Tandem furo[3,4-b]pyridine formation-Diels-Alder reaction: an approach to the synthesis of nitrogen containing heterocyclic analogues of 1-arylnaphthalene lignans

Article abstract of DOI:10.1016/j.tet.2007.09.007

The coupling of Fischer carbene complexes with 2-alkynyl-3-pyridine carbonyl derivatives has been examined. The reaction affords furo[3,4-b]pyridine as transient intermediates; the latter undergo [4+2] cycloaddition with an electron-deficient dienophile.

Full text of DOI:10.1016/j.tet.2007.09.007

Tetrahedron 63 (2007) 12015–12025
Tandem furo[3,4-b]pyridine formation—Diels–Alder reaction: an
approach to the synthesis of nitrogen containing heterocyclic
analogues of 1-arylnaphthalene lignans
*
Gouranga P. Jana and Binay K. Ghorai
Department of Chemistry, Bengal Engineering and Science University, Shibpur, Howrah 711103, West Bengal, India
Received 19 April 2007; revised 22 August 2007; accepted 6 September 2007
Available online 11 September 2007
Abstract—The coupling of Fischer carbene complexes with 2-alkynyl-3-pyridine carbonyl derivatives has been examined. The reaction
affords furo[3,4-b]pyridine as transient intermediates; the latter undergo [4+2] cycloaddition with an electron-deficient dienophile. Acid/
base-induced ring opening of the exo-cycloadducts followed by aromatization give substituted quinolines related to heterocyclic analogues
of 1-arylnaphthalene lignans. An intramolecular variant of this protocol is also feasible with use of unactivated alkenyl tethers; however, the
bridged cycloadducts are unisolable as they undergo spontaneous ring opening to yield alcohol. This method is also useful for the in situ
generation of the furo[3,4-b]quinoline intermediate for the first time, which can be trapped with dienophiles.
Ó 2007 Elsevier Ltd. All rights reserved.
1. Introduction
utilized for the generation of heteroaromatic isobenzofurans.
In this paper, we wish to report the one step generation of
furo[3,4-b]pyridine intermediates3 through the coupling of
o-alkynylpyridine carbonyl derivatives 4 with a Fischer car-
bene complex 5. Although, furo[3,4-b]pyridines are unsta-
ble, they have been proven to be useful4 for the synthesis
of heterocyclic analogues of 1-arylnaphthalene lignans of
biological significance.5 Our synthetic plan towards aryl-
quinoline lignan derivative 9 is outlined in Scheme 1. This
involves the generation of substituted furo[3,4-b]pyridine
intermediate 6 by coupling of 2-alkynyl-3-pyridine carbonyl
derivatives 4 with Fischer carbene complex 5 followed by
Diels–Alder reaction with an added dienophile to give cyclo-
adduct 8, which is readily convertible to heterolignans 9 by
treatment with acid or base. The possible alternative path-
way is formation of pyrone derivative 7, which could also
lead to 9 via intermolecular Diels–Alder reaction followed
by CO2 extrusion.6
While the o-quinoid 10p-electron isobenzofuran system has
remained the subject of intense theoretical, structural and
reactivity studies,1,2 little, if any, work has been done with the
analogous furo[3,4-b]pyridines.3 Parent furo[3,4-b]pyridine
(1) and furo[3,4-b]quinoline (2) are unknown, with the only
method so far available in the literature being the in situ
generation of substituted furo[3,4-b]pyridine intermediates
from treatment of 2-(a-acetoxy-3,4-dimethoxybenzyl)-2-
pyridine-3-carboxaldehyde (3) with acid.4
CHO
O
O
OAc
N
N
N
1
2
3
OMe
OMe
One of the efficient and interesting methods for the genera-
tion of isobenzofurans involves the coupling of Fischer car-
bene complexes with o-alkynylbenzoyl derivatives.2 These
isobenzofurans are unstable, but readily undergo inter- and
intramolecular Diels–Alder reactions when suitable dieno-
philes are present. So far, this methodology has not been
2. Results and discussion
Our studies began with the 2-bromo-3-pyridine carboxalde-
hyde (10), which was prepared by the regioselective ortho-
lithiation of 2-bromopyridine with LDA at ꢀ78 ꢁC followed
by quenching with DMF according to the procedure de-
scribed by Sakamoto et al.7 The Sonogashira coupling of
10 with trimethylsilylacetylene afforded alkyne aldehyde
11 in 85% yield. Conversion of 11 to the corresponding
alkyne carbonyl derivatives 12 was then accomplished by
Keywords: Carbene complexes; Chromium; Azaisobenzofuran; Diels–
Alder reaction; Heterolignan.
* Corresponding author. Tel.: +91 33 26684561; fax: +91 33 26682916;
e-mail: bkghorai@yahoo.co.in
0040–4020/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2007.09.007

12016
G. P. Jana, B. K. Ghorai / Tetrahedron 63 (2007) 12015–12025
Cr(CO)5
Ar
Ar
Ar
Cr(CO)3
Cr(CO)3
Me
OMe
O
O
5
O
vs
OMe
Me
N
N
N
Me3Si
7
O
OMe
SiMe3
Me3Si
Me
4
6
O
O
N R1
O
N R1
O
Ar
Ar
O
H
H
O
R1
R1
O
N
N
O
N
N
O
OMe
O
Me3Si
Me
Me
8
9
Scheme 1. Our strategy towards arylquinoline lignan derivative.
treatment with an aryl-Grignard reagent in diethyl ether and
subsequent oxidation with PDC as depicted in Scheme 2.
The corresponding benzo analogue 14 was prepared by the
palladium-catalyzed Sonogashira reaction of 3-formyl-2-
iodoquinoline (13),8 which on exposure to an aryl-Grignard
reagent in diethyl ether followed by PDC oxidation resulted
alkyne carbonyl derivative 15 (Scheme 3).
21 was the major product of the reaction. The stereochemis-
try of the oxa-bridged adduct 20 was assigned as exo based
on the 0 Hz coupling of HA and HB, and the chemical shifts
of HB and HC (<4 ppm).2a,9 The absence of coupling be-
tween HA and HB suggests that the dihedral angle between
these hydrogen is about 90ꢁ (Karplus curve). A free azaiso-
benzofuran is unlikely in the reaction of 11 based on the high
exo selectivity, coupled with the substantial lifetime of the
intermediate at 70 ꢁC. The observed azaisobenzofurans
could be stabilized by complexation with chromium,10 and
thus the adducts could result from an oxidative insertion–
reductive elimination sequence.11 The reaction process was
also carried out without the acid treatment. After filtration
through Celite and purification by column chromatography
(silica gel) a mixture of ketone 20 and quinoline derivative
21 was obtained. Attempt to isolate enol ether 19 was unsuc-
cessful, as it readily converted to the corresponding ketone
20 and quinoline derivative 21 during column chromato-
graphy on silica gel. Here the [4+2] oxa-bridged adduct 20
underwent spontaneous ring cleavage followed by dehydra-
tion upon treatment with aqueous hydrochloric acid to give
stable quinoline derivative 21. The possibility of a pyrone
derivative 7 from this reaction was initially expected based
on the formation of pyrone derivatives from the coupling
of carbene complexes with heteroaromatic alkyne alde-
hydes.6 In this reaction, formation of pyrone derivative 7
was not detected, which could result from the insertion of
CO with the intermediate alkyne carbene complex 16.
Although, pyrone derivative 7 can also lead to the product
quinoline derivative 21 via intermolecular Diels–Alder reac-
tion followed by CO2 extrusion. In these examples, capture of
the intermediate vinylcarbene complex 16 by the oxygen might
precede any CO insertion processes and hence pyridinopyrone
derivative 7 formation is not observed.6 The formation of
azaisobenzofuran intermediate 6 in these studies might be
attributed to the lowered ring strain involved, compared to
furan and thiophene systems.
R
CHO
CHO
b
a
O
N
N
N
Br
SiMe3
SiMe3
12A, R=Ph
12B, R=p-tol
11
10
Scheme 2. Reagents and conditions: (a) trimethylsilylacetylene,
(Ph3P)2PdCl2, CuI, THF, Et3N, rt, 85%; (b) (i) RMgBr; (ii) CrO3, 2Py,
12A (88%), 12B (68%).
