From triazoles to imidazolines through the sequential N-H insertion of α-imino rhodium-carbenes into β-enamino esters/enamine-imine tautomerization/conjugate addition cascade

Article abstract of DOI:10.1021/jo501785d

A rhodium(II)-catalyzed denitrogenative coupling of N-sulfonyl-1,2,3-triazoles with ambiphilic β-enamino esters affords 2,5-dihydro-1H-imidazoles (3-imidazolines) with broad functional group tolerance. Mechanistic studies using a deuterium-labeled triazol

Full text of DOI:10.1021/jo501785d

Note
pubs.acs.org/joc
From Triazoles to Imidazolines through the Sequential N−H Insertion
of α‑Imino Rhodium−Carbenes into β‑Enamino Esters/Enamine−
Imine Tautomerization/Conjugate Addition Cascade
Hyun Ji Jeon,† Da Jung Jung,† Ju Hyun Kim, Youngmee Kim, Jean Bouffard, and Sang-gi Lee*
Department of Chemistry and Nano Science (BK 21 Plus), Ewha Womans University, 120-750 Seoul, Korea
S
* Supporting Information
ABSTRACT: A rhodium(II)-catalyzed denitrogenative coupling
of N-sulfonyl-1,2,3-triazoles with ambiphilic β-enamino esters
affords 2,5-dihydro-1H-imidazoles (3-imidazolines) with broad
functional group tolerance. Mechanistic studies using a
deuterium-labeled triazole suggest that the reaction proceeds in
a cascade through the N−H insertion of an α-imino rhodium−
carbene, followed by enamine−imine tautomerization and
conjugate addition. Moreover, the reaction proceeds with high
diastereoselectivity for α-substituted β-enamino esters (R3 = Me, Ph) to give a single diastereomer.
iazo compounds are ambiphilic (ambivalent) reagents
that are widely used in organic synthesis.1 While the
our group6a and others (Murakami6b and Yoo6c groups)
independently reported the stereoselective insertion of A into
the CO bond of N,N-disubstituted amides to afford cis-
diamino enones.
D
diazo carbon is the preferred site of attack by electrophiles, the
polarity of the carbon is reversed when the diazo compounds
are converted to metal−carbene complexes. This reactivity
umpolung greatly expands the synthetic utility of diazo
compounds.2 In particular, the diverse reactivity of rhodium
carbene complexes A derived in situ from diazo imines 1′,
which are formed by ring-chain tautomerization of N-sulfonyl-
1,2,3-triazoles 1, has recently gained considerable attention (eq
1).3 The electrophilic nature of the carbene carbon, when
β-Enamino esters also possess an ambivalent character that
combines a nucleophilic enamine with an electrophilic α,β-
unsaturated ester (Michael acceptor), and have been employed
as useful reagents in the synthesis of various heterocycles.7
Given our continuing interest for β-enamino ester derivatives,8
we envisioned that the ambiphilic β-enamino esters would be
promising partners to couple with the putative α-imino
rhodium−carbene A.9 With the exception of a recent report
by Reddy and co-workers claiming that β-enamino esters could
react with α-diazo ketones to form α-diazo imine intermediates
on the route to pyrroles (eq 2),10 the reactions of β-enamino
esters with metal−carbenes have no precedents to the best of
our knowledge. Herein, we report a sequential N−H insertion
of α-imino rhodium−carbene A into β-enamino esters,
followed by enamine−imine tautomerization and conjugate
addition of the resulting bis-enamide, which provides an
efficient catalytic method for the transformation of N-sulfonyl-
1,2,3-triazoles 1 to 2,5-dihydro-1H-imidazoles (3-imidazolines)
3 (eq 3). Whereas many synthetic efforts have been directed
toward the preparation of 2- and 4-imidazolines,11 reports on
the synthesis of 3-imidazolines remain rare.12
Our investigations started with the reaction of the triazole 1a
(R = Tolyl, R1 = Ph) with 1.1 equiv of enamino ester 2a (R2 =
Ph, R′ = Et) in toluene in the presence of 2.5 mol %
Rh2(OAc)2, which gave the corresponding imidazole 3aa in
76% yield (entry 1, Table 1). When the reaction was conducted
either in the absence of Rh2(OAc)4 or with Cu(OAc)2 in place
of the rhodium catalyst, the reaction was not clean, and no
combined with the nucleophilic character of the nitrogen atom
of the α-imino group, enables a palette of reactivity with
nitriles,4a alkynes,4b,c allenes,4d isocynates,4e α,β-unsaturated
aldehydes,4f furans,4g indoles,4h and aromatic hydrocarbons
(intramolecularly)4i to provide various nitrogen heterocycles.4
The carbene complex A also inserts into the O−H bond of
H2O, alcohols, and carboxylic acids, and the N−H bond of
primary and secondary amides, and carbamates.5 More recently,
Received: August 3, 2014
Published: September 26, 2014
© 2014 American Chemical Society
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The Journal of Organic Chemistry
Note
a
Table 1. Optimization of the Reaction Conditions
b
entry
Rh(II)
solvent
toluene
T (°C)/h
yield (%)
1
2
3
4
5
6
7
Rh2(OAc)4
Rh2(S-DOSP)4
Rh2(tBuCO2)4
Rh2(TPA)4
Rh2(S-NTTL)4
Rh2(Oct)4
100/4
100/4
100/4
100/4
100/4
100/4
100/2
100/4
80/4
76
68
78
44
63
83
87
78
64
78
80
82
52
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
PhCl
Rh2(Oct)4
c
8
Rh2(Oct)4
disappearance of intermediate 4ai, and complete conversion
to the corresponding imidazole 3ai with 71% yield (eq 5).
On the basis of the labeling experiment and intermediacy of
bis-enamine 4 implying the enamine−imine tautomerization,
two different pathways can be considered for the formation of
3. One possible route would be the N-nucleophilic addition of
enamino ester 2 to the electrophilic carbene carbon, forming
enamine ylide B to afford bis-enamine 4. The enamine−imine
tautomerization to 4′, followed by conjugate addition, could
afford 3 (path a in Scheme 1). Another possibility is that the
9
10
11
12
13
Rh2(Oct)4
Rh2(Oct)4
100/4
100/4
100/4
100/4
Rh2(Oct)4
ClCH2CH2Cl
cyclohexane
CHCl3
Rh2(Oct)4
Rh2(Oct)4
a
Reaction conditions: 1a (0.3 mmol), 2a (0.33 mmol), Rh(II) (2.5
b
mol %), solvent (1.5 mL). Isolated yield after silica column
chromatography. Reaction in the presence of 1.0 mol % of catalyst.
Rh2(S-DOSP)4: tetrakis[(S)-N-(p-dodecylphenylsulfonyl)prolinato]-
dirhodium(II). TPA: triphenylacetate. Rh2(S-NTTL)4: tetrakis[(S)-
N-(1,8-naphthoyl)-tert-leucinate]dirhodium(II).
c
Scheme 1. Possible Reaction Pathways of Rhodium−
Carbene A with β-Enamino Ester 2
product could be isolated. Screening of the reaction conditions
as shown in Table 1 ultimately led to an optimal protocol in
which triazole 1a is reacted with 1.1 equiv of 2a in toluene in
the presence of 2.5 mol % Rh2(Oct)4 at 100 °C for 2.0 h to
afford 3aa in 87% yield (entry 7, Table 1). The structure of 3aa
was unambiguously determined by spectroscopic analyses and
X-ray crystallography, and is clearly consistent with the imine
tautomer (CN bond length: 1.279 Å; Figure 1).13 Preference
imino ester tautomer 2′ reacted with A to generate ketimine
ylide B′ first, then tautomerized to the enamine ylide B (path b
in Scheme 1). Finally, alternate cyclization from the Rh-bound
zwitterionic intermediates B/B′ may not entirely be ruled out
at present.
