In Situ Generation of Quinolinium Ylides from Diazo Compounds: Copper-Catalyzed Synthesis of Indolizine

Article abstract of DOI:10.1021/acs.joc.7b01042

The Cu-catalyzed three-component reaction between quinolines, diazo compounds, and alkenes has been established for direct construction of indolizine derivatives via quinolinium ylides. This methodology is distinguished by the use of a commercially inexpensive catalyst and readily available starting materials, wide substrate scope, and operational simplicity.

Full text of DOI:10.1021/acs.joc.7b01042

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Article
In Situ Generation of Quinolinium Ylides from Diazo
Compounds: Copper-Catalyzed Synthesis of Indolizine
Rongxiang Chen, YanWei Zhao, Hongmei Sun, Ying Shao,
Yudong Xu, Meihua Ma, Liang Ma, and Xiaobing Wan
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.7b01042 • Publication Date (Web): 01 Aug 2017
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In Situ Generation of Quinolinium Ylides from Diazo
Compounds: Copper-Catalyzed Synthesis of
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Indolizine
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Rongxiang Chen,† Yanwei Zhao,† Hongmei Sun,†,* Ying Shao,†,‡ Yudong Xu,†
Meihua Ma,† Liang Ma,† and Xiaobing Wan†,*
†Key Laboratory of Organic Synthesis of Jiangsu Province, College of Chemistry,
Chemical Engineering and Materials Science, Soochow University, Suzhou 215123, P.
R. China
‡ Jiangsu Key Laboratory of Advanced Catalytic Materials and Technology, Advanced
catalysis and Green Manufacturing Collaborative Innovation Center, Changzhou
University, Changzhou 213164, P. R. China..
wanxb@suda.edu.cn, sunhm@suda.edu.cn
Abstract
The Cu-catalyzed three-component reaction between quinolines, diazo compounds,
and alkenes has been established for direct construction of indolizine derivatives via
quinolinium ylides. This methodology is distinguished by the use of a commercially
inexpensive catalyst and readily available starting materials, wide substrate scope and
operational simplicity.
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Introduction
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As special nitrogen ylides, pyridinium ylides are a class of important intermediates
with wide applications in organic synthesis.1 They are readily accessible nucleophiles
and can undergo a wide range of conversion reactions, such as Michael addition,2
cyclopropanation,3 and 1,3-dipolar cycloaddition.4 Traditionally, methods to generate
pyridinium ylides mainly involve the use of pyridinium salts with the aid of bases
(Scheme 1a).5 However, these methods usually suffer from some inherent limitations,
including formation of large amounts of conjugate-acid waste, narrow substrate scope,
and the need for polar solvents. Catalytic formation of pyridinium ylides from
pyridine and diazo compounds6 is definitely a more efficient and green strategy than
traditional strategies with respect to step economy. In 1993, Padwa et al. reported the
Rh(II)-catalyzed reaction of α-diazoacetophenone, pyridine, and dimethyl
acetylenedicarboxylate,7 which proceeds through in situ generation of pyridinium
ylide (Scheme 1b). Afterwards, the group of Barluenga and Tomás disclosed the first
successful example of metal-catalyzed cyclization of pyridine with alkenyldiazo
compounds, leading to substituted indolizines (Scheme 1c).8 Recently, Dowden’s
group developed iron- and copper-catalyzed stereoselective synthesis of
tetrahydroindolines by using pyridines, diazo compounds, and electrophilic alkenes,
which made a contribution for developing the multicomponent reactions of
pyridinium ylides from metal carbenes (Scheme 1d).9 To our surprise, little attention
has been paid to generation of quinolinium ylides from quinolines and diazo
compounds. In addition, using an inexpensive transition metal as a catalyst with wide
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substrate scope presents an important challenge in this field.
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Scheme 1. The in Situ Formation of Pyridinium Ylides
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Indolizine derivatives are particular structural units in the heterocycle class, some
of which widely occur in natural products and biologically active substances.10 In
particular, synthetic pharmaceuticals bearing this structural unit have been widely
applied to clinical treatment as antifungal,11 anticancer,12 anti-inflammatory13 and
antitubercular agents.14 Based on these applications, development of efficient
methodologies for the synthesis of indolizines has attracted great attention in recent
years. Traditionally, indolizines are synthesized by cyclization of pyridines with a free
C-2 position,15 cyclization of pyridines with specific C-2 functionalization,16
cycloisomerization from alkynylpyridine derivatives,17 the reaction of pyridotriazoles
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with alkynes,18 and 1,3-dipolar cycloaddition.4g,19 Although a variety of synthetic
methods for construction of indolizines have been reported, these methods often have
drawbacks. Thus, it is still highly valuable to develop more simple and efficient
strategies for construction of indolizines. Herein, we report in situ generation of
quinolinium ylides from quinolines and diazo compounds using inexpensive copper as
a catalyst and subsequent oxidative cyclization to give indolizine derivatives with a
broad substrate scope under mild conditions (Scheme 1e).
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Results and Discussion
Firstly, we investigated the reaction of quinoline 1a, dimethyl fumarate 2a, and ethyl
diazoacetate 3a. It was found that the reaction gave the desired product 4a in 73%
yield using CuF2 as catalyst and DCE as solvent at 80 °C after 24 h, along with the
formation of by-product 4a' from the dimerization of ethyl diazoacetate 3a and
subsequent reaction with quinoline 1a (Table 1, entry 1). Encouraged by this
promising result, further solvent screening was performed and 1,1,2-trichloroethane
gave the higher yield of 83% (Table 1, entries 2–14). The mixed solvent system of
DCE/1,1,2-trichloroethane (1:1) gave 87% yield (entry 15). Subsequently,
investigation of different copper catalysts showed that other copper catalysts also
gave product but in lower yield (entries 16–22). It should be noted that no desired
product 4a was produced in the absence of copper catalyst (entry 23). Other common
metal catalysts were found to not be suitable for this transformation (entry 24).
Further examination on reduced reaction time and amount of catalyst showed less
efficient results (entries 25-31). No desired product 4a was detected under N2
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atmosphere (entry 32, see Scheme 2 late). In sharp contrast, product 4a was isolated
in 85% yield under O2 atmosphere, indicating that molecular oxygen acts as an
essential oxidant for this indolizine formation reaction (entry 33). When dimethyl
maleate was used instead of dimethyl fumarate, 4a was generated in 69% yield (entry
34). Notably, 80% yield of 4a was obtained even in the absence of PPh3 (entry 35),
indicating it served as an additive in this transformation. The exact structure of 4a was
unambiguously determined by X-ray crystallography (see Supporting information).
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Table 1 Optimizations of Reaction Conditions of Quinoline 1a, Olefin 2a and
Diazo Compound 3aa
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aReaction condition: 0.5 mmol of 2a, 1.5 mmol of 1a, 1.5 mmol of 3a in 2 mL of
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solvent at 80 C. Isolated yield of 4a. FeCl3, NiCl2.6H2O, Pd(OAc)2, Rh2(OAc)4,
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Co(acac)2, Mn(OAc)3.2H2O, RuCl3. under N2. under O2. dimethyl maleate instead
of 2a. gno PPh3.
With the optimal reaction conditions in hand (Table 1, entry 15), the scope and
generality of the quinoline, electron-deficient olefin, and diazo compound derivative
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in this transformation were investigated. As shown in Table 2, quinoline substrates
with substituents at 4, 6, and 8 positions could be converted to the corresponding
products (4b–4g) in satisfactory yields. In addition to dimethyl fumarate, we
investigated the substrate scope with respect to alkenes. A variety of mono- and
disubstituted electron-deficient alkenes, including acrylic ester and fumarate esters,
gave the corresponding products (4h–4r) in moderate to excellent yields. It is
noteworthy that a variety of functional groups, such as cyano (4i), trifluoromethyl (4l)
and hydroxyl (4m), were tolerated under the standard conditions. Furthermore,
isobornyl acrylate with rigid structure was also a suitable substrate in this
transformation (4o). Next, the scope of the synthesis of pyrrolo[1,2-a]quinolines for
different diazo compounds was evaluated. In all of the cases, the different ester groups
in the α-diazo compounds reacted well to give the corresponding
pyrrolo[1,2-a]quinolines in modest to good yields (4s–4aa). Diazo compound
containing furan heteroaryl was also compatible with this transformation, giving the
desired product 4y in 81% yield. In addition, a variety of functional groups, such as
allyl (4v, 4x) and propargyl (4z) groups, did not affect the reaction profile. Dimethyl
diazoacetamide also gave the corresponding product 4w in 20% yield.
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Table 2. Scope of Quinolines 1, Olefins 2 and Diazo Compounds 3a
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aReaction conditions: 1 (1.5 mmol), 2 (0.5 mmol), 3 (1.5 mmol), CuF2 (0.1 mmol),
PPh3 (0.1 mmol) in DCE/1,1,2-trichloroethane (1 mL : 1 mL) at 80 oC for 24 h under
air.
Table 3. Scope of Isoquinolines 5, Olefins 2 and Diazo compounds 3a
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aReaction conditions: 5 (1.25 mmol), 2 (0.5 mmol), 3 (1.25 mmol), CuF2 (0.1 mmol)
in DCE/1,1,2-trichloroethane (1 mL : 1 mL) at 80 oC for 24 h under air..
As well as pyrrolo[1,2-a]quinoline, pyrrolo[2,1-a]isoquinoline derivatives20 are also
the focus of this research. With the optimized reaction conditions established (see
Table S1), we investigated the generality and limitations of representative substrates
containing synthetically useful functional groups. As shown in Table 3, the reaction is
not significantly affected by the substituents on the aromatic ring of isoquinoline,
giving the corresponding pyrrolo[2,1-a]isoquinolines (6b–6e) in reasonable yields.
