Synthesis of 1-azaxanthones by condensation of 1,3-bis(trimethylsilyloxy)-1,3-butadienes with 3-(cyano)benzopyrylium triflates and subsequent domino 'retro-Michael/nitrile-addition/heterocyclization' reaction

Article abstract of DOI:10.1016/j.tet.2008.02.105

Functionalized 1-azaxanthones (5-oxo-5H-[1]-benzopyrano[2,3-b]pyridines) were prepared by TMSOTf-mediated condensation of 1,3-bis(trimethylsilyloxy)-1,3-butadienes with 3-cyanochromones and subsequent base-mediated domino 'retro-Michael/nitrile-addition/h

Full text of DOI:10.1016/j.tet.2008.02.105

Tetrahedron 64 (2008) 5416–5425
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Tetrahedron
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Synthesis of 1-azaxanthones by condensation of 1,3-bis(trimethylsilyloxy)-
1,3-butadienes with 3-(cyano)benzopyrylium triflates and subsequent
domino ‘retro-Michael/nitrile-addition/heterocyclization’ reaction
Muhammad A. Rashid a, Nasir Rasool a, Bettina Appel a, Muhammad Adeel a, Vahuni Karapetyan a,
,b,
Satenik Mkrtchyan a, Helmut Reinke a, Christine Fischer b, Peter Langer a
*
a
¨
Institut fu¨r Chemie, Universitat Rostock, Albert-Einstein-Str. 3a, 18059 Rostock, Germany
b Leibniz-Institut fu¨r Katalyse e. V. an der Universita¨t Rostock, Albert-Einstein-Str. 29a, 18059 Rostock, Germany
a r t i c l e i n f o
a b s t r a c t
Article history:
Functionalized 1-azaxanthones (5-oxo-5H-[1]-benzopyrano[2,3-b]pyridines) were prepared by TMSOTf-
mediated condensation of 1,3-bis(trimethylsilyloxy)-1,3-butadienes with 3-cyanochromones and sub-
sequent base-mediated domino ‘retro-Michael/nitrile-addition/heterocyclization’ reaction.
Ó 2008 Elsevier Ltd. All rights reserved.
Received 4 January 2008
Accepted 25 February 2008
Available online 18 March 2008
1. Introduction
2. Results and discussion
1-Azaxanthones (i.e., 5-oxo-5H-[1]-benzopyrano[2,3-b]pyri-
dines) are of considerable pharmacological relevance. For example,
they show anti-inflammatory activity and represent inhibitors
of the passive cutaneous anaphylaxis.1 1-Azaxanthones are avail-
able, based on pioneering work of Ghosh and co-workers,2a by
base-mediated reaction of 3-cyanochromones with active methy-
lene compounds.2 Despite its preparative utility, the scope of this
approach is limited to specific substrates and substitution patterns.
4-(Trimethylsilyloxy)benzopyrylium triflates can be readily gen-
erated by addition of trimethylsilyl-trifluoromethanesulfonate
(TMSOTf) to chromones. Their reaction with nucleophiles allows
the regioselective functionalization of carbon atom C-2 of the
chromone moiety. The formal [4þ2]-cycloaddition of 1,3-butadi-
enes with 4-(trimethylsilyloxy)benzopyrylium triflates was first
reported by Akiba and co-workers.3 Later, the TMSOTf-mediated
[4þ2]-cycloaddition of 1,3-butadienes with 3-cyanochromone, via
its 4-(trimethylsilyloxy)benzopyrylium triflate, has been reported.4
In the course of our interest in the development of new domino
reactions5 of 4-(silyloxy)benzopyrylium triflates,6 we recently
reported7 the TMSOTf-mediated reaction of 3-cyanochromones
with 1,3-bis(trimethylsilyloxy)-1,3-butadienes.8 These reactions
allow a convenient synthesis of functionalized 1-azaxanthones,
which are not readily available by other methods. Herein, full
details of our methodology and a comprehensive study related to
its preparative scope are reported.