Figure 1. X-ray structure of 3aa. For clarity, hydrogens and disordered
atoms were omitted. Selected bond distances: C18−N12 1.462(5) Å,
N12−C19 1.279(6) Å, C19−C110 1.510(6) Å, C110−N11 1.453(5)
Å, N11−C18 1.504(5) Å.
Under optimized reaction conditions, we investigated the
scope of this reaction with respect to triazole 1 using β-
enamino ester 2a as a coupling partner (Table 2). As previously
observed in rhodium(II)-catalyzed couplings of triazoles with
DMF,6a the reactivity of 4-phenyl substituted triazoles 1b−1j
having different substituents on the phenyl ring was not greatly
influenced by their electronic properties, but could be affected
by sterics. For example, the triazoles having electron-donating
methyl (1b and 1c), methoxy groups (1e), and electron-
withdrawing halogens (1f, 1h, and 1i) at the meta- and para-
positions afforded the corresponding imidazolines 3 in good
yields; the p-cyanophenyl substituted triazole 1j is an exception
and gave a slightly lower yield of imidazoline 3ja (entry 9,
Table 2). 4-Phenyltriazoles bearing methyl (1d) and fluorine
for the imine tautomer is corroborated by DFT calculations,
which favor it over the enamine tautomer by ca. 7.3 kcal/mol.14
In order to get insight into the reaction mechanism, the
coupling reaction of deuterium-labeled triazole 1a-d, prepared
by the Cu-catalyzed cycloaddition of deuterated phenyl-
acetylene and tosyl azide, with 2a was carried out and found
to result in the scrambling of deuterium at the two methylene
groups of 3aa-d (eq 4). Moreover, during the reaction of 1a
with 2i having a pentafluorophenyl group, we could fortunately
detect and isolate the bis-enamine intermediate 4ai in 47%
yield along with 3ai (27%) when the reaction was carried out
for 2 h. Prolonging this reaction to 4 h leads to the
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The Journal of Organic Chemistry
Note
a b
,
Although the corresponding bis-enamine 4ad was formed in
66% yield as a major product, the yield of 3ad was not
improved further at higher reaction temperatures or upon
prolonged reaction times. A heteroaromatic furyl-substituted β-
enamino ester 2j also afforded the corresponding imidazoline
3aj in good yield (entry 9, Table 3). Alkyl-substituted enamino
esters 2k−2n were also tolerated and gave the corresponding
imidazolines 3ak−3an in good to excellent yields (entries 10−
12, Table 3).
Table 2. Scope with Respect to Triazole 1
As shown in eq 6, when the N-tosyl group of 1 was changed
to alkanesulfonyls such as butanesulfonyl triazole 1m, the
a
Reaction conditions: 1 (0.3 mmol), 2a (0.33 mmol), Rh(Oct)4 (2.5
b
mol %), solvent (1.5 mL). Isolated yield after silica column
chromatography.
(1g) substituents at the ortho-position afforded imidazolines
3da (entry 3, Table 2) and 3ga (entry 6, Table 2), respectively,
in more modest yields. The reaction conditions were also
successfully applied to alkyl-substituted triazole 1k to afford the
imidazoline 3ka in moderate yield (entry 10, Table 1). The
cyclohexenyl-substituted triazole 1l was also successfully
transannulated to the corresponding imidazoline 3la in a
yield of 73% (entry 11, Table 2).
The reaction also showed broad substrate scope with respect
to β-enamino esters 2 (Table 3). As shown in Table 3, the
a b
,
Table 3. Scope with Respect to β-Enamino Ester 2
reaction efficiency remained high, providing the corresponding
imidazoline 3ma in 90% yield. However, the methanesulfonyl
substituted 3na was isolated from the reaction in a lower yield
of 54%, although its yield was slightly increased (63%) by
employing Rh2(t-BuCO2)4 as a catalyst. Under the standard
conditions, α-methyl- 2o and α-phenyl-substituted β-enamino
esters 2p were also successfully incorporated to afford the
racemic mixtures of the single diastereomers 3ao and 3ap,
respectively (eq 7). Formation of a single diastereomer, the
structure of which was confirmed by X-ray crystallography for
3ao,13 may be ascribed to the protonation under thermody-
namic control of the enolates formed after conjugate cyclization
of imino enamine 4′. The reaction can also be carried out in a
tandem one-pot fashion starting from a sulfonyl azide and a
terminal alkyne. For instance, a solution triazole 1a was
prepared by the cycloaddition of phenylacetylene and p-
toluenesulfonyl azide at room temperature for 3 h in the
presence of 5 mol % of CuTC catalyst. Enamino ester 2a and
the Rh catalyst were added, and the reaction mixture was then
stirred at 100 °C for 2 h to afford imidazoline 3aa in 64% yield
based on phenylacetylene (eq 8).
a
Reaction conditions: 1a (0.3 mmol), 2 (0.33 mmol), Rh2(Oct)4 (2.5
b
mol %), solvent (1.5 mL). Isolated yield after silica column
chromatography.
reactions of triazole 1a with β-phenyl β-enamino esters 2b−2i
bearing electron-donating and electron-withdrawing substitu-
tents on the phenyl ring afforded the corresponding imidazo-
lines 3ab−3ai in high yields (entries 1−8, Table 3), except the
reaction with sterically congested ortho-methyl substituted 2d
that afforded only 27% yield of 3ad (entry 3, Table 3).
In summary, we have found that a rhodium(II)-catalyzed
denitrogenative coupling of N-sulfonyl-1,2,3-triazoles with
ambiphilic β-enamino esters affords 2,5-dihydro-1H-imidazoles.
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The Journal of Organic Chemistry
Note
(FAB) m/z: [M + H]+ Calcd for C27H29N2O4S 477.1848; Found
477.1851.
Ethyl {4-(2-Methylphenyl)-1-[(4-methylphenyl)sulfonyl]-2-phenyl-
2,5-dihydro-1H-imidazol-2-yl}acetate (3da). Yield: 54% (77 mg);
Eluents: n-hexane/EtOAc = 6/1; pale yellow solid; mp: 132−134 °C;
1H NMR (300 MHz, CDCl3) δ 1.91 (t, J = 7.1 Hz, 3H), 2.30 (s, 3H),
Mechanistic investigations support the intermediacy of a bis-
enamine formed by insertion of the Rh(II) carbene into the
N−H bond of the enamino ester, which then tautomerizes and
cyclizes in a conjugate addition to give the five-membered N-
heterocycles. When α-substituted enamino esters were
employed, the reactions were found to proceed with complete
diastereoselectivity (>99% d.r.). The reaction can also be
carried out in a tandem one-pot fashion starting from a sulfonyl
azide and a terminal alkyne, avoiding isolation of triazole to
minimize generation of waste.
2.53 (s, 3H), 3.58 (d, J = 15.9 Hz, 1H), 4.02−4.10 (m, 3H), 4.62 (d, J
= 14.1 Hz, 1H), 4.97 (d, J = 14.1 Hz, 1H), 6.99 (d, J = 8.2 Hz, 2H),
7.07 (d, J = 8.2 Hz, 2H), 7.22−7.38 (m, 8H), 7.41−7.49 (m, 1H)
ppm; 13C NMR (75 MHz, CDCl3) δ 14.2, 21.5, 22.3, 41.9, 58.9, 60.5,
95.8, 126.0, 126.7, 126.8, 128.3, 128.4, 129.1, 129.4, 130.2, 130.7,
132.0, 136.6, 139.1, 139.7, 142.8, 167.6, 169.5 ppm. HRMS (FAB) m/
z: [M + H]+ Calcd for C27H29N2O4S 477.1848; Found 477.1851.
