, 3H), 2.93 (dd, J = 6.2, 15.4
Hz, 1H). 13C NMR (75 MHz, CDCl3): δ 166.3, 158.9, 158.0, 142.8,
136.0, 131.7, 129.7, 128.9, 128.2, 127.5, 123.6, 114.1, 101.1, 68.5, 55.2,
50.4, 39.6. IR: 2947 (s), 1686 (s), 1611 (s), 1588 (s), 1571 (s), 1511
(m) cm−1. HRMS (EI) m/z: [M]+ calcd for C25H23NO3, 385.1678;
found, 385.1680.
Methyl 5-(4-Methoxyphenyl)-2-phenyl-1-((S)-1-phenylethyl)-4,5-
dihydro-1H-pyrrole-3-carboxylate (5n). According to the general
procedure, cyclopropane 4b (75 mg, 0.242 mmol) was added to a
stirring solution of Ni(ClO4)2·6H2O (13.3 mg, 0.0363 mmol) and (S)-
1-phenylethan-1-amine (0.04 mL, 0.298 mmol) in DCM (5 mL) to
afford 5n (90.3 mg, 90% yield) after purification via flash
chromatography (25% EtOAc/hexane, Rf = 0.38) as a colorless oil.
1
Diastereomeric ratio: 1:1. H NMR (300 MHz, CDCl3): δ 7.55−7.42
(m, 9.00), 7.38−7.28 (m, 2.52), 7.28−7.22 (m, 3.20), 7.14−7.09 (m,
1.95), 7.01−6.95 (m, 3.94), 6.93−6.87 (m, 3.49), 6.61−6.55 (m, 1.54),
4.70−4.49 (m, 2.52), 4.40 (dd, J = 6.1, 12.2 Hz, 0.91), 3.83 (s, 3.01),
3.73 (s, 2.48), 3.51−3.41 (m, 6.66), 3.32 (dd, J = 12.2, 15.3 Hz, 1.04),
2.77−2.62 (m, 1.58), 1.39 (d, J = 7.0 Hz, 2.45), 1.08 (d, J = 7.3 Hz,
2.88). 13C NMR (75 MHz, CDCl3): δ 166.6, 166.5, 162.5, 162.1,
158.9, 158.2, 141.3, 140.2, 138.5, 137.2, 133.0, 132.6, 129.2, 129.0,
128.5, 128.3, 128.3, 127.7, 127.6, 127.5, 127.4, 127.0, 126.8, 126.2,
114.1, 113.4, 113.3, 98.7, 96.2, 77.6, 77.1, 76.7, 61.3, 60.7, 55.3, 55.3,
54.8, 54.6, 50.3, 50.2, 39.9, 19.4, 16.2. IR: 2943 (s), 1683 (m), 1611
(s), 1583 (s) cm−1. HRMS (EI) m/z: [M]+ calcd for C27H27NO3,
413.1991; found, 413.1995.
Methyl 1-Benzyl-2,5-diphenyl-4,5-dihydro-1H-pyrrole-3-carboxy-
late (5o). According to the general procedure, cyclopropane 4o (75
mg, 0.242 mmol) was added to a stirring solution of Ni(ClO4)2·6H2O
(14.7 mg, 0.0402 mmol) and benzylamine (0.04 mL, 0.321 mmol) in
toluene (5 mL) to afford 5o (84.2 mg, 85% yield) after purification via
flash chromatography (25% EtOAc/hexane, Rf = 0.48) as a colorless
oil. 1H NMR (300 MHz, CDCl3): δ 7.51−7.25 (m, 13H), 7.01 (dd, J =
1.8, 7.6 Hz, 2H), 4.67 (dd, J = 8.0, 12.3 Hz, 1H), 4.33 (d, J = 15.7 Hz,
1H), 3.70 (d, J = 15.7 Hz, 1H), 3.53 (s, 3H), 3.45 (dd, J = 12.3, 15.3
Hz, 1H), 2.91 (dd, J = 8.0, 15.2 Hz, 1H). 13C NMR (75 MHz,
CDCl3): δ 166.4, 161.9, 142.5, 136.9, 131.9, 128.9, 128.8, 128.4, 128.1,
127.7, 127.6, 127.3, 126.8, 125.8, 96.4, 77.4, 77.0, 76.6, 63.6, 50.1, 48.4,
38.2. IR: 3029 (s), 2946 (s), 1663 (s), 1613 (s), 1579 (s) cm−1. HRMS
(EI) m/z: [M]+ calcd for C25H23NO2, 369.1729; found, 369.1722.