The TMSOTf-mediated reaction of 1a with 1,3-bis(trimethyl-
silyloxy)-1,3-butadiene 2a, readily available in two steps from
methyl acetoacetate,9 afforded the condensation product 3a by
regioselective attack of the terminal carbon atom of 2a onto carbon
atom C-2 of 1a and subsequent hydrolysis. Treatment of an ethanol
solution of crude 3a with triethylamine afforded 1-azaxanthone 4a
(Scheme 1). The base-mediated retro-Michael reaction of 3a gave
open-chained intermediate B. The attack of the hydroxy group onto
the nitrile gave intermediate C. The attack of the imino nitrogen
atom onto the carbonyl group (intermediate D) and subsequent
aromatization byextrusion of water afforded 4a. The transformation
of 3a into 4a can be regarded as a domino ‘retro-Michael/nitrile-
addition/heterocyclization’ reaction.
The reaction of 1,3-bis(trimethylsilyloxy)-1,3-butadienes 2a–c,
prepared from methyl, ethyl and isopropyl acetoacetate, with
parent 3-cyanochromone (1a) and with the alkyl- and halogen-
substituted 3-cyanochromones 1b–g afforded products 3a–j, which
were transformed, by reaction with NEt3, into the 1-azaxanthones
4a–j (Scheme 2, Table 1). The reaction of parent 3-cyanochromone
(1a) with 1,3-bis(trimethylsilyloxy)-1,3-butadiene 2d, prepared
from methyl 3-oxopentanoate, afforded 3a. Treatment of 3a with
triethylamine afforded dibenzo[b,d]pyran-6-one 5a rather than the
expected methyl-substituted azaxanthone 4k. The formation of 5a
can be explained by a competing domino ‘retro-Michael/aldol/
lactonization’ reaction (Scheme 3).10 In contrast, the reaction of
2e (derived from ethyl 3-oxopentanoate) with chlorinated 3-
cyanochromone 1e afforded azaxanthone 4l (via 3l). The reaction
of parent cyanochromone 1a with 1,3-bis(silyl enol ether) 2f, pre-
pared from ethyl 3-oxohexanoate, afforded 3m. Treatment of the
* Corresponding author. Tel.: þ49 381 4986410; fax: þ49 381 4986412.
E-mail address: peter.langer@uni-rostock.de (P. Langer).
0040-4020/$ – see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2008.02.105

M.A. Rashid et al. / Tetrahedron 64 (2008) 5416–5425
5417
Table 1
Products and yields
O
OSiMe3
CN
CN
Me3SiOTf
R1
R2
R3
R4
R5
R6
% (4,5)a
-
1
2
4
5
OTf
+
CH2Cl2
20 °C, 1 h
O
1a
O
a
a
a
b
c
d
e
f
a
b
c
a
c
a
a
a
a
c
d
e
f
f
f
g
h
i
i
j
j
k
l
a
b
c
d
e
f
g
h
i
j
k
l
m
n
o
p
q
r
s
t
u
v
w
x
y
z
aa
ab
ac
ad
ae
af
ag
ah
ai
aj
ak
al
am
an
ao
ap
aq
H
H
H
H
H
H
H
H
H
H
Me
Me
Et
Et
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
Me
Et
OMe
OEt
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
Me
H
H
H
H
H
H
H
H
H
H
H
H
H
H
Me
H
H
Me
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
Cl
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
Cl
H
Cl
H
H
H
Cl
H
H
H
H
H
H
H
H
41
46
42
40
31
41
37
48
A
OiPr
OEt
Me
Et
iPr
Cl
Cl
Br
Br
H
Cl
H
Cl
Me
H
H
H
Cl
H
Cl
H
Me3SiO
OiPr
OEt
OSiMe3
OMe
1) 0 to 20 °C,
12 h
2) HCl (10%)
+
OEt
OEt
2a
g
g
a
e
a
e
h
a
a
a
e
a
e
a
a
a
e
b
a
a
f
OEt
34
32
OiPr
OMe
OEt
O
O
O
O