Ethyl {4-(4-Methoxyphenyl)-1-[(4-methylphenyl)sulfonyl]-2-phe-
nyl-2,5-dihydro-1H-imidazol-2-yl}acetate (3ea). Yield: 82% (121
mg); Eluents: n-hexane/EtOAc = 4/1; pale yellow solid; mp: 141−143
EXPERIMENTAL SECTION
■
All reactions were performed under an argon atmosphere using
standard Schelenk techniques. Reaction flasks were flame-dried under
a stream of argon. Anhydrous solvents and other purchased reagents
were used without further purification. Anhydrous solvent was
transferred by an oven-dried syringe. Rh2(tBuCO2)4 and Rh2(S-
NTTL)4 were synthesized according to the reported procedures.15 N-
Sulfonylated-1,2,3-triazoles (1a−1k)16 and β-enamino esters (2a−
2o)17 were prepared according to the literature procedures. The NMR
spectra were recorded at 300 MHz for 1H, 75.5 MHz for 13C, and 282
MHz for 19F. HRMS data were obtained by electron ionization and
fast atom bombardment with a magnetic sector-electronic sector
double focusing mass analyzer.
1
°C; H NMR (300 MHz, CDCl3) δ 1.17 (t, J = 7.1 Hz, 3H), 2.31 (s,
3H), 3.54 (d, J = 15.9 Hz, 1H), 3.83 (s, 3H), 3.98−4.10 (m, 2H), 4.14
(d, J = 15.9 Hz, 1H), 4.59 (d, J = 13.9 Hz, 1H), 4.96 (d, J = 14.0 Hz,
1H), 6.88−6.95 (m, 2H), 6.98 (d, J = 8.3 Hz, 2H), 7.06 (d, J = 8.3 Hz,
2H), 7.16−7.31 (m, 5H), 7.74 (d, J = 8.9 Hz, 2H) ppm; 13C NMR (75
MHz, CDCl3) δ 14.2, 21.4, 41.9, 55.5, 57.0, 60.4, 95.1, 114.2, 123.7,
126.7, 128.2, 128.4, 129.1, 129.6, 136.6, 139.6, 142.7, 162.6, 165.6,
169.4 ppm. HRMS (FAB) m/z: [M + H]+ Calcd for C27H29N2O5S
493.1797; Found 493.1796.
Ethyl {4-(4-Fluorophenyl)-1-[(4-methylphenyl)sulfonyl]-2-phenyl-
2,5-dihydro-1H-imidazol-2-yl}acetate (3fa). Yield: 87% (125 mg);
Eluents: n-hexane/EtOAc = 4/1; pale yellow solid; mp: 140−142 °C;
1H NMR (300 MHz, CDCl3) δ 1.17 (t, J = 7.1 Hz, 3H), 2.30 (s, 3H),
3.55 (d, J = 16.1 Hz, 1H), 3.99−4.11 (m, 2H), 4.16 (d, J = 16.1 Hz,
1H), 4.62 (d, J = 14.1 Hz, 1H), 4.99 (d, J = 14.1 Hz, 1H), 6.96 (d, J =
8.2 Hz, 2H), 7.05−7.16 (m, 4H), 7.18−7.32 (m, 5H), 7.80 (dd, J =
8.7, 5.4 Hz, 2H) ppm; 13C NMR (75 MHz, CDCl3) δ 14.1, 21.4, 41.5,
57.1, 60.4, 95.2, 115.8, 116.1, 126.6, 126.7, 127.4 (d, J = 3.8 Hz) 128.3,
128.5, 129.1, 130.0, 130.1, 136.4, 139.3, 142.8, 164.9 (d, J = 251.3 Hz),
165.2, 169.3 ppm. HRMS (FAB) m/z: [M + H]+ Calcd for
C26H26FN2O4S 481.1597; Found 481.1598.
General Procedure for the Synthesis of 2,5-Dihydro-1H-
imidazoles (3-Imidazolines). Triazole 1 (0.3 mmol), β-enamino
ester 2 (0.33 mmol), and Rh2(Oct)4 (2.5 mol %, 5.8 mg, 7.59 × 10−3
mmol) catalyst, and toluene (1.5 mL) were successively added into a
flame-dried vial reactor. The mixure was then heated at 100 °C for 2 h.
After cooling to room temperature, the reaction mixture was
concentrated under reduced pressure. The residue was purified by
silica chromatography to afford the corresponding 2,5-dihydro-1H-
imidazoles 3.
Ethyl {1-[(4-Methylphenyl)sulfonyl]-2,4-diphenyl-2,5-dihydro-1H-
imidazol-2-yl}acetate (3aa). Yield: 87% (121 mg); Eluents: n-
1
hexane/EtOAc = 4/1; pale yellow solid; mp: 115−117 °C; H NMR
Ethyl {4-(2-Fluorophenyl)-1-[(4-methylphenyl)sulfonyl]-2-phenyl-
2,5-dihydro-1H-imidazol-2-yl}acetate (3ga). Yield: 52% (77 mg);
Eluents: n-hexane/EtOAc = 4/1; pale yellow solid; mp: 116−118 °C;
1H NMR (300 MHz, CDCl3) δ 1.19 (t, J = 7.1 Hz, 3H), 2.30 (s, 3H),
(300 MHz, CDCl3) δ 1.18 (t, J = 7.1 Hz, 3H), 2.31 (s, 3H), 3.56 (d, J
= 16.0 Hz, 1H), 3.98−4.10 (m, 2H), 4.16 (d, J = 16.0 Hz, 1H), 4.63
(d, J = 14.1 Hz, 1H), 5.01 (d, J = 14.1 Hz, 1H), 6.99 (d, J = 8.1 Hz,
2H), 7.07 (d, J = 8.3 Hz, 2H), 7.15−7.33 (m, 5H), 7.39−7.55 (m,
3H), 7.80 (d, J = 6.9 Hz, 2H) ppm; 13C NMR (75 MHz, CDCl3) δ
14.2, 21.5, 41.8, 57.2, 60.5, 95.3, 126.7, 126.8, 127.8, 128.3, 128.5,
128.9, 129.1, 131.1, 132.0, 136.6, 139.4, 142.8, 166.5, 169.4 ppm.
HRMS (FAB) m/z: [M + H]+ Calcd for C26H27N2O4S: 463.1692;
Found 463.1693.
3.56 (d, J = 15.9 Hz, 1H), 4.00−4.26 (m, 3H), 4.68 (dd, J = 15.4, 3.0
Hz, 1H), 5.00 (dd, J = 15.4, 2.7 Hz, 1H), 6.99 (d, J = 8.2 Hz, 2H), 7.08
(d, J = 8.2 Hz, 2H), 7.11−7.32 (m, 7H), 7.40−7.51 (m, 1H), 8.00−
8.15 (m, 1H) ppm; 13C NMR (75 MHz, CDCl3) δ 14.2, 21.5, 41.8,
59.2 (d, J = 12.8 Hz), 93.8, 116.4 (d, J = 21.9 Hz), 119.1 (d, J = 12.8
Hz), 124.8 (d, J = 3.0 Hz), 126.8 (d, J = 7.6 Hz), 128.4, 128.5, 129.1,
130.2 (d, J = 3.0 Hz), 133.8 (d, J = 8.3 Hz), 136.6, 139.3, 142.8, 161.9
(d, J = 253.7 Hz), 163.3 (d, J = 3.0 Hz), 169.4 ppm. HRMS (FAB) m/
z: [M + H]+ Calcd for C26H26FN2O4S 481.1597; Found 481.1600
Ethyl {4-(4-Chlorophenyl)-1-[(4-methylphenyl)sulfonyl]-2-phenyl-
2,5-dihydro-1H-imidazol-2-yl}acetate (3ha). Yield: 81% (121 mg);
Eluents: n-hexane/EtOAc = 4/1; pale yellow solid; mp: 127−129 °C;
1H NMR (300 MHz, CDCl3) δ 1.16 (t, J = 7.1 Hz, 3H), 2.29 (s, 3H),
3.54 (d, J = 16.1 Hz, 1H), 4.01 (q, J = 7.0 Hz, 2H), 4.15 (d, J = 16.1
Hz, 1H), 4.61 (d, J = 14.2 Hz, 1H), 4.98 (d, J = 14.1 Hz, 1H), 6.98 (d,
J = 8.1 Hz, 2H), 7.07 (d, J = 8.1 Hz, 2H), 7.15−7.32 (m, 5H), 7.39 (d,
J = 8.4 Hz, 2H), 7.72 (d, J = 8.4 Hz, 2H) ppm; 13C NMR (75 MHz,
CDCl3) δ 14.2, 21.4, 41.6, 57.1, 60.5, 95.3, 126.6, 126.7, 128.3, 129.1,
129.5, 136.5, 138.1, 139.2, 142.9, 165.4, 169.4 ppm. HRMS (FAB) m/
z: [M + H]+ Calcd for C26H26ClN2O4S 497.1302; Found 497.1304.