Methyl 1-Benzyl-5-(4-fluorophenyl)-2-phenyl-4,5-dihydro-1H-
pyrrole-3-carboxylate (5p). According to the general procedure,
cyclopropane 4p (70 mg, 0.235 mmol) was added to a stirring solution
of Ni(ClO4)2·6H2O (12.9 mg, 0.0352 mmol) and benzylamine (0.03
mL, 0.282 mmol) in DCM (5 mL) to afford 5p (79.8 mg, 88% yield)
after purification via flash chromatography (25% EtOAc/hexane, Rf =
0.39) as a colorless oil. 1H NMR (300 MHz, CDCl3): δ 7.49−7.43 (m,
5H), 7.32−7.23 (m, 5H), 7.07 (t, J = 8.7 Hz, 2H), 7.00−6.95 (m, 2H),
4.62 (dd, J = 8.1, 12.3 Hz, 1H), 4.29 (d, J = 15.8 Hz, 1H), 3.65 (d, J =
15.7 Hz, 1H), 3.52 (s, 3H), 3.41 (dd, J = 12.3, 15.3 Hz, 1H), 2.85 (dd,
J = 8.1, 15.3 Hz, 1H). 13C NMR (75 MHz, CDCl3): δ 166.4, 163.9,
161.8, 160.6, 138.3, 136.8, 131.8, 129.1, 128.5, 128.2, 127.7, 127.4,
115.8, 115.5, 96.6, 63.0, 50.2, 48.5, 38.4. IR: 2948 (s), 1682 (s), 1610
(s), 1582 (s), 1508 (s) cm−1. HRMS (EI) m/z: [M]+ calcd for
C25H22FNO2, 387.1635; found, 387.1626.
Methyl 1-Benzyl-4-methyl-2,5-diphenyl-4,5-dihydro-1H-pyrrole-
3-carboxylate (5v). According to the general procedure, cyclopropane
4v (71 mg, 0.241 mmol) was added to a stirring solution of
Ni(ClO4)2·6H2O (13.2 mg, 0.0362 mmol) and benzylamine (0.03 mL,
0.290 mmol) in toluene (5 mL) to afford 5v (40.3 mg, 44% yield) after
purification via flash chromatography (25% EtOAc/hexane, Rf = 0.51)
1
as a colorless oil. H NMR (300 MHz, CDCl3): δ 7.52−7.23 (m,
13H), 7.03−6.98 (m, 2H), 4.33 (d, J = 15.7 Hz, 1H), 4.04 (d, J = 5.5
Hz, 1H), 3.70 (d, J = 15.7 Hz, 1H), 3.49 (s, 3H), 3.18−3.08 (m, 1H),
1.28 (d, J = 6.6 Hz, 3H). 13C NMR (75 MHz, CDCl3): δ 166.7, 161.4,
142.1, 137.1, 132.1, 129.0, 128.8, 128.5, 128.2, 127.7, 127.5, 127.3,
126.5, 102.2, 71.7, 50.0, 48.4, 45.6, 21.8. IR: 3029 (s), 2949 (s), 1731
(s), 1665 (s), 1570 (s) cm−1. HRMS (EI) m/z: [M]+ calcd for
C26H25NO2, 383.1885; found, 383.1888.