R
CHO
I
CHO
a
b
O
N
N
N
SiMe3
SiMe3
13
14
15, R=p-tol
Scheme 3. Reagents and conditions: (a) trimethylsilylacetylene,
(Ph3P)2PdCl2, CuI, THF, Et3N, rt, 86%; (b) (i) RMgBr; (ii) CrO3, 2Py, 69%.
Coupling of pyridine carboxaldehyde 11, carbene complex 5
and N-phenylmaleimide (w1:1:1 ratio) in refluxing tetrahy-
drofuran for 12 h followed by acidic hydrolysis afforded
a mixture of the oxa-bridged adduct 20 and quinoline deriv-
ative 21 (Scheme 4). In this reaction, coupling of the carbene
complex with the alkyne initially provides intermediate
alkyne carbene complex 16, which is then captured by the
oxygen to form the carbonyl ylide derivative 17. Loss of
metal from the carbonyl ylide leads to the isobenzofuran de-
rivative 6, which then undergoes Diels–Alder reaction with
N-phenylmaleimide. In this reaction, quinoline derivative
The furo[3,4-b]pyridine intermediate forming reaction was
tested for different heteroaromatic alkynyl carbonyl

G. P. Jana, B. K. Ghorai / Tetrahedron 63 (2007) 12015–12025
12017
Cr(CO)5
OMe
5
H
O
Me
CHO
C
CHO
CHO
Cr(CO)4
OMe
Me
O
vs
Cr(CO)4
OMe
Me
THF, reflux
SiMe3
N
N
N
N
Cr(CO)3
OMe
Me3Si
Me3Si
Me3Si
Me
18
17
11
16
(Exclusive Product)
(Not Observed)
X
H
Cr(CO)3
O
N
H
O
OMe
Me
Me3Si
N
O
OMe
6 (Ar=H)
Me3Si
O
Me
7 (Ar=H)
N Ph
O
HA
HB
H
O
N
O
N
O
H
O
N
O
H3O+
O
Ph
O
Ph
Ph
N
N
N
H
HC
O
Me
O
OMe
O
Me3Si
Me
Me
20
21
19
Scheme 4.
derivatives; the results are presented in Table 1. This reaction
process was found to be general and afforded a mixture of
oxa-bridged compound 22 and quinoline 23 derivatives.
Since the azaisobenzofurans derived from the benzophenone
analogues appeared to be fairly stable, a two-step process
(sequential azaisobenzofuran synthesis—Diels–Alder cou-
pling) was attempted. The reaction of alkyne carbonyl com-
pounds 12 with carbene complex 5 for 0.5 h was followed by
addition of N-phenylmaleimide/N-methylmaleimide as a
dienophile and the crude product was treated with aqueous
hydrochloric acid to result in a mixture of exo Diels–Alder
adduct 22 and quinoline derivative 23 (entries B–D). In these
cases with N-phenylmaleimide, the oxa-bridged compounds
are the major products (entries B, D), although the ratio was
reversed when N-methylmaleimide was used (entry C).
The reaction process was also carried out with dimethyl
maleate as dienophile. The reaction of pyridine carbonyl
compound 12A and carbene complex 5 with dimethyl mal-
eate afforded the mixture of enol ether 24 and the corre-
sponding ketone 25 with no acid treatment at the end of
the reactions. However, the enol ether 24 is not stable in
chloroform and it readily converted to the corresponding
ketone 25. The isolated yield of 25 from 12A was 35%.
The oxa-bridged compound 25 was converted to the quino-
line derivative 26 on treatment with aqueous hydrochloric
Table 1. Generation and trapping of furo[3,4-b]pyridine with maleimides formed by the coupling reaction of Fischer carbene complexes 5 with alkynyl pyr-
idinoyl derivatives 11 or 12
O
N R1
1.
R
R
R
O
N
O
O
O
HB
HC
Cr(CO)5
OMe
O
THF, reflux, 12 h
2. H3O+
R1
N R1
O
+
O
+
Me
N
N
N
SiMe3
5
O
O
Me
Me
11/ 12
23
22
Entry
R
R1
Yielda of 22
Yielda of 23
A
B
C
D
H
Ph
Ph
Ph
Ph
Me
Ph
5
43
10
30
35
11
42
18
p-Tol
a
Isolated yield in %.

12018
G. P. Jana, B. K. Ghorai / Tetrahedron 63 (2007) 12015–12025
acid. Although the reaction was incomplete, the yield of 26
with respect to recovered starting material 25 is 60%. The
quinoline derivative 27 was obtained in 20% yield from
the three-component coupling of pyridine carboxaldehyde
11, carbene complex 5 and dimethyl maleate, followed by
treatment of the crude reaction mixtures with aqueous
hydrochloric acid (Scheme 5).
HA and HB, the chemical shifts of HB and HC (<4 ppm)
and N-Me signal in the proton NMR at d w3.0, where
applicable.2a,9
The oxa-bridge in the initially formed cycloadducts 22/28
from the three-component coupling of alkynyl carbonyl de-
rivatives, carbene complex and dienophile, could be readily
cleaved leading to the substituted quinolines 23/substituted
benzoquinolines 29 using DBU in refluxing toluene
(Scheme 6).5a,b However, this process is not efficient as
the average yield of this process 40–50%. Although, oxa-
bridged compounds 20, 22C, 25 and 28B were readily con-
verted to the quinoline derivatives 21, 23C, 26 and 29B on
treatment with aqueous hydrochloric acid, but partial con-
version of 22B, 22D and 28A to the corresponding quinoline
derivatives 23B, 23D and 29A took place under the same
conditions. Compounds 23 (R¼Ph or p-tol), 26 (R¼Ph)
The three-component coupling of benzopyridine alkynyl al-
dehyde 14/benzopyridine alkynyl carbonyl derivative 15,
carbene complex 5 and N-methylmaleimide/N-phenylmale-
imide were also examined, which led to the mixture of [4+2]
oxa-bridged adduct 28 and benzoquinoline derivative 29,
through the in situ generation of the hitherto unknown
system, furo[3,4-b]quinoline (Table 2). As in the previous
case, the stereochemistry of the oxa-bridge adduct 28 is
assigned as exo based on the lack of a coupling between
CO2Me
R
R
H
CO2Me
Cr(CO)5
O
CO2Me
O
+
Me
OMe
THF, reflux
N
CO2Me
OMe
N
H
SiMe3
5
Me3Si
Me
11 / 12A
24, R =Ph
R
R
H
CO2Me
CO2Me
H3O+
O
N
CO2Me
O
N
CO2Me
O
H
Me
Me
26, R =Ph, 60%
27, R =H, 20% from 11
25, R =Ph, 35% from 12A
Scheme 5.
Table 2. Generation and trapping of furo[3,4-b]quinolines with maleimides formed by the coupling reaction of Fischer carbene complex 5 with alkynyl pyr-
idinoyl derivatives 14 or 15
O
N
R1
1.
R
R
R
O
N
O
O
N
O
HB
HC
O
Cr(CO)5
OMe
O
THF, reflux, 12 h
2. H3O+
R1
+
R1
O
+
Me
N
N
N
SiMe3
5
O
O
Me
Me
14 / 15
29
28
Entry
R
R1
Yielda of 28
Yielda of 29
A
B
C
H
H
p-Tol
Ph
Me
Me
40
6b
—
10
36
48
a
Isolated yield in %.
Obtained as a mixture of 28B and 29B, as in this case oxa-bridged compound readily converted to the corresponding benzoquinoline derivative in chloroform
at room temperature.
b

G. P. Jana, B. K. Ghorai / Tetrahedron 63 (2007) 12015–12025
12019
and 29 (R¼p-tol) may be viewed as heterocyclic analogues
dienophile followed by exposure to silica gel gave a crystal-
line dicarbonyl compound 34, which may result from the
insertion of oxygen into the intermediate alkenylcarbene
complex 16 (Scheme 8).
of potentially bioactive 1-arylnaphthalene lignans.5
R
R
O
O
H
H
DBU
N R1
O
N R1
O
O
3. Conclusion
toluene, reflux
N
N
O
1.5 h
O
In conclusion, we have demonstrated a new route to the gen-
eration of furo[3,4-b]pyridines/furo[3,4-b]quinolines from
the coupling of alkynyl carbonyl derivative with Fischer
carbene complexes. In fact this is the first report of in situ
generation of furo[3,4-b]quinoline intermediates. The inter-
mediates can be trapped through Diels–Alder reaction with
dienophiles leading to the synthesis of nitrogen containing
heterocyclic analogues of 1-arylnaphthalene lignans in a
single step. Our results clearly indicate that this methodology
provides rapid entry into heteroaromatic o-quinodime-
thanes. Further work utilizing azaisobenzofuran intermedi-
ates is currently underway in our laboratory.