For various substituted acrylates, the groups on the acrylates were tolerated under
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standard conditions (6f–6n). Notably, isobornyl acrylate and dodecaperfluoroheptyl
acrylate were also suitable and gave 6o and 6p in 53% and 68% yield, respectively. A
series of diazoesters were also tested under the optimized reaction conditions. The
ester group on the diazo compounds did not affect the reaction profile, and the
corresponding products (6q−6v) were obtained in moderate to excellent yields.
Diazoester substrates bearing a heterocyclic skeleton also proceeded well, giving the
corresponding products (6w and 6x) in good yields.
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Table 4. Scope of Pyridines 7, Olefins 2 and Diazo Compounds 3a
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aReaction conditions: 7 (1.5 mmol), 2 (0.5 mmol), 3 (1.5 mmol), CuF2 (0.1 mmol),
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PPh3 (0.1 mmol) in dioxane/toluene (1 mL : 1 mL) at 80 oC for 24 h under air.
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Compared with quinoline and isoquinoline in a similar reaction system, pyridine
derivatives showed lower reactivity. After screening a series of reaction conditions,
the expected product 8a was isolated in 51% yield (see Table S2). The synthetic
application of this reaction system can be extended to a variety of indolizine
compounds, as shown in Table 4. Substrates with electron-withdrawing substituents
on the pyridine ring, such as –CO2Et, –CN, and –COCH3, proceeded better than those
with electron-donating groups. In addition, 2-phenylpyridine gave the corresponding
indolizine product 8f. For substituted acrylates, the reaction proceeded smoothly to
give the desired products (8g–8m). When dibutyl fumarate was used as the substrate,
product 8n was obtained in 44% yield. Subsequently, different diazo reagents were
included to the reaction system, and the corresponding products (8o–8t) were
obtained in satisfactory yields.
To investigate the reaction mechanism for this transformation, control experiments
were performed, as shown in Scheme 2. When 1a, 2a, and 3a were reacted under N2
atmosphere, intermediate 9 and 10 rather than product 4a was detected by LC-MS and
intermediate 9 was separated in 56% yield (Scheme 2a), indicating in situ generation
of intermediate 9 and 10 and subsequent oxidation by molecular oxygen may be
involved in this indolizine formation reaction. To illustrate whether copper works in
the oxidation process, intermediate 9 was subjected to reaction system under oxygen
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atmosphere (Scheme 2b), 4a was achieved in 19% yield in absence of copper catalyst.
In sharp contrast, 4a was delivered in 80% yield in presence of copper catalyst, which
suggests both copper catalyst and molecular oxygen are key factors for this oxidation
process. In addition, we suspected the cycloaddition reaction21 between 2a and 3a and
consecutive ring-opening process were involved in this transformation. When 11 or
12 (the cycloaddition product between 2a and 3a) were subjected into the reaction
system, no product 4a was detected (Scheme 2c-d), excluding the possibility of them
as the reaction intermediates in this transformation.
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Scheme 2. The Control Experiments
Based on the above results and previously reported studies,9,22 a plausible
mechanism is proposed for copper-catalyzed synthesis of indolizine derivatives
(Scheme 3). First, diazo substrate A reacts copper to form the copper carbene species
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B with elimination of N2. Copper carbene species B is then attacked by pyridine to
give pyridinium ylide intermediate C, which sequentially produces intermediate D by
dissociation of the copper salt. Intermediate D then undergoes 1, 3-dipolar [3+2]
cycloaddition reaction with the olefin to give tetrahydroindolizine intermediate E.
Finally, the desired product F is formed followed by oxidation by the copper/O2
system.23
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Scheme 3. ProposedReaction Mechanism
Conclusions
In conclusion, we have developed a copper-catalyzed reaction for simple and
concise construction of indolizine derivatives through in situ generation of
quinolinium ylides from quinoline and diazo compounds under mild reaction
conditions. A variety of indolizines were synthesized from available starting materials
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with an inexpensive copper salt catalyst and the reaction showed broad scope. Further
investigation of the scope and application of in situ generation of quinoline ylides
from diazo compounds is currently underway.
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Experimental Section
General Information. Unless otherwise stated all manipulations were carried out
under air atmosphere. Column chromatography was generally performed on silica gel
(300-400 mesh) and reactions were monitored by thin layer chromatography (TLC)
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using UV light to visualize the course of the reactions. The H (400MHz) and C
NMR (100MHz) data were recorded on Varian 400 M spectrometers using CDCl3 as
solvent. The chemical shifts (δ) are reported in ppm and coupling constants (J) in Hz.
1H NMR spectra was recorded with tetramethylsilane (δ= 0.00 ppm) as internal
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reference; C NMR spectra was recorded with CDCl3 (δ = 77.00 ppm) as internal
reference. High resolution mass spectra were obtained using BRUKER micrOTOF-Q
III instrument with ESI source. IR and X-ray were performed by the State-authorized
Analytical Center in Soochow University.
General procedures for the synthesis of diazo compounds
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Method A:24a To a solution of substituted acetoacetate (10 mmol) in acetonitrile (12
mL) was added Et3N (1.31g, 13 mmol). The reaction mixture was cooled in an ice
bath and a solution of tosyl azide (2.17 g, 11 mmol) in acetonitrile (12 ml) was added
slowly. The reaction mixture was allowed to warm to r.t. After stirring for 10 h,
solvent was removed under reduced pressure. The residue was dissolved in ether (60
mL) and washed with 5% aqueous KOH solution. To the residue in ethyl ether was
added 5% KOH (50 mL), and the reaction mixture was stirred for 1h. The organic
phase was separated, dried over Na2SO4, and concentrated under reduced pressure.
Purification by chromatography over a column of silica gel provided the desired
product.
Method B:24b The corresponding alcohol (10 mmol) and NaHCO3 (2.5 g, 30 mmol)
were dissolved in acetonitrile (30 mL) and bromoacetyl bromide (1.3 mL, 15 mmol)
was added slowly at 0 °C. After stirring 30 min at this temperature, the reaction was
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quenched with H2O. The solution was extracted with CH2Cl2 three times. The organic
phase was washed with brine and dried over MgSO4. The solvent was evaporated, and
the residue was used in the next reaction without purification. The bromoacetate thus
obtained and N, N'-ditosylhydrazine (6.8 mg, 2.0 mmol) were dissolved in THF (5.0
mL) and cooled to 0 °C. DBU (7.5 mL, 5.0 mmol) was added dropwise and stirred at
the temperature for 10 minutes. After the quenching of the reaction by the addition of
saturated NaHCO3 solution, this was extracted with Et2O three times. The organic
phase was washed with brine, dried over MgSO4 and evaporated to give the crude
diazoacetate. The crude product thus obtained was purified by chromatography over a
column of silica gel using petroleum and EtOAc as eluent to afford the desired
product.
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General procedures for the synthesis of 4a−4aa
Cupric fluoride (0.1 mmol, 20 mol%), triphenylphosphine (0.1 mmol, 20 mol%),
olefin (0.5 mmol) were added to test tube (18 mm * 200 mm).
1,1,2-trichloroethane/dichloroethane (1/1, 2.0 mL), quinoline (1.5 mmol, 3 equiv),
diazo compound ( 1.5 mmol, 3 equiv) were added at one time via syringe. The test
o
tube was open air. The reaction mixture was stirred at 80 C for 24 h. Thereafter the
reaction was quenched by the addition of HCl (0.1 mol/L, 10 mL) and the resulting
mixture was extracted with EtOAc (3 x 10 mL). The combined organic fractions were
dried over Na2SO4, and the solvent was removed under vacuum. The crude product
thus obtained was purified by chromatography over a column of silica gel using
petroleum and EtOAc as eluent to afford the desired product.
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General procedures for the synthesis of 6a–6x
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Cupric fluoride (0.1 mmol, 20 mol%), olefin (0.5 mmol) were added to test tube.
1,1,2-trichloroethane/dichloroethane (1/1, 2.0 mL), isoquinoline (1.25 mmol, 2.5
equiv), diazo compound ( 1.25 mmol, 2.5 equiv) were added at one time via syringe.
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The test tube was open air. The reaction mixture was stirred at 80 C for 24 h.
Thereafter the reaction was quenched by the addition of HCl (0.1 mol/L, 10 mL) and
the resulting mixture was extracted with EtOAc (3 x 10 mL). The combined organic
fractions were dried over Na2SO4, and the solvent was removed under vacuum. The
crude product thus obtained was purified by chromatography over a column of silica
gel using petroleum and EtOAc as eluent to afford the desired product.
General procedures for the synthesis of 8a−8t
Cupric fluoride (0.1 mmol, 20 mol%), triphenylphosphine (0.1 mmol, 20 mol%),
olefin (0.5 mmol) were added to test tube (18mm * 200 mm). dioxane/toluene(1/1, 2.0
mL), pyridine (1.5 mmol, 3 equiv), diazo compound ( 1.5 mmol, 3 equiv) were
added at one time via syringe. The test tube was open air. The reaction mixture was
stirred at 80 oC for 24 h. Thereafter the reaction was quenched by the addition of HCl
(0.1 mol/L, 10 mL) and the resulting mixture was extracted with EtOAc (3 x 10 mL).
The combined organic fractions were dried over Na2SO4, and the solvent was
removed under vacuum. The crude product thus obtained was purified by
chromatography over a column of silica gel using petroleum and EtOAc as eluent to
afford the desired product.