Methyl 1-Benzyl-2-ethyl-5-(4-methoxyphenyl)-4,5-dihydro-1H-
pyrrole-3-carboxylate (5w). According to the general procedure,
cyclopropane 4w (44 mg, 0.168 mmol) was added to a stirring
solution of Ni(ClO4)2·6H2O (9.20 mg, 0.0252 mmol) and benzyl-
amine (0.02 mL, 0.202 mmol) in DCM (5 mL) to afford 5w (49.1 mg,
85% yield) after purification via flash chromatography (25% EtOAc/
1
hexane, Rf = 0.48) as a yellow oil. H NMR (300 MHz, CDCl3): δ
7.36−7.25 (m, 3H), 7.13−7.04 (m, 4H), 6.86 (dd, J = 2.1, 6.6 Hz,
2H), 4.55−4.45 (m, 2H), 3.88−3.80 (m, 4H), 3.67 (s, 1H), 3.30−3.16
(m, 2H), 2.70 (dd, J = 7.6, 14.9 Hz, 1H), 2.59−2.45 (m, 1H), 1.22 (t, J
= 7.5 Hz, 3H). 13C NMR (75 MHz, CDCl3): δ 167.2, 165.9, 159.1,
137.2, 134.7, 128.6, 128.1, 127.3, 127.0, 114.0, 92.8, 63.6, 55.2, 50.0,
49.7, 47.0, 37.4, 19.1, 12.7. IR: 2936 (s), 1699 (s), 1669 (s), 1610 (s),
1577 (s), 1511 (m) cm−1. HRMS (EI) m/z: [M]+ calcd for
C22H25NO3, 351.1834; found, 351.1832.
Methyl 1-Benzyl-5-(4-nitrophenyl)-2-phenyl-4,5-dihydro-1H-pyr-
role-3-carboxylate (5q). According to the general procedure,
cyclopropane 4q (45 mg, 0.138 mmol) was added to a stirring
solution of Ni(ClO4)2·6H2O (6.1 mg, 0.0166 mmol) and benzylamine
(0.01 mL, 0.133 mmol) in toluene (5 mL) to afford 5q (14.1 mg, 31%
yield) after purification via flash chromatography (25% EtOAc/hexane,
3037
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The Journal of Organic Chemistry
Article
Methyl 1-Benzyl-5-(4-methoxyphenyl)-2-(thiophen-2-yl)-4,5-di-
hydro-1H-pyrrole-3 carboxylate (5x). According to the general
procedure, cyclopropane 4x (80 mg, 0.253 mmol) was added to a
stirring solution of Ni(ClO4)2·6H2O (13.9 mg, 0.0379 mmol) and
benzylamine (0.03 mL, 0.304 mmol) in DCM (5 mL) to afford 5x
(84.2 mg, 83% yield) after purification via flash chromatography (25%
MHz, CDCl3): δ 7.34−7.27 (m, 3H), 7.20−7.16 (m, 4H), 7.03 (d, J =
8.6 Hz, 2H), 6.84−6.80 (m, 3H), 6.78−6.75 (m, 3H), 6.61 (s, 1H),
5.41 (q, J = 7.2 Hz, 1H), 3.80 (s, 3H), 3.63 (s, 3H), 1.54 (d, J = 7.2
Hz, 3H). 13C NMR (126 MHz, CDCl3): δ 165.1, 159.2, 142.1, 139.3,
134.5, 132.7, 131.9, 130.5, 128.1, 128.1, 127.6, 127.0, 126.1, 126.1,
125.6, 125.5, 113.3, 77.3, 77.0, 76.8, 55.2, 54.0, 50.7, 19.4. IR: 2953 (s),
2941 (s), 1702 (m), 1611 (s), 1566 (s), 1533 (s) cm−1. HRMS (EI)
m/z: [M]+ calcd for C27H25NO3, 411.1834; found, 411.1836.
Methyl 1-Benzyl-2-ethyl-5-(4-methoxyphenyl)-1H-pyrrole-3-car-
boxylate (7w). DDQ (39.6 mg, 0.174 mmol) was added to a solution
of dihydropyrrole 5w (40.8 mg, 0.116 mmol) in toluene (5.8 mL) to
afford pyrrole 7w (25 mg, 62%) as a colorless oil after purification via
flash chromatography (25% EtOAc/hexane, Rf = 0.54). 1H NMR (500
MHz, CDCl3): δ 7.31−7.21 (m, 4H), 7.19−7.15 (m, 2H), 6.89 (d, J =
7.4 Hz, 2H), 6.84−6.80 (m, 2H), 6.60 (s, 1H), 5.11 (s, 2H), 3.83 (s,
3H), 3.78 (s, 3H), 2.87 (q, J = 7.5 Hz, 2H), 1.09 (t, J = 7.5 Hz, 3H).