Ethyl {4-(4-Bromophenyl)-1-[(4-methylphenyl)sulfonyl]-2-phenyl-
2,5-dihydro-1H-imidazol-2-yl}acetate (3ia). Yield: 80% (130 mg);
Eluents: n-hexane/EtOAc = 4/1; pale yellow solid; mp: 133−135 °C;
1H NMR (300 MHz, CDCl3) δ 1.67 (t, J = 7.1 Hz, 3H), 2.23 (s, 3H),
Ethyl {4-(4-Methylphenyl)-1-[(4-methylphenyl)sulfonyl]-2-phenyl-
2,5-dihydro-1H-imidazol-2-yl}acetate (3ba). Yield: 80% (114 mg);
Eluents: n-hexane/EtOAc = 4/1; pale yellow solid; mp: 104−105 °C;
1H NMR (300 MHz, CDCl3) δ 1.17 (t, J = 7.1 Hz, 3H), 2.31 (s, 3H),
2.39 (s, 3H), 3.55 (d, J = 15.9 Hz, 1H), 3.99−4.10 (m, 2H), 4.15 (d, J
= 15.9 Hz, 1H), 4.60 (d, J = 14.1 Hz, 1H), 4.98 (d, J = 14.1 Hz, 1H),
6.98 (d, J = 8.2 Hz, 2H), 7.06 (d, J = 8.4 Hz, 2H), 7.18−7.32 (m, 7H),
7.68 (d, J = 8.2 Hz, 2H) ppm; 13C NMR (75 MHz, CDCl3) δ 14.2,
21.4, 21.6, 41.8, 57.1, 60.4, 95.2, 126.7(126.67), 126.7(126.70), 127.8,
128.2, 128.3, 128.4, 129.0, 129.5, 136.6, 139.5, 142.5, 142.7, 166.3,
169.4 ppm. HRMS (FAB) m/z: [M + H]+ Calcd for C27H29N2O4S
477.1848; Found 477.1850.
Ethyl {4-(3-Methylphenyl)-1-[(4-methylphenyl)sulfonyl]-2-phenyl-
2,5-dihydro-1H-imidazol-2-yl}acetate (3ca). Yield: 80% (114 mg);
Eluents: n-hexane/EtOAc = 4/1; pale yellow solid; mp: 143−144 °C;
1H NMR (300 MHz, CDCl3) δ 1.17 (t, J = 7.1 Hz, 3H), 2.28 (s, 3H),
2.35 (s, 3H), 3.56 (d, J = 16.0 Hz, 1H), 4.00−4.11 (m, 2H), 4.17 (d, J
= 16.0 Hz, 1H), 4.63 (d, J = 14.1 Hz, 1H), 5.01 (d, J = 14.1 Hz, 1H),
6.97 (d, J = 8.2 Hz, 2H), 7.07 (d, J = 8.2 Hz, 2H), 7.18−7.34 (m, 7H),
7.55 (d, J = 5.8 Hz, 1H), 7.66 (s, 1H) ppm; 13C NMR (75 MHz,
CDCl3) δ 14.1, 21.2, 21.4, 41.7, 57.2, 60.3, 95.1, 125.0, 126.6(126.59),
126.6(126.64), 128.2(128.15), 128.2(128.21), 128.4, 128.7, 129.0,
130.9, 132.7, 136.5, 138.6, 139.3, 142.7, 166.6, 169.3 ppm. HRMS
3.54 (d, J = 16.1 Hz, 1H), 4.03(q, J = 7.1 Hz, 2H), 4.15 (d, J = 16.1
Hz, 1H), 4.61 (d, J = 14.2 Hz, 1H), 4.98 (d, J = 14.2 Hz, 1H), 6.99 (d,
J = 8.2 Hz, 2H), 7.08 (d, J = 8.3 Hz, 2H), 7.13−7.35 (m, 5H), 7.55 (d,
J = 8.5 Hz, 2H), 7.66 (d, J = 8.5 Hz, 2H) ppm; 13C NMR (75 MHz,
CDCl3) δ 14.2, 21.5, 41.5, 60.5, 95.4, 126.6, 126.8, 128.4, 128.6, 129.2,
9868
dx.doi.org/10.1021/jo501785d | J. Org. Chem. 2014, 79, 9865−9871

The Journal of Organic Chemistry
Note
129.3, 130.0, 132.1, 136.5, 139.2, 142.9, 165.6, 169.4 ppm. HRMS
(FAB) m/z: [M + H]+ Calcd for C26H2679BrN2O4S 541.0797; Found
541.0794, Calcd for C26H2681BrN2O4S 543.0776; Found 543.0740.
Ethyl {4-(4-Cyanophenyl)-1-[(4-methylphenyl)sulfonyl]-2-phenyl-
2,5-dihydro-1H-imidazol-2-yl}acetate (3ja). Yield: 58% (85 mg);
Eluents: n-hexane/EtOAc = 4/1; pale yellow solid; mp: 148−150 °C;
1H NMR (300 MHz, CDCl3) δ 1.19 (t, J = 7.1 Hz, 3H), 2.32 (s, 3H),
3.55 (d, J = 16.4 Hz, 1H), 4.04 (q, J = 7.1 Hz, 2H), 4.16 (d, J = 16.4
Hz, 1H), 4.65 (d, J = 14.3 Hz, 1H), 5.02 (d, J = 14.3 Hz, 1H), 7.01 (d,
J = 8.2 Hz, 2H), 7.10 (d, J = 8.2 Hz, 2H), 7.15−7.36 (m, 5H), 7.72 (d,
J = 8.3 Hz, 2H), 7.93 (d, J = 8.3 Hz, 2H) ppm; 13C NMR (75 MHz,
CDCl3) δ 14.2, 21.5, 41.2, 57.2, 60.5, 95.5, 115.2, 118.1, 126.5, 126.8,
128.4(128.38), 128.4(128.43), 128.7, 129.2, 132.6, 134.9, 136.4, 139.0,
143.1, 165.2, 169.3 ppm. HRMS (FAB) m/z: [M + H]+ Calcd for
C27H26N3O4S 488.1644; Found 488.1643.
Eluents: n-hexane/EtOAc = 4/1; pale yellow solid; mp: 128−130 °C;
1H NMR (300 MHz, CDCl3) δ 1.18 (t, J = 7.1 Hz, 3H), 2.13 (s, 3H),
2.31 (s, 3H), 3.55 (d, J = 16.0 Hz, 1H), 4.01−4.19 (m, 3H), 4.66 (d, J
= 14.2 Hz, 1H), 5.04 (d, J = 14.1 Hz, 1H), 6.74 (s, 1H), 6.98 (d, J =
8.3 Hz, 2H), 7.04−7.20 (m, 5H), 7.40−7.54 (m, 3H), 7.78−7.88 (m,
2H) ppm; 13C NMR (75 MHz, CDCl3) δ 14.1, 21.3(21.29),
21.3(21.30), 41.7, 57.3, 60.3, 95.0, 123.5, 126.6, 127.4, 127.7, 128.1,
128.8, 128.9, 129.1, 131.0, 131.9, 136.5, 137.8, 138.9, 142.6, 166.2,
169.3 ppm. HRMS (FAB) m/z: [M + H]+ Calcd for C27H29N2O4S
477.1848; Found 477.1850.