O
1) NEt3, EtOH
20 °C, 12 h
a
0 (34)b
41
CN
OMe
O
2) HCl (1 M)
b
OEt
OEt
OEt
OMe
OMe
OEt
17 (34)b
46
N
OMe
O
Et
38
4a
3a
c
d
nPr
0 (37)b
0 (42)b
25
nBu
nHept
retro-Michael
nHept
OEt
38
38
30
62
63
50
40
32
31
66
44
33
42
51
56
63
- H2O
Allyl
Allyl
Ph
4-Me(C6H4)
4-Cl(C6H4)
2-MeO(C6H4)
2-MeO(C6H4)
MeO
OMe
OMe
OMe
OMe
OMe
OMe
OMe
OMe
OEt
O
O
O
CN
H
H
Cl
Me
H
OMe
O
m
n
n
o
p
p
q
r
O-
O
O
N
OMe
OH
+
HNEt3
D
B
PhO
PhO
H
- NEt3
O
OEt
Cl
Me
Cl
H
Me
Me
Cl
H
H
H
H
H
heterocyclization
nitrile-addition
h
f
4-Cl(C6H4)O
4-Me(C6H4)O
PhS
4-Cl(C6H4)S
4-Me(C6H4)S
4-MeO(C6H4)S
H
OMe
OMe
OEt
OEt
OEt
a
h
b
f
a
a
a
a
a
a
a
a
s
t
O
u
v
w
x
y
z
aa
ab
ac
ad
OEt
OEt
45
31
34
N-
OMe
O
O
HNEt3
+
H
OMe
OEt
OMe
OMe
OMe
Ph
C
–(CH2)3–
36
–CH2CHMeCH2–
–(CH2)4–
32c
0
Scheme 1. Mechanism of the formation of 4a.
–(CH2)9–
H
H
H
0
0
0
H
H
H
H
latter with base resulted in formation of a separable mixture of
ethyl-substituted azaxanthone 4m and dibenzo[b,d]pyran-6-one
5b. In contrast, the exclusive formation of azaxanthones 4n,o was
observed when substituted cyanochromones 1e and 1h were
employed. The propyl- and butyl-substituted dibenzo[b,d]pyran-6-
ones 5c and 5d were isolated from the reaction of parent cyano-
chromone 1a with 1,3-bis(trimethylsilyloxy)-1,3-butadienes 2g and
2h. The reaction of 2i with 1a and 1e exclusively afforded the
Me
a
b
c
Yields of isolated products 4 over two steps (based on 1).
Yields in brackets refer to 5a–d (for structures see Scheme 3).
dr¼2:3.
heptyl-substituted azaxanthones 4r and 4s, respectively. The allyl-
substituted azaxanthones 4t and 4u were prepared from 2j.
The reaction of 4-aryl-1,3-bis(trimethylsilyloxy)-1,3-butadienes
2k–n with 3-cyanochromones 1a,b,e gave the products 3v–z, which
weretransformed intothe3-aryl-1-azaxanthones4v–z. 3-Methoxy-
Me3SiO
OSiMe3
R3
R1
OR2
O
NC
O
1) NEt3
EtOH
O
O
R1 R2
2a-z
CN
R1
R4
R5
CN
OH
2) HCl
O
O
i
O
O
O
R3
O
O
R4
R6
CN
R1 R2
R1 = see Table 1
R2 = Me, Et
5a-d
3k,m,p,q
+
R5
3a-am
O
R6
1a-h
- R2OH
ii
O
O
O
R1
R4
R5
NC
R1
CN
R1
O
O
N
R3
OH
OR2
- H2O
R6
OH
R2
O
4a-am
OH
O
OR2
Scheme 2. Synthesis of 1-azaxanthones 4a–am: (i) (1) 1a–h, Me3SiOTf, 1 h, 20 ꢀC, (2)
2a–z, CH2Cl2, 0/20 ꢀC, 12 h, (3) HCl (10%); (ii) (1) NEt3, EtOH, 20 ꢀC, 12 h, (2) HCl
(1 M).
E
F
Scheme 3. Mechanism of the formation of 5a–d.

5418
M.A. Rashid et al. / Tetrahedron 64 (2008) 5416–5425
1-azaxanthone 4aa was prepared from 4-methoxy-1,3-bis-
(trimethylsilyloxy)-1,3-butadiene 2o, which is available from
methyl 4-methoxyacetoacetate. The reaction of 4-aryloxy-1,3-
bis(trimethylsilyloxy)-1,3-butadienes 2p–r with 1a,f,h afforded the
condensation products 3ab–ae, which were transformed into the
3-aryloxy-1-azaxanthones 4ab–ae. Starting with 4-thioaryloxy-1,3-
bis(trimethylsilyloxy)-1,3-butadienes 2s–v, the 3-thioaryloxy-1-
azaxanthones 4af–ai were prepared. 1-Azaxanthones 4aj and
4ak were prepared from 1a and from 2-methyl- and 2-ethyl-1,3-
bis(trimethylsilyloxy)-1,3-butadienes 2w and 2x, respectively.
