Synthesis of Dihydro-2-oxopyrrole (DPO) Building Blocks Catalyzed by Potassium Carbonate

Article abstract of DOI:10.1002/ejoc.201901504

A dimerization and cyclization cascade reaction of 2-sulfonaminoacrylates catalyzed by K₂CO₃ provides dihydro-2-oxopyrrole (DPO) derivatives. This straightforward and atom-economic transformation features a simple experimental operation with easily available starting materials, a broad substrate scope as well as good functional group tolerance. The desired DPO building blocks are obtained in moderate to good yields.

Full text of DOI:10.1002/ejoc.201901504

A Journal of
Accepted Article
Title: A Potassium Carbonate-Catalyzed Efficient and Straightforward
Synthesis of Dihydro-2-oxopyrrole (DPO) Building Blocks
Authors: Min Shi, Y.-S. Zhang, H.-Z. Gui, and Y. Wei
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To be cited as: Eur. J. Org. Chem. 10.1002/ejoc.201901504
Link to VoR: http://dx.doi.org/10.1002/ejoc.201901504
Supported by

10.1002/ejoc.201901504
European Journal of Organic Chemistry
DOI: 10.1002/ejoc.xxxxxxxxxx
Inorganic base-catalysis
A Potassium Carbonate-Catalyzed Efficient and Straightforward
Synthesis of Dihydro-2-oxopyrrole (DPO) Building Blocks
Yan-Shun Zhang,[a] Hou-Ze Gui,[a] Yin Wei,[b] Min Shi*[a,b]
Abstract: An inorganic base K2CO3-catalyzed cascade
dimerization and cyclization reactions of 2-sulfonaminoacrylates
to give dihydro-2-oxopyrrole (DPO) derivatives has been
disclosed in this paper. This straightforward and atom-economic
transformation featured by a simple experimental operation with
easily available starting materials and broad substrate scope as
well as good functional group tolerance, giving the desired DPO
building blocks in moderate to good yields.
Introduction
Dihydro-2-oxopyrrole (DPO) moiety is a common element
within many biologically active natural products and
pharmacologically important compounds such as Oteromycin,[1]
a
HIV integrase inhibitor and a antagonist of endothelin receptor;
Pyrrocidine,[2] a potential antibiotic; Ypaoamide,[3] a feeding
deterrent; and Glimepiride,[4] an antidiabetes drug (Figure 1).
Moreover, many DPO’s derivatives themselves also exhibited
useful bioactive characters such as antimalarial,[5] pesticidal,[6]
herbicidal,[7] etc.
H
O
O
H
H
O
NH
O
OH
H
N
O
H
Oteromycin
Pyrrocidine
Scheme 1. Previous synthetic protocols and this work.
O
O
O
The first synthetic approach is multicomponent reactions
(MCRs)[8] using electron-deficient alkynes, aldehydes/acyl
chlorides, and amines as substrates in the presence of Lewis
acids. In these MCRs, the reactions generally started from the
condensation of aldehydes and amines to generate imine
intermediates, which then reacted with alkenes to afford the
desired products (Scheme 1, a). During the last decades,
transition-metal-catalytic methods have become powerful
synthetic tools in the synthesis of DPO derivatives. Transition-
metal-catalysts such as Pd,[9] Ru,[10] Rh,[11] Cu[12] etc have been
applied for the synthesis of DPO derivatives via the reactions of
metal-activated alkenes or aldehydes with in situ generated
imines from the reactions of activated aldehydes and amines or
triazoles (Scheme 1, b). Moreover, ring-closing metathesis
(RCM)[13] is a common technique for crafting heterocycles and
carbocycles. Keum and his co-workers[13a] have reported a novel
synthetic methodology through RCM reaction of diene amide,
which was prepared via four components Ugi reaction, to afford
DPO scaffolds in one step. In 2016, Gondal’s group[13c] reported
another example for obtaining DPO derivatives via RCM reaction
of 4-step prepared diene amides starting from commercially
available allyl chloride (Scheme 1, c). However, all of these
synthetic methods had their shortages and limitations such as the
use of expensive metal catalysts and multistep synthesis of
starting materials.
N
H
N
H
HO
O
Ypaoamide
O
O
N
O
O
HN
NH
S
NH
O
Glimepiride
Figure 1. Some natural products and commercially available drugs containing
DPO moiety.
Due to the significant usefulness of DPO derivatives, a number
of synthetic methods for the preparation of functionalized DPO
scaffolds have been developed by organic chemists. As shown in
Scheme 1, the main synthetic methodologies to access DPO
derivatives have been summarized (previous work).
[a]
[b]
Key Laboratory for Advanced Materials and Institute of Fine
Chemicals, School of Chemistry & Molecular Engineering, East
China University of Science and Technology, Meilong Road
No.130, Shanghai, 200237 (China).