Ethyl {2-(2-Methylphenyl)-1-[(4-methylphenyl)sulfonyl]-4-phenyl-
2,5-dihydro-1H-imidazol-2-yl}acetate (3ad). Yield: 27% (39 mg);
Eluents: n-hexane/EtOAc = 6/1; pale yellow solid; mp: 124−126 °C;
1H NMR (300 MHz, CDCl3) δ 1.14 (t, J = 7.1 Hz, 3H), 1.54 (s, 3H),
2.33 (s, 3H), 3.60 (d, J = 15.1 Hz, 1H), 4.01 (q, J = 7.1 Hz, 2H), 4.15
(d, J = 15.2 Hz, 1H), 4.62 (d, J = 14.2 Hz, 1H), 5.14 (d, J = 14.3 Hz,
1H), 6.8 (d, J = 7.3 Hz, 1H), 7.01 (d, J = 8.3 Hz, 2H), 7.07 (d, J = 8.3
Hz, 2H), 7.20−7.27 (m, 1H), 7.28−7.35 (m, 1H), 7.40−7.52 (m, 3H),
7.67 (d, J = 7.8 Hz, 1H), 7.78 (d, J = 6.9 Hz, 2H) ppm; 13C NMR (75
MHz, CDCl3) δ 14.2, 20.4, 21.6, 43.9, 58.2, 60.5, 95.7, 126.0, 126.7,
127.8, 127.9, 128.6, 129.0, 129.1, 131.1, 132.1, 133.1, 136.5, 136.7,
138.1, 142.9, 167.8, 169.7 ppm. HRMS (FAB) m/z: [M + H]+ Calcd
for C27H29N2O4S 477.1848; Found 477.1850.
Ethyl {1-[(4-Methylphenyl)sulfonyl]-4-(2-phenylethyl)-2-phenyl-
2,5-dihydro-1H-imidazol-2-yl}acetate (3ka). Yield: 68% (100 mg);
1
Eluents: n-hexane/EtOAc = 4/1; yellow liquid; H NMR (300 MHz,
CDCl3) δ 1.25 (t, J = 7.1 Hz, 3H), 2.32 (s, 3H), 2.68−2.87 (m, 2H),
2.88−3.09 (m, 2H), 3.43 (d, J = 16.2, 1H), 3.96−4.18 (m, 4H), 4.49
(d, J = 14.5 Hz, 1H), 6.93−6.99 (m, 5H), 7.09−7.31 (m, 9H) ppm;
13C NMR (75 MHz, CDCl3) δ 14.2, 21.4, 31.8, 33.1, 41.3, 59.1, 60.3,
94.7, 126.4, 126.5, 126.6, 128.1, 128.3, 128.4, 128.6, 129.0, 136.5,
139.0, 140.3, 142.6, 169.4, 171.3 ppm. HRMS (FAB) m/z: [M + H]+
Calcd for C28H31N2O4S 491.2005; Found 491.2006.
Ethyl {2-(4-Methoxyphenyl)-1-[(4-methylphenyl)sulfonyl]-4-phe-
nyl-2,5-dihydro-1H-imidazol-2-yl}acetate (3ae). Yield: 84% (124
mg); Eluents: n-hexane/EtOAc = 4/1; pale yellow solid; mp: 141−143
Ethyl {4-(Cyclohex-1-en-1-yl)-1-[(4-methylphenyl)sulfonyl]-2-phe-
nyl-2,5-dihydro-1H-imidazol-2-yl}acetate (3la). Yield: 73% (125
mg); Eluents: n-hexane/EtOAc = 4/1; pale yellow solid; mp: 54−56
1
°C; H NMR (300 MHz, CDCl3) δ 1.17 (t, J = 7.1 Hz, 3H), 2.32 (s,
3H), 3.53 (d, J = 16.0 Hz, 1H), 3.80 (s, 3H), 3.98−4.18 (m, 3H) 4.63
(d, J = 14.2 Hz, 1H), 4.99 (d, J = 14.2 Hz, 1H), 6.72 (d, J = 8.9 Hz,
2H), 7.00 (d, J = 8.2 Hz, 2H), 7.04−7.18 (m, 4H), 7.35−7.55 (m,
3H), 7.74−7.83 (m, 2H) ppm; 13C NMR (75 MHz, CDCl3) δ 14.1,
21.4, 41.9, 55.3, 57.1, 60.3, 95.0, 113.4, 126.7, 127.7, 127.9, 128.8,
129.0, 131.0, 131.5, 131.9, 136.6, 142.7, 159.6, 166.1, 169.4 ppm.
HRMS (FAB) m/z: [M + H]+ Calcd for C27H29N2O5S 493.1797;
Found 493.1798.
Ethyl {2-(4-Bromophenyl)-1-[(4-methylphenyl)sulfonyl]-4-phenyl-
2,5-dihydro-1H-imidazol-2-yl}acetate (3af). Yield: 91% (147 mg);
Eluents: n-hexane/EtOAc = 4/1; pale yellow solid; mp: 126−128 °C;
1H NMR (300 MHz, CDCl3) δ 1.17 (t, J = 7.1 Hz, 3H), 2.35 (s, 3H),
3.52 (d, J = 16.0 Hz, 1H), 3.98−4.12 (m, 3H), 4.69 (d, J = 14.3 Hz,
1H), 5.03 (d, J = 14.3 Hz, 1H), 7.01−7.10 (m, 4H), 7.15 (d, J = 8.3
Hz, 2H), 7.27−7.35 (m, 2H), 7.40−7.55 (m, 3H), 7.76−7.84 (m, 2H)
ppm; 13C NMR (75 MHz, CDCl3) δ 14.2, 21.6, 41.6, 57.5, 60.6, 94.7,
122.9, 126.6, 127.9, 128.5, 129.0, 129.3, 130.9, 131.3, 132.2, 136.8,
138.5, 143.2, 167.0, 169.1 ppm. HRMS (FAB) m/z: [M + H]+ Calcd
for C26H2679BrN2O4S 541.0797; Found 541.0799, Calcd for C26H26-
81BrN2O4S 543.0776; Found 543.0781.
Ethyl {2-(4-Fluorophenyl)-1-[(4-methylphenyl)sulfonyl]-4-phenyl-
2,5-dihydro-1H-imidazol-2-yl}acetate (3ag). Yield: 83% (120 mg);
Eluents: n-hexane/EtOAc = 4/1; pale yellow solid; mp: 120−122 °C;
1H NMR (300 MHz, CDCl3) δ 1.17 (t, J = 7.1 Hz, 3H), 2.33 (s, 3H),
1
°C; H NMR (300 MHz, CDCl3) δ 1.16 (t, J = 7.1 Hz, 3H), 1.48−
1.60 (m, 4H), 2.10−2.20 (m, 2H), 2.20−2.32 (m, 5H), 3.40 (d, J =
15.8 Hz, 1H), 3.96−4.08 (m, 3H), 4.28 (d, J = 13.5 Hz, 1H), 4.63 (d, J
= 13.5 Hz, 1H), 6.22 (brs, 1H), 6.86−6.98 (m, 4H), 7.05−7.24 (m,
5H) ppm; 13C NMR (75 MHz, CDCl3) δ 14.1, 21.3, 21.7, 21.8, 24.3,
26.0, 41.7, 56.2, 60.2, 94.8, 126.6(126.57), 126.6(126.61), 128.1, 128.2,
128.9, 132.4, 136.5, 137.6, 139.5, 142.5, 167.5, 169.4 ppm. HRMS
(FAB) m/z: [M + H]+ Calcd for C26H31N2O4S 467.2005; Found
467.2006.