The procedure for synthesis of intermediate 9
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Cupric fluoride (0.1 mmol, 20 mol%), triphenylphosphine (0.1 mmol, 20 mol%),
dimethyl fumarate (0.5 mmol) were added to 10 mL Schlenk-type sealed tube.
1,1,2-trichloroethane/dichloroethane (1/1, 2.0 mL), quinoline (1.5 mmol, 3 equiv),
ethyl diazoacetate ( 1.5 mmol, 3 equiv) were added at one time under nitrogen. The
reaction mixture was stirred at 80 oC for 24 h. Thereafter the reaction was quenched
by the addition of HCl (0.1 mol/L, 10 mL) and the resulting mixture was extracted
with EtOAc (3 x 10 mL). The combined organic fractions were dried over Na2SO4,
and the solvent was removed under vacuum. The crude product thus obtained was
purified by silica gel column chromatography (ethyl acetate/petroleum ether = 1/10,
v/v) to afford compound 9 in 56% yield.
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The procedure for oxidation of intermediate 9.
To a 10 mL Schlenk-type sealed tube, intermediate 9 (0.2 mmol) were dissolved
in 1,1,2-trichloroethane/dichloroethane (1/1, 1.0 mL) under oxygen. The reaction
mixture was stirred at 80 °C for 24 h. After the reaction was cooled to the room
temperature, the reaction mixture was concentrated under reduced pressure. The
residue was purified by silica gel column chromatography (ethyl acetate/petroleum
ether = 1/5, v/v) to afford desired product 4a in 19% yield.
To a 10 mL Schlenk-type sealed tube, intermediate 9 (0.2 mmol), CuF2 (20
mmol%) were dissolved in 1,1,2-trichloroethane/dichloroethane (1/1, 1.0 mL) under
oxygen. The reaction mixture was stirred at 80 °C for 24 h. After the reaction cooled
to the room temperature. The reaction mixture was concentrated under reduced
pressure. The residue was purified by silica gel column chromatography (ethyl
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acetate/petroleum ether = 1/5, v/v) to afford desired product 4a in 80% yield.
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Experimental data of products:
9
1-ethyl 2,3-dimethyl pyrrolo[1,2-a]quinoline-1,2,3-tricarboxylate (4a). Light yellow solid;
yield 154 mg (87%); mp: 131.0-133.8 oC; 1H NMR (400 MHz, CDCl3) δ 8.20 (d, J = 9.4 Hz, 1H),
8.09 (d, J = 8.7 Hz, 1H), 7.75 (dd, J = 7.8, 1.3 Hz, 1H), 7.62 – 7.53 (m, 2H), 7.51 – 7.43 (m, 1H),
4.43 (q, J = 7.1 Hz, 2H), 3.99 (s, 3H), 3.90 (s, 3H), 1.40 (t, J = 7.1 Hz, 3H); 13C NMR (101 MHz,
CDCl3) δ 165.7, 162.9, 160.3, 137.3, 132.3, 130.4, 128.3, 128.1, 128.0, 125.3, 124.9, 119.2, 117.4,
117.1, 104.7, 61.3, 52.3, 51.3, 13.6; HRMS (ESI-TOF) m/z: [M+H]+ Calcd. For C19H18NO6:
356.1129, Found: 356.1115; IR (neat, cm-1): υ 3358, 1699, 1448, 1257, 1156, 1112, 750.
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1-ethyl 2,3-dimethyl 7-methylpyrrolo[1,2-a]quinoline-1,2,3-tricarboxylate (4b). Yellow solid;
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yield 153 mg (83%); mp: 121.4-123.7 C; H NMR (400 MHz, CDCl3) δ 8.21 – 8.12 (m, 1H),
7.97 (d, J = 8.8 Hz, 1H), 7.51 (d, J = 9.2 Hz, 2H), 7.38 (d, J = 8.8 Hz, 1H), 4.43 (q, J = 7.1 Hz,
2H), 3.99 (s, 3H), 3.90 (s, 3H), 2.47 (s, 3H), 1.40 (t, J = 7.1 Hz, 3H); 13C NMR (101 MHz, CDCl3)
δ 165.7, 162.9, 160.3, 137.1, 135.2, 130.4, 130.2, 129.4, 127.9, 127.8, 124.9, 118.9, 117.2, 117.0,
104.5, 61.2, 52.2, 51.2, 20.4, 13.6; HRMS (ESI-TOF) m/z: [M+H]+ Calcd. For C20H20NO6:
370.1285, Found: 370.1277; IR (neat, cm-1): υ 3037, 1690, 1447, 1219, 1183, 1083, 816.
1-ethyl 2,3-dimethyl 7-methoxypyrrolo[1,2-a]quinoline-1,2,3-tricarboxylate (4c). Yellow solid;
yield 188 mg (98%); mp: 124.7-126.4 oC; 1H NMR (400 MHz, CDCl3) δ 8.15 (d, J = 9.4 Hz, 1H),
8.04 (d, J = 9.4 Hz, 1H), 7.49 (d, J = 9.4 Hz, 1H), 7.17 (dd, J = 9.4, 2.9 Hz, 1H), 7.11 (d, J = 2.8
13
Hz, 1H), 4.42 (q, J = 7.1 Hz, 2H), 3.98 (s, 3H), 3.89 (s, 6H), 1.40 (t, J = 7.1 Hz, 3H); C NMR
(101 MHz, CDCl3) δ 165.8, 162.9, 160.3, 156.6, 136.6, 130.2, 127.8, 126.9, 126.2, 120.7, 117.4,
117.1, 117.0, 108.9, 104.5, 61.2, 55.1, 52.2, 51.2, 13.6; HRMS (ESI-TOF) m/z: [M+H]+ Calcd.
For C20H20NO7: 386.1234, Found: 386.1242; IR (neat, cm-1): υ 2951, 1699, 1453, 1259, 1162,
1113, 836.
1-ethyl 2,3-dimethyl 7-chloropyrrolo[1,2-a]quinoline-1,2,3-tricarboxylate (4d). Brown solid;
yield 86 mg (44%); mp: 134.8-136.6 oC; 1H NMR (400 MHz, CDCl3) δ 8.23 (d, J = 9.4 Hz, 1H),
8.08 (d, J = 9.2 Hz, 1H), 7.72 (d, J = 2.2 Hz, 1H), 7.50 (dd, J = 13.1, 6.0 Hz, 2H), 4.43 (q, J = 7.1
Hz, 2H), 3.99 (s, 3H), 3.90 (s, 3H), 1.40 (t, J = 7.1 Hz, 3H); 13C NMR (101 MHz, CDCl3) δ 165.4,
162.6, 160.1, 137.0, 130.9, 130.7, 130.7, 128.1, 127.2, 126.8, 126.1, 120.8, 118.4, 117.6, 105.2,
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61.4, 52.3, 51.4, 13.5; HRMS (ESI-TOF) m/z: [M+H]+ Calcd. For C19H1735ClNO6: 390.0739,
C19H1737ClNO6: 392.0715, Found: 390.0733, 392.0713; IR (neat, cm-1): υ 2958, 1700, 1441, 1253,
1179, 1120, 805.
9
1-ethyl 2,3-dimethyl 7-bromopyrrolo[1,2-a]quinoline-1,2,3-tricarboxylate (4e). Brown solid;
yield 104 mg (48%); mp: 131.7-133.2 oC; 1H NMR (400 MHz, CDCl3) δ 8.22 (d, J = 9.4 Hz, 1H),
8.01 (d, J = 9.2 Hz, 1H), 7.88 (d, J = 2.1 Hz, 1H), 7.64 (dd, J = 9.2, 2.2 Hz, 1H), 7.47 (d, J = 9.4
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Hz, 1H), 4.42 (q, J = 7.1 Hz, 2H), 3.99 (s, 3H), 3.91 (s, 3H), 1.40 (t, J = 7.1 Hz, 3H); C NMR
(101 MHz, CDCl3) δ 165.4, 162.6, 160.1, 137.0, 131.1, 130.9, 130.7, 130.3, 126.7, 126.4, 121.0,
118.7, 118.3, 117.6, 105.3, 76.9, 76.6, 76.2, 61.4, 52.3, 51.4, 13.5; HRMS (ESI-TOF) m/z:
[M+H]+ Calcd. For C19H1779BrNO6: 434.0239, C19H1781BrNO6: 436.0239, Found: 434.0247,
436.0250; IR (neat, cm-1): υ 2965, 1702, 1444, 1260, 1196, 1125, 811.
1-ethyl 2,3-dimethyl 5-methylpyrrolo[1,2-a]quinoline-1,2,3-tricarboxylate (4f). Brown solid;
yield 109 mg (59%); mp: 127.4-129.7 oC; 1H NMR (400 MHz, CDCl3) δ 8.09 (d, J = 9.1 Hz, 2H),
7.89 (dd, J = 8.0, 1.0 Hz, 1H), 7.62 – 7.54 (m, 1H), 7.51 (t, J = 7.2 Hz, 1H), 4.41 (q, J = 7.1 Hz,
2H), 3.99 (s, 3H), 3.90 (s, 3H), 2.63 (s, 3H), 1.39 (t, J = 7.1 Hz, 3H); 13C NMR (101 MHz, CDCl3)
δ 165.8, 163.0, 160.3, 137.5, 135.5, 132.1, 130.6, 127.8, 125.2, 125.1, 124.6, 119.6, 116.9, 116.6,
103.6, 61.2, 52.2, 51.2, 19.0, 13.6; HRMS (ESI-TOF) m/z: [M+H]+ Calcd. For C20H20NO6:
370.1285, Found: 370.1291; IR (neat, cm-1): υ 2957, 1699, 1444, 1260, 1165, 1013, 758.