State Key Laboratory of Organometallic Chemistry, Center for
Excellence in Molecular Synthesis, University of Chinese
Academy of Sciences, Shanghai Institute of Organic Chemistry,
Chinese Academy of Sciences, 345 Lingling Road, Shanghai
200032 China. E-mail: mshi@mail.sioc.ac.cn
Recently, 2-aminoacrylate 1 has become an extremely useful
synthon in organic synthesis based on its unique electronic
properties and multifunctional groups. When the protecting group
(PG) of amino moiety was an acyl group (Ac), 2-aminoacrylate
could sever as a Michael acceptor to undertake an addition of a
nucleophile in the presence of N-heterocyclic carbene (NHC)
catalyst.[14] However, 2-aminoacrylate could also display its
potential nucleophilicity under the same conditions when the PG
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/ejoc.xxxxxxxx or from the author.
1
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10.1002/ejoc.201901504
European Journal of Organic Chemistry
was a sulfonyl group.[15] Furthermore, the sulfonyl group protected
2-aminoacrylate could in situ isomerize to its imine equivalent to
participate in the reaction as an electrophile,[16] avoiding the
instability and limitations of imine substance.[17] On the basis of
these findings, we envisaged that sulfonyl group protected 2-
of K2CO3 gave 2a in 82% yield as well (entry 21). Performing the
reaction in DCE at 90 C (in a sealed reaction tube) provided 2a
o
in 80% yield (entry 22). Thus, the optimal conditions are identified
as that this cascade dimerization and cyclization should be
carried out with 1a (0.4 mmol) in toluene (4.0 mL) at 90 oC for 4 h
in the presence of K2CO3 (10 mol%) (for more information on the
optimization of the reaction conditions, see Table S1 in the
Supporting Information).
aminoacrylates
could
undergo
cascade
intermolecular
nucleophilic dimerization and cyclization to afford the desired
DPO skeleton in the presence of a base. Herein, we wish to
report a facile synthetic approach for the rapid construction of
dihydro-2-oxopyrrole (DPO) building blocks from easily
accessible methyl 2-sulfonaminoacrylates using K2CO3 (10 mol%)
as the catalyst (Scheme 1, this work).
Results and Discussion
We started the investigation on the reaction of 1a (0.4 mmol)
o
and PBu3 (20 mol%) in toluene (4.0 mL) at 75 C and found that
the desired product 2a was given in 58% yield after 4 h through a
cascade dimerization and cyclization (Table 1, entry 1). A range
of alkyl and aryl phosphines were then examined and we
identified that PEt3, P(4-MeOC6H4)3, PPh2Me, PPhMe2 and dppm
could catalyze the reaction, giving 2a in moderate yields ranging
from 30%-46%, but less nucleophilic PPh3 and P(4-CF3C6H4)3
could not trigger the reaction (entries 2-8). Moreover, the use of
nitrogen-containing Lewis base DABCO instead of PBu3
produced 2a in 36% yield (entry 9). The examination of solvent
effects using PBu3 as the catalyst with ethyl acetate (EA), 1,2-
dichloroethane (DCE), and 1,4-dioxane revealed that these
solvents did not facilitate the production of 2a (entries 10-12).
Interestingly, when 100 mol% of AgOAc was used as the catalyst
at 83 oC (boiling point of DCE), the desired product 2a was
obtained in 71% yield (entry 13). Encouraged by this result, we
tried to decrease the amount of AgOAc to 20 mol% or 10 mol%,
but found that 2a was afforded in lower yields as 25%
respectively (entries 14 and 15). The use of other metal salts
such as AgOTf, Cu(OTf)2 or AgSbF6 had no catalytic activity for
this reaction, suggesting that the counter ion with strong basicity
might play an important role in this transformation (entries 16-18).
Table 1. Optimization of the reaction conditions for the synthesis of 2a.
Scheme 2. Substrate scope for the production of 2.[a],[b]
With the optimized reaction conditions in hand, the substrate
scope of this reaction was then explored. The results are
summarized in Scheme 2. First, a number of para-substituted aryl
sulfonamides were examined. For substrates 1a-1h bearing
either an electron-deficient or electron-rich aromatic ring, the
reaction proceeded smoothly, affording the corresponding
products 2a-2h in moderate to good yields ranging from 56% to
84%. The structure of 2a has been unambiguously determined by
X-ray diffraction.[18] The ORTEP drawing is shown in Figure 2 and
the CIF data are presented in the Supporting Information.