Ethyl [1-(Butylsulfonyl)-2,4-diphenyl-2,5-dihydro-1H-imidazol-2-
yl]acetate (3ma). Yield: 90% (116 mg); Eluents: n-hexane/EtOAc =
4/1; pale yellow solid; mp: 102−104 °C; 1H NMR (300 MHz,
CDCl3) δ 0.72 (t, J = 7.3 Hz, 3H), 1.05−1.23 (m, 5H), 1.35−1.58 (m,
2H), 2.04−2.46 (m, 2H), 3.48 (d, J = 15.9, 1H), 3.98−4.13 (m, 3H),
4.79 (d, J = 14.5 Hz, 1H), 5.07 (d, J = 14.5 Hz, 1H), 7.31−7.60 (m,
8H), 7.80−7.91 (m, 2H) ppm; 13C NMR (75 MHz, CDCl3) δ 13.4,
14.2, 21.5, 24.9, 41.7, 52.4, 58.1, 60.4, 94.3, 126.4, 127.8, 128.6, 129.0,
131.0, 132.1, 139.8, 167.2, 169.5 ppm. HRMS (FAB) m/z: [M + H]+
Calcd for C23H29N2O4S 429.1848; Found 429.1849.
Ethyl [1-(Methylsulfonyl)-2,4-diphenyl-2,5-dihydro-1H-imidazol-
2-yl]acetate (3na). Yield: 54% (63 mg); Eluents: n-hexane/EtOAc
1
= 4/1; pale yellow solid; mp: 116−118 °C; H NMR (300 MHz,
CDCl3) δ 1.16 (t, J = 7.1 Hz, 3H), 2.21 (s, 3H), 3.51 (d, J = 15.9, 1H),
3.95−4.14 (m, 3H), 4.73 (d, J = 14.4 Hz, 1H), 5.00 (d, J = 14.4 Hz,
1H), 7.32−7.58 (m, 8H), 7.86 (d, J = 7.0 Hz, 2H) ppm; 13C NMR (75
MHz, CDCl3) δ 14.2, 38.3, 41.8, 57.2, 60.4, 94.7, 126.5, 127.8, 128.7,
128.9, 129.0, 130.9, 132.1, 140.0, 166.8, 169.4 ppm. HRMS (FAB) m/
z: [M + H]+ Calcd for C20H23N2O4S 387.1379; Found 387.1380.
Ethyl {2-(4-Methylphenyl)-1-[(4-methylphenyl)sulfonyl]-4-phenyl-
2,5-dihydro-1H-imidazol-2-yl}acetate (3ab). Yield: 83% (119 mg);
Eluents: n-hexane/EtOAc = 4/1; pale yellow solid; mp: 130−132 °C;
1H NMR (300 MHz, CDCl3) δ 1.15 (t, J = 7.1 Hz, 3H), 2.31 (d, J =
3.54 (d, J = 16.0 Hz, 1H), 3.98−4.16 (m, 3H), 4.66 (d, J = 14.2 Hz,
1H), 5.01 (d, J = 14.2 Hz, 1H), 6.83−6.97 (m, 2H), 7.04 (d, J = 8.2
Hz, 2H), 7.12−7.24 (m, 4H), 7.40−7.55 (m, 3H), 7.75−7.86 (m, 2H)
ppm; 13C NMR (75 MHz, CDCl3) δ 14.1, 21.4, 41.8, 57.2, 60.4, 94.7,
115.0 (d, J = 21.8 Hz), 126.6, 127.8, 128.6 (d, J = 8.3 Hz), 128.9,
129.1, 130.9, 132.1, 135.5 (d, J = 3.8 Hz), 136.7, 143.0, 162.7 (d, J =
246.0 Hz), 166.7, 169.1 ppm. HRMS (FAB) m/z: [M + H]+ Calcd for
C26H26FN2O4S 481.1597; Found 481.1598.
Ethyl {1-[(4-Methylphenyl)sulfonyl]-4-phenyl-2-[4-(trifluoro-
methyl)phenyl]-2,5-dihydro-1H-imidazol-2-yl}acetate (3ah). Yield:
83% (132 mg); Eluents: n-hexane/EtOAc = 4/1; pale yellow solid;
mp: 153−155 °C; 1H NMR (300 MHz, CDCl3) δ 1.17 (t, J = 7.1 Hz,
3H), 2.29 (s, 3H), 3.58 (d, J = 16.0 Hz, 1H), 3.96−4.18 (m, 3H), 4.76
(d, J = 14.3 Hz, 1H), 5.09 (d, J = 14.3 Hz, 1H), 6.98 (d, J = 8.1 Hz,
2H), 7.12 (d, J = 8.2 Hz, 2H), 7.30 (d, J = 8.3 Hz, 2H), 7.38−7.56 (m,
5H), 7.81 (d, J = 7.1 Hz, 2H) ppm; 13C NMR (75 MHz, CDCl3) δ
14.1, 21.3, 41.5, 57.6, 60.6, 94.4, 123.9 (q, J = 270.0 Hz), 125.1 (q, J =
3.8 Hz), 126.4, 127.2, 127.9, 128.9, 129.2, 130.5 (q, J = 32.3 Hz),
5.1 Hz, 6H), 3.54 (d, J = 16.0 Hz, 1H), 3.94−4.09 (m, 2H), 4.13 (d, J
= 16.0 Hz, 1H), 4.66 (d, J = 14.2 Hz, 1H), 5.00 (d, J = 14.2 Hz, 1H),
6.94−7.02 (m, 4H), 7.03−7.15 (m, 4H), 7.37−7.50 (m, 3H), 7.75−
7.84 (m, 2H) ppm; 13C NMR (75 MHz, CDCl3) δ 14.1, 21.1, 21.4,
41.6, 57.2, 60.3, 95.0, 126.5, 126.7, 127.7, 128.8(128.76),
128.8(128.78), 128.9, 131.1, 131.8, 136.4, 136.6, 138.2, 142.6, 166.1,
169.4 ppm. HRMS (FAB) m/z: [M + H]+ Calcd for C27H29N2O4S
477.1848; Found 477.1850.
Ethyl {2-(3-Methylphenyl)-1-[(4-methylphenyl)sulfonyl]-4-phenyl-
2,5-dihydro-1H-imidazol-2-yl}acetate (3ac). Yield: 85% (121 mg);
9869
dx.doi.org/10.1021/jo501785d | J. Org. Chem. 2014, 79, 9865−9871

The Journal of Organic Chemistry
Note
130.8, 132.3, 136.6, 143.1, 143.2, 167.4, 169.0 ppm. HRMS (FAB) m/
z: [M + H]+ Calcd for C27H26F3N2O4S 531.1565; Found 531.1567.
Ethyl {1-[(4-Methylphenyl)sulfonyl]-2-(pentafluorophenyl)-4-phe-
nyl-2,5-dihydro-1H-imidazol-2-yl}acetate (3ai). Yield: 71% (118
mg); Eluents: n-hexane/EtOAc = 4/1; yellow solid; mp: 130−132
2H), 4.64 (s, 2H), 7.23−7.32 (m, 2H), 7.34−7.48 (m, 3H), 7.68−7.75
(m, 2H) 7.79 (d, J = 8.3 Hz, 2H) ppm; 13C NMR (75 MHz, CDCl3) δ
14.0, 21.6, 24.0, 24.2, 24.5, 42.7, 49.3, 57.3, 60.1, 97.7, 127.2, 127.6,
128.8, 129.6, 131.4, 137.5, 143.3, 164.7, 169.3 ppm. HRMS (FAB) m/
z: [M + H]+ Calcd for C24H31N2O4S 443.2005; Found 443.2007.