1-ethyl 2,3-dimethyl 9-methylpyrrolo[1,2-a]quinoline-1,2,3-tricarboxylate (4g). Light yellow
solid; yield 33 mg (18%); mp: 147.1-150.1 oC; 1H NMR (400 MHz, CDCl3) δ 8.14 (d, J = 9.2 Hz,
1H), 7.61 (dd, J = 7.1, 1.8 Hz, 1H), 7.57 (d, J = 9.3 Hz, 1H), 7.48 – 7.37 (m, 2H), 4.32 (q, J = 7.1
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Hz, 2H), 4.00 (s, 3H), 3.91 (s, 3H), 2.51 (s, 3H), 1.31 (t, J = 7.1 Hz, 3H); C NMR (101 MHz,
CDCl3) δ 165.8, 163.1, 159.9, 138.4, 133.0, 131.0, 129.2, 129.0, 128.4, 126.5, 125.2, 125.2, 121.3,
116.4, 104.4, 60.9, 52.3, 51.3, 19.6, 13.6; HRMS (ESI-TOF) m/z: [M+H]+ Calcd. For C20H20NO6:
370.1285, Found: 370.1294; IR (neat, cm-1): υ 2949, 1697, 1453, 1257, 1140, 1108, 822.
diethyl pyrrolo[1,2-a]quinoline-1,3-dicarboxylate (4h). Brown solid; yield 89 mg (57%); mp:
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64.9-67.3 C; H NMR (400 MHz, CDCl3) δ 8.40 (d, J = 8.7 Hz, 1H), 8.27 (d, J = 9.3 Hz, 1H),
7.96 (s, 1H), 7.75 (dd, J = 7.8, 1.0 Hz, 1H), 7.65 – 7.52 (m, 2H), 7.46 (t, J = 7.5 Hz, 1H), 4.42 (dq,
J = 14.3, 7.1 Hz, 4H), 1.44 (q, J = 7.2 Hz, 6H); 13C NMR (101 MHz, CDCl3) δ 163.6, 161.3, 138.9,
132.9, 128.1, 127.8, 127.2, 125.9, 124.8, 124.7, 119.9, 119.6, 117.3, 107.0, 76.9, 76.6, 76.2, 60.6,
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59.6, 14.0, 13.9; HRMS (ESI-TOF) m/z: [M+H]+ Calcd. For C18H18NO4: 312.1230, Found:
312.1234; IR (neat, cm-1): υ 2977, 1686, 1449, 1234, 1160, 1078, 753.
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ethyl 3-cyanopyrrolo[1,2-a]quinoline-1-carboxylate (4i). Brown solid; yield 95 mg (72%); mp:
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89.0-91.9 C; H NMR (400 MHz, CDCl3) δ 8.47 (d, J = 8.7 Hz, 1H), 7.77 (dd, J = 7.8, 1.2 Hz,
1H), 7.72 (s, 1H), 7.66 – 7.59 (m, 1H), 7.57 (s, 2H), 7.50 (t, J = 7.5 Hz, 1H), 4.45 (q, J = 7.1 Hz,
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2H), 1.44 (t, J = 7.1 Hz, 3H); C NMR (101 MHz, CDCl3) δ 160.5, 140.7, 132.9, 128.5, 128.4,
127.7, 125.8, 125.5, 124.6, 120.9, 119.5, 115.1, 114.6, 86.2, 76.9, 76.6, 76.3, 61.0, 13.9; HRMS
(ESI-TOF) m/z: [M+H]+ Calcd. For C16H13N2O2: 265.0972, Found: 265.0982; IR (neat, cm-1): υ
2980, 2217, 1701, 1370, 1259, 1158, 753.
1-ethyl 3-methyl pyrrolo[1,2-a]quinoline-1,3-dicarboxylate (4j). Light yellow solid; yield 83
mg (56%); mp: 110.9-113.2 oC; 1H NMR (400 MHz, CDCl3) δ 8.40 (d, J = 8.7 Hz, 1H), 8.25 (d, J
= 9.3 Hz, 1H), 7.95 (s, 1H), 7.74 (d, J = 7.8 Hz, 1H), 7.57 (dd, J = 17.6, 9.0 Hz, 2H), 7.45 (t, J =
7.5 Hz, 1H), 4.43 (q, J = 7.1 Hz, 2H), 3.92 (s, 3H), 1.44 (t, J = 7.1 Hz, 3H); 13C NMR (101 MHz,
CDCl3) δ 164.0, 161.3, 138.9, 132.9, 128.1, 127.8, 127.3, 125.9, 124.8, 124.7, 120.0, 119.6, 117.2,
106.6, 60.6, 50.8, 13.9; HRMS (ESI-TOF) m/z: [M+H]+ Calcd. For C17H16NO4: 298.1074, Found:
298.1090; IR (neat, cm-1): υ 2979, 1700, 1447, 1329, 1156, 1082, 752.
3-butyl 1-ethyl pyrrolo[1,2-a]quinoline-1,3-dicarboxylate (4k). Light yellow solid; yield 78 mg
(46%); mp: 56.9-58.4 oC; 1H NMR (400 MHz, CDCl3) δ 8.39 (d, J = 8.7 Hz, 1H), 8.27 (d, J = 9.3
Hz, 1H), 7.95 (s, 1H), 7.75 (d, J = 7.7 Hz, 1H), 7.64 – 7.52 (m, 2H), 7.46 (t, J = 7.1 Hz, 1H), 4.44
(q, J = 7.1 Hz, 2H), 4.35 (t, J = 6.7 Hz, 2H), 1.79 (m, J = 14.6, 6.8 Hz, 2H), 1.52 (dt, J = 15.0, 7.4
Hz, 2H), 1.45 (t, J = 7.1 Hz, 3H), 1.00 (t, J = 7.4 Hz, 3H); 13C NMR (101 MHz, CDCl3) δ 163.7,
161.3, 138.8, 132.9, 128.1, 127.8, 127.2, 125.8, 124.8, 124.7, 119.9, 119.6, 117.3, 107.0, 63.6,
60.6, 30.5, 18.9, 13.9, 13.4; HRMS (ESI-TOF) m/z: [M+H]+ Calcd. For C20H22NO4: 340.1543,
Found: 340.1554; IR (neat, cm-1): υ 2957, 1698, 1462, 1242, 1154, 1079, 756.
1-ethyl 3-(2,2,2-trifluoroethyl) pyrrolo[1,2-a]quinoline-1,3-dicarboxylate (4l). White solid;
yield 88 mg (48%); mp: 103.2-105.9 oC; 1H NMR (400 MHz, CDCl3) δ 8.39 (d, J = 8.7 Hz, 1H),
8.20 (d, J = 9.3 Hz, 1H), 7.96 (s, 1H), 7.77 (d, J = 7.8 Hz, 1H), 7.66 – 7.57 (m, 2H), 7.48 (t, J =
7.5 Hz, 1H), 4.73 (q, J = 8.5 Hz, 2H), 4.46 (q, J = 7.1 Hz, 2H), 1.46 (t, J = 7.1 Hz, 3H); 13C NMR
(101 MHz, CDCl3) δ 161.5, 161.2, 139.4, 132.8, 128.2, 128.1, 128.1, 125.8, 125.1, 124.7, 122.9 (q,
J = 122.8 Hz), 120.5, 119.6, 116.8, 104.6, 59.5(q, J = 110.1 Hz), 59.0, 13.9; 19F NMR (376 MHz,
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CDCl3) δ -73.52; HRMS (ESI-TOF) m/z: [M+H]+ Calcd. For C18H15F3NO4: 366.0948, Found:
366.0964; IR (neat, cm-1): υ 2957, 1698, 1426, 1278, 1152, 1081, 755.
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1-ethyl 3-(2-hydroxyethyl) pyrrolo[1,2-a]quinoline-1,3-dicarboxylate (4m). Brown solid; yield
57 mg (35%); mp: 94.9-97.3 oC; 1H NMR (400 MHz, CDCl3) δ 8.35 (d, J = 8.7 Hz, 1H), 8.20 (d, J
= 9.3 Hz, 1H), 7.93 (s, 1H), 7.71 (d, J = 7.8 Hz, 1H), 7.61 – 7.54 (m, 1H), 7.51 (d, J = 9.3 Hz, 1H),
7.44 (t, J = 7.5 Hz, 1H), 4.47 (m, J = 5.4, 3.7 Hz, 2H), 4.43 (q, J = 7.1 Hz, 2H), 4.03 – 3.93 (m,
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2H), 2.61 (s, 1H), 1.44 (t, J = 7.1 Hz, 3H); C NMR (101 MHz, CDCl3) δ 163.9, 161.2, 139.0,
132.8, 128.1, 127.8, 127.5, 125.8, 124.9, 124.6, 120.0, 119.5, 117.0, 106.1, 65.5, 61.1, 60.7, 13.9;
HRMS (ESI-TOF) m/z: [M+H]+ Calcd. For C18H18NO5: 328.1179, Found: 328.1175; IR (neat,
cm-1): υ 2982, 1701, 1545, 1178, 1083, 1029, 756.