Substrate 1i, in which the aromatic ring had no substituent (R1 =
H), gave the corresponding product 2i in 68% yield, suggesting
that the electronic property of aromatic ring did not have
significant impact on the reaction outcome. As can be seen from
Scheme 2, substrate 1j, bearing a meta-substituted aromatic ring,
furnished the desired product 2j in 60% yield. In the case of
substrate 1k, in which two substituents were both introduced at
the ortho- and meta-positions of the benzene ring, the desired
product 2k was obtained in 28% yield if the reaction was
performed overnight, perhaps due to the steric effect. Moreover,
substrates 1l and 1m bearing heteroaromatic rings such as
substituted pyridine and thiophene as well as substrate 1n having
a fused naphthalene in their sulfonamide moieties were also
tolerated, giving the corresponding products 2l-2n in 60%, 34%
and 78% yields, respectively. Furthermore, we also found that the
reaction proceeded smoothly when the sulfonamide moiety was a
methylsulfonyl group (substrate 1o) and cyclopropylsulfonyl group
(substrate 1p), affording the desired products 2o and 2p in 46%
and 64% yields, respectively. However, no reaction occurred
when R3 was an acyl or a Boc protecting group (substrates 1r and
1s), presumably due to the electronic effect. The reaction also
Therefore, we next attempted to use K2CO3 (10 mol%) and
Cs2CO3 (10 mol%) as the catalysts in this reaction and found that
carrying out the reaction in toluene at 90 C afforded 2a in 83%
o
and 82% yields, respectively (entries 19 and 20). Using 100 mol%
2
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10.1002/ejoc.201901504
European Journal of Organic Chemistry
had good substrate compatibility for ester moiety R2. Replacing
methyl ester with ethyl ester (substrate 1s), benzyl ester
(substrate 1t), phenyl ester (substrate 1u) and naphthyl ester
(substrate 1v) gave the corresponding products 2s-2v in good
yields ranging from 70% to 81%. Moreover, we have also
investigated the reactivity of trisubstituted olefin substrate 1w in
this reaction. Unfortunately, none of the desired product could be
formed under the standard conditions presumably due to the
steric effect. It should be noted that this transformation could be
carried out in a gram scale, delivering 2a in 78% yield, indicating
the practical usefulness of this new synthetic protocol (Scheme 2).
Scheme 4. Proposed reaction mechanism.
Conclusions
In summary, we have disclosed a novel and efficient inorganic
base K2CO3-catalyzed cascade dimerization and cyclization
reactions of 2-sulfonaminoacrylate derivatives to synthesize
dihydro-2-oxopyrrole (DPO) derivatives in moderate to good
yields in one step. In this atom-economic and metal-free
transformation, the starting materials are easily available and the
experimental operations are simple along with broad substrate
scope and good functional group tolerance. Furthermore, gram-
scale synthesis makes this protocol to be more efficient and
practical. Further investigations on the application of this protocol
to the synthesis of biologically active DPO derivatives are
underway.
Figure 2. X-ray crystal structure of product 2a
A
hetero-dimerization reaction was also examined with
substrates 1a and 1v, but a complex mixture was obtained
without the selectivity (Scheme 3).
Scheme 3. Investigation on the hetero-dimerization
Experimental Section
A plausible reaction mechanism for this reaction is shown in
Scheme 4 using 1a as a model substrate. K2CO3 abstracted a
proton from NHTs group of 1a to generate intermediate I, which
attacked the ester moiety of another substrate 1a to afford
intermediate II. The release of MeO- from intermediate II
produced the dienyl amide compound III, which subsequently
underwent deprotonation and isomerization to give intermediate
IV. An intramolecular cyclization of intermediate IV took place to
produce intermediate V, which could be reprotonated to give the
precursor VI. Isomerization of VI produced the desired product 2a
via a proton migration. The in situ generated MeO- or intermediate
V could act as a base as well in the catalytic cycle, rendering that
the use of catalytic amount of K2CO3 is possible for this novel
cascade dimerization and cyclization process.
General methods: Proton nuclear magnetic resonance (1H NMR)
spectra, carbon nuclear magnetic resonance (13C NMR) spectra
and fluorous nuclear magnetic resonance (19F NMR) spectra
were recorded at 400, 100 and 367 MHz, respectively. Data are
presented as follows: chemical shift (ppm), multiplicity (s = singlet,
d = doublet, t = triplet, q = quartet, m = multiplet), coupling
constants in Hertz (Hz) and integration. Mass and High
Resolution Mass Spectra (HRMS) spectra were recorded by
DART or ESI method. The employed solvents were dry up by
standard methods when necessary. Commercially obtained
reagents were used without further purification. For thin-layer
chromatography (TLC), silica gel plates (Huanghai GF254) were
used. Flash column chromatography was carried out using 300-
400 mesh silica gel at increased pressure.
General Procedure for the Synthesis of 1: To a 100 mL round-
bottom flask was added sulfonamide (22.0 mmol), methyl
pyruvate (20.0 mmol), p-toluenesulfonic acid (0.2 mmol), p-
methoxyphenol (0.2 mmol) and toluene (50 mL). The resulting
mixture was stirred and heated under reflux for 18 hours. Then,
the solvent was removed under reduced pressure and the residue
was purified by
a flash column chromatography (eluent:
petroleum ether/ethyl acetate = 4/1) to give the corresponding
product 1.
General Procedure for the Synthesis of 2: To a 10 mL Schlenk
tube was added substrate 1 (0.4 mmol, 2.0 eq.) and K2CO3 (0.02
mmol, 10 mol%) and then toluene (4.0 mL) was added into tube.