Methyl 2-{1-[(4-Methylphenyl)sulfonyl]-2,4-diphenyl-2,5-dihydro-
1H-imidazol-2-yl}propanoate (3ao). Yield: 84% (116 mg); Eluents:
n-hexane/EtOAc = 4/1; pale yellow solid; mp: 124−126 °C; 1H NMR
(300 MHz, CDCl3) δ 1.36 (d, J = 7.0 Hz, 2H), 2.27 (s, 3H), 3.59 (s,
3H), 4.44 (d, J = 14.6, 1H), 4.54 (q, J = 7.0 Hz, 1H), 4.83 (d, J = 14.6
Hz, 1H), 6.85 (d, J = 8.4 Hz, 2H), 6.92 (d, J = 8.3 Hz, 2H), 7.18−7.36
(m, 5H), 7.42−7.58 (m, 3H), 7.83−7.92 (m, 2H) ppm; 13C NMR (75
MHz, CDCl3) δ 12.6, 21.5, 46.9, 51.8, 56.3, 99.5, 126.8, 127.8, 128.0,
128.5, 128.9, 129.1, 130.8, 132.2, 135.9, 137.8, 142.9, 166.5, 173.0
ppm. HRMS (FAB) m/z: [M + H]+ Calcd for C26H27N2O4S
463.1691; Found 463.1690.
1
°C; H NMR (300 MHz, CDCl3) δ 1.15 (t, J = 7.1 Hz, 3H), 2.39 (s,
3H), 3.70−3.92 (m, 2H) 3.99 (q, J = 7.1 Hz, 2H), 4.81 (d, J = 13.8 Hz,
1H), 4.95 (d, J = 13.9 Hz, 1H), 7.19 (d, J = 8.1 Hz, 2H), 7.39−7.56
(m, 5H) 7.74 (d, J = 7.1 Hz, 2H) ppm; 13C NMR (75 MHz, CDCl3) δ
14.1, 21.4, 43.4 (t, J = 6.8 Hz),, 57.8 (t, J = 3.0 Hz), 60.6, 93.2, 126.6,
127.9, 129.0, 129.4, 130.5, 132.4, 136.2, 137.8 (dm, J = 256.7 Hz),
144.1, 146.0 (dm, J = 248.4 Hz), 168.5 (t, J = 2.3 Hz), 169.2 ppm; 19F
NMR (282 MHz, CDCl3) δ −138.8 (d, J = 14.1 Hz), −153.7 (dt, J =
21.2, 2.8 Hz), −162.2 (td, J = 22.6, 5.6 Hz) ppm. HRMS (FAB) m/z:
[M + H]+ Calcd for C26H22F5N2O4S 553.1220; Found 553.1218.
Ethyl {2-(Furan-3-yl)-1-[(4-methylphenyl)sulfonyl]-4-phenyl-2,5-
dihydro-1H-imidazol-2-yl}acetate (3aj). Yield: 68% (92 mg);
Eluents: n-hexane/EtOAc = 4/1; pale yellow solid; mp: 132−134
Ethyl Phenyl(2-{1-[(4-methylphenyl)sulfonyl]-2,4-diphenyl-2,5-di-
hydro-1H-imidazol-2-yl})acetate (3ap). Yield: 65% (105 mg);
Eluents: n-hexane/EtOAc = 4/1; pale yellow solid; mp: 172−174
1
°C; H NMR (300 MHz, CDCl3) δ 1.19 (t, J = 7.1 Hz, 3H), 2.36 (s,
1
°C; H NMR (300 MHz, CDCl3) δ 1.14 (t, J = 7.1 Hz, 3H), 2.24 (s,
3H), 3.55 (d, J = 16.3 Hz, 1H), 3.96 (d, J = 16.3 Hz, 1H), 4.01−4.18
(m, 2H), 4.70 (d, J = 14.0 Hz, 1H), 4.96 (d, J = 14.0 Hz, 1H), 6.31
(dd, J = 3.3, 1.8 Hz, 1H), 6.49 (d, J = 3.0 Hz, 1H), 6.99 (d, J = 1.2 Hz,
1H), 7.14 (d, J = 8.2 Hz, 2H), 7.33 (d, J = 8.3 Hz, 2H), 7.37−7.52 (m,
3H), 7.71−7.83 (m, 2H) ppm; 13C NMR (75 MHz, CDCl3) δ 14.1,
21.5, 41.0, 57.0, 60.5, 90.9, 108.8, 110.3, 126.9, 127.8, 128.8, 129.3,
131.0, 131.9, 136.2, 142.6, 143.0, 151.7, 167.1, 168.6 ppm. HRMS
(FAB) m/z: [M + H]+ Calcd for C24H25N2O5S 452.1406; Found
453.1485.
Ethyl {2-Benzyl-1-[(4-methylphenyl)sulfonyl]-4-phenyl-2,5-dihy-
dro-1H-imidazol-2-yl}acetate (3ak). Yield: 71% (101 mg); Eluents:
n-hexane/EtOAc = 4/1; pale yellow solid; mp: 114−116 °C; 1H NMR
(300 MHz, CDCl3) δ 0.97 (t, J = 7.1 Hz, 3H), 2.37 (s, 3H), 3.13 (d, J
= 17.3 Hz, 1H), 3.41−3.58 (m, 3H), 3.65 (q, J = 7.1 Hz, 2H), 4.08 (d,
J = 13.7 Hz, 1H), 4.47 (d, J = 13.7 Hz, 1H), 7.12−7.30 (m, 5H), 7.31−
7.45 (m, 5H), 7.58 (d, J = 7.1 Hz, 2H), 7.77 (d, J = 8.1 Hz, 2H) ppm;
13C NMR (75 MHz, CDCl3) δ 13.9, 21.5, 41.2, 47.1, 57.1, 60.0, 96.8,
126.7, 127.1, 127.4, 127.7, 128.6, 129.6, 131.2, 131.5, 131.6, 135.2,
137.4, 143.3, 165.5, 168.9 ppm. HRMS (FAB) m/z: [M + H]+ Calcd
for C27H29N2O4S 477.1848; Found 477.1850.
Ethyl {1-[(4-Methylphenyl)sulfonyl]-2-(2-phenylethyl)-4-phenyl-
2,5-dihydro-1H-imidazol-2-yl}acetate (3al). Yield: 69% (101 mg);
Eluents: n-hexane/EtOAc = 4/1; pale yellow solid; mp: 116−117 °C;
1H NMR (300 MHz, CDCl3) δ 1.04 (t, J = 7.1 Hz, 3H), 2.32−2.52
(m, 5H), 2.52−2.73 (m, 2H), 3.08 (d, J = 16.8 Hz, 1H), 3.41 (d, J =
16.8 Hz, 1H), 3.79 (q, J = 7.1 Hz, 2H), 4.71 (s, 2H), 7.09−7.18 (m,
3H), 7.18−7.32 (m, 4H), 7.34−7.53 (m, 3H), 7.68−7.77 (m, 2H),
7.82 (d, J = 8.3 Hz, 2H) ppm; 13C NMR (75 MHz, CDCl3) δ 14.1,
21.6, 29.4, 42.3, 42.6, 57.8, 60.2, 97.0, 125.9, 127.2, 127.7, 128.4, 128.6,
128.9, 129.8, 131.3, 131.8, 137.5, 141.4, 143.5, 165.9, 169.2 ppm.
HRMS (FAB) m/z: [M + H]+ Calcd for C28H31N2O4S 491.2005;
Found 491.2007.