Me
23 / 29
Me
22 / 28
Scheme 6.
The coupling of alkynyl carbonyl compounds with carbene
complexes for the generation and trapping of a-phenylsub-
stituted furo[3,4-b]pyridines can also be extended to intra-
molecular cases (Scheme 7). Towards this g,d-unsaturated
Fischer carbene complex 30 was prepared from carbene
complex 5 via deprotonation using n-BuLi at ꢀ78 ꢁC fol-
lowed by addition of an excess allylic bromide as reported
by Herndon et al.2j Thus the coupling of carbene complex
30 with alkynyl carbonyl derivative 12A under the same con-
ditions as previously described undergoes an exo-selective
intramolecular Diels–Alder reaction12 through the genera-
tion of azaisobenzofuran intermediate 31 leading to a pyr-
idine fused to the hydronaphthalene derivative 33 in one
pot and in good yield. The initial Diels–Alder adduct 32, re-
sulting from 31, appears to be unstable with respect to ring
opening processes.1 The high-yielding intramolecular
[4+2] cycloaddition reaction of 31 is obviously related to en-
tropic factors, which place the tethered double bond in close
proximity to the diene system.
4. Experimental
4.1. General
All melting points are uncorrected. Unless otherwise noted,
all reactions were carried out under an inert atmosphere in
flame dried flasks. Solvents and reagents were dried and pu-
rified by distillation before use as follows: tetrahydrofuran,
toluene, hexane, diethyl ether from sodium benzophenone
ketyl; dichloromethane and chloroform from P2O5; DMF
and diisopropylamine from CaH2; triethylamine and pyri-
dine from solid KOH. After drying, organic extracts were
evaporated under reduced pressure and the residue was col-
umn chromatographed on silica gel (Spectrochem, particle
size 100–200 mesh), using an ethyl acetate–petroleum ether
(60–80 ꢁC) mixture as eluent unless specified otherwise.
Various attempts to isolate the heteroaromatic isobenzo-
furans 6 were unsuccessful owing to their extreme instabil-
ity. The reaction of alkyne carbonyl compound 12A with
carbene complex in refluxing THF for 4 h in absence of
Cr(CO)5
OMe
Ph
Ph
Ph OH
Ph
30
O
H
H
O
O
THF, reflux
65%
N
N
N
N
SiMe3
Me3Si
Me3Si
Me3Si
OMe
OMe
O
12A
33
31
32
Scheme 7.
Cr(CO)5
OMe
Ph
R
Ph
5
Me
O
O
Silica gel
O
O
Cr(CO)4
THF, reflux
N
N
Me3Si
N
SiMe3
OMe
Me
OMe
Me
H
12A
34
16 (R=Ph)
Scheme 8.

12020
G. P. Jana, B. K. Ghorai / Tetrahedron 63 (2007) 12015–12025
4.2. General procedure 1—for synthesis of alkynyl
pyridine/quinoline carboxaldehyde 11, 14
was added to a red solution of CrO3$2Py [prepared from vig-
orously stirred suspension of CrO3 (6 mmol) and pyridine
(12 mmol) in dry CH2Cl2 (12 mL) for 1.5 h at room temper-
ature] and stirred at room temperature for 4 h. The mixture
was then diluted with Et2O (10 mL) and passed through
a bed of silica gel (5 g). The solution was then concentrated
under reduced pressure and purified by column chromato-
graphy (silica gel, ethyl acetate/petroleum ether 2:8).
A mixture of aldehyde (1 mmol), Pd(PPh3)2Cl2 (0.05 mmol),
PPh3 (0.025 mmol), trimethylsilylacetylene (1.5 mmol) and
triethylamine (1.5 mmol) in THF (5 mL) was stirred for
20 min at room temperature, and then CuI (0.01 mmol)
was added. The reaction was stirred for 12–16 h at room
temperature, and the solvent was removed on a rotary evap-
orator. The residue was treated with dichloromethane and
filtered through Celite. The filtrate was concentrated and
the residue was purified by chromatography (silica gel, ethyl
acetate/petroleum ether 1:9).
4.3.1. Phenyl-(2-trimethylsilylethynylpyridine-3-yl)meth-
anone (12A). Starting from aldehyde 11 (406 mg, 2 mmol)
and phenylmagnesium bromide (0.5 M, 4.4 mL, 2.2 mmol),
following the general procedure 2, the product was obtained
as a white needle 12A (0.49 g, 88%). Mp 58–59 ꢁC; Rf (20%
EtOAc/petroleum ether) 0.65; IR (KBr, cmꢀ1): 2168, 1668;
1H NMR (500 MHz, CDCl3): d 8.77 (dd, 1H, J¼4.8, 1.7 Hz),
7.90–7.84 (m, 3H), 7.66 (m, 1H), 7.54–7.49 (m, 2H), 7.44
(dd, 1H, J¼7.5, 4.8 Hz), 0.0 (s, 9H); 13C NMR (125 MHz,
CDCl3): d 196.2, 152.0, 141.2, 139.0, 137.5, 137.0, 134.4,
130.9 (2C), 129.3 (2C), 123.7, 102.8, 102.3, 0.0 (3C); MS:
m/e (relative intensity): 281 (MH++1, 26), 280 (MH+,
100), 206 (3). Anal. Calcd for C17H17NOSi: C, 73.08; H,
6.13; N, 5.01. Found: C, 72.93; H, 6.27; N, 4.86.
4.2.1. 2-Trimethylsilylethynylpyridine-3-carboxaldehyde
(11).7 General procedure 1 was followed using 2-bromo-3-pyr-
idine carboxaldehyde (10)7 (0.74 g, 3.99 mmol), Pd(PPh3)2Cl2
(0.14 g, 0.2 mmol), PPh3 (26 mg, 0.1 mmol), trimethylsilyl-
acetylene (0.59 g, 6.0 mmol) and triethylamine (0.60 g,
6 mmol) in THF (20 mL), followed by CuI (7 mg,
0.04 mmol). After column chromatography a single fraction
was isolated and assigned as compound 11 (0.689 g, 85%).
IR (KBr, cmꢀ1): 2850, 2745, 2158, 1700; 1H NMR
(400 MHz, CDCl3): d 10.55 (s, 1H), 8.77 (dd, 1H, J¼5.0,
1.8 Hz), 8.17 (dd, 1H, J¼8.0, 1.8 Hz), 7.39 (dd, 1H, J¼8.0,
5.0 Hz), 0.30 (s, 9H); 13C NMR (125 MHz, CDCl3): d
191.3, 154.8, 146.1, 134.9, 132.5, 123.9, 103.3, 99.7, 0.0 (3C).
4.3.2. p-Tolyl-(2-trimethylsilylethynylpyridine-3-yl)me-
thanone (12B). Starting from aldehyde 11 (406 mg,
2 mmol) and p-tolylmagnesium bromide (0.5 M, 4.4 mL,
2.2 mmol), following the general procedure 2, the product
12B was obtained (0.40 g, 68%) as a colourless thick liquid.
Rf (20% EtOAc/petroleum ether) 0.62; IR (KBr, cmꢀ1):
4.2.2. 2-Trimethylsilylethynylquinoline-3-carboxalde-
hyde (14). General procedure 1 was followed using 3-for-
myl-2-iodoquinoline (13)8 (1.13 g, 3.99 mmol), Pd(PPh3)2Cl2
(0.14 g, 0.2 mmol), PPh3 (26 mg, 0.1 mmol) and trimethyl-
silylacetylene (0.59 g, 6.0 mmol) and triethylamine
(0.60 g, 6.0 mmol) in THF (20 mL), followed by CuI
(7 mg, 0.04 mmol). After column chromatography a single
fraction was isolated as a white needle and assigned as com-
pound 14 (0.87 g, 86%). Mp 88–89 ꢁC; Rf (10% EtOAc/
petroleum ether) 0.73; IR (KBr, cmꢀ1): 2849, 2729, 2165,
1
2166, 1655; H NMR (400 MHz, CDCl3): d 8.60 (dd, 1H,
J¼4.8, 1.4 Hz), 7.71 (dd, 1H, J¼7.8, 1.4 Hz), 7.62 (d, 2H,
J¼8.0 Hz), 7.28 (dd, 1H, J¼7.8, 4.8 Hz), 7.17 (d, 2H, J¼8.0
Hz), 2.33 (s, 3H), ꢀ0.10 (s, 9H); 13C NMR (100 MHz,
CDCl3): d 194.7, 150.8, 144.4, 140.0, 138.2, 135.9, 133.9,
130.0 (2C), 128.9 (2C), 122.6, 101.4, 101.3, 21.4, ꢀ0.8
(3C); MS: m/e (relative intensity): 294 (MH+, 100). Anal.