The resulting reaction mixture was stirred at 90 oC. Upon reaction
completion, the mixture was filtered through a celite. The filtrate
3
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10.1002/ejoc.201901504
European Journal of Organic Chemistry
was concentrated under reduced pressure and the residue was
purified by a silica gel flash chromatography (eluent: petroleum
ether/ethyl acetate = 2/1) to afford the desired products 2 in
moderate to good yields.
1H), 7.79 (d, J = 8.4 Hz, 2H), 7.84 (d, J = 8.4 Hz, 2H), 7.89 (d, J =
8.4 Hz, 2H), 7.98 (d, J = 8.4 Hz, 2H). 13C NMR (CD3COCD3, 100
MHz, TMS) δ 21.1, 52.9, 69.4, 124.7, 128.1, 129.2, 129.6, 130.5,
132.2, 132.4, 137.7, 138.1, 163.2, 168.6. IR (neat) ν 3290, 1707,
1645, 1441, 1353, 1254, 1153, 1078, 833, 777 cm-1. HRMS (ESI)
calcd. for C19H20Br2N3O7S2: 623.9104, found: 623.9092.
o
Compound 2a: 80 mg, yield: 83%; white solid. MP: 155-157 C.
1H NMR (CD3COCD3, 400 MHz, TMS) δ 1.84 (s, 3H), 2.40 (s, 3H),
2.43 (s, 3H), 3.71 (s, 3H), 6.08 (s, 1H), 7.39 (d, J = 8.0 Hz, 2H),
7.43 (d, J = 8.0 Hz, 2H), 7.82 (d, J = 8.4 Hz, 2H), 7.93 (d, J = 8.4
Hz, 2H), 9.04 (s, 1H). 13C NMR (CD3COCD3, 100 MHz, TMS) δ
20.6, 20.7, 21.2, 52.7, 69.1, 123.8, 127.4, 128.7, 129.4, 129.7,
129.8, 135.8, 136.1, 144.7, 145.7, 163.2, 168.8. IR (neat) ν 3228,
1732, 1658, 1435, 1359, 1287, 1154, 1117, 867, 810, 660 cm-1.
HRMS (ESI) calcd. for C21H26N3O7S2: 496.1207, found: 496.1210.
Compound 2h: 66 mg, yield: 56%; yellow oil. 1H NMR
(CD3COCD3, 400 MHz, TMS) δ 1.90 (s, 3H), 3.75 (s, 3H), 6.83 (s,
1H), 7.97 (d, J = 8.4 Hz, 2H), 8.01 (d, J = 8.4 Hz, 2H), 8.19 (d, J =
8.4 Hz, 2H), 8.28 (d, J = 8.4 Hz, 2H). 13C NMR (CD3COCD3, 100
MHz, TMS) δ 21.0, 52.9, 69.6, 123.4 (q, JC-F = 275.0 Hz), 123.5 (q,
JC-F = 270.5 Hz), 125.1, 126.2 (q, JC-F = 3.7 Hz), 126.4 (q, JC-F
=
3.8 Hz), 128.2, 129.5, 129.6, 134.6 (q, JC-F = 32.7 Hz), 135.0 (q,
JC-F = 32.5 Hz), 142.1, 142.6, 163.2, 168.5. 19F NMR (376 MHz,
CD3COCD3, CFCl3) δ -58.67 (s, 3F), -58.57 (s, 3F). IR (neat) ν
3230, 1746, 1723, 1406, 1321, 1169, 1129, 1110, 1061, 842, 713
cm-1. HRMS (ESI) calcd. for C21H20F6N3O7S2: 604.0641, found:
604.0649.
Compound 2b: 83 mg, yield: 82%; yellow oil. 1H NMR
(CD3COCD3, 400 MHz, TMS) δ 1.71-1.23 (m, 6H), 1.85 (s, 3H),
2.70 (q, J = 7.6 Hz, 2H), 2.72 (q, J = 7.6 Hz, 2H), 3.71 (s, 3H),
6.69 (s, 1H), 7.42 (d, J = 8.4 Hz, 2H), 7.46 (d, J = 8.4 Hz, 2H),
7.86 (d, J = 8.4 Hz, 2H), 7.87 (d, J = 8.4 Hz, 2H), 9.13 (s, 1H). 13
C
Compound 2i: 62 mg, yield: 68%; yellow oil. 1H NMR
(CD3COCD3, 400 MHz, TMS) δ 1.85 (s, 3H), 3.71 (s, 3H), 6.72 (s,
1H), 7.57-7.61 (m, 2H), 7.62-7.65 (m, 2H), 7.67-7.70 (m, 2H),
7.73-7.77 (m, 2H), 7.95 (d, J = 7.6 Hz, 2H), 8.06 (d, J = 7.6 Hz,
2H), 9.21 (s, 1H). 13C NMR (CD3COCD3, 100 MHz, TMS) δ 21.2,
52.8, 69.2, 124.2, 127.3, 128.5, 129.0, 129.2, 129.8, 133.7, 134.5,
138.7, 138.9, 163.2, 168.7. IR (neat) ν 3199, 1723, 1660, 1448,
1365, 1270, 1153, 1086, 878, 760 cm-1. HRMS (ESI) calcd. for
C19H22N3O7S2: 468.0894, found: 468.0896.