The reaction of 1a with cyclohexanone-derived 1,3-bis-
(trimethylsilyloxy)-1,3-butadienes 2y and 2z gave 3al and 3am,
which were transformed into the tetracyclic azaxanthones 4al and
4am, respectively. The employment of 7- and 12-membered cyclic
1,3-bis(trimethylsilyloxy)-1,3-butadienes 2aa and 2ab proved to be
unsuccessful. The reaction of 3-cyanochromones with 1,3-diketone-
derived 1,3-bis(silyl enol ethers), such as 1-phenyl-1,3-bis-
(trimethylsilyloxy)-1,3-butadiene (2ac) or 2,4-bis(trimethylsilyl-
oxy)-1,3-pentadiene (2ad), resulted in the formation of complex
mixtures.
aryloxy- or thioaryloxy-substituent, are again relatively good. These
results can be explained by the assumption that, despite their steric
effect, all these substituents exert an advantageous electronic effect
in the first step (the addition of the diene onto the pyrylium salt) or
in the second step (formation of intermediate B in Scheme 1). The
yields of tetracyclic products 4al and 4am are rather low and the
synthesis of analogues containing larger annulated rings was not
possible at all. This might be explained by steric effects. The failure
of the synthesis of 3ap and 3aq (and, thus, of the corresponding 1-
azaxanthones) can be explained by the generally lower reactivity
of 1,3-diketone- compared to b-ketoester-derived 1,3-bis-
(trimethylsilyloxy)-1,3-butadienes.
In conclusion, a variety of 1-azaxanthones were prepared by
TMSOTf-mediated condensation of 1,3-bis(trimethylsilyloxy)-
1,3-butadienes with 3-cyanochromones and subsequent base-
mediated domino ‘retro-Michael/lactonization/aldol’ reaction.
Noteworthy, the syntheses can be carried out under mild condi-
tions and the reactions proceed in acceptable yields with very good
regio- and chemoselectivity. The products are not readily available
by other methods.
The structures of all products were proved by spectroscopic
methods. The structure of 4t was independently confirmed by
X-ray crystal structure analysis (Fig. 1).11
3. Experimental section
3.1. General comments
The overall yields of 1-azaxanthones 4a–am are, in most cases,
only moderate. However, it has to be taken into account that the
yields refer to two steps. In fact, a 50% overall yield is obtained
when each individual step proceeds in ca. 70% yield. The moderate
yields can be explained by the fact that, for the first step, the
conversion is often not complete. However, the yields could not
be increased by employment of an excess of the 1,3-bis-
(trimethylsilyloxy)-1,3-butadiene or by longer reaction times.
The yields depend on the type of 1,3-bis(trimethylsilyloxy)-1,3-
butadiene and 3-cyanaochromone employed. The synthesis of
3-alkyl-1-azachromones from parent 3-cyanochromone is prob-
lematic, due to the competing formation of dibenzo[b,d]pyran-6-
ones, which might be related to the steric influence of the alkyl
group. In contrast, the synthesis of 3-alkyl-1-azachromones de-
rived from substituted 3-cyanochromones proved to be possible.
Relatively good yields are observed for 1-azaxanthones 4v–x pre-
pared from the phenyl- and 4-chlorophenyl-substituted dienes 2k–
m. The yields dropped for products 4y,z, which were prepared from
diene 2n (containing the sterically more demanding 2-methoxy-
phenyl group). The yields of 1-azaxanthones 4ab–ai, containing an
All solvents were dried by standard methods and all reactions
were carried out under an inert atmosphere. For 1H and 13C NMR
spectra the deuterated solvents indicated were used. Mass spec-
trometric data (MS) were obtained by electron ionization (EI,
70 eV), chemical ionization (CI, H2O) or electrospray ionization
(ESI). For preparative scale chromatography, silica gel (60–200
mesh) was used. Melting points are uncorrected.