Calcd for C18H19NOSi: C, 73.68; H, 6.53; N, 4.77. Found:
C, 73.49; H, 6.39; N, 4.91.
1
1697; H NMR (400 MHz, CDCl3): d 10.68 (s, 1H), 8.69
(s, 1H), 8.12 (d, 1H, J¼8.3 Hz), 7.92 (d, 1H, J¼8.3 Hz),
7.83 (t, 1H, J¼7.6 Hz), 7.60 (t, 1H, J¼7.6 Hz), 0.32 (s,
9H); 13C NMR (125 MHz, CDCl3): d 191.3, 150.4, 144.0,
137.1, 133.3, 130.0, 129.8, 129.2, 128.7, 126.9, 102.7,
100.4, 0.01 (3C); MS: m/e (relative intensity): 254 (MH+,
100). Anal. Calcd for C15H15NOSi: C, 71.11; H, 5.97; N,
5.53. Found: C, 70.92; H, 6.12; N, 5.42.
4.3.3. p-Tolyl-(2-trimethylsilylethynylquinoline-3-yl)meth-
anone (15). Starting from aldehyde 14 (506 mg, 2 mmol)
and p-tolylmagnesium bromide (0.5 M, 4.4 mL, 2.2 mmol),
following the general procedure 2, the product 15 was ob-
tained as a thick brown liquid (0.47 g, 69%). Rf (20%
EtOAc/petroleum ether) 0.72; IR (KBr, cmꢀ1): 2164,
1
1662; H NMR (500 MHz, CDCl3): d 8.29 (s, 1H), 8.17
4.3. General procedure 2—synthesis of alkynyl pyridine/
quinoline carbonyl derivatives 12, 15
(dd, 1H, J¼8.0, 1.0 Hz), 7.87 (dd, 1H, J¼8.0, 1.0 Hz),
7.81 (ddd, 1H, J¼8.0, 7.0, 1.0 Hz), 7.75 (d, 2H, J¼
8.0 Hz), 7.61 (ddd, 1H, J¼8.0, 7.0, 1.0 Hz), 7.27 (d, 2H,
J¼8.0 Hz), 2.44 (s, 3H), 0.0 (s, 9H); 13C NMR (125 MHz,
CDCl3): d 195.7, 149.1, 145.4, 141.0, 137.2, 136.5, 135.4,
132.1, 131.2 (2C), 130.1, 129.9 (2C), 128.9, 128.8, 127.1,
103.0, 102.4, 22.5, 0.0 (3C). Anal. Calcd for C22H21NOSi:
C, 76.93; H, 6.16; N, 4.08. Found: C, 76.78; H, 6.35; N, 3.87.
To a stirred solution of aldehyde (2 mmol) in dry diethyl
ether (10 mL) was added dropwise a solution of arylmagne-
sium bromide (2.2 mmol) in dry diethyl ether [prepared from
arylbromide (3 mmol) and magnesium (4 mmol) in 10 mL
dry diethyl ether] over a period of 20 min at 0 ꢁC. After
3 h stirring the mixture was allowed to come at room temper-
ature and then quenched with saturated aqueous NH4Cl
(5 mL). The organic layer was separated and the aqueous
layer was extracted with diethyl ether (3ꢂ10 mL). The com-
bined organic layer was washed with brine (5 mL) and dried
over anhydrous Na2SO4. The solvent was removed under re-
duced pressure and the crude alcohol was used in the next
step. A solution of crude alcohol in dry CH2Cl2 (2 mL)
4.4. General procedure 3—coupling of carbene complex
with alkynyl pyridine/quinoline carboxaldehyde and
maleimides/dimethyl maleate
To a refluxing solution of alkynyl aldehyde 11 or 14
(1 mmol) and maleimide/dimethyl maleate (1 mmol) in
THF (5 mL) was added a solution of carbene complex 5

G. P. Jana, B. K. Ghorai / Tetrahedron 63 (2007) 12015–12025
12021
(1.1 mmol) in THF (10 mL) over a period of 1 h. After the
addition was complete, the mixture was heated to reflux
for a period of 12 h. The mixture was allowed to cool to
room temperature and concentrated on a rotary evaporator.
EtOAc (20 mL) was added and the residue was filtered
through Celite (1.0 g). The solvent was removed on a rotary
evaporator, and the crude products were dissolved in ether
(20 mL). To this solution of crude product in ether was added
aqueous HCl (1:1) (0.5 mL) and the mixture was stirred for
6 h at room temperature. The organic layer was separated.
The aqueous layer was neutralized with saturated NaHCO3
solution (3 mL) and extracted with ethyl acetate
(3ꢂ10 mL). The combined organic layer (diethyl ether layer
and ethyl acetate layer) was washed with water (3 mL) and
brine (3 mL), and dried over anhydrous Na2SO4. Evapora-
tion of solvent and purification by chromatography gave
the pure products.
complex 5 (138 mg, 0.55 mmol), alkynyl aldehyde 11
(101 mg, 0.5 mmol) and dimethyl maleate (77 mg,
0.5 mmol). The crude product was purified using column
chromatography (silica gel, ethyl acetate/petroleum ether
2:3) to yield the white needle quinoline derivative 27
(30 mg, 20%). Mp 115 ꢁC; Rf (40% EtOAc/petroleum ether)
1
0.68; IR (KBr, cmꢀ1): 1733, 1717; H NMR (300 MHz,
CDCl3): d 9.01 (d, 1H, J¼3.3 Hz), 8.47 (s, 1H), 8.25 (d,
1H, J¼7.6 Hz), 7.52 (dd, 1H, J¼8.2, 4.2 Hz), 4.44 (s, 2H),
3.96 (s, 6H), 2.23 (s, 3H); 13C NMR (125 MHz, CDCl3):
d 205.2, 169.0, 166.0, 152.4, 147.9, 135.6, 134.3, 133.5,
130.9, 127.4, 126.1, 122.8, 52.8 (2C), 43.2, 29.7; MS
(FAB): m/e (relative intensity): 302 (62, MH+), 270 (100),
105 (42). Anal. Calcd for C16H15NO5: C, 63.78; H, 5.02;
N, 4.65. Found: C, 63.69; H, 5.18; N, 4.87.