3-cyclohexyl 1-ethyl pyrrolo[1,2-a]quinoline-1,3-dicarboxylate (4n). Light yellow solid; yield
75 mg (41%); mp: 66.6-68.8 oC; 1H NMR (400 MHz, CDCl3) δ 8.36 (d, J = 8.7 Hz, 1H), 8.25 (d, J
= 9.3 Hz, 1H), 7.95 (s, 1H), 7.70 (dd, J = 7.9, 1.4 Hz, 1H), 7.55 (ddd, J = 8.7, 7.2, 1.5 Hz, 1H),
7.51 (d, J = 9.3 Hz, 1H), 7.45 – 7.37 (m, 1H), 5.12 – 5.00 (m, 1H), 4.44 (q, J = 7.1 Hz, 2H), 2.01
(m, J = 9.5, 5.3 Hz, 2H), 1.82 (m, J = 8.9, 4.1 Hz, 2H), 1.69 – 1.55 (m, 3H), 1.52 – 1.31 (m, 6H);
13C NMR (101 MHz, CDCl3) δ 163.1, 161.3, 138.7, 132.8, 128.0, 127.7, 127.0, 125.9, 124.7,
124.6, 119.8, 119.5, 117.3, 107.4, 71.8, 60.6, 31.4, 25.0, 23.4, 13.9; HRMS (ESI-TOF) m/z:
[M+H]+ Calcd. For C22H24NO4: 366.1700, Found: 366.1712; IR (neat, cm-1): υ 2923, 1693, 1463,
1220, 1173, 1077, 755.
exo-1-ethyl
3-((1S,2S,4S)-1,7,7-trimethylbicyclo[2.2.1]heptan-2-yl)
pyrrolo[1,2-a]quinoline-1,3-dicarboxylate (4o). Yellow liquid; yield 92 mg (44%); [α]2D0 = –2.4
(c 1, CHCl3); 1H NMR (400 MHz, CDCl3) δ 8.38 (dd, J = 21.5, 9.0 Hz, 2H), 7.79 (d, J = 7.8 Hz,
1H), 7.62 (dd, J = 13.9, 8.7 Hz, 2H), 7.49 (t, J = 7.5 Hz, 1H), 5.01 (t, J = 5.8 Hz, 1H), 4.50 (q, J =
7.1 Hz, 2H), 2.04 – 1.94 (m, 2H), 1.89 – 1.74 (m, 2H), 1.67 (td, J = 12.2, 3.9 Hz, 1H), 1.49 (t, J =
7.1 Hz, 3H), 1.31 (m, J = 12.8, 8.2, 3.8 Hz, 2H), 1.23 (s, 3H), 1.04 (s, 3H), 0.96 (s, 3H); 13C NMR
(101 MHz, CDCl3) δ 163.2, 161.4, 138.8, 132.9, 128.1, 127.7, 127.1, 125.6, 124.8, 124.7, 119.8,
119.5, 117.3, 107.3, 80.3, 60.6, 48.5, 46.6, 44.7, 38.6, 33.4, 26.6, 19.8, 19.7, 13.9, 11.3; HRMS
(ESI-TOF) m/z: [M+H]+ Calcd. For C26H30NO4: 420.2169, Found: 420.2181; IR (neat, cm-1): υ
2953, 1695, 1422, 1215, 1178, 1071, 753.
3-(2,2,3,3,4,4,5,5,6,6,7,7-dodecafluoroheptyl)
1-ethyl
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pyrrolo[1,2-a]quinoline-1,3-dicarboxylate (4p). White solid; yield 87 mg (44%); mp: 77.8-80.2
oC; 1H NMR (400 MHz, CDCl3) δ 8.39 (d, J = 8.7 Hz, 1H), 8.22 (d, J = 9.3 Hz, 1H), 7.95 (s, 1H),
7.78 (dd, J = 7.9, 1.3 Hz, 1H), 7.68 – 7.57 (m, 2H), 7.53 – 7.45 (m, 1H), 6.07 (tt, J = 51.9, 5.2 Hz,
1H), 4.86 (t, J = 13.7 Hz, 2H), 4.46 (q, J = 7.1 Hz, 2H), 1.46 (t, J = 7.1 Hz, 3H); 13C NMR (101
MHz, CDCl3) δ 161.6, 161.2, 139.4, 132.8, 128.2, 128.1, 128.1, 125.8, 125.1, 124.7, 120.6, 119.6,
116.8, 107.1, 104.5, 60.8, 58.7 (t, J = 58.7 Hz), 13.8; 19F NMR (376 MHz, CDCl3) δ -119.20 (td, J
= 13.5, 3.5 Hz), -121.93 – -122.24 (m, 2F), -123.37 (s, 4F), -129.35 – -129.54 (m, 2F), -136.93 –
-137.12 (m, 2F); HRMS (ESI-TOF) m/z: [M+H]+ Calcd. For C23H16F12NO4: 598.0882, Found:
598.0896; IR (neat, cm-1): υ 2942, 1700, 1421, 1179, 1136, 1089, 744.
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2,3-dibutyl 1-ethyl pyrrolo[1,2-a]quinoline-1,2,3-tricarboxylate (4q). Yellow solid; yield 182
mg (83%); mp: 64.4-67.2 oC; 1H NMR (400 MHz, CDCl3) δ 8.27 (d, J = 9.4 Hz, 1H), 8.08 (d, J =
8.6 Hz, 1H), 7.77 (d, J = 7.8 Hz, 1H), 7.66 – 7.53 (m, 2H), 7.48 (t, J = 7.5 Hz, 1H), 4.44 (q, J =
7.1 Hz, 2H), 4.35 (dt, J = 18.6, 6.7 Hz, 4H), 1.84 – 1.69 (m, 4H), 1.55 – 1.44 (m, 4H), 1.41 (t, J =
7.1 Hz, 3H), 0.98 (t, J = 7.3 Hz, 6H); 13C NMR (101 MHz, CDCl3) δ 165.3, 162.6, 160.4, 137.4,
132.4, 130.5, 128.3, 128.0, 127.9, 125.2, 124.9, 119.2, 117.4, 117.2, 104.9, 65.4, 64.0, 61.2, 30.4,
30.0, 18.8, 18.8, 13.6, 13.3; HRMS (ESI-TOF) m/z: [M+H]+ Calcd. For C25H30NO6: 440.2068,
Found: 440.2065; IR (neat, cm-1): υ 2958, 1692, 1439, 1256, 1188, 1111, 821.
3-(2-(2-ethoxyethoxy)ethyl) 1-ethyl pyrrolo[1,2-a]quinoline-1,3-dicarboxylate (4r). Brown
solid; yield 101 mg (57%); mp: 58.0-60.5 oC; 1H NMR (400 MHz, CDCl3) δ 8.45 (d, J = 8.7 Hz,
1H), 8.33 (d, J = 9.3 Hz, 1H), 8.03 (s, 1H), 7.80 (dd, J = 7.9, 1.3 Hz, 1H), 7.68 – 7.58 (m, 2H),
7.55 – 7.47 (m, 1H), 4.59 – 4.53 (m, 2H), 4.48 (q, J = 7.1 Hz, 2H), 3.95 – 3.89 (m, 2H), 3.77 (dd,
J = 5.8, 3.7 Hz, 2H), 3.68 (dd, J = 5.7, 3.7 Hz, 2H), 3.59 (q, J = 7.0 Hz, 2H), 1.49 (t, J = 7.1 Hz,
13
3H), 1.25 (t, J = 7.0 Hz, 3H); C NMR (101 MHz, CDCl3) δ 163.5, 161.3, 139.0, 132.9, 128.1,
127.8, 127.3, 126.0, 124.8, 124.7, 120.0, 119.6, 117.3, 106.6, 70.2, 69.4, 69.0, 66.2, 62.7, 60.6,
14.7, 13.9; HRMS (ESI-TOF) m/z: [M+H]+ Calcd. For C22H26NO6: 400.1755, Found: 400.1766;
IR (neat, cm-1): υ 2873, 1695, 1497, 1177, 1125, 1082, 754.
1-isopropyl 2,3-dimethyl pyrrolo[1,2-a]quinoline-1,2,3-tricarboxylate (4s). Light yellow solid;
yield 147 mg (80%); mp: 102.3-104.1 oC; 1H NMR (400 MHz, CDCl3) δ 8.20 (d, J = 9.4 Hz, 1H),
8.08 (d, J = 8.6 Hz, 1H), 7.75 (d, J = 7.7 Hz, 1H), 7.66 – 7.53 (m, 2H), 7.47 (t, J = 7.4 Hz, 1H),
5.32 (m, 1H), 4.00 (s, 3H), 3.91 (s, 3H), 1.41 (d, J = 6.3 Hz, 6H); 13C NMR (101 MHz, CDCl3) δ
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166.1, 163.4, 160.4, 137.6, 132.8, 130.5, 128.8, 128.4, 128.4, 125.8, 125.3, 119.7, 118.3, 117.6,
105.1, 69.8, 52.7, 51.7, 21.7; HRMS (ESI-TOF) m/z: [M+H]+ Calcd. For C20H20NO6: 370.1285,
Found: 370.1298; IR (neat, cm-1): υ 2956, 1698, 1444, 1211, 1177, 1100, 750.
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1-benzyl 2,3-dimethyl pyrrolo[1,2-a]quinoline-1,2,3-tricarboxylate (4t). Brown solid; yield
150 mg (72%); mp: 130.2-132.6 oC; 1H NMR (400 MHz, CDCl3) δ 8.21 (d, J = 9.4 Hz, 1H), 8.07
(d, J = 8.4 Hz, 1H), 7.76 (dd, J = 7.7, 1.2 Hz, 1H), 7.59 (d, J = 9.4 Hz, 1H), 7.55 – 7.44 (m, 4H),
7.40 (m, 3H), 5.40 (s, 2H), 3.88 (s, 3H), 3.61 (s, 3H); 13C NMR (101 MHz, CDCl3) δ 165.4, 162.8,
160.2, 137.5, 134.4, 132.3, 130.7, 128.6, 128.3, 128.2, 128.2, 128.1, 125.4, 124.9, 119.3, 117.1,
117.1, 104.8, 67.3, 52.0, 51.3; HRMS (ESI-TOF) m/z: [M+H]+ Calcd. For C24H20NO6: 418.1285,
Found: 418.1290; IR (neat, cm-1): υ 2956, 1701, 1146, 1258, 1217, 1054, 751.