NMR (CD3COCD3, 100 MHz, TMS) δ 14.5, 14.6, 21.3, 28.4, 28.5,
52.8, 69.1, 123.7, 127.5, 128.4, 128.6, 128.8, 129.4, 129.9, 135.8,
136.0, 136.3, 150.7, 151.7, 163.2, 168.8. IR (neat) ν 3240, 2928,
1731, 1361, 1255, 1165, 1087, 834, 778 cm-1. HRMS (ESI) calcd.
for C23H30N3O7S2: 524.1520, found: 524.1522.
Compound 2c: 76 mg, yield: 68%; yellow oil. 1H NMR
(CD3COCD3, 400 MHz, TMS) δ 1.32 (s, 9H), 1.34 (s, 9H), 1.85 (s,
3H), 3.70 (s, 3H), 6.68 (s, 1H), 7.62-7.69 (m, 4H), 7.88 (d, J = 8.4
Hz, 2H), 7.98 (d, J = 8.4 Hz, 2H), 9.14 (s, 1H). 13C NMR
(CD3COCD3, 100 MHz, TMS) δ 26.4, 35.4, 35.5, 40.1, 40.2, 57.9,
74.3, 128.5, 131.1, 131.2, 132.4, 133.7, 135.0, 141.0, 141.2,
162.5, 163.5, 168.4, 173.9. IR (neat) ν 3245, 2920, 1743, 1666,
1391, 1137, 1116, 831, 761 cm-1. HRMS (ESI) calcd. for
C27H38N3O7S2: 580.2146, found: 580.2154.
Compound 2j: 58 mg, yield: 60%; yellow oil. 1H NMR
(CD3COCD3, 400 MHz, TMS) δ 1.89 (s, 3H), 3.75 (s, 3H), 6.83 (s,
1H), 7.49 (td, J = 8.8, 2.4Hz, 1H), 7.56 (td, J = 8.8, 2.4Hz, 1H),
7.64-7.72 (m, 3H), 7.80 (d, J = 8.0 Hz, 2H), 7.90 (d, J = 8.0 Hz,
1H), 9.36 (s, 1H). 13C NMR (CD3COCD3, 100 MHz, TMS) δ 21.0,
52.9, 69.5, 114.4 (d, JC-F = 24.7 Hz), 115.6 (d, JC-F = 25.4 Hz),
120.8 (d, JC-F = 21.2 Hz), 121,7 (d, JC-F = 21.2 Hz), 123.4 (d, JC-F
Compound 2d: 86 mg, yield: 84%; yellow oil. 1H NMR
(CD3COCD3, 400 MHz, TMS) δ 1.85 (s, 3H), 3.73 (s, 3H), 3.90 (s,
3H), 6.66 (s, 1H), 7.08 (d, J = 8.8 Hz, 2H), 7.11 (d, J = 8.8 Hz,
2H), 7.88 (d, J = 8.8 Hz, 2H), 7.99 (d, J = 8.8 Hz, 2H). 13C NMR
(CD3COCD3, 100 MHz, TMS) δ 26.5, 58.0, 60.5, 60.6, 74.2, 119.2,
119.4, 128.6, 134.8, 135.1, 135.5, 136.2, 136.3, 168.4, 168.9,
169.6, 174.1. IR (neat) ν 2922, 2852, 1730, 1594, 1497, 1355,
1258, 1152, 1115, 1087, 832, 803 cm-1. HRMS (ESI) calcd. for
C21H26N3O9S2: 528.1106, found: 528.1109.
= 3.3 Hz), 124.6 (d, JC-F = 3.3 Hz), 125.1, 129.5, 131.3 (d, JC-F
=
7.8 Hz), 131.5 (d, JC-F = 8.0 Hz), 140.4 (d, JC-F = 7.4 Hz), 140.9 (d,
JC-F = 6.9 Hz), 160.8 (d, JC-F = 36.0 Hz), 163.2, 163.3 (d, JC-F
=
36.5 Hz), 168.5. 19F NMR (376 MHz, CD3COCD3, CFCl3) δ -
110.67 (s, 1F), -110.46 (s, 1F). IR (neat) ν 3249, 1759, 1703,
1472, 1368, 1294, 1166, 780, 695, 679 cm-1. HRMS (ESI) calcd.
for C19H16F2N2O7NaS2: 509.0259, found: 509.0262.