4.4.4. Coupling of carbene complex 5 with 2-trimethyl-
silylethynylquinoline-3-carboxaldehyde (14) and N-phe-
nylmaleimide (Table 2, entry A). General procedure 3
4.4.1. Coupling of carbene complex 5 with 2-trimethyl-
silylethynylpyridine-3-carboxaldehyde (11) and N-phe-
nylmaleimide (Table 1, entry A). General procedure 3 was
followed using carbene complex 5 (275 mg, 1.1 mmol),
alkynyl aldehyde 11 (203 mg, 1 mmol) and N-phenylmalei-
mide (173 mg, 1 mmol). The crude product was purified
using column chromatography (silica gel, ethyl acetate/
petroleum ether 1:3) to yield the quinoline derivative 21
(115 mg, 35%) and the oxa-bridged compound 20 (17 mg,
5%) as white solids. Compound 21: mp 232 ꢁC (decom-
posed); Rf (25% EtOAc/petroleum ether) 0.48; IR (KBr,
was followed using carbene complex
5
(138 mg,
0.55 mmol), alkynyl aldehyde 14 (127 mg, 0.50 mmol)
and N-phenylmaleimide (87 mg, 0.50 mmol). The crude
product was purified using column chromatography (silica
gel, ethyl acetate/petroleum ether 1: 3) to yield benzoquino-
line derivative 29A (19 mg, 10%) and oxa-bridged com-
pound 28A (80 mg, 40%) as white solids. Compound 29A:
mp 137–138 ꢁC; Rf (25% EtOAc/petroleum ether) 0.71; IR
1
(KBr, cmꢀ1): 1764, 1714; H NMR (500 MHz, CDCl3):
d 8.90 (s, 1H), 8.49 (s, 1H), 8.24 (d, 1H, J¼8.5 Hz), 8.03
(d, 1H, J¼8.5 Hz), 7.87 (t, 1H, J¼7.5 Hz), 7.64 (t, 1H,
J¼7.5 Hz), 7.57–7.46 (m, 4H), 7.43 (t, 1H, J¼7.0 Hz),
5.15 (s, 2H), 2.54 (s, 3H); 13C NMR (125 MHz, CDCl3):
d 205.1, 167.1, 166.1, 149.7, 148.9, 139.0, 137.0, 131.9,
131.7, 130.2, 129.1 (2C), 128.3, 128.2, 127.7, 127.44,
127.4, 127.3, 126.6 (2C), 126.1, 125.2, 40.9, 30.7; MS:
m/e (relative intensity): 381 (MH+, 67), 254 (100), 186
(24), 153 (27). Anal. Calcd for C24H16N2O3: C, 75.78; H,
4.24; N, 7.36. Found: C, 75.92; H, 4.21; N, 7.28. Compound
28A: mp 163–165 ꢁC; Rf (25% EtOAc/petroleum ether)
1
cmꢀ1): 1716; H NMR (300 MHz, CDCl3): d 8.99 (d, 1H,
J¼3.6 Hz), 8.32 (s, 1H), 8.31 (d, 1H, J¼6.0 Hz), 7.55 (dd,
1H, J¼8.1, 4.1 Hz), 7.50–7.32 (m, 5H), 4.97 (s, 2H), 2.40
(s, 3H); 13C NMR (75 MHz, CDCl3): d 205.1, 167.5,
166.4, 152.5, 149.8, 138.4, 136.5, 131.8, 131.0, 129.4,
129.3, 128.9, 128.6, 128.0, 126.8 (2C), 124.3, 123.8, 40.9,
30.8; MS (FAB): m/e (relative intensity): 331 (42, MH+),
176 (15), 154 (100), 136 (99), 107 (58). Anal. Calcd for
C20H14N2O3: C, 72.72; H, 4.27; N, 8.48. Found: C, 72.56;
H, 4.43; N, 8.27. Compound 20: mp>250 ꢁC; Rf (25%
1
1
EtOAc/petroleum ether) 0.20; IR (KBr, cmꢀ1): 1711; H
0.47; IR (KBr, cmꢀ1): 1712; H NMR (400 MHz, CDCl3):
NMR (300 MHz, CDCl3): d 8.47 (br s, 1H), 7.72 (br s,
1H), 7.27–7.60 (m, 6H), 5.82 (s, 1H), 3.38–3.75 (m, 4H),
2.35 (s, 3H); 13C NMR (75 MHz, CDCl3): d 203.2, 175.4,
174.4, 165.9, 149.3, 138.3, 132.2, 130.0 (2C), 129.7,
128.8, 127.3 (2C), 123.4, 87.9, 80.6, 52.2, 50.0, 42.8, 31.7;
MS (FAB): m/e (relative intensity): 371 (100, M++Na),
349 (46, MH+), 198 (56), 176 (56). Anal. Calcd for
C20H16N2O4: C, 68.96; H, 4.63; N, 8.04. Found: C, 68.79;
H, 4.84; N, 7.85.
d 8.13 (d, 1H, J¼8.0 Hz), 8.04 (s, 1H), 7.85 (d, 1H,
J¼8.0 Hz), 7.73 (t, 1H, J¼7.2 Hz), 7.59 (t, 1H, J¼7.2 Hz),
7.50 (t, 2H, J¼7.2 Hz), 7.42 (t, 1H, J¼7.2 Hz), 7.32 (d,
2H, J¼7.2 Hz), 5.95 (s, 1H), 3.79 (d, 1H, J¼17.7 Hz),
3.59 (d, 1H, J¼6.8 Hz), 3.55 (d, 1H, J¼17.7 Hz), 3.33 (d,
1H, J¼6.8 Hz), 2.36 (s, 3H); 13C NMR (125 MHz,
CDCl3): d 202.7, 174.7, 173.6, 164.7, 147.2, 134.0, 131.6,
129.7, 129.7, 129.2 (2C), 128.8, 128.2, 127.2, 127.0, 126.5
(2C), 126.4, 87.2, 79.8, 51.3, 48.4, 41.7, 31.1; MS (FAB):
m/e (relative intensity): 399 (100, MH+), 381 (5), 367 (18),
226 (25), 182 (35). Anal. Calcd for C24H18N2O4: C, 72.35;
H, 4.55; N, 7.03. Found: C, 72.14; H, 4.73; N, 6.86.
4.4.2. Coupling of carbene complex 5 with 2-trimethyl-
silylethynylpyridine-3-carboxaldehyde (11) and N-phe-
nylmaleimide. General procedure 3 was followed using
carbene complex 5 (192 mg, 0.77 mmol), alkynyl aldehyde
11 (142 mg, 0.7 mmol) and N-phenylmaleimide (121 mg,
0.7 mmol) with the exception that acid hydrolysis was not
employed as the last step. The crude product was purified us-
ing column chromatography (silica gel, ethyl acetate/petro-
leum ether 1:3) to yield the oxa-bridged compound 20
(37 mg, 15%) and quinoline derivative 21 (65 mg, 28%).
4.4.5. Coupling of carbene complex 5 with 2-trimethyl-
silylethynylquinoline-3-carboxaldehyde (14) and N-meth-
ylmaleimide (Table 2, entry B). General procedure 3 was
followed using carbene complex 5 (217 mg, 0.87 mmol),
alkynyl aldehyde 14 (200 mg, 0.79 mmol) and N-methyl-
maleimide (88 mg, 0.79 mmol). The crude product was puri-
fied using column chromatography (silica gel, ethyl acetate/
petroleum ether 25:75) to yield benzoquinoline derivative
29B (90 mg, 36%) as a thick brown liquid and oxa-bridged
compound 28B (16 mg, 6%). However, the oxa-bridged
4.4.3. Dimethyl 8-(2-oxopropyl)quinoline-6,7-dicarboxy-
late (27). General procedure 3 was followed using carbene

12022
G. P. Jana, B. K. Ghorai / Tetrahedron 63 (2007) 12015–12025
compound 28B in chloroform is slowly converted to the
29B. Compound 29B: Rf (25% EtOAc/petroleum ether)
0.66; IR (KBr, cmꢀ1): 1762, 1703, 1602; 1H NMR
(400 MHz, CDCl3): d 8.92 (s, 1H), 8.44 (s, 1H), 8.23 (d,
1H, J¼8.4 Hz), 8.04 (d, 1H, J¼8.4 Hz), 7.86 (t, 1H,
J¼7.6 Hz), 7.65 (t, 1H, J¼7.6 Hz), 5.08 (s, 2H), 3.25 (s,
3H), 2.53 (s, 3H); 13C NMR (125 MHz, CDCl3): d 205.7,
168.7, 167.7, 150.1, 149.3, 139.5, 136.7, 132.2, 130.7,
130.6, 128.6, 128.4, 128.3, 128.1, 127.1, 124.9, 41.3, 31.2,
24.8; MS: m/e (relative intensity): 319 (MH+, 100), 292
(40), 138 (21), 125 (43). Anal. Calcd for C19H14N2O3: C,
71.69; H, 4.43; N, 8.80. Found: C, 71.63; H, 4.56; N, 8.96.
Compound 28B (contaminated with 11% 29B): Rf (25%
EtOAc/petroleum ether) 0.20; IR (KBr, cmꢀ1): 1762, 1706,
1602; 1H NMR (400 MHz, CDCl3): d 8.05 (d, 1H,
J¼8.0 Hz), 7.96 (s, 1H), 7.80 (d, 1H, J¼8.0 Hz), 7.70 (t,
1H, J¼8.0 Hz), 7.56 (t, 1H, J¼7.6 Hz), 5.80 (s, 1H), 3.67
(d, 1H, J¼17.6 Hz), 3.48 (d, 1H, J¼17.6 Hz), 3.42 (d, 1H,
J¼6.8 Hz), 3.16 (d, 1H, J¼6.8 Hz), 3.04 (s, 3H), 2.33 (s,
3H); MS: m/e (relative intensity): 337 (MH+, 100), 319
(30), 295 (61), 286 (18), 277 (10).