13C NMR (126 MHz, CDCl3): δ 165.7, 159.2, 142.6, 138.2, 133.7,
1
EtOAc/hexane, Rf = 0.42) as a colorless oil. H NMR (300 MHz,
CDCl3): δ 7.47 (dd, J = 1.2, 5.1 Hz, 1H), 7.33−7.20 (m, 6H), 7.11
(dd, J = 3.6, 5.1 Hz, 1H), 7.03 (dd, J = 1.8, 7.8 Hz, 2H), 6.91 (dd, J =
2.1, 6.6 Hz, 2H), 4.60 (dd, J = 8.4, 12.3 Hz, 1H), 4.45 (d, J = 15.8 Hz,
1H), 3.83 (s, 2H), 3.71 (d, J = 15.7 Hz, 1H), 3.57 (s, 1H), 3.37 (dd, J
= 12.3, 15.6 Hz, 1H), 2.87 (dd, J = 8.5, 15.6 Hz, 1H). 13C NMR (75
MHz, CDCl3): δ 166.1, 159.1, 154.2, 137.0, 134.4, 131.1, 129.2, 128.4,
128.1, 127.7, 127.4, 127.3, 126.8, 114.1, 98.9, 77.4, 77.0, 76.6, 63.2,
55.2, 50.3, 49.8, 48.6, 38.3. IR: 2944 (s), 2835 (s), 1662 (s), 1596 (s),
1509 (m) cm−1. HRMS (EI) m/z: [M]+ calcd for C24H23NO3S,
405.1399; found, 405.1402.
130.5, 128.8, 128.8, 127.3, 125.5, 125.0, 113.8, 111.3, 109.5, 77.3, 77.0,
76.8, 55.2, 50.8, 47.4, 19.2, 14.1. IR: 2943 (s), 1713 (m), 1610 (m),
1567 (s) cm−1. HRMS (EI) m/z: [M]+ calcd for C22H23NO3,
349.1678; found, 349.1682.
Methyl 1-Benzyl-5-(4-methoxyphenyl)-2-oxopyrrolidine-3-car-
boxylate (5y). According to the general procedure, cyclopropane 4y
(100 mg, 0.378 mmol) was added to a stirring solution of Ni(ClO4)2·
6H2O (20.8 mg, 0.0568 mmol) and benzylamine (0.05 mL, 0.454
mmol) in DCM (6 mL) to afford 5y (81 mg, 63% yield) after
purification via flash chromatography (25% EtOAc/hexane, Rf = 0.11)
as a colorless oil. Diastereomeric ratio: 2:1. 1H NMR (300 MHz,
CDCl3): δ 7.30−7.22 (m, 5.00), 7.18−7.12 (m, 1.50), 7.08−6.99 (m,
4.73), 6.94−6.86 (m, 3.19), 5.05 (dd, J = 14.5, 19.8 Hz, 1.51), 4.51
(dd, J = 5.7, 8.2 Hz, 0.80), 4.29 (t, J = 7.9 Hz, 0.70), 3.84−3.81 (m,
6.41), 3.80 (s, 2.52), 3.74−3.68 (m, 1.27), 3.65−3.54 (m, 1.53), 3.52−
3.42 (m, 1.95), 2.74−2.64 (m, 0.97), 2.63−2.54 (m, 0.68), 2.41−2.32
(m, 0.77), 2.17−2.06 (m, 0.93). 13C NMR (75 MHz, CDCl3): δ 170.6,
170.0, 159.5, 135.7, 131.3, 128.6, 128.1, 127.5, 114.3, 59.5, 59.1, 55.2,
52.6, 48.2, 47.9, 44.5, 32.5, 32.1. IR: 2953 (s), 1739 (s), 1686 (m),
1612 (s), 1586 (s), 1513 (m) cm−1. HRMS (EI) m/z: [M]+ calcd for
C20H21NO4, 339.1471; found, 339.1470.
ASSOCIATED CONTENT
■
S
* Supporting Information
1H and 13C NMR spectra for all new compounds. This material
is available free of charge via the Internet at http://pubs.acs.org.
AUTHOR INFORMATION
Corresponding Author
*E-mail: stefan.france@chemistry.gatech.edu.
■
Notes
The authors declare no competing financial interest.