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1-tert-butyl 2,3-dimethyl pyrrolo[1,2-a]quinoline-1,2,3-tricarboxylate (4u). Light yellow solid;
yield 143 mg (75%); mp: 151.1-152.6 oC; 1H NMR (400 MHz, CDCl3) δ 8.20 (d, J = 9.4 Hz, 1H),
8.07 (d, J = 8.6 Hz, 1H), 7.76 (dd, J = 7.8, 1.2 Hz, 1H), 7.67 – 7.54 (m, 2H), 7.53 – 7.42 (m, 1H),
4.01 (s, 3H), 3.91 (s, 3H), 1.64 (s, 9H); 13C NMR (101 MHz, CDCl3) δ 165.7, 163.0, 159.6, 136.9,
132.3, 129.5, 128.3, 127.9, 127.7, 125.2, 124.8, 119.2, 118.9, 117.2, 104.5, 82.8, 52.2, 51.2, 27.5;
HRMS (ESI-TOF) m/z: [M+H]+ Calcd. For C21H22NO6: 384.1442, Found: 384.1438; IR (neat,
cm-1): υ 2947, 1703, 1449, 1185, 1147, 810, 743.
1-allyl 2,3-dimethyl pyrrolo[1,2-a]quinoline-1,2,3-tricarboxylate (4v). Light yellow solid; yield
o
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161 mg (88%); mp: 97.0-99.5 C; H NMR (400 MHz, CDCl3) δ 8.21 (dd, J = 9.3, 7.4 Hz, 1H),
8.09 (dd, J = 8.6, 4.9 Hz, 1H), 7.80 – 7.72 (m, 1H), 7.65 – 7.53 (m, 2H), 7.53 – 7.42 (m, 1H), 6.04
(ddt, J = 16.4, 10.4, 5.9 Hz, 1H), 5.46 (dd, J = 17.2, 1.4 Hz, 1H), 5.35 (dd, J = 10.4, 1.1 Hz, 1H),
13
4.87 (dd, J = 5.9, 1.1 Hz, 2H), 3.97 (s, 3H), 3.91 (s, 3H); C NMR (101 MHz, CDCl3) δ 166.1,
163.3, 160.5, 137.9, 132.8, 131.4, 131.2, 128.8, 128.6, 125.8, 125.3, 119.7, 119.4, 117.6, 117.6,
105.3, 100.0, 66.5, 52.8, 51.8; HRMS (ESI-TOF) m/z: [M+H]+ Calcd. For C20H18NO6: 368.1129,
Found: 368.1135; IR (neat, cm-1): υ 2955, 1703, 1482, 1256, 1218, 1177, 750.
dimethyl 1-(dimethylcarbamoyl)pyrrolo[1,2-a]quinoline-2,3-dicarboxylate (4w). Brown solid;
yield 35 mg (20%); mp: 160.4-163.2 oC; 1H NMR (400 MHz, CDCl3) δ 8.08 (d, J = 9.5 Hz, 1H),
7.90 (d, J = 8.6 Hz, 1H), 7.76 (dd, J = 7.8, 1.4 Hz, 1H), 7.57 – 7.52 (m, 1H), 7.51 – 7.44 (m, 1H),
7.42 (d, J = 9.5 Hz, 1H), 3.92 (d, J = 4.1 Hz, 6H), 3.28 (s, 3H), 2.91 (s, 3H); 13C NMR (101 MHz,
CDCl3) δ 164.4, 163.8, 163.7, 133.9, 132.3, 128.9, 128.8, 125.2, 125.1, 124.6, 123.6, 119.3, 117.7,
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115.4, 105.3, 52.0, 51.2, 37.9, 34.7; HRMS (ESI-TOF) m/z: [M+H]+ Calcd. For C19H19N2O5:
355.1288, Found: 355.1297; IR (neat, cm-1): υ 2949, 1696, 1632, 1449, 1222, 1086, 811.
1-cinnamyl 2,3-dimethyl pyrrolo[1,2-a]quinoline-1,2,3-tricarboxylate (4x). Light yellow solid;
yield 166 mg (75%); mp: 102.2-104.3 oC; 1H NMR (400 MHz, CDCl3) δ 8.22 (d, J = 9.4 Hz, 1H),
8.12 (d, J = 8.6 Hz, 1H), 7.76 (dd, J = 7.8, 1.4 Hz, 1H), 7.63 – 7.53 (m, 2H), 7.52 – 7.41 (m, 3H),
7.34 (dd, J = 10.1, 4.7 Hz, 2H), 7.29 (dd, J = 6.7, 1.7 Hz, 1H), 6.78 (d, J = 15.9 Hz, 1H), 6.39 (dt,
J = 15.9, 6.5 Hz, 1H), 5.03 (dd, J = 6.5, 1.1 Hz, 2H), 3.90 (s, 6H); 13C NMR (101 MHz, CDCl3) δ
165.6, 162.8, 160.1, 137.5, 135.6, 134.6, 132.3, 130.77, 128.4, 128.2, 128.2, 128.2, 127.8, 126.2,
125.4, 124.9, 121.7, 119.3, 117.2, 117.1, 104.8, 65.8, 52.4, 51.3; HRMS (ESI-TOF) m/z:
[M+H]+ Calcd. For C26H22NO6: 444.1442, Found: 444.1455; IR (neat, cm-1): υ 2922, 1740, 1700,
1296, 1149, 916, 750.
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1-(furan-2-ylmethyl) 2,3-dimethyl pyrrolo[1,2-a]quinoline-1,2,3-tricarboxylate (4y). Light
yellow solid; yield 164 mg (81%); mp: 159.4-162.3 oC; 1H NMR (400 MHz, CDCl3) δ 8.18 (d, J =
9.4 Hz, 1H), 8.02 (d, J = 8.6 Hz, 1H), 7.74 (dd, J = 7.8, 1.4 Hz, 1H), 7.61 – 7.41 (m, 4H), 6.55 (d,
J = 3.2 Hz, 1H), 6.42 (dd, J = 3.2, 1.9 Hz, 1H), 5.36 (s, 2H), 3.89 (s, 3H), 3.81 (s, 3H); 13C NMR
(101 MHz, CDCl3) δ 165.4, 162.8, 159.8, 148.2, 143.0, 137.5, 132.26, 131.0, 128.3, 128.2, 128.1,
125.3, 124.8, 119.2, 117.0, 116.8, 111.1, 110.3, 104.8, 58.5, 52.2, 51.3; HRMS (ESI-TOF) m/z:
[M+H]+ Calcd. For C22H18NO7: 408.1078, Found: 408.1087; IR (neat, cm-1): υ 2723, 1702, 1446,
1218, 1178, 1081, 750.
1-but-2-yn-1-yl 2,3-dimethyl pyrrolo[1,2-a]quinoline-1,2,3-tricarboxylate (4z). Brown solid;
yield 117 mg (62%); mp: 134.4-136.7 oC; 1H NMR (400 MHz, CDCl3) δ 8.20 (d, J = 9.4 Hz, 1H),
8.10 (d, J = 8.6 Hz, 1H), 7.76 (dd, J = 7.8, 1.4 Hz, 1H), 7.63 – 7.53 (m, 2H), 7.52 – 7.44 (m, 1H),
4.93 (q, J = 2.3 Hz, 2H), 4.03 (s, 3H), 3.91 (s, 3H), 1.91 (t, J = 2.4 Hz, 3H); 13C NMR (101 MHz,
CDCl3) δ 165.4, 162.8, 159.6, 137.5, 132.3, 131.0, 128.3, 128.2, 128.2, 125.4, 124.8, 119.2, 117.0,
116.7, 104.8, 83.5, 72.1, 53.5, 52.4, 51.3, 3.2; HRMS (ESI-TOF) m/z: [M+H]+ Calcd. For
C21H18NO6: 380.1129, Found: 380.1146; IR (neat, cm-1): υ 2948, 1695, 1421, 1213, 1149, 1080,
755.
2,3-dimethyl 1-(2-(trimethylsilyl)ethyl) pyrrolo[1,2-a]quinoline-1,2,3-tricarboxylate (4aa).
Yellow solid; yield 165 mg (80%); mp: 89.2-91.6 oC; 1H NMR (400 MHz, CDCl3) δ 8.15 (dd, J =
9.4, 1.5 Hz, 1H), 8.06 (d, J = 8.7 Hz, 1H), 7.71 (d, J = 7.8 Hz, 1H), 7.60 – 7.49 (m, 2H), 7.43 (t, J
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= 7.5 Hz, 1H), 4.50 – 4.38 (m, 2H), 3.98 (s, 3H), 3.88 (s, 3H), 1.18 – 1.10 (m, 2H), 0.07 (s, 9H);
13C NMR (101 MHz, CDCl3) δ 165.6, 162.9, 160.5, 137.1, 132.28, 130.2, 128.3, 128.0, 127.9,
125.2, 124.8, 119.1, 117.7, 117.0, 104.6, 63.8, 52.2, 51.2, 16.8, -2.0; HRMS (ESI-TOF) m/z:
[M+H]+ Calcd. For C22H26NO6Si: 428.1524, Found: 428.1546; IR (neat, cm-1): υ 2953, 1710, 1445,
1215, 1160, 814, 733.