151.7, 149.3, 139.7, 136.5, 135.3, 133.2, 131.4, 130.9,
129.8 (2C), 128.8 (2C), 128.7, 128.2 (2C), 128.1, 127.4,
126.6 (2C), 123.4, 123.2, 40.6, 29.6; MS: m/e (relative inten-
sity): 407 (MH+, 100), 325 (5), 309 (8); Anal. Calcd for
C26H18N2O3: C, 76.83; H, 4.46; N, 6.89. Found: C, 76.59;
H, 4.62; N, 6.68. Compound 22B: mp 186–188 ꢁC; Rf
(25% EtOAc/petroleum ether) 0.21; IR (KBr, cmꢀ1): 1713;
1H NMR (400 MHz, CDCl3): d 8.44 (d, 1H, J¼4.4 Hz),
7.61 (d, 2H, J¼7.2 Hz), 7.49 (t, 3H, J¼7.2 Hz), 7.45–7.36
(m, 3H), 7.32 (m, 1H), 7.13 (d, 3H, J¼7.2 Hz), 3.89 (d,
1H, J¼4.0 Hz), 3.70 (d, 1H, J¼17.8 Hz), 3.60 (d, 1H,
J¼17.8 Hz), 3.56 (d, 1H, J¼4.0 Hz), 2.38 (s, 3H); 13C
NMR (75 MHz, CDCl3): d 203.1, 173.3, 171.9, 164.8,
148.0, 140.6, 133.0, 131.6, 129.0 (2C), 128.6 (2C), 128.5
(2C), 127.3, 126.3 (2C), 125.7 (2C), 122.3, 90.2, 86.3,
52.9, 50.3, 42.4, 30.8; MS (FAB): m/e (relative intensity):
425 (MH+, 38), 252 (35), 219 (50), 191 (70), 159 (67), 147
(92), 105 (100). Anal. Calcd for C26H20N2O4: C, 73.57; H,
4.75; N, 6.60. Found: C, 73.35; H, 4.95; N, 6.41.
4.5.2. Coupling of carbene complex 5 with phenyl-(2-tri-
methylsilylethynylpyridine-3-yl)methanone (12A) and
N-methylmaleimide (Table 1, entry C). General procedure
4 was followed using carbene complex 5 (175 mg,
0.7 mmol), alkynyl carbonyl derivatives 12A (177 mg,
0.63 mmol) and N-methylmaleimide (70 mg, 0.63 mmol).
The crude product was purified using column chromato-
graphy (silica gel, ethyl acetate/petroleum ether 1:3) to yield
the quinoline derivative 23C (91 mg, 42%) and the oxa-
bridged compound 22C (23 mg, 10%) as white solids. Com-
pound 23C: mp 160–163 ꢁC; Rf (25% EtOAc/petroleum
4.5. General procedure 4—coupling of carbene complex
with alkynyl pyridine/quinoline carbonyl derivatives
and maleimides/dimethyl maleate
To a refluxing solution of alkynyl carbonyl derivatives 12 or
15 (1 mmol) in THF (2 mL) was added a solution of carbene
complex 5 (1.1 mmol) in THF (10 mL) over a period of
0.5 h. After the addition was complete, the mixture was
heated to reflux for 0.5 h. The dienophile (1 mmol) in THF
(3 mL) was then added to the solution at reflux. The mixture
was heated at reflux for an additional 12 h and then allowed
to cool to room temperature and concentrated on a rotary
evaporator. EtOAc (20 mL) was added and the residue was
filtered through Celite (1.0 g). The solvent was removed
on a rotary evaporator, and the crude products were dis-
solved in ether (20 mL). To this solution of crude product
in ether was added aqueous HCl (1:1) (0.5 mL) and the mix-
ture was stirred for 6 h at room temperature. The organic
layer was separated. The aqueous layer was neutralized
with saturated NaHCO3 solution (3 mL) and extracted
with ethyl acetate (3ꢂ10 mL). The combined organic layer
(diethyl ether layer and ethyl acetate layer) was washed
with water (3 mL) and brine (3 mL), and dried over anhy-
drous Na2SO4. Evaporation of solvent and purification by
chromatography gave the pure products.
1
ether) 0.62; IR (KBr, cmꢀ1): 1762, 1711, 1611; H NMR
(400 MHz, CDCl3): d 8.99 (dd, 1H, J¼4.0, 1.6 Hz), 8.09
(dd, 1H, J¼8.4, 1.6 Hz), 7.58–7.50 (m, 3H), 7.46 (dd, 1H,
J¼8.4, 4.0 Hz), 7.39–7.33 (m, 2H), 5.03 (s, 2H), 3.13 (s,
3H), 2.49 (s, 3H); 13C NMR (125 MHz, CDCl3): d 205.7,
168.7, 167.3, 152.0, 149.4, 137.0, 136.4, 135.2, 133.9,
131.2, 130.3 (2C), 129.6, 129.2, 128.9, 128.7 (2C), 123.6,
41.3, 31.0, 24.5; MS: m/e (relative intensity): 345 (MH+,
100), 282 (51), 250 (61). Anal. Calcd for C21H16N2O3: C,
73.24; H, 4.68; N, 8.13. Found: C, 73.11; H, 4.85; N, 7.98.
Compound 22C: mp 171 ꢁC; Rf (25% EtOAc/petroleum
1
ether) 0.20; IR (KBr, cmꢀ1): 1769, 1725, 1700; H NMR
(400 MHz, CDCl3): d 8.40 (dd, 1H, J¼5.2, 1.2 Hz), 7.58–
7.54 (m, 2H), 7.51–7.46 (m, 2H), 7.44–7.41 (m, 1H), 7.39
(dd, 1H, J¼7.6, 1.2 Hz), 7.08 (dd, 1H, J¼7.6, 5.2 Hz), 3.69
(d, 1H, J¼6.8 Hz), 3.62 (d, 1H, J¼17.6 Hz), 3.54 (d, 1H,
J¼17.6 Hz), 3.43 (d, 1H, J¼6.8 Hz), 2.90 (s, 3H), 2.38 (s,
3H); 13C NMR (100 MHz, CDCl3): d 203.1, 174.1, 172.9,
164.6, 147.9, 140.3, 132.9, 128.4, 128.3 (2C), 127.1, 125.7
(2C), 122.1, 89.6, 85.7, 52.6, 50.3, 42.2, 30.8, 25.0; MS: m/e
(relative intensity: 363 (MH+, 100), 321 (25), 288 (8), 252
(90), 210 (68), 153 (27). Anal. Calcd for C21H18N2O4: C,
69.60; H, 5.01; N, 7.73. Found: C, 69.89; H, 4.70; N, 7.93.
4.5.1. Coupling of carbene complex 5 with phenyl-(2-tri-
methylsilylethynylpyridine-3-yl)methanone (12A) and
N-phenylmaleimide (Table 1, entry B). General procedure
4 was followed using carbene complex 5 (110 mg,
0.44 mmol), alkynyl carbonyl derivatives 12A (110 mg,
0.39 mmol) and, N-phenylmaleimide (68 mg, 0.39 mmol).
The crude product was purified using column chromato-
graphy (silica gel, ethyl acetate/petroleum ether 1:3) to yield
the quinoline derivative 23B (18 mg, 11%) and the oxa-
bridged compound 22B (71 mg, 43%) as white solids. Com-
pound 23B: mp 212–215 ꢁC; Rf (25% EtOAc/petroleum
4.5.3. Coupling of carbene complex 5 with p-tolyl-(2-tri-
methylsilylethynylpyridine-3-yl)methanone (12B) and N-
phenylmaleimide (Table 1, entry D). General procedure 4
was followed using carbene complex 5 (170 mg, 0.68 mmol),
alkynyl carbonyl derivatives 12B (180 mg, 0.61 mmol) and
N-phenylmaleimide (107 mg, 0.62 mmol). The crude prod-
uct was purified using column chromatography (silica gel,
ethyl acetate/petroleum ether 1:3) to yield the quinoline
1
ether) 0.63; IR (KBr, cmꢀ1): 1723; H NMR (400 MHz,
CDCl3): d 9.03 (dd, 1H, J¼4.4, 1.6 Hz), 8.14 (dd, 1H,
J¼8.0, 1.6 Hz), 7.57–7.32 (m, 11H), 5.01 (s, 2H) 2.50 (s,
3H); 13C NMR (100 MHz, CDCl3): d 205.3, 167.0, 165.6,

G. P. Jana, B. K. Ghorai / Tetrahedron 63 (2007) 12015–12025
12023
derivative 23D (46 mg, 18%) and the oxa-bridged com-
pound 22D (80 mg, 30%) as white solids. Compound 23D:
mp 158–159 ꢁC; Rf (25% EtOAc/petroleum ether) 0.67; IR
N-methylmaleimide (Table 2, entry C). General procedure
4 was followed using carbene complex 5 (200 mg,
0.80 mmol), alkynyl carbonyl derivatives 15 (250 mg,
0.73 mmol) and N-methylmaleimide (81 mg, 0.73 mmol).