Compound 2k: 30 mg, yield: 28%; yellow oil. 1H NMR
(CD3COCD3, 400 MHz, TMS) δ 1.90 (s, 3H), 3.71 (s, 3H), 6.82 (s,
1H), 7.42-7.51 (m, 2H), 7.55-7.68 (m, 2H), 7.69-7.73 (m, 1H),
7.81-7.85 (m,1H). 13C NMR (CD3COCD3, 100 MHz, TMS) δ 20.4,
52.9, 70.0, 117.4 (d, JC-F = 27.3 Hz), 118.7 (d, JC-F = 27.7 Hz),
Compound 2e: 77 mg, yield: 74%; yellow solid. MP: 162-164 oC.
1H NMR (CD3COCD3, 400 MHz, TMS) δ 1.87 (s, 3H), 3.74 (s, 3H),
6.74 (s, 1H), 7.63 (d, J = 8.4 Hz, 2H), 7.68 (d, J = 8.4 Hz, 2H),
7.95 (d, J = 8.8 Hz, 2H), 8.05 (d, J = 8.8 Hz, 2H). 13C NMR
(CD3COCD3, 100 MHz, TMS) δ 21.1, 52.9, 69.4, 124.7, 129.1,
129.2, 129.4, 129.7, 130.5, 137.2, 137.7, 139.4, 140.4, 163.2,
168.6. IR (neat) ν 3102, 2922, 1730, 1704, 1476, 1366, 1285,
1170, 1084, 859, 827, 753 cm-1. HRMS (ESI) calcd. for
C19H20Cl2N3O7S2: 536.0114, found: 536.0114.
119.3 (d, JC-F = 7.4 Hz), 119,5 (d, JC-F = 7.8 Hz), 122.9 (dd, JC-F
=
24.1, 8.9 Hz), 124.1 (dd, JC-F = 24.1, 8.9 Hz), 126.5, 127.2 (dd, JC-
F = 14.4, 7.7 Hz), 127.8 (dd, JC-F = 16.6, 7.4 Hz), 129.0, 153.9 (dd,
JC-F = 17.9, 2.7 Hz), 156.3 (dd, JC-F = 21.1, 2.7 Hz), 156.5 (dd, JC-F
= 18.6, 2.5 Hz), 158.8 (dd, JC-F = 18.6, 2.5 Hz), 163.4, 168.3. 19F
NMR (376 MHz, CD3COCD3, CFCl3) δ -114.24- -114.04 (m, 2F), -
113.03- -112.89 (m, 1F), -112.07- -112.01 (m, 1F). IR (neat) ν
3262, 1732, 1490, 1253, 1161, 1117, 1088, 820, 693, 661 cm-1.
HRMS (ESI) calcd. for C19H18F4N3O7S2: 540.0517, found:
540.0520.
Compound 2f: 72 mg, yield: 74%; yellow oil. 1H NMR
(CD3COCD3, 400 MHz, TMS) δ 1.87 (s, 3H), 3.75 (s, 3H), 6.75 (s,
1H), 7.37 (d, J = 8.8 Hz, 2H), 7.42 (d, J = 8.8 Hz, 2H), 8.04 (dd, J
= 8.4, 5.2 Hz, 2H), 8.14 (dd, J = 8.4, 5.2 Hz, 2H). 13C NMR
(CD3COCD3, 100 MHz, TMS) δ 21.2, 52.9, 69.3, 116.0, 116.2,
116.4, 124.5, 129.7, 130.5 (d, JC-F = 9.7 Hz), 132.0 (d, JC-F = 13.6
Hz), 134.7 (d, JC-F = 2.9 Hz), 135.2 (d, JC-F = 3.2 Hz), 164.5 (d, JC-
F = 52.6 Hz), 167.6 (d, JC-F = 54.2 Hz), 168.7. 19F NMR (376 MHz,
CD3COCD3, CFCl3) δ -105.02 ~ -104.99 (m, 1F), -103.56 ~ -
103.50 (m, 1F). IR (neat) ν 2913, 2851, 1733, 1590, 1493, 1364,
1154, 1086, 837, 690 cm-1. HRMS (ESI) calcd. for
C19H20F2N3O7S2: 504.0705, found: 504.0709.
Compound 2l: 58 mg, yield: 60%; yellow oil. 1H NMR
(CD3COCD3, 400 MHz, TMS) δ 1.90 (s, 3H), 2.45 (s, 3H), 2.47 (s,
3H), 3.70 (s, 3H), 6.75 (s, 1H), 7.90-7.97 (m, 3H), 8.10 (d, J = 8.0
Hz, 1H), 8.50 (s, 1H), 8.57 (s, 1H). 13C NMR (CD3COCD3, 100
MHz, TMS) δ 17.5, 17.6, 21.0, 52.7, 69.0, 122.3, 123.9, 125.6,
129.9, 138.2, 138.3, 138.6, 139.3, 150.5, 150.6, 152.9, 153.5,
163.2, 168.8. IR (neat) ν 2917, 1740, 1653, 1365, 1258, 1176,
1120, 1105, 874, 669 cm-1. HRMS (ESI) calcd. for C19H21N4O7S2:
481.0846, found: 481.0853.
Compound 2g: 79 mg, yield: 65%; yellow oil. 1H NMR
(CD3COCD3, 400 MHz, TMS) δ 1.88 (s, 3H), 3.75 (s, 3H), 6.77 (s,
4
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10.1002/ejoc.201901504
European Journal of Organic Chemistry
Compound 2m: 32 mg, yield: 34%; yellow oil. 1H NMR
(CD3COCD3, 400 MHz, TMS) δ 1.91 (s, 3H), 3.75 (s, 3H), 6.77 (s,
1H), 7.19-7.25 (m, 2H), 7.78-7.80 (m, 1H), 7.91-7.95 (m, 2H),
8.05-8.07 (m, 1H), 9.48 (s, 1H). 13C NMR (CD3COCD3, 100 MHz,
TMS) δ 21.1, 52.8, 69.6, 124.6, 127.5, 127.6, 129.6, 133.7, 133.9,
135.7, 135.9, 138.5, 138.9, 162.8, 168.6. IR (neat) ν 3219, 1720,
1657, 1371, 1268, 1166, 1154, 1016, 862, 777 cm-1. HRMS (ESI)
calcd. for C15H18N3O7S4: 480. 0022, found: 480.0025.
Compound 2v: 96 mg, yield: 81%; red oil. 1H NMR (CD3COCD3,
400 MHz, TMS) δ 1.99 (s, 3H), 2.28 (s, 3H), 2.39 (s, 3H), 6.95 (s,
1H), 7.22 (dd, J = 8.0, 2.0 Hz, 1H), 7.35 (d, J = 8.0 Hz, 2H), 7.41
(d, J = 8.0 Hz, 2H), 7.51-7.60 (m, 3H), 7.91-8.03 (m, 7H), 9.26 (s,
1H). 13C NMR (CD3COCD3, 100 MHz, TMS) δ 25.8, 25.9, 26.2,
74.3, 123.5, 125.8, 128.0, 131.3, 132.1, 132.7, 132.9, 133.1,
133.6, 133.8, 134.9, 135.0, 135.7, 136.9, 138.9, 141.0, 141.2,
149.9, 151.1, 153.6, 168.4, 172.7. IR (neat) ν 2916, 1730, 1716,
1287, 1150, 1122, 1087, 816, 720, 702, 687 cm-1. HRMS (ESI)
calcd. for C30H26N2O7NaS2: 613.1074, found: 613.1059.
Compound 2n: 86 mg, yield: 78%; yellow oil. 1H NMR
(CD3COCD3, 400 MHz, TMS) δ 1.88 (s, 3H), 3.57 (s, 3H), 6.84 (s,
1H), 7.66-7.72 (m, 4H), 7.88-8.05 (m, 6H), 8.09-8.13 (m, 2H),
8.59 (s, 1H), 8.66 (s, 1H), 9.29 (s, 1H). 13C NMR (CD3COCD3,
100 MHz, TMS) δ 21.2, 52.7, 69.2, 122.1, 122.9, 124.4, 127.8,
127.9, 129.0, 129.2, 129.3, 129.6, 129.7, 129.8, 130.7, 131.7,
131.8, 135.1, 135.52, 135.56, 163.3, 168.8. IR (neat) ν 3257,
2914, 1744, 1710, 1456, 1362, 1164, 1129, 1117, 813, 752 cm-1.
HRMS (ESI) calcd. for C27H26N3O7S2: 568.1207, found: 568.1199.
Acknowledgements
We are grateful for the financial support from the National Basic
Research Program of China [(973)-2015CB856603], the Strategic
Priority Research Program of the Chinese Academy of Sciences
(Grant No. XDB20000000) and sioczz201808, the National
Natural Science Foundation of China (220472096, 21372241,
21572052, 20672127, 21421091, 21372250, 21121062,
21302203, 20732008, 21772037, 21772226 and 21861132014),
and the Fundamental Research Funds for the Central Universities
222201717003.
Compound 2o: 30 mg, yield: 46%; yellow oil. 1H NMR
(CD3COCD3, 400 MHz, TMS) δ 1.91 (s, 3H), 3.18 (s, 3H), 3.41 (s,
3H), 3.80 (s, 3H), 6.61 (s, 1H). 13C NMR (CD3COCD3, 100 MHz,
TMS) δ 26.7, 44.1, 46.0, 58.2, 74.8, 127.7, 135.6, 169.5, 174.3.
IR (neat) ν 3296, 1759, 1724, 1662, 1453, 1347, 1147, 1125, 983,
757 cm-1. HRMS (ESI) calcd. for C9H14N2O7NaS2: 349. 0135,
found: 349.0132.
Received: ((will be filled in by the editorial staff))
Published online on ((will be filled in by the editorial staff))
Keywords: inorganic base-catalyzed; cycloaddition; dihydro-2-
oxopyrrole derivatives
Compound 2p: 48 mg, yield: 64%; yellow oil. 1H NMR
(CD3COCD3, 400 MHz, TMS) δ 1.07-1.121 (m, 6H), 1.33-1.36 (m,
2H), 1.88 (s, 3H), 2.83-2.88 (m, 1H), 3.06-3.12 (m, 1H), 3.77 (s,
3H), 6.63 (s, 1H), 8.79 (s, 1H). 13C NMR (CD3COCD3, 100 MHz,
TMS) δ 4.80, 4.82, 5.2, 5.8, 21.5, 30.1, 31.8, 52.8, 68.9, 122.9,
130.4 164.1, 169.0. IR (neat) ν 3250, 1753, 1712, 1654, 1466,
1356, 1153, 1129, 885 cm-1. HRMS (ESI) calcd. for
C13H18N2O7NaS2: 401. 0448, found: 401.0445.
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Compound 2s: 72 mg, yield: 73%; yellow oil. 1H NMR
(CD3COCD3, 400 MHz, TMS) δ 1.14 (t, J = 7.2 Hz, 3H), 1.83 (s,
3H), 2.40 (s, 3H), 2.43 (s, 3H), 4.10-4.23 (m, 2H), 6.65 (s, 1H),
7.39 (d, J = 8.4 Hz, 2H), 7.43 (d, J = 8.4 Hz, 2H), 7.83 (d, J = 8.4
Hz, 2H), 7.94 (d, J = 8.4 Hz, 2H), 9.11 (s, 1H). 13C NMR
(CD3COCD3, 100 MHz, TMS) δ 13.3, 20.6, 20.7, 21.1, 62.2, 69.2,
123.6, 127.4, 128.6, 129.5, 129.7, 129.8, 135.9, 136.1, 144.7,
145.7, 163.2, 168.2. IR (neat) ν 3222, 2925, 1732, 1663, 1439,
1290, 1166, 1110, 1090, 813, 708 cm-1. HRMS (ESI) calcd. for
C22H28N3O7S2: 510.1363, found: 510.1368.
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1
Compound 2t: 78 mg, yield: 70%; yellow oil. H NMR (CD3Cl,
400 MHz, TMS) δ 1.89 (s, 3H), 2.34 (s, 3H), 2.38 (s, 3H), 5.18 (q,
J = 12.8 Hz, 2H), 6.46 (s, 1H), 7.10 (s, 1H), 7.17 (d, J = 8.0 Hz,
2H), 7.23 (d, J = 8.0 Hz, 2H), 7.28 (t, J = 4.0 Hz, 2H), 7.34-7.36
(m, 3H), 7.65 (d, J = 8.0 Hz, 2H), 7.91 (d, J = 8.0 Hz, 2H). 13C
NMR (CD3Cl, 100 MHz, TMS) δ 21.5, 21.6, 21.9, 68.3, 69.7,
122.1, 127.0, 128.0, 128.4, 128.5, 128.8, 129.0, 129.4, 129.8,
134.6, 135.0, 135.1, 144.9, 145.6, 163.4, 168.2. IR (neat) ν 3400,
2964, 1746, 1729, 1456, 1258, 1165, 1083, 844, 812, 799 cm-1.
HRMS (ESI) calcd. for C27H30N3O7S2: 572.1520, found: 572.1521.
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Compound 2u: 83 mg, yield: 77%; yellow oil. 1H NMR
(CD3COCD3, 400 MHz, TMS) δ 1.94 (s, 3H), 2.38 (s, 3H), 2.43 (s,
3H), 6.85 (s, 1H), 7.05 (d, J = 8.0 Hz, 2H), 7.31 (t, J = 7.2 Hz, 1H),
7.38 (d, J = 8.0 Hz, 2H), 7.43-7.48 (m, 4H), 7.90 (d, J = 8.4 Hz,
2H), 7.99 (d, J = 8.4 Hz, 2H), 9.27 (s, 1H). 13C NMR (CD3COCD3,
100 MHz, TMS) δ 20.6, 20.7, 20.9, 69.0, 121.3, 122.8, 126.3,
127.5, 128.4, 129.5, 129.7, 129.8, 130.4, 135.8, 136.0, 144.7,
145.9, 150.8, 163.1, 167.3. IR (neat) ν 3286, 2921, 1719, 1653,
1368, 1177, 1153, 1067, 842, 739, 700 cm-1. HRMS (ESI) calcd.
for C26H28N3O7S2: 558.1363, found: 558.1373.
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for this paper. These data can be obtained free of charge from The
Cambridge Crystallographic Data Centre.
5
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10.1002/ejoc.201901504
European Journal of Organic Chemistry
Inorganic base-catalysis
Yan-Shun Zhang, Hou-Ze Gui, Yin
Wei and Min Shi* __________
Page – Page
A
Potassium
Catalyzed Efficient
Straightforward Synthesis of
Carbonate-
and
We have disclosed a novel and efficient inorganic base K2CO3-catalyzed cascade dimerization
and cyclization reactions of 2-sulfonaminoacrylate derivatives to synthesize dihydro-2-
oxopyrrole (DPO) derivatives in moderate to good yields in one step.
Dihydro-2-oxopyrrole
Building Blocks
(DPO)
6
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