Ethyl {2-Butyl-1-[(4-methylphenyl)sulfonyl]-4-phenyl-2,5-dihy-
dro-1H-imidazol-2-yl}acetate (3am). Yield: 66% (88 mg); Eluents:
n-hexane/EtOAc = 4/1; pale yellow solid; mp: 118−120 °C; 1H NMR
(300 MHz, CDCl3) δ 0.78 (t, J = 7.3 Hz, 3H), 0.98−1.11 (m, 5H),
1.19−1.30 (m, 2H), 2.01−2.15 (m, 1H), 2.19−2.32 (m, 1H), 2.40 (s,
3H), 3.06 (d, J = 16.6 Hz, 1H), 3.40 (d, J = 16.6 Hz, 1H), 3.83 (q, J =
7.1 Hz, 2H), 4.60 (d, J = 13.8 Hz, 1H), 4.70 (d, J = 13.8 Hz, 1H), 7.29
(d, J = 8.1 Hz, 2H), 7.32−7.49 (m, 3H), 7.65−7.78 (m, 2H), 7.79 (d, J
= 8.3 Hz, 2H) ppm; 13C NMR (75 MHz, CDCl3) δ 14.0, 14.1, 21.5,
22.5, 25.1, 40.1, 43.1, 57.5, 60.1, 97.3, 127.0, 127.5, 128.8, 129.6, 131.3,
131.6, 137.6, 143.3, 165.2, 169.4 ppm. HRMS (FAB) m/z: [M + H]+
Calcd for C24H31N2O4S 443.2005; Found 443.2006.
3H), 3.60 (d, J = 14.6 Hz, 1H), 3.90−4.05 (m, 1H), 4.09−4.28 (m,
2H), 5.68 (s, 1H), 6.76 (d, J = 8.3 Hz, 2H), 6.86 (d, J = 8.2 Hz, 2H),
7.15−7.28 (m, 5H), 7.28−7.51 (m, 6H), 7.59−7.70 (m, 2H), 7.70−
7.78 (m, 2H) ppm; 13C NMR (75 MHz, CDCl3) δ 14.0, 21.4, 56.0,
58.9, 60.7, 98.9, 126.4, 127.7(127.65), 127.7(127.74) 128.1(128.05),
128.1(128.10), 128.6, 128.7, 128.9, 130.7, 131.7, 131.9, 133.6, 136.4,
137.4, 142.6, 167.4, 169.9 ppm. HRMS (FAB) m/z: [M + H]+ Calcd
for C32H31N2O4S 539.2005; Found 539.2006.
Ethyl 3-(2-Methylphenyl)-3-([{2-[(4-methylphenyl)sulfonyl]-
amino}-1-phenylethenyl]amino)prop-2-enoate (4ad). Yield: 66%
(94 mg); Eluents: n-hexane/EtOAc = 4/1; pale yellow solid; mp:
1
54−56 °C; H NMR (300 MHz, CDCl3) δ 1.31 (t, J = 7.1 Hz, 3H),
1.94 (s, 3H), 2.44 (s, 3H), 4.21 (q, J = 7.1 Hz, 2H), 4.76 (s, 1H), 6.23
(d, J = 11.0 Hz, 1H), 6.58 (d, J = 7.6 Hz, 1H), 6.65−6.73 (m, 1H),
6.78−6.90 (m, 3H), 6.93−7.00 (m, 1H), 7.01−7.08 (m, 3H), 7.23 (d, J
= 12.3 Hz, 1H), 7.33 (d, J = 8.3 Hz, 2H), 7.78 (d, J = 8.2 Hz, 2H), 9.69
(s, 1H) ppm; 13C NMR (75 MHz, CDCl3) δ 14.6, 19.4, 21.7, 59.3,
90.6, 117.5, 123.2, 124.9, 125.7, 126.9, 127.3, 128.1, 128.6, 130.0,
130.1, 135.1, 135.3, 137.2, 137.8, 144.2, 162.0, 170.7 ppm. HRMS (EI)
m/z: [M]+ Calcd for C27H28N2O4S 476.1770; Found 476.1770.
Ethyl 3-(2-Pentafluorophenyl)-3-([{2-[(4-methylphenyl)sulfonyl]-
amino}-1-phenylethenyl]amino)prop-2-enoate (4ai). Yield: 47%
(70 mg); Eluents: n-hexane/EtOAc = 6/1; pale yellow solid; mp:
1
68−70 °C; H NMR (300 MHz, CDCl3) δ 1.33 (t, J = 7.1 Hz, 3H),
2.44 (s, 1H), 4.23 (q, J = 7.1 Hz, 2H), 4.88 (s, 1H), 6.38 (s, 1H), 6.95
(t, J = 3.7 Hz, 2H), 7.10−7.18 (m, 3H), 7.34 (d, J = 8.1 Hz, 2H), 7.78
(d, J = 8.3 Hz, 2H), 9.57 (s, 1H) ppm; 13C NMR (75 MHz, CDCl3) δ
14.3, 14.4, 21.6, 60.2, 93.5, 111 (m), 118.3, 121.5, 125.1, 126.8, 127.9,
128.6, 130.1, 136.5, 136.9, 137.2 (dm, J = 241.6 Hz), 143.6 (dm, J =
249.2 Hz), 144.4, 146.6, 169.6 ppm; 19F NMR (282 MHz, CDCl3) δ
−139.0 (dm, J = 22.6 Hz), −151.9 (t, J = 21.2 Hz), −161.6 (tm, J =
21.2 Hz) ppm. HRMS (EI) m/z: [M]+ Calcd for C26H21F5N2O4S
552.1142; Found 552.1140.
ASSOCIATED CONTENT
■
S
* Supporting Information
X-ray crystal data of 3aa and 3ao, details for DFT calculations
of 3aa imine and enamine forms, and copies of H and 13C
1
NMR spectra for all compounds. This material is available free
of charge via the Internet at http://pubs.acs.org.
AUTHOR INFORMATION
Corresponding Author
*E-mail: sanggi@ewha.ac.kr (S.-g.L.).
■
Ethyl {2-(2-Methylpropyl)-1-[(4-methylphenyl)sulfonyl]-4-phenyl-
2,5-dihydro-1H-imidazol-2-yl}acetate (3an). Yield: 84% (111 mg);
1
Eluents: n-hexane/EtOAc = 4/1; yellow solid; mp: 68−70 °C; H
Author Contributions
NMR (300 MHz, CDCl3) δ 0.87 (d, J = 6.6 Hz, 3H), 0.95 (d, J = 6.7
Hz, 3H), 1.02 (t, J = 7.1 Hz, 3H), 1.65−1.80 (m, 1H), 2.05 (dd, J =
14.3, 7.0 Hz, 1H), 2.24 (dd, J = 14.3, 4.3 Hz, 1H), 2.40 (s, 3H), 3.04
(d, J = 16.9 Hz, 1H), 3.35 (d, J = 16.9 Hz, 1H), 3.75 (d, J = 7.1 Hz,
†These authors contributed equally to this work.
Notes
The authors declare no competing financial interest.
9870
dx.doi.org/10.1021/jo501785d | J. Org. Chem. 2014, 79, 9865−9871

The Journal of Organic Chemistry
Note
H.; Chun, Y. S.; Lee, S.-g. J. Org. Chem. 2013, 78, 11483. (e) Kim, J.
H.; Bouffard, J.; Lee, S.-g. Angew. Chem., Int. Ed. 2014, 53, 6435.
(9) We found that the reaction of 1a with the zinc bromide complex
of 2a, the Blaise reaction intermediate, in the presence of Rh2(OAc)4
did not lead to isolable products.
ACKNOWLEDGMENTS
■
The authors acknowledge the financial support of this work
from the Korea Research Foundation (NRF-2011-0016344 for
S.-g.L. and 2013R1A1A2011320 for J.B.). We thank Dr. Sung
Hong Kim at the Daegu Center of Korea Basic Science Institute
for spectrometric analyses.
(10) Reddy, B. V. S.; Reddy, M. R.; Rao, Y. G.; Yadav, J. S.; Sridhar,
B. Org. Lett. 2013, 15, 464.
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