The crude product was purified using column chromato-
graphy (silica gel, ethyl acetate/petroleum ether 3:7) to yield
the benzoquinoline derivative 29C (143 mg, 48%) as a yel-
low solid. Mp>250 ꢁC; Rf (30% EtOAc/petroleum ether)
0.71; IR (KBr, cmꢀ1): 1758, 1699, 1646; 1H NMR
(500 MHz, CDCl3): d 8.73 (s, 1H), 8.32 (d, 1H, J¼8.0
Hz), 7.90 (d, 1H, J¼8.0 Hz), 7.87 (t, 1H, J¼7.3 Hz), 7.59
(t, 1H, J¼7.3 Hz), 7.42 (d, 2H, J¼7.5 Hz), 7.36 (d, 2H,
J¼7.5 Hz), 5.21 (s, 2H), 3.17 (s, 3H), 2.58 (s, 3H) 2.54 (s,
3H); 13C NMR (125 MHz, CDCl3): d 206.1, 168.6, 167.2,
149.6, 149.2, 140.7, 139.2, 138.5, 135.7, 132.3, 131.1,
130.4 (2C), 130.3, 129.6 (2C), 129.0, 128.7, 128.4, 127.8,
127.5, 122.7, 41.4, 31.7, 24.6, 22.0; MS: m/e (relative inten-
sity): 409 (MH+, 100), 309 (10), 288 (5). Anal. Calcd for
C26H20N2O3: C, 76.45; H, 4.94; N, 6.86. Found: C, 76.24;
H, 5.13; N, 6.68.
1
(KBr, cmꢀ1): 1711; H NMR (300 MHz, CDCl3): d 9.04
(d, 1H, J¼3.0 Hz), 8.20 (d, 1H, J¼8.4 Hz), 7.51 (d, 1H,
J¼8.4, 3.9 Hz), 7.48–7.29 (m, 9H), 5.11 (s, 2H), 2.50 (s,
3H), 2.47 (s, 3H); 13C NMR (125 MHz, CDCl3): d 205.3,
167.0, 165.6, 151.7, 149.3, 140.0, 138.5, 136.5, 135.1,
131.4, 131.0, 130.1, 129.7 (2C), 128.9 (2C), 128.7 (2C),
128.0, 127.4, 126.5 (2C), 123.3, 123.1, 40.6, 30.4, 21.3;
MS: m/e (relative intensity): 421 (100, MH+), 403 (5), 266
(4), 153 (54). Anal. Calcd for C27H20N2O3: C, 77.13; H,
4.79; N, 6.66. Found: C, 76.94; H, 4.95; N, 6.78. Compound
22D: mp 181 ꢁC; Rf (25% EtOAc/petroleum ether) 0.21; IR
(KBr, cmꢀ1): 1779, 1725, 1713; 1H NMR (300 MHz,
CDCl3): d 8.42 (d, 1H, J¼4.5 Hz), 7.55–7.26 (m, 9H),
7.23–7.08 (m, 2H), 3.89 (d, 1H, J¼6.7 Hz), 3.68 (d, 1H,
J¼17.8 Hz), 3.59 (d, 1H, J¼17.6 Hz), 3.53 (d, 1H,
J¼6.8 Hz), 2.39 (s, 6H); 13C NMR (100 MHz, CDCl3):
d 203.2, 173.4, 171.9, 164.7, 147.9, 140.5, 138.1, 131.4,
129.9, 129.1 (2C), 128.8 (2C), 128.4, 127.0, 126.2 (2C),
125.4 (2C), 122.1, 90.0, 86.0, 52.7, 50.1, 42.3, 30.7, 21.6.
MS (FAB) m/e (relative intensity): 439 (MH+, 56), 421
(MH+ꢀH2O, 10), 349 (20), 322 (26), 266 (62), 222 (47),
136 (100). Anal. Calcd for C27H22N2O4: C, 73.96; H, 5.06;
N, 6.39. Found: C, 73.71; H, 4.96; N, 6.61.
4.6. Dimethyl 8-(2-oxopropyl)-5-phenylquinoline-
6,7-dicarboxylate (26)
To a solution of the oxa-bridged compound 25 (R¼Ph)
(40 mg, 0.1 mmol) in ether (10 mL) was added aqueous HCl
(1:1) (0.1 mL) and the mixturewas stirred for 6 h at room tem-
perature. The organic layer was separated. The aqueous layer
was neutralized with saturated NaHCO3 solution (1.0 mL)
and extracted with ethyl acetate (3ꢂ5 mL). The combined or-
ganic layer (diethyl ether layer and ethyl acetate layer) was
washed with water (1 mL) and brine (1 mL), and dried over
anhydrous Na2SO4. Evaporation of solvent and purification
by chromatography (silica gel, ethyl acetate/petroleum ether
2:8) to yield the quinoline derivative 26 (17 mg) as a yellow
solid. In this reaction, starting material 25 (10 mg) was recov-
ered. The yield of 26 with respect to recovered starting mate-
rialis60%.Mp107–109 ꢁC;Rf (20%EtOAc/petroleumether)
4.5.4. Coupling of carbene complex 5 with phenyl-(2-tri-
methylsilylethynylpyridine-3-yl)methanone (12A) and
dimethyl maleate (Scheme 5). General procedure 4 was
followed using carbene complex 5 (112 mg, 0.45 mmol),
alkynyl carbonyl derivatives 12A (100 mg, 0.36 mmol) and
dimethyl maleate (52 mg, 0.36 mmol), with the exception
that acid hydrolysis was not employed at the last step. The
crude product was purified using column chromatography
(silica gel, ethyl acetate/petroleum ether 1:4) to yield a mix-
ture of the oxa-bridged enol ether 24 as a brownish thick liq-
uid and the oxa-bridged ketone 25 (R¼Ph) as a white solid.
However, the enol ether 24 is not stable enough in chloro-
form and it readily converted to the stable 25 (50 mg, 35%
from 12A). Compound 24: Rf (20% EtOAc/petroleum ether)
1
0.48; IR (KBr, cmꢀ1): 1734, 1716; H NMR (500 MHz,
CDCl3): d 8.96 (s, 1H), 7.93 (d, 1H, J¼8.0 Hz), 7.52–7.42
(m, 3H), 7.40 (dd, 1H, J¼8.0, 3.5 Hz), 7.35–7.28 (m, 2H),
4.71 (s, 2H), 3.89 (s, 3H), 3.51 (s, 3H), 2.32 (s, 3H); 13C
NMR (125 MHz, CDCl3): d 205.3, 168.4, 167.9, 151.0,
146.6, 138.8, 136.3, 135.6, 134.7, 131.2, 130.1, 129.9 (2C),
128.2 (4C), 122.7, 52.7, 52.1, 43.1, 30.0; MS: m/e (relative
intensity): 378 (MH+, 57), 346 (100), 314 (12), 286 (7), 242
(5). Anal. Calcd for C22H19NO5: C, 70.02; H, 5.07; N, 3.71.
Found: C, 69.98; H, 5.19; N, 3.87.