3.2. General procedure for the synthesis of azaxanthones
4a–am and dibenzo[b,d]pyran-6-ones 5a–d
To neat 3-cyanochromone 1 (1.0 equiv) was added Me3SiOTf
(1.3 equiv) and CH2Cl2 (1 mL) at 20 ꢀC. After stirring for 1 h, CH2Cl2
and 1,3-bis(trimethylsilyloxy)-1,3-butadiene 2 (1.3 equiv) were
added at 0 ꢀC. The mixture was stirred for 12 h at 20 ꢀC and
subsequently poured into hydrochloric acid (10%). The organic and
the aqueous layer were separated and the latter was extracted with
CH2Cl2 (3ꢁ100 mL). The combined organic layers were washed
with water, dried (Na2SO4), filtered and the filtrate was concen-
trated in vacuo. The residue was filtered through a pad of silica gel
(EtOAc/hexane¼5:1) to give crude 3a–am. To an ethanol solution
(10 mL) of 3a–am was added NEt3 (2.0 equiv) and the solution was
stirred for 12 h at 20 ꢀC. To the solution were subsequently added
an aqueous solution of hydrochloric acid (1 M) and ether (50 mL).
The organic and the aqueous layer were separated and the latter
was extracted with ether (3ꢁ100 mL). The combined organic layers
were washed with water, dried (Na2SO4), filtered and the filtrate
was concentrated in vacuo. The residue was purified by column
chromatography (silica gel, EtOAc/hexane).
3.2.1. Methyl 2-(4-azaxanthon-3-yl)acetate (4a)
Starting with 3-cyanochromone (1a) (300 mg, 1.75 mmol),
Me3SiOTf (0.41 mL, 2.28 mmol), 2a (593 mg, 2.28 mmol), CH2Cl2
(15 mL), methanol (20 mL) and triethylamine (885 mg, 1.21 mL,
8.75 mmol), 4a was isolated as a yellow solid (193 mg, 41%),
mp¼138 ꢀC. 1H NMR (300 MHz, CDCl3): d¼3.77 (s, 3H, OCH3), 4.01
(s, 2H, CH2), 7.44 (m, 2H, Ar), 7.61 (d, 3J¼8.4 Hz, 1H, Ar), 7.79 (m, 1H,
Ar), 8.31 (dd, 3J¼7.9 Hz, 4J¼1.6 Hz, 1H, Ar), 8.69 (d, 3J¼7.9 Hz, 1H,
Ar). 13C NMR (DEPT, 75.5 MHz, CDCl3): d¼34.9 (CH2), 52.5 (OCH3),
115.4 (C), 118.5, 121.5 (CH), 121.7 (C), 124.8, 126.7, 135.7, 138.1 (CH),
155.7, 159.9 (C), 160.0 (C), 169.8 (C]O, ester), 177.4 (C]O, ketone).
Figure 1. ORTEP plot of 4t (50% probability level).

M.A. Rashid et al. / Tetrahedron 64 (2008) 5416–5425
5419
IR (KBr, cmꢂ1): ~n¼3438 (m), 2955 (m), 1739 (s), 1662 (s), 1645 (s),
1553 (m), 1463 (s), 1436 (m), 1401 (s), 1345 (m), 1274 (m), 1202 (s),
1164 (s), 1106 (s), 987 (w), 778 (m), 467 (w). UV–vis (CH3CN, nm):
lmax: 332, 285, 264. Fluorescence (CH3CN, nm): Flmax (lEx): 420
(352). MS (EI, 70 eV): m/z (%)¼269 (Mþ, 100), 238 (16), 225 (21), 211
(68), 182 (42), 127 (11), 59 (13). HRMS (FT-ICR) calcd for C15H12NO4
([Mþ1]þ): 270.07608; found: 270.07605.
14), 225 ([MꢂCO2CH2CH3]þ, 100), 196 (18). Anal. Calcd (%) for
C17H15NO4 (297): C, 68.68; H, 5.09; N, 4.71. Found: C, 68.93; H,
5.91; N, 4.48.