1-(1-Benzyl-2-methyl-5-phenyl-4,5-dihydro-1H-pyrrol-3-yl)ethan-
1-one (5z). According to the general procedure, cyclopropane 4z (80
mg, 0.396 mmol) was added to a stirring solution of Ni(ClO4)2·6H2O
(21.7 mg, 0.0594 mmol) and benzylamine (0.05 mL, 0.475 mmol) in
DCM (7 mL) to afford 5z (89.4 mg, 78% yield) after purification via
flash chromatography (25% EtOAc/hexane, Rf = 0.037) as a yellow oil.
1H NMR (500 MHz, CDCl3): δ 7.38−7.27 (m, 6H), 7.23−7.20 (m,
2H), 7.04 (d, J = 7.0 Hz, 2H), 4.61 (dd, J = 7.9, 11.9 Hz, 1H), 4.57 (d,
J = 16.5 Hz, 1H), 3.85 (d, J = 16.5 Hz, 1H), 3.33 (ddd, J = 1.1, 12.0,
14.4 Hz, 1H), 2.82 (ddd, J = 1.2, 7.9, 14.3 Hz, 1H), 2.50 (s, 3H), 2.08
(s, 3H). 13C NMR (126 MHz, CDCl3): δ 192.3, 160.8, 142.0, 136.4,
128.9, 128.8, 128.0, 127.5, 127.0, 127.0, 105.9, 77.3, 77.0, 76.8, 65.0,
47.2, 38.7, 29.0, 13.2. IR: 3028 (s), 2917 (s), 1712 (s), 1621 (m), 1536
(s) cm−1. HRMS (EI) m/z: [M]+ calcd for C20H21NO, 291.1623;
found, 291.1622.
ACKNOWLEDGMENTS
S.F. gratefully acknowledges financial support from the
National Science Foundation (CAREER award CHE-1056687).
■
REFERENCES
■
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1-(1-Benzyl-2,5-diphenyl-4,5-dihydro-1H-pyrrol-3-yl)ethan-1-one
(5aa). According to the general procedure, cyclopropane 4aa (90 mg,
0.341 mmol) was added to a stirring solution of Ni(ClO4)2·6H2O
(18.7 mg, 0.0511 mmol) and benzylamine (0.04 mL, 0.409 mmol) in
DCM (8 mL) to afford 5aa (60.9 mg, 51% yield) after purification via
flash chromatography (25% EtOAc/hexane, Rf = 0.037) as a colorless
1
oil. H NMR (300 MHz, CDCl3): δ 7.57−7.50 (m, 2H), 7.40−7.28
(m, 9H), 7.27−7.22 (m, 2H), 7.10−7.05 (m, 2H), 4.70−4.55 (m, 2H),
3.93 (d, J = 16.4 Hz, 1H), 3.43 (dd, J = 11.6, 14.8 Hz, 1H), 2.97 (dd, J
= 7.9, 14.8 Hz, 1H), 2.20 (s, 3H). 13C NMR (75 MHz, CDCl3): δ
190.3, 162.7, 143.2, 141.5, 136.1, 129.3, 128.8, 128.8, 128.8, 128.0,
127.9, 127.6, 127.2, 127.0, 126.9, 107.2, 77.4, 77.0, 76.6, 65.2, 47.5,
39.0, 14.0. IR: 3059 (s), 3028 (s), 2922 (s), 1712 (s), 1598 (m), 1538
(m) cm−1. HRMS (EI) m/z: [M]+ calcd for C25H23NO, 353.1780;
found, 353.1769.
Synthesis of Pyrroles. Methyl (S)-5-(4-Methoxyphenyl)-2-
phenyl-1-(1-phenylethyl)-1H-pyrrole-3-carboxylate (7n). DDQ
(44.9 mg, 0.198 mmol) was added to a solution of dihydropyrrole
5n (54.5 mg, 0.132 mmol) in toluene (6.6 mL) to afford pyrrole 7n
(35 mg, 65%) as a colorless oil after purification via flash
chromatography (25% EtOAc/hexane, Rf = 0.51). 1H NMR (500
3038
dx.doi.org/10.1021/jo5001059 | J. Org. Chem. 2014, 79, 3030−3039

The Journal of Organic Chemistry
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(16) At higher amine loadings in the reactions at reflux, more side
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acids in the range of pKa 5−10 (PPTS, NEt3HCl, and NH4Cl).
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Ni catalyst for both the standard and tandem cyclopropanation/
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