1
0.41; IR (KBr, cmꢀ1): 1736, 1609; H NMR (300 MHz,
CDCl3): d 8.47 (d, 1H, J¼4.9 Hz), 7.68 (d, 2H, J¼7.5 Hz),
7.37–7.55 (m, 4H), 7.08 (dd, 1H, J¼7.4, 5.1 Hz), 3.84 (d,
1H, J¼5.1 Hz), 3.73 (d, 1H, J¼5.1 Hz), 3.72 (s, 3H), 3.70
(s, 3H), 3.60 (s, 3H), 2.19 (s, 3H), 0.13 (s, 9H); MS (FAB)
m/e (relative intensity): 482 (MH+, 30), 337 (100), 306
(50). Compound 25: mp 113–115 ꢁC; Rf (25% EtOAc/petro-
1
leum ether) 0.29; IR (KBr, cmꢀ1): 1734, 1712; H NMR
(500 MHz, CDCl3): d 8.42 (d, 1H, J¼5.0 Hz), 7.68 (d, 2H,
J¼5.0 Hz), 7.50–7.40 (m, 4H), 7.13 (dd, 1H, J¼7.5,
5.0 Hz), 4.17 (d, 1H, J¼5.0 Hz), 3.79 (s, 3H), 3.72 (d, 1H,
J¼17.0 Hz), 3.52 (s, 3H), 3.33 (d, 1H, J¼5.0 Hz), 3.26 (d,
1H, J¼17.0 Hz), 2.23 (s, 3H); 13C NMR (125 MHz,
CDCl3): d 203.6, 171.6, 170.6, 165.5, 148.0, 138.5, 135.1,
129.9, 129.1, 128.6 (2C), 127.5 (2C), 121.9, 89.5, 86.4,
54.2, 53.7, 52.5, 52.2, 42.5, 31.1; MS: m/e (relative inten-
sity): 396 (MH+, 57), 378 (MH+ꢀH2O, 2), 346 (15), 252
(100), 210 (29). Anal. Calcd for C22H21NO6: C, 66.83; H,
5.35; N, 3.54. Found: C, 67.11; H, 5.04; N, 3.75.
4.7. General procedure 5—the aromatization of the
oxa-bridged compounds 22 and 28 using DBU
To a stirred solution of oxa-bridged compounds (1 mmol) in
toluene (5 mL) was added dropwise DBU (10 mmol) at
room temperature. The mixture was heated at reflux for
1.5 h giving a reddish brown solution, cooled to room tem-
perature, washed with 10% aqueous HCl, dried over anhy-
drous Na2SO4, and concentrated under reduced pressure.
The crude products were purified by column chromato-
graphy using ethyl acetate/petroleum ether as eluent.
4.5.5. Coupling of carbene complex 5 with p-tolyl-(2-tri-
methylsilylethynylquinoline-3-yl)methanone (15) and
4.7.1. 9-(2-Oxopropyl)-5,7-diphenylpyrrolo[3,4-g]quino-
line-6,8-dione (23B). General procedure 5 was followed

12024
G. P. Jana, B. K. Ghorai / Tetrahedron 63 (2007) 12015–12025
using oxa-bridged compound 22B (40 mg, 0.09 mmol) and
DBU (0.14 mL, 0.94 mmol). The crude product was purified
by using column chromatography (silica gel, ethyl acetate/
petroleum ether 1:4) to yield 23B (19 mg, 50%).
of carbene complex 5 (118 mg, 0.47 mmol) in THF (5 mL)
over a period of 1 h. After the addition was complete, the
mixture was heated at reflux for a period of 4 h. The mixture
was allowed to cool to room temperature and concentrated
on a rotary evaporator. EtOAc (20 mL) was added and the
residue was filtered through Celite (1.0 g). The solvent was
removed, the crude product was dissolved in chloroform
(20 mL) and stirred with silica gel for 6 h. The solvent was
removed and the residue purified by chromatography (silica
gel, ethyl acetate/petroleum ether 2:8), which gave a white
needles 34 (38 mg, 31%). Mp 152 ꢁC; Rf (20% EtOAc/petro-
4.7.2. 9-(2-Oxopropyl)-7-phenyl-5-p-tolylpyrrolo[3,4-g]-
quinoline-6,8-dione (23D). General procedure 5 was
followed using oxa-bridged compound 22D (122 mg,
0.28 mmol) and DBU (0.42 mL, 2.78 mmol). The crude prod-
uct was purified by using column chromatography (silica gel,
ethyl acetate/petroleum ether 1:4) to yield 23D (56 mg, 48%).
1
leum ether) 0.62; IR (KBr, cmꢀ1): 1670, 1580; H NMR
4.7.3. 4-(2-Oxopropyl)-2-phenylpyrrolo[3,4-b]acridine-
1,3-dione (29A). General procedure 5 was followed using
oxa-bridged compound 28A (30 mg, 0.07 mmol) and DBU
(0.11 mL, 0.75 mmol). The crude product was purified by
using column chromatography (silica gel, ethyl acetate/
petroleum ether 1:4) to yield 29A (11 mg, 40%).
(500 MHz, CDCl3): d 8.75 (dd, 1H, J¼3.6, 1.0 Hz), 7.76–
7.70 (m, 3H), 7.60–7.50 (m, 2H), 7.42 (t, 2H, J¼6.0 Hz),
6.88 (s, 1H), 3.82 (s, 3H), 2.23 (s, 3H); 13C NMR
(125 MHz, CDCl3): d 195.8, 188.1, 176.8, 154.5, 149.0,
137.0, 136.5, 135.9, 132.9, 129.1 (2C), 128.4 (2C), 125.2,
95.1, 55.9, 20.3; MS: m/e (relative intensity): 282 (MH+,
100), 210 (75). Anal. Calcd for C17H15NO3: C, 72.58; H,
5.37; N, 4.98. Found: C, 72.61; H, 5.32; N, 4.91.
4.8. 5-Hydroxy-5-phenyl-10-trimethylsilyl-6,6a,7,8-
tetrahydro-5H-benzo[h]quinoline-9-one (33)
To a solution of alkynyl ketone 12A (200 mg, 0.71 mmol) in
THF (3 mL) at reflux was added a solution of g,d-unsatu-
rated carbene complex 302j (250 mg, 0.86 mmol) in THF
(10 mL) over a period of 1 h. After the addition was com-
plete, the mixture was heated at reflux for 18 h. The reaction
mixture was cooled to room temperature. The THF was
removed under reduced pressure, ethyl acetate (10 mL)
was added and the residue was filtered through Celite
(1.0 g). The solvent was removed on a rotary evaporator,
and the crude products were dissolved in ether (20 mL).
To this solution of crude product in ether was added aqueous
HCl (1:1) (0.5 mL) and the mixture was stirred for 4 h at
room temperature. The organic layer was separated. The
aqueous layer was neutralized with saturated NaHCO3 solu-
tion (3 mL) and extracted with ethyl acetate (3ꢂ10 mL). The
combined organic layer (diethyl ether layer and ethyl acetate
layer) was washed with water (3 mL) and brine (3 mL), and
dried over anhydrous Na2SO4. Evaporation of solvent and
purified by column chromatography (silica gel, ethyl ace-
tate/petroleum ether 3:7) afforded a white solid alcohol 33
(168 mg, 65%). Mp 160 ꢁC; Rf (30% EtOAc/petroleum
ether) 0.57; IR (KBr, cmꢀ1): 3444, 1639; 1H NMR
(400 MHz, CDCl3): d 8.60 (dd, 1H, J¼4.4, 1.6 Hz), 7.79
(dd, 1H, J¼8.0, 1.6 Hz), 7. 34 (dd, 1H, J¼8.0, 4.4 Hz),
7.32–7.26 (m, 3H), 7.13–7.06 (m, 2 H), 2.50 (s, 1H
exchangeable with D2O), 2.50–2.36 (m, 3H), 2.25 (ddd,
1H, J¼18.0, 14.4, 5.2 Hz), 2.14 (t, 1H, J¼12.4 Hz), 1.87
(m, 1H), 1.75 (m, 1H), 0.18 (s, 9H); 13C NMR (125 MHz,
CDCl3): d 203.6 (s), 162.7 (s), 151.03 (s), 147.7 (d),146.0
(s) 142.8 (s), 139.9 (s) 136.0 (d), 128.3 (d, 2C), 127.8 (d),
126.7 (d, 2C), 124.9 (d), 75.1 (s), 48.3 (t), 37.5 (t), 35.8
(d), 28.9 (t), 2.8 (q, 3C); MS: m/e (relative intensity): 364
(100, MH+), 348 (MH+ꢀH2O, 10), 314, 153. Anal. Calcd
for C22H25NO2Si: C, 72.69; H, 6.93; N, 3.85. Found: C,
72.58; H, 7.05; N, 3.71.
Acknowledgements
Financial support from CSIR [No. 01 (1874)/03-EMR-II]
and UGC [No. F. 12-24/2004(SR)], Government of India is
gratefully acknowledged. We thank Soumita Mukherjee for
experimental assistance. We thank Professor J. W. Herndon,
Department of Chemistry and Biochemistry, New Mexico
State University, Las Cruces, New Mexico, USA for help.
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