3.2.5. Isopropyl 2-(4-aza-8-ethylxanthon-3-yl)acetate (4e)
Starting with 3-cyano-6-ethylchromone (1c) (141 mg,
0.71 mmol), Me3SiOTf (205 mg, 0.17 mL, 0.92 mmol), 2c (266 mg,
0.92 mmol), CH2Cl2 (20 mL), EtOH (20 mL) and triethylamine
(465 mg, 0.64 mL, 4.60 mmol), 4e was isolated as a yellow solid
(58 mg, 31%), mp¼127 ꢀC. 1H NMR (300 MHz, CDCl3): d¼1.29 (m,
9H, CH2CH3, OCH(CH3)2), 2.79 (q, 3J¼7.6 Hz, 2H, CH2CH3), 3.95 (s,
2H, CH2), 5.09 (sept, 3J¼6.3 Hz, 1H, OCH(CH3)2), 7.43 (d, 3J¼7.9 Hz,
1H, Ar), 7.53 (d, 3J¼8.6 Hz, 1H, Ar), 7.62 (dd, 3J¼8.6 Hz, 4J¼2.2 Hz,
1H, Ar), 8.12 (d, 4J¼2.2 Hz, 1H, Ar), 8.69 (d, 3J¼7.9 Hz, 1H, Ar). 13C
NMR (DEPT, 75.5 MHz, CDCl3): d¼15.5 (CH2CH3), 21.8 (OCH(CH3)2),
28.3 (CH2CH3), 44.4 (CH2), 69.1 (OCH(CH3)2), 115.2 (C), 118.4 (CH),
121.3, 121.4 (C), 124.8, 135.8, 137.9, 141.0 (CH), 154.0, 159.1, 160.2 (C),
168.9 (C]O, ester), 177.5 (C]O, ketone). IR (KBr, cmꢂ1): ~n¼3436
(m), 2977 (m), 2934 (m), 1724 (s), 1669 (s), 1612 (s), 1586 (s), 1563
(m), 1491 (m), 1444 (s), 1398 (s), 1307 (m), 1282 (m), 1208 (m), 1180
3.2.2. Ethyl 2-(4-azaxanthon-3-yl)acetate (4b)
Starting with 3-cyanochromone (1a) (300 mg, 1.75 mmol),
Me3SiOTf (506 mg, 0.41 mL, 2.28 mmol), 2b (626 mg, 2.28 mmol),
CH2Cl2 (15 mL), EtOH (20 mL) and triethylamine (891 mg, 1.22 mL,
8.77 mmol), 4b was isolated as a yellow solid (229 mg, 46%),
mp¼127 ꢀC.1H NMR (300 MHz, CDCl3): d¼1.29 (t, 3J¼7.0 Hz, 3H, CH3),
3.99 (s, 2H, CH2), 4.23 (q, 3J¼7.0 Hz, 2H, OCH2CH3), 7.44 (m, 2H, Ar),
7.62 (d, 3J¼8.3 Hz, 1H, Ar), 7.79 (m, 1H, Ar), 8.31 (dd, 3J¼7.9 Hz,
4J¼1.7 Hz,1H,Ar), 8.69(d,3J¼7.9 Hz,1H,Ar).13CNMR (DEPT, 75.5 MHz,
CDCl3): d¼14.2 (CH3), 44.2 (CH2), 61.5 (OCH2), 115.3 (C), 118.5, 121.5
(CH), 121.7 (C), 124.7, 126.7, 135.6, 137.9 (CH), 155.7, 159.9, 160.2 (C),
169.3 (C]O, ester),177.34 (C]O, ketone). IR (KBr, cmꢂ1): ~n¼2985 (m),
2928 (m), 1728 (s), 1669 (s), 1602 (s), 1564 (s), 1472 (s), 1406 (s), 1372
(m),1323 (m),1282 (s),1191 (s),1207 (s),1104 (s),1024 (m), 767 (s), 750
(m). UV–vis (CH3CN, nm): lmax (lg 3): 236 (4.36), 285 (4.20), 331 (3.92).
MS (EI, 70 eV): m/z (%)¼283 (Mþ, 85), 238 (16), 212 (12), 211 ([MꢂCO2,
H2C]CH2]þ 100), 182 (10), 127 (5). HRMS (EI, 70 eV) