Efficient synthesis of pyrrolo[2,1-a]isoquinoline and pyrrolo[1,2-a] quinoline derivatives via one-pot two-step metal-catalyzed three-component reactions

Article abstract of DOI:10.1002/cjoc.201100238

A sequential one-pot two-step reaction for efficient synthesis of pyrrolo[2,1-a]isoquinoline and pyrrolo[1,2-a]quinoline derivatives in good yields has been successfully developed. The reaction included firstly Cu-catalyzed three-component reaction of iso

Full text of DOI:10.1002/cjoc.201100238

FULL PAPER
DOI: 10.1002/cjoc.201100238
Efficient Synthesis of Pyrrolo[2,1-a]isoquinoline and
Pyrrolo[1,2-a]quinoline Derivatives via One-pot Two-
step Metal-catalyzed Three-component Reactions
Wu, Lei(吴磊)
Sun, Jing(孙晶)
Yan, Chaoguo*(颜朝国)
College of Chemistry & Chemical Engineering Yangzhou University, Yangzhou 225002, China
A sequential one-pot two-step reaction for efficient synthesis of pyrrolo[2,1-a]isoquinoline and pyrrolo[1,2-a]-
quinoline derivatives in good yields has been successfully developed. The reaction included firstly Cu-catalyzed
three-component reaction of isoquinoline (quinoline), acetylenedicarboxylate and alkynylbenzene and then
Pd-catalyzed intramolecular C(sp)-C(sp2) coupling reaction of initially formed 1-alkenyl-2-alkynyl-1,2-dihydroiso-
quinoline (1,2-dihydroquinoline).
Keywords indolizine, pyrrolo[2,1-a]isoquinoline, isoquinoline, C-C coupling reaction, three-component reaction
Introduction
Results and Discussion
Indolizines constitutes the core structure of many
naturally occurring alkaloids and have displayed impor-
tant biological activities which can find a variety of ap-
plications in pharmaceutical use.[1,2] Consequently, the
syntheses of indolizines have attracted much attention in
the past years.[3-5] Among various synthetic approaches
for indolizines, 1,3-dipolar cycloaddition reaction of
pyridinium N-ylide generated in situ from a pyridinium
salt in the presence of a base with an electron-deficient
alkene/alkyne is the most typical methodology, which
has been proved to be versatile in terms of efficiency
and to have a wide scope of applications.[6-10] Recently
the metal-catalyzed C—N bond-forming procedures
have proved to be efficient methods for versatile in-
odolizine derivatives.[11,12] These include CuX-mediated
cycloisomerization of alkynyl pyridines,[13] and Pd/Cu
catalyzed one-pot synthesis of 3-aminoindolizines
through the cascade coupling/cycloisomerization reac-
tions of propargyl amines or amides with heteroaryl
bromides.[14] However, the starting materials were not
easy to synthesize in some cases. Thus developing prac-
tical synthetic routes for the efficient synthesis of indol-
izine derivatives is still highly desirable. As part of our
continuing effort into the design of new multicompo-
nent reactions for the preparation of N,O-containing
heterocycles,[15] herein we report the efficient synthesis
of the functionalized pyrrolo[2,1-a]isoquinolines and
pyrrolo[1,2-a]quinolines via one-pot two-step metal-
catalyzed three-component coupling reaction.
As shown in Scheme 1, we anticipated smooth in-
tramolecular cyclization of 1-alkenyl-2-alkynyl-1,2-
dihydroisoquinoline 1 by the Pd-catalyzed C(sp)-C(sp2)
coupling reactions, which is inspired by the several
successful examples of preparation of indenes by
Pd-catalyzed carbocylization reaction of 1-alkenyl-2-
alkynylbenzene.[16] To test this idea, the cyclization
precursor 1a was first prepared by the three-component
reaction of isoquinoline, dimethyl acetylenedicarboxy-
late and phenylacetylene according to the reported pro-
cedure.[17] Then the Pd-catalyzed cyclization reaction
was performed by employing 1a in the presence of 5
mol% of Pd(OAc)2 and 20 mol% CuCl2 in DMAc as
solvent, which was used in the Pd-catalyzed synthesis of
indene.[16a] After stirring the reaction mixture at 80 ℃
for about 10 h, we are pleased to isolate the expected
cyclization product 2a in 63% yield. In order to increase
the yield of product, the reaction conditions are
screened with choice of the solvent, temperature and
catalyst. The reaction gave low yields of 2a in 45%
yield in DMF and less than 30% of 2a in solvent such as
THF, toluene, CH3CN and dioxane. PdCl2 showed much
less activity for this reaction (33% of 2a) and more than
20 mol% of CuCl2 could not increase the yield further.
The optimized reaction condition is similar to the that of
the reported Pd-catalyzed tandem reaction for indene.[16a]
Then the similar cyclizations of 1,2-dihydroisoquinoli-
nes 1b and 1c were also carried out in this optimized
condition and the corresponding pyrrolo[2,1-a] isoquinolines
*
E-mail: cgyan@yzu.edu.cn
Received August 15, 2011; accepted September 24, 2011; published online February 29, 2012.
590
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Chin. J. Chem. 2012, 30, 590—596

Efficient Synthesis of Pyrrolo[2,1-a]isoquinoline and Pyrrolo[1,2-a]quinoline Derivatives
Scheme 1 Preparation routes of pyrrolo[2,1-a]isoquinolines
N
CO2CH3
CO2CH3
CO2CH3
1. Cul, DCM, r.t.
O
N
2. Pd(OAc)2, CuCl2, DMAc, 80 °C
CO2CH3
R
R
2a−2c
N
CO2CH3
CO2CH3
Pd(OAc)2, CuCl2
DMAc, 80 °C
Cul, DCM, r. t.
R
1a−1c
2b and 2c were produced in 55% and 60% yields.
this protocol to other nitrogen-containing heterocycles,
quinoline was also used to react with arylacetylenes and
acetylenedicarboxylates in the one-pot two-step Pd-
catalyzed reaction. All reactions proceeded smoothly to
result in the required pyrrolo[1,2-a]quinolines 2g—2l in
moderate yields (Table 1, Entries 7—12), which indi-
cates that this one-pot two-step three-component reac-
tion has a broad variety of substrates.
This initially successful preparation of pyrrolo-
[2,1-a]isoquinolines 2a—2c encouraged us to combine
the two separated metal-catalyzed reactions into a one-
pot two-step procedure without separating the cycliza-
tion precursor 1. Hence after completion of first Cu-
catalyzed three-component reaction of isoquinoline,
acetylenedicarboxylate and phenylacetylene in DCM,
the catalyst Pd(OAc)2 and CuCl2 as well as the solvent
DMAc were added and the mixture was heated to 80 ℃
for 10 h. Under this sequential reaction procedure the
pyrrolo[2,1-a]isoquinolines 2a was also prepared in
nearly same yield (60%). Thus a one-pot two-step
three-component reaction is successfully established.
Under similar reaction conditions isoquinoline, p-methyl
and p-methoxyphenylacetylenes and diethyl acetylene-
dicarboxylates were utilized to give the corresponding
pyrrolo[2,1-a]isoquinoline derivatives 2b—2f in mod-
erate to good yields (Table 1). In an attempt of extend
The structures of the prepared pyrrolo[2,1-a]iso-
quinolines and pyrrolo[1,2-a]quinoline 2a—2l were
1
established by IR, MS, H and 13C NMR spectroscopy
and confirmed by the X-ray determination of single
crystal structures of 2a and 2k (Figure 1). It should be
pointed out that these compounds have been prepared
by 1,3-dipolar addition reaction of isoquinolinium or
quinolinium bromides with electron-deficient al-
kynes.[18,19] Recently Yavari reported the preparation of
these compounds from the three-component reaction of
activated acetylenes, benzoylnitromethanes, and
Table 1 Ppreparation of benzoindolizines 2a—2l via one-pot two-step reactions
Entry Compd.
Isoquinoline/quinoline
Acetylene-dicarboxylate Aryl acetylene
Product
Yield/%
N
COOCH3
COOCH3
COOCH3
1
60
2a
O
COOCH3
N
N
COOCH3
COOCH3
COOCH3
COOCH3
O
2
54
2b
N
Chin. J. Chem. 2012, 30, 590—596
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Wu, Sun & Yan
FULL PAPER
Continued
Yield/%
Entry Compd.
Isoquinoline/quinoline
Acetylene-dicarboxylate Aryl acetylene
Product
N
COOCH3
COOCH3
O
COOCH3
3
57
2c
N
COOCH3
OCH3
OCH3
N
COOEt
COOEt
COOEt
COOEt
4
62
2d
O
N
N
COOEt
COOEt
COOEt
COOEt
O
5
48
2e
N
N
COOEt
COOEt
COOEt
O
6
51
2f
N
COOEt
OCH3
OCH3
COOCH3
O
N
7
8
58
54
2g
2h
N
N
COOCH3
COOCH3
H3CO2C
CO2CH3
O
N
COOCH3
COOCH3
H3CO2C
CO2CH3
O
N
9
52
2i
OCH3
N
N
COOCH3
H3CO2C
CO2CH3
OCH3
COOEt
COOEt
O
N
10
63
2j
EtO2C
CO2Et
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Chin. J. Chem. 2012, 30, 590—596

Efficient Synthesis of Pyrrolo[2,1-a]isoquinoline and Pyrrolo[1,2-a]quinoline Derivatives
Continued
Yield/%
Entry Compd.
Isoquinoline/quinoline
Acetylene-dicarboxylate Aryl acetylene
Product
COOEt
O
N
11
55
2k
N
COOEt
COOEt
EtO2C
CO2Et
O
N
12
45
2l
OCH3
N
COOEt
OCH3
EtO2C
CO2Et
lenes. Prominent among the advantages of this new
method are novelty, operational simplicity, and good
yields. Applications to other metal-catalyzed multi-
component reactions are in progress in our laboratory.
Experimental
General procedure for the preparation of pyrrolo-
[2,1-a]isoquinolines and pyrrolo[1,2-a]quinolines
(2a—2l) from one-pot two-step three-component re-
actions
Acetylenedicarboxylate (1.2 mmol) was added to a
stirred solution of CuI (0.05 mmol), isoquinoline (1.0
mmol), arylacetylene (1.0 mmol) in dichloromethane
(5.0 mL). The resulting reaction mixture was stirred at
room temp. for 2 h. Then Pd(OAc)2 (0.05 mmol, 5
mol%), CuCl2 (0.2 mmol, 20 mol%) and DMA (6.0 mL)
were added. The mixture was stirred at 80 ℃ for an ad-
ditional 10 h. Then the reaction was quenched with wa-
ter, extracted with EtOAc (10 mL×2), dried by anhy-
drate Na2SO4. The solvent was evaporated and the resi-
due was subjected to silica gel column chromatography
(100—200 mesh) using light petroleum/ethyl acetate
(4∶1) as eluent, affording the pure product for analysis.
2a: Dimethyl 1-benzoylpyrrolo[2,1-a] isoquino-
Figure 1 Molecular structure of 2k.
isoquinoline.[20]
Although we have not investigated the reaction
mechanism in an experimental manner, a reasonable
reaction paths was proposed in Scheme 2 based on pre-
viously reported formation of the cyclization precur-
sor[17] and sequential Pd-catalyzed carbocylization reac-
tion.[16a] At first isoquinoline reacts with acetylenedi-
carboxylate to form a zwitterionic intermediate (A),
which in turn reacts with phenylacetylene activated by
CuI to furnish the desired 1-alkenyl-2-alkynyl-
1,2-dihydroisoquinoline 1. Secondly the Pd(Ac)2 acti-
vated C-C triple band was attacked by nucleophilic car-
banion to result in a five-membered ring intermediate (B)
with an exocyclic double band. Hydration of the car-
banion (B) gives an enol intermediate (C). Then inter-
mediate (C) was tautomerized to the ketone form, which
at last was dehydrogenated to give the final product 2
under the catalysis of CuCl2.
1
line-2,3-dicarboxylate, yellow solid, m.p. 146—148 ℃; H
NMR (600 MHz, CDCl3) δ: 9.21 (brs, 1H, CH), 8.07—
8.06 (m, 1H, CH), 7.90 (brs, 2H, ArH), 7.68 (brs, 1H,
ArH), 7.56 (brs, 1H, ArH), 7.50 (brs, 1H, ArH), 7.43
(brs, 2H, ArH), 7.36 (brs, 1H, ArH), 7.19—7.18 (m, 1H,
ArH), 3.92 (s, 3H, OCH3), 3.50 (s, 3H, OCH3); 13C
NMR (150 MHz, CDCl3) δ: 193.5, 166.5, 165.0, 164.3,
160.8, 138.4, 133.4, 129.8, 129.3, 128.7, 128.6, 128.1,
127.2, 127.0, 125.3, 123.9, 117.0, 116.0, 115.7,
52.7,52.2, 52.2, 52.1; IR (KBr) ν: 3670 (w), 2950 (w),
1742 (s), 1699 (s), 1650 (s), 1511 (m), 1438 (m), 1375
(m), 1211 (s), 1095 (m), 886 (w), 790 (w), 742 (w)
Conclusions
－
＋
＋
1
In summary we have described an efficient synthetic
procedure for pyrrolo[2,1-a]isoquinolines and pyrrolo-
[1,2-a]quinolines in good yields by the one-pot two-step
metal-catalyzed three-component reactions of isoquino-
line (quinoline), acetylenedicarboxylates and arylacety-
cm ; MS (ESI ) m/z (%): 410.23 ([M＋Na] , 100).
2b: Dimethyl 1-p-methylbenzoylpyrrolo[2,1-a]-
isoquinoline-2,3-dicarboxylate, yellow solid, m.p .160
1
—162 ℃; H NMR (600 MHz, CDCl3) δ: 9.21 (d, J＝
7.2 Hz, 1H, CH), 8.04 (d, J＝7.2 Hz, 1H, CH), 7.81 (d,
Chin. J. Chem. 2012, 30, 590—596
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593

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FULL PAPER
Scheme 2 Plausible reaction mechanism
N
CO2CH3
CO2CH3
CO2CH3
+N
CO2CH3
CO2CH3
ArC CH
CuI
-
N
-
CO2CH3
Ar
A
1
Pd(OAc)2
N
CO2CH3
CO2CH3
N
CO2CH3
CO2CH3
N
CO2CH3
CO2CH3
O
H2O
CuCl2
HO
O
-
Ar
Ar
Ar
2
C
B
J＝8.4 Hz, 2H, ArH), 7.68 (d, J＝7.8 Hz, 1H, ArH),
7.50 (t, J＝7.5 Hz, 1H, ArH), 7.36 (t, J＝7.8 Hz, 1H,
ArH), 7.23 (d, J＝7.8 Hz, 2H, ArH), 7.18 (d, J＝7.8 Hz,
1H, ArH), 3.92 (s, 3H, OCH3), 3.53 (s, 3H, OCH3), 2.41
(s, 3H, CH3); 13C NMR (150 MHz, CDCl3) δ: 193.2,
165.0, 160.9, 157.2, 144.5, 135.8, 131.8, 130.0, 129.3,
129.1, 128.6, 128.1, 127.2, 126.8, 125.2, 124.2, 124.0,
117.2, 115.6, 114.1, 52.3, 52.1, 21.8; IR (KBr) ν: 3672
(w), 2951 (w), 1737 (s), 1703 (s), 1649 (s), 1509 (m),
1457 (m), 1376 (m), 1215 (vs), 1099 (m), 892 (w), 792
128.1, 127.3, 127.2, 125.2, 124.2, 124.0, 116.8, 115.5,
114.3, 61.5, 61.2, 14.0, 13.7; IR (KBr) ν: 3675 (w),
2981 (w), 1740 (s), 1696 (s), 1651 (s), 1509 (m), 1388
－
1
(m), 1211 (vs), 1098 (s), 791 (m), 738 (w) cm ; MS
(ESI＋) m/z (%): 438.25 ([M＋Na]＋, 100).
2e: Diethyl 1-p-methxylbenzoylpyrrolo[2,1-a]-
isoquinoline-2,3-dicarboxylate, yellow solid, m.p. 116
1
℃; H NMR (600 MHz, CDCl3) δ: 9.25 (d, J＝7.8 Hz,
1H, CH), 8.05 (d, J＝8.4 Hz, 1H, ArH), 7.83 (d, J＝7.8
Hz, 2H, ArH), 7.69 (d, J＝7.8 Hz, 1H, ArH), 7.50 (d,
J＝7.5 Hz, 1H, ArH), 7.36 (d, J＝7.5 Hz, 1H, ArH),
7.23 (d, J＝7.8 Hz, 2H, ArH), 7.18 (d, J＝7.8 Hz, 1H,
CH), 4.40 (q, J＝7.2 Hz, 2H, CH2), 3.96 (q, J＝7.2 Hz,
2H, CH2), 2.41 (s, 3H, CH3), 1.36 (t, J＝7.2 Hz, 3H,
CH3), 1.10 (t, J＝7.2 Hz, 3H, CH3); 13C NMR (150
MHz, CDCl3) δ: 193.2, 164.6, 160.5, 144.4, 135.9,
131.7, 130.1, 129.2, 129.0, 128.5, 128.0, 127.2, 127.1,
125.2, 124.2, 124.0, 117.0, 115.4, 114.2, 61.5, 61.1,
21.8, 14.0, 13.7; IR (KBr) ν: 3670 (w), 2982 (w), 1704
(s), 1651 (s), 1517 (m), 1470 (m), 1377 (m), 1223 (vs),
－
＋
＋
1
(m) cm ; MS (ESI ) m/z (%): 424.30 ([M＋Na] ,
100).
2c: Dimethyl 1-p-methoxybenzoylpyrrolo[2,1-a]-
isoquinoline-2,3-dicarboxylate, yellow solid, m.p. 124
1
—126 ℃; H NMR (600 MHz, CDCl3) δ: 9.22 (d, J＝
7.8 Hz, 1H, CH), 8.03 (d, J＝7.8 Hz, 1H, CH), 7.90 (d,
J＝8.4 Hz, 2H, ArH), 7.69 (d, J＝7.2 Hz, 1H, ArH),
7.50 (t, J＝7.2 Hz, 1H, ArH), 7.37 (t, J＝7.2 Hz, 1H,
ArH), 7.19 (d, J＝7.2 Hz, 1H, ArH), 6.91 (d, J＝8.4 Hz,
2H, ArH), 3.93 (s, 3H, OCH3), 3.86 (s, 3H, OCH3), 3.58
(s, 3H, OCH3); 13C NMR (150 MHz, CDCl3) δ: 192.1,
165.1, 164.0, 160.9, 132.2, 131.5, 131.2, 129.0, 128.6,
128.5, 128.1, 127.2, 126.7, 125.2, 124.2, 124.0, 117.2,
115.5, 114.1, 113.8, 55.5, 52.3, 52.2, 52.1; IR (KBr) ν:
3671 (w), 2954 (w), 1714 (s), 1647 (s), 1595 (m), 1509
(m), 1456 (m), 1371 (m), 1311 (w), 1221 (vs), 1169 (s),
－
＋
1
1099 (m), 1052 (w), 797 (w) cm ; MS (ESI ) m/z (%):
452.35 ([M＋Na]＋, 100).
2f: Diethyl 1-p-methoxybenzoylpyrrolo[2,1-a]-
isoquinoline-2,3-dicarboxylate, white solid, m.p. 118 ℃;
1H NMR (600 MHz, CDCl3) δ: 9.24 (d, J＝7.8 Hz, 1H,
CH), 8.03 (d, J＝8.4 Hz, 1H, ArH), 7.92 (d, J＝8.4 Hz,
2H, ArH), 7.69 (d, J＝7.8 Hz, 1H, ArH), 7.50 (d, J＝7.5
Hz, 1H, ArH), 7.37 (d, J＝7.5 Hz, 1H, ArH), 7.17 (d,
J＝7.8 Hz, 1H, CH), 6.91 (d, J＝8.4 Hz, 2H, ArH), 4.40
(q, J＝7.2 Hz, 2H, CH2), 4.02 (q, J＝7.2 Hz, 2H, CH2),
3.86 (s, 3H, OCH3), 1.37 (t, J＝7.2 Hz, 3H, CH3), 1.11
(t, J＝7.2 Hz, 3H, CH3); 13C NMR (150 MHz, CDCl3) δ:
192.1, 164.7, 164.0, 160.5, 132.4, 131.5, 131.3, 129.0,
128.4, 128.1, 127.2, 126.9, 125.1, 124.3, 124.0, 117.0,
115.3, 114.1, 113.8, 61.5, 61.1, 55.5, 14.1, 13.8; IR
(KBr) ν: 3671 (w), 2982 (w), 1704 (s), 1648 (s), 1597
(m), 1511 (m), 1465 (m), 1220 (vs), 1169 (m), 1098 (m),
－
＋
1
1097 (m), 934 (w), 797 (m) cm ; MS (ESI ) m/z (%):
440.24 ([M＋Na]＋, 100).
2d: Diethyl 1-benzoylpyrrolo[2,1-a]isoquinoline-
1
2,3-dicarboxylate, white solid, m.p. 114 ℃; H NMR
(600 MHz, CDCl3) δ: 9.26 (d, J＝6.0 Hz, 1H, CH), 8.07
(d, J＝7.2 Hz, 1H, ArH), 7.93 (d, J＝6.6 Hz, 2H, ArH),
7.70 (d, J＝7.2 Hz, 1H, ArH), 7.58 (brs, 1H, ArH), 7.50
(d, J＝6.6 Hz, 1H, ArH), 7.45 (d, J＝7.2 Hz, 2H, ArH),
7.37 (d, J＝6.6 Hz, 1H, ArH), 7.20 (d, J＝6.0 Hz, 1H,
CH), 4.40 (q, J＝6.0 Hz, 2H, CH2), 3.93 (q, J＝6.0 Hz,
2H, CH2), 1.35 (t, J＝5.6 Hz, 3H, CH3), 1.08 (t, J＝5.6
Hz, 3H, CH3); 13C NMR (150 MHz, CDCl3) δ: 193.5,
164.6, 160.5, 138.4, 133.5, 132.0, 129.1, 128.6, 128.5,
－
＋
1
1031 (m), 855 (w), 799 (m), 613 (w) cm ; MS (ESI )
m/z (%): 468.31 ([M＋Na]＋, 100).
594
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Efficient Synthesis of Pyrrolo[2,1-a]isoquinoline and Pyrrolo[1,2-a]quinoline Derivatives
2g: Dimethyl 3-benzoylpyrrolo[1,2-a]quinoline-1,2-
dicarboxylate, yellow solid, m.p. 140—142 ℃; H
1637 (s), 1507 (m), 1436 (m), 1384 (w), 1221 (vs), 1113
－
1
1
(m), 1020 (m), 962 (w), 859 (w), 802 (m), 753 (m) cm ;
NMR (600 MHz, CDCl3) δ: 7.94 (d, J＝9.0 Hz, 1H,
CH), 7.76—7.79 (m, 3H, ArH), 7.72 (d, J＝9.0 Hz, 1H,
CH), 7.59 (t, J＝7.8 Hz, 1H, ArH), 7.54 (t, J＝7.2 Hz,
1H, ArH), 7.50 (t, J＝7.2 Hz, 1H, ArH), 7.44 (q, J＝7.5
Hz, 3H, ArH), 4.06 (s, 3H, OCH3), 3.40 (s, 3H, OCH3);
13C NMR (150 MHz, CDCl3) δ: 191.3, 164.3, 163.5,
140.0, 135.3, 132.5, 132.3, 129.2, 129.0, 128.9, 128.4,
126.6, 126.0, 125.5, 124.0, 121.0, 117.7, 117.5, 114.9,
53.3, 51.9; IR (KBr) ν: 3677 (w), 2953 (w), 1723 (vs),
1638 (s), 1512 (s), 1435 (m), 1378 (w), 1220 (vs), 1108
MS (ESI＋) m/z (%): 438.26 ([M＋Na]＋, 100).
2k: Diethyl 3-p-methylbenzoylpyrrolo[1,2-a]-
quinoline-1,2-dicarboxylate, white solid, m.p 118—120
1
℃; H NMR (600 MHz, CDCl3) δ: 7.97 (d, J＝9.0 Hz,
1H, CH), 7.75 (d, J＝7.8 Hz, 1H, ArH), 7.73 (d, J＝8.4
Hz, 2H, ArH), 7.65 (d, J＝9.6 Hz, 1H, ArH), 7.58 (t,
J＝8.2 Hz, 1H, ArH), 7.49 (d, J＝7.5 Hz, 1H, ArH),
7.39 (d, J＝9.0 Hz, 1H, CH), 7.24 (d, J＝7.8 Hz, 2H,
ArH), 4.55 (q, J＝7.2 Hz, 2H, CH2), 3.92 (q, J＝7.2 Hz,
2H, CH2), 2.42 (s, 3H, CH3), 1.44 (t, J＝7.2 Hz, 3H,
CH3), 0.98 (t, J＝7.2 Hz, 3H, CH3); 13C NMR (150
MHz, CDCl3) δ: 191.0, 163.9, 163.2, 143.2, 137.3,
134.8, 132.6, 129.4, 129.2, 129.0, 128.7, 126.0, 125.8,
125.6, 123.7, 121.4, 117.8, 117.6, 115.2, 62.6, 61.2,
58.5, 21.6, 18.5, 13.9, 13.6; IR (KBr) ν: 3672 (w), 2983
(w), 1724 (vs), 1638 (s), 1505 (m), 1436 (m), 1384 (m),
1221 (vs), 1110 (m), 1022 (m), 960 (w), 857 (w), 801
－
＋
1
(m), 959 (w), 812 (w), 757 (w) cm ; MS (ESI ) m/z
(%): 410.21 ([M＋Na]＋, 100).
2h: Dimethyl 3-p-methylbenzoylpyrrolo[1,2-a]-
quinoline-1,2-dicarboxylate, yellow solid, m.p. 114—
1
116 ℃; H NMR (600 MHz, CDCl3) δ: 7.93 (d, J＝8.4
Hz, 1H, CH), 7.76 (d, J＝8.4 Hz, 1H, CH), 7.70 (d, J＝
7.8 Hz, 2H, ArH), 7.65 (d, J＝9.0 Hz, 1H, ArH), 7.59 (t,
J＝8.1 Hz, 1H, ArH), 7.50 (t, J＝7.2 Hz, 1H, ArH),
7.40 (d, J＝9.0 Hz, 1H, ArH), 7.25 (d, J＝7.8 Hz, 2H,
ArH), 4.06 (s, 3H, OCH3), 3.45 (s, 3H, OCH3), 2.42 (s,
3H, CH3); 13C NMR (150 MHz, CDCl3) δ: 191.0, 164.3,
163.5, 143.2, 137.2, 135.0, 132.6, 129.2, 129.1, 129.0,
128.9, 126.2, 125.9, 125.4, 123.9, 120.9, 117.7, 117.5,
115.3, 58.4, 53.3, 52.0, 21.7, 18.4; IR (KBr) ν: 3665 (w),
2950 (w), 1727 (s), 1634 (s), 1514 (m), 1436 (m), 1380
(w), 1222 (vs), 1110 (m), 1054 (w), 936 (w), 809 (m),
－
＋
1
(m), 754 (w), 684 (w), 610 (w) cm ; MS (ESI ) m/z
(%): 452.22 ([M＋Na]＋, 100).
2l: Diethyl 3-p-methoxbenzoylpyrrolo[1,2-a]-
quinoline-1,2-dicarboxylate, white solid, 50%, m.p.
1
100—102 ℃; H NMR (600 MHz, CDCl3) δ: 7.97 (d,
J＝9.0 Hz, 1H, CH), 7.82 (d, J＝8.4 Hz, 2H, ArH), 7.75
(d, J＝7.8 Hz, 1H, ArH), 7.61 (d, J＝9.6 Hz, 1H, ArH),
7.57 (t, J＝7.8 Hz, 1H, ArH), 7.49 (t, J＝7.2 Hz, 1H,
ArH), 7.37 (d, J＝9.0 Hz, 1H, CH), 6.93 (d, J＝8.4 Hz,
2H, ArH), 4.55 (q, J＝7.1 Hz, 2H, CH2), 3.97 (d, J＝
7.1Hz, 2H, CH2), 3.87 (s, 3H, OCH3), 1.45 (t, J＝7.2 Hz,
3H, CH3), 1.00 (t, J＝7.2 Hz, 3H, CH3); 13C NMR (150
MHz, CDCl3) δ: 190.0, 163.9, 163.3, 163.2, 134.4,
132.6, 131.6, 129.2, 128.7, 125.8, 125.7, 125.4, 123.2,
121.5, 117.7, 117.4, 115.4, 113.6, 62.6, 61.2, 58.4, 55.5,
18.4, 13.9, 13.6; IR (KBr) ν: 3673 (w), 2981 (w), 1722
(vs), 1646 (s), 1600 (m), 1508 (m), 1435 (m), 1386 (m),
1232 (vs), 1183 (vs), 1109 (w), 1020 (m), 959 (w), 855
－
＋
＋
1
758 (m) cm ; MS (ESI ) m/z (%): 424.24 ([M＋Na] ,
100).
2i: Dimethyl 3-p-methoxybenzoylpyrrolo[1,2-a]-
quinoline-1,2-dicarboxylate, yellow solid, m.p. 122—
1
124 ℃; H NMR (600 MHz, CDCl3) δ: 7.92 (d, J＝9.0
Hz, 1H, CH), 7.80 (d, J＝9.0 Hz, 2H, ArH), 7.75 (d, J＝
7.2 Hz, 1H, ArH), 7.59 (d, J＝8.4 Hz, 2H, ArH), 7.49 (t,
J＝7.5 Hz, 1H, ArH), 7.37 (d, J＝9.0 Hz, 1H, CH), 6.93
(d, J＝9.0 Hz, 2H, ArH), 4.07 (s, 3H, OCH3), 3.87 (s,
3H, OCH3), 3.51 (s, 3H, OCH3); 13C NMR (150 MHz,
CDCl3) δ: 190.0, 164.3, 163.6, 163.2, 134.6, 132.5,
131.4, 130.9, 129.2, 128.8, 125.9, 125.4, 123.5, 121.0,
117.7, 117.4, 113.6, 58.4, 55.5, 53.3, 52.1, 18.4; IR
(KBr) ν: 3666 (w), 2952 (w), 1724 (vs), 1606 (s), 1497
(m), 1440 (m), 1385 (w), 1223 (vs), 1173 (m), 1032 (m),
－
＋
1
(m), 805 (m), 753 (w), 609 (w) cm ; MS (ESI ) m/z
(%): 468.34 ([M＋Na]＋, 100).
Acknowledgement
This work was financially supported by the National
Natural Science Foundation of China (Grant No.
20972132).
－
＋
1
925 (w), 806 (w), 614 (w) cm ; MS (ESI ) m/z (%):
440.22 ([M＋Na]＋, 100).
2j: Diethyl 3-benzoylpyrrolo[1,2-a]quinoline-1,2-
1
dicarboxylate, white solid, m.p.102—104 ℃; H NMR
Supporting Information Available
(600 MHz, CDCl3) δ: 7.98 (d, J＝8.4 Hz, 1H, CH), 7.82
(d, J＝7.8 Hz, 2H, ArH), 7.77 (d, J＝7.8 Hz, 1H, ArH),
7.72 (d, J＝8.4 Hz, 1H, CH), 7.59 (t, J＝7.8 Hz, 1H,
ArH), 7.55 (t, J＝7.8 Hz, 1H, ArH), 7.50 (t, J＝7.5 Hz,
1H, ArH),7.46—7.41 (m, 3H, ArH), 4.55 (q, J＝7.2 Hz,
2H, CH2), 3.86 (q, J＝7.2 Hz, 2H, CH2), 1.44 (t, J＝6.9
Hz, 3H, CH3), 0.95 (t, J＝6.9 Hz, 3H, CH3); 13C NMR
(150 MHz, CDCl3) δ: 191.3, 163.8, 163.1, 140.0, 135.1,
132.7, 132.4, 129.2, 129.1, 128.8, 128.4, 126.3, 125.9,
125.5, 123.8, 121.6, 117.8, 117.6, 114.8, 62.6, 61.3,
13.9, 13.5; IR (KBr) ν: 3673 (w), 2984 (w), 1725 (s),
Crystallographic data of 2a (CCDC 830600) and 2k
(CCDC 830601) have been deposited at the Cambridge
Crystallographic Database Centre.
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