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triethyl pyrrolo[1,2-a]quinoline-1,2,3-tricarboxylate (4a'). Yellow solid; mp: 81.9-83.3 oC; 1H
NMR (400 MHz, CDCl3) δ 8.23 (d, J = 9.4 Hz, 1H), 8.06 (d, J = 8.7 Hz, 1H), 7.78 – 7.69 (m, 1H),
7.60 – 7.52 (m, 2H), 7.46 (t, J = 7.4 Hz, 1H), 4.51 – 4.41 (m, 4H), 4.38 (q, J = 7.1 Hz, 2H), 1.49 –
1.36 (m, 9H); 13C NMR (101 MHz, CDCl3) δ 165.2, 162.5, 160.4, 137.4, 132.3, 130.5, 128.3,
128.0, 127.9, 125.2, 124.8, 119.1, 117.3, 117.1, 104.8, 61.3, 61.2, 60.0, 13.8, 13.7, 13.6; HRMS
(ESI-TOF) m/z: [M+H]+ Calcd. For C21H22NO6: 384.1442, Found: 384.1447; IR (neat, cm-1): υ
2980, 1697, 1436, 1209, 1178, 1077, 813.
3-ethyl 1,2-dimethyl pyrrolo[2,1-a]isoquinoline-1,2,3-tricarboxylate (6a)15b,25. Light yellow
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solid; yield 147 mg (83%); mp: 120.4-122.1 C; H NMR (400 MHz, CDCl3) δ 9.54 – 9.42 (m,
1H), 9.41 – 9.28 (m, 1H), 7.74 (dd, J = 5.7, 3.2 Hz, 1H), 7.69 – 7.55 (m, 2H), 7.28 – 7.15 (m, 1H),
4.43 (q, J = 7.1 Hz, 2H), 4.01 (s, 3H), 3.98 (s, 3H), 1.44 (t, J = 7.1 Hz, 3H); 13C NMR (101 MHz,
CDCl3) δ 166.0, 163.8, 159.5, 134.1, 129.6, 129.3, 128.7, 127.5, 126.7, 126.4, 123.9, 123.4, 115.4,
113.0, 107.2, 60.7, 52.1, 51.6, 13.6; HRMS (ESI-TOF) m/z: [M+H]+ Calcd. For C19H18NO6:
356.1129, Found: 356.1137; IR (neat, cm-1): υ 2937, 1690, 1273, 1120, 1052, 1023, 783.
3-ethyl 1,2-dimethyl 8-methylpyrrolo[2,1-a]isoquinoline-1,2,3-tricarboxylate (6b). Yellow
solid; yield 147 mg (80%); mp: 154.2-156.4 oC; 1H NMR (400 MHz, CDCl3) δ 9.31 (dd, J = 15.3,
8.1 Hz, 2H), 7.47 (s, 1H), 7.42 (dd, J = 8.7, 1.4 Hz, 1H), 7.12 (d, J = 7.5 Hz, 1H), 4.38 (q, J = 7.1
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Hz, 2H), 3.97 (s, 3H), 3.92 (s, 3H), 2.50 (s, 3H), 1.39 (t, J = 7.1 Hz, 3H); C NMR (101 MHz,
CDCl3) δ 166.1, 163.7, 159.5, 139.1, 134.5, 129.7, 129.5, 129.1, 126.7, 126.1, 123.4, 121.7, 115.2,
112.7, 106.6, 60.6, 52.0, 51.6, 21.0, 13.6; HRMS (ESI-TOF) m/z: [M+H]+ Calcd. For C20H20NO6:
370.1285, Found: 370.1297; IR (neat, cm-1): υ 2954, 1697, 1329, 1118, 1081, 1039, 790.
3-ethyl 1,2-dimethyl 8-bromopyrrolo[2,1-a]isoquinoline-1,2,3-tricarboxylate (6c). White solid;
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yield 147 mg (68%); mp: 168.6-171.2 C; H NMR (400 MHz, CDCl3) δ 9.34 (dd, J = 17.1, 8.3
Hz, 2H), 7.82 (d, J = 1.9 Hz, 1H), 7.66 (dd, J = 9.0, 2.0 Hz, 1H), 7.07 (d, J = 7.6 Hz, 1H), 4.38 (q,
J = 7.1 Hz, 2H), 3.95 (d, J = 19.7 Hz, 6H), 1.39 (t, J = 7.1 Hz, 3H); 13C NMR (101 MHz, CDCl3)
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δ 166.2, 164.0, 159.8, 134.0, 131.2, 131.0, 130.3, 129.1, 129.0, 124.9, 123.5, 123.0, 114.7, 113.7,
107.8, 61.3, 52.6, 52.2, 14.1; HRMS (ESI-TOF) m/z: [M+H]+ Calcd. For C19H1779BrNO6:
434.0239, C19H1781BrNO6: 436.0219, Found: 434.0246, 436.0234; IR (neat, cm-1): υ 2947, 1400,
1222, 1200, 1121, 785.
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3-ethyl 1,2-dimethyl 7-bromopyrrolo[2,1-a]isoquinoline-1,2,3-tricarboxylate (6d). White solid;
yield 121 mg (56%); mp: 146.5-148.1 oC; 1H NMR (400 MHz, CDCl3) δ 9.38 (dd, J = 8.1, 5.5 Hz,
2H), 7.84 (dd, J = 7.7, 0.7 Hz, 1H), 7.64 (d, J = 7.8 Hz, 1H), 7.42 (t, J = 8.1 Hz, 1H), 4.40 (q, J =
13
7.1 Hz, 2H), 3.97 (s, 3H), 3.93 (s, 3H), 1.40 (t, J = 7.1 Hz, 3H); C NMR (101 MHz, CDCl3) δ
166.2, 164.1, 159.8, 133.5, 133.1, 130.4, 128.7, 128.4, 126.7, 125.9, 125.1, 121.6, 114.4, 113.6,
108.2, 77.38, 77.0, 76.7, 61.3, 52.6, 52.3, 14.1; HRMS (ESI-TOF) m/z: [M+H]+ Calcd. For
C19H1779BrNO6: 434.0239, C19H1781BrNO6: 436.0219, Found: 434.0244, 436.0231; IR (neat, cm-1):
υ 2949, 1697, 1446, 1221, 1181, 1118, 782.
3-ethyl 1,2-dimethyl 7-chloropyrrolo[2,1-a]isoquinoline-1,2,3-tricarboxylate (6e). Yellow
solid; yield 130 mg (67%); mp: 163.9-164.8 oC; 1H NMR (400 MHz, CDCl3) δ 9.38 (d, J = 7.8 Hz,
1H), 9.34 (d, J = 8.5 Hz, 1H), 7.64 (dd, J = 4.4, 3.4 Hz, 2H), 7.48 (t, J = 8.1 Hz, 1H), 4.39 (q, J =
13
7.1 Hz, 2H), 3.97 (s, 3H), 3.93 (s, 3H), 1.40 (t, J = 7.1 Hz, 3H); C NMR (101 MHz, CDCl3) δ
165.7, 163.6, 159.3, 133.0, 130.6, 129.9, 129.0, 127.5, 126.9, 125.5, 125.3, 124.4, 113.2, 111.2,
107.8, 60.8, 52.1, 51.8, 13.6; HRMS (ESI-TOF) m/z: [M+H]+ Calcd. For C19H1735ClNO6:
390.0739, C19H1737ClNO6: 392.0715, Found: 390.0748, 392.0732; IR (neat, cm-1): υ 2950, 1716,
1493, 1221, 1180, 1125, 783.
3-ethyl 1-methyl pyrrolo[2,1-a]isoquinoline-1,3-dicarboxylate (6f)26. Light yellow solid; yield
71mg (48%); mp: 131.0-133.6 oC; 1H NMR (400 MHz, CDCl3) δ 9.79 (d, J = 8.1 Hz, 1H), 9.33 (d,
J = 7.5 Hz, 1H), 7.99 (s, 1H), 7.67 (dd, J = 7.6, 1.3 Hz, 1H), 7.64 – 7.54 (m, 2H), 7.13 (d, J = 7.5
13
Hz, 1H), 4.39 (q, J = 7.1 Hz, 2H), 3.94 (s, 3H), 1.42 (t, J = 7.1 Hz, 3H); C NMR (101 MHz,
CDCl3) δ 164.6, 160.5, 135.4, 129.1, 128.3, 127.2, 127.2, 126.1, 124.7, 124.4, 123.8, 115.4, 114.4,
108.6, 60.0, 51.2, 14.0; HRMS (ESI-TOF) m/z: [M+H]+ Calcd. For C17H16NO4: 298.1074, Found:
298.1082; IR (neat, cm-1): υ 2949, 1706, 1229, 1185, 1077, 799, 760.
diethyl pyrrolo[2,1-a]isoquinoline-1,3-dicarboxylate (6g). Light yellow solid; yield 74 mg
(48%); mp: 118.7-119.8 oC; 1H NMR (400 MHz, CDCl3) δ 9.80 (d, J = 8.1 Hz, 1H), 9.35 (d, J =
7.5 Hz, 1H), 8.01 (s, 1H), 7.68 (dd, J = 7.6, 1.4 Hz, 1H), 7.65 – 7.55 (m, 2H), 7.14 (d, J = 7.5 Hz,
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1H), 4.46 – 4.35 (m, 4H), 1.45 (dd, J = 15.6, 7.2 Hz, 6H); 13C NMR (101 MHz, CDCl3) δ 164.2,
160.6, 135.4, 129.1, 128.3, 127.3, 127.2, 126.2, 124.7, 124.4, 123.8, 115.4, 114.4, 109.1, 60.0,
60.0, 14.0, 14.0; HRMS (ESI-TOF) m/z: [M+H]+ Calcd. For C18H18NO4: 312.1230, Found:
312.1242; IR (neat, cm-1): υ 2979, 1694, 1230, 1185, 1075, 798, 754.
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1-butyl 3-ethyl pyrrolo[2,1-a]isoquinoline-1,3-dicarboxylate (6h). White solid; yield 81 mg
(48%); mp: 75.8-77.9 oC; 1H NMR (400 MHz, CDCl3) δ 9.80 (d, J = 8.1 Hz, 1H), 9.36 (d, J = 7.5
Hz, 1H), 8.00 (s, 1H), 7.68 (dd, J = 7.6, 1.2 Hz, 1H), 7.65 – 7.54 (m, 2H), 7.14 (d, J = 7.5 Hz, 1H),
4.39 (dt, J = 13.3, 6.9 Hz, 4H), 1.90 – 1.75 (m, 2H), 1.59 – 1.47 (m, 2H), 1.44 (t, J = 7.1 Hz, 3H),
1.02 (t, J = 7.4 Hz, 3H); 13C NMR (101 MHz, CDCl3) δ 164.3, 160.6, 135.4, 129.1, 128.3, 127.3,
127.2, 126.2, 124.6, 124.4, 123.8, 115.4, 114.4, 109.1, 64.0, 60.0, 30.5, 18.9, 14.0, 13.4; HRMS
(ESI-TOF) m/z: [M+H]+ Calcd. For C20H22NO4: 340.1543, Found: 340.1555; IR (neat, cm-1): υ
2962, 1686, 1227, 1189, 1156, 1076, 817.
1-tert-butyl 3-ethyl pyrrolo[2,1-a]isoquinoline-1,3-dicarboxylate (6i). Light yellow solid; yield
1
59 mg (35%); mp: 124.0-126.3 oC; H NMR (400 MHz, CDCl3) δ 9.73 (d, J = 8.3 Hz, 1H), 9.35
(d, J = 7.5 Hz, 1H), 7.93 (s, 1H), 7.70 – 7.53 (m, 3H), 7.13 (d, J = 7.5 Hz, 1H), 4.41 (q, J = 7.1 Hz,
13
2H), 1.67 (s, 9H), 1.44 (t, J = 7.1 Hz, 3H); C NMR (101 MHz, CDCl3) δ 163.8, 160.6, 135.0,
129.1, 128.1, 127.2, 127.1, 126.1, 124.8, 124.5, 123.8, 115.0, 114.2, 111.0, 80.2, 60.0, 28.0, 14.0;
HRMS (ESI-TOF) m/z: [M+H]+ Calcd. For C20H22NO4: 340.1543, Found: 340.1555; IR (neat,
cm-1): υ 2971, 1696, 1204, 1142, 1073, 798, 757.
ethyl 1-acetylpyrrolo[2,1-a]isoquinoline-3-carboxylate (6j). Light yellow solid; yield 55 mg
o
1
(39%); mp: 102.2-105.2 C; H NMR (400 MHz, CDCl3) δ 9.81 – 9.74 (m, 1H), 9.33 (d, J = 7.5
Hz, 1H), 7.92 (s, 1H), 7.70 – 7.65 (m, 1H), 7.64 – 7.56 (m, 2H), 7.17 (d, J = 7.5 Hz, 1H), 4.41 (q,
J = 7.1 Hz, 2H), 2.70 (s, 3H), 1.45 (t, J = 7.1 Hz, 3H); 13C NMR (101 MHz, CDCl3) δ 193.1,
160.4, 134.9, 129.3, 128.7, 127.4, 127.1, 126.1, 125.0, 124.7, 123.5, 118.1, 115.4, 115.1, 60.1,
29.5, 14.0; HRMS (ESI-TOF) m/z: [M+H]+ Calcd. For C17H16NO3: 282.1125, Found: 282.1133;
IR (neat, cm-1): υ 2976, 1687, 1655, 1229, 1076, 804, 696.
3-ethyl 1-(2,2,2-trifluoroethyl) pyrrolo[2,1-a]isoquinoline-1,3-dicarboxylate (6k). White solid;
yield 97 mg (53%); mp: 150.2-152.1 oC; 1H NMR (400 MHz, CDCl3) δ 9.83 – 9.59 (m, 1H), 9.34
(d, J = 7.5 Hz, 1H), 8.00 (s, 1H), 7.75 – 7.66 (m, 1H), 7.65 – 7.56 (m, 2H), 7.16 (d, J = 7.5 Hz,
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1H), 4.74 (q, J = 8.5 Hz, 2H), 4.41 (q, J = 7.1 Hz, 2H), 1.45 (t, J = 7.1 Hz, 3H); C NMR (101
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MHz, CDCl3) δ 162.1, 160.3, 136.2, 129.3, 128.7, 127.3, 127.1, 126.3, 124.7, 124.1, 123.8,
123.2(q, J = 278.8 Hz)115.91, 114.86, 106.39, 60.20, 59.84(q, J = 110.1 Hz), 13.96; 19F NMR
(376 MHz, CDCl3) δ -73.42; HRMS (ESI-TOF) m/z: [M+H]+ Calcd. For C18H15F3NO4: 366.0948,
Found: 366.0956; IR (neat, cm-1): υ 2992, 1691, 1154, 1083, 970, 807, 756.
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ethyl 1-cyanopyrrolo[2,1-a]isoquinoline-3-carboxylate (6l)20b. Light yellow solid; yield 104 mg
(79%); mp: 156.4-158.7 oC; 1H NMR (400 MHz, CDCl3) δ 9.22 (d, J = 7.5 Hz, 1H), 8.85 (dd, J =
6.3, 2.9 Hz, 1H), 7.74 – 7.67 (m, 2H), 7.67 – 7.58 (m, 2H), 7.14 (d, J = 7.5 Hz, 1H), 4.40 (q, J =
7.1 Hz, 2H), 1.43 (t, J = 7.1 Hz, 3H); 13C NMR (101 MHz, CDCl3) δ 159.7, 136.2, 128.9, 128.2,
128.0, 126.6, 123.7, 123.6, 123.2, 123.0, 116.6, 116.6, 114.5, 84.5, 60.4, 13.9; HRMS (ESI-TOF)
m/z: [M+H]+ Calcd. For C16H13N2O2: 265.0972, Found: 265.0968; IR (neat, cm-1): υ 3129, 2220,
1708, 1252, 1122, 846, 687.
1-cyclohexyl 3-ethyl pyrrolo[2,1-a]isoquinoline-1,3-dicarboxylate (6m). White solid; yield 80
mg (44%); mp: 111.6-113.6 oC; 1H NMR (400 MHz, CDCl3) δ 9.81 (d, J = 8.0 Hz, 1H), 9.35 (d, J
= 7.5 Hz, 1H), 7.99 (s, 1H), 7.68 (dd, J = 7.6, 1.4 Hz, 1H), 7.64 – 7.53 (m, 2H), 7.13 (d, J = 7.5 Hz,
1H), 5.16 – 4.92 (m, 1H), 4.41 (q, J = 7.1 Hz, 2H), 2.14 – 2.00 (m, 2H), 1.91 – 1.79 (m, 2H), 1.67
13
– 1.57 (m, 3H), 1.54 – 1.30 (m, 6H); C NMR (101 MHz, CDCl3) δ 163.8, 160.6, 135.3, 129.1,
128.2, 127.3, 127.1, 126.1, 124.6, 124.5, 123.8, 115.3, 114.3, 109.7, 72.4, 60.0, 31.4, 25.1, 23.6,
14.0; HRMS (ESI-TOF) m/z: [M+H]+ Calcd. For C22H24NO4: 366.1700, Found: 366.1713; IR
(neat, cm-1): υ 2942, 1693, 1215, 1167, 1037, 797, 754.
1,2-dibutyl 3-ethyl pyrrolo[2,1-a]isoquinoline-1,2,3-tricarboxylate (6n). Yellow solid; yield
o
1
171 mg (78%); mp: 65.5-67.6 C; H NMR (400 MHz, CDCl3) δ 9.44 (dd, J = 8.5, 4.7 Hz, 1H),
9.35 (d, J = 7.5 Hz, 1H), 7.74 – 7.67 (m, 1H), 7.64 – 7.56 (m, 2H), 7.20 (d, J = 7.5 Hz, 1H), 4.43 –
4.31 (m, 6H), 1.84 – 1.71 (m, 4H), 1.55 – 1.43 (m, 4H), 1.40 (t, J = 7.1 Hz, 3H), 0.99 (t, J = 7.4
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Hz, 6H); C NMR (101 MHz, CDCl3) δ 165.6, 163.6, 159.6, 134.0, 129.7, 129.3, 128.6, 127.4,
126.8, 126.4, 124.0, 123.4, 115.3, 113.0, 107.6, 65. 3, 64.7, 60.6, 30.2, 30.1, 18.9, 18.7, 13.7, 13.3,
13.3; HRMS (ESI-TOF) m/z: [M+H]+ Calcd. For C25H30NO6: 440.2068, Found: 440.2071; IR
(neat, cm-1): υ 2960, 1695, 1211, 1187, 1082, 797, 728.
exo-3-ethyl
1-((1S,2S,4S)-1,7,7-trimethylbicyclo[2.2.1]heptan-2-yl)
pyrrolo[2,1-a]isoquinoline-1,3-dicarboxylate (6o). White solid; yield 111 mg (53%); mp:
108.3-110.5 oC; [α]2D0 = 5.4 (c 1, CHCl3); 1H NMR (400 MHz, CDCl3) δ 9.85 (d, J = 8.2 Hz, 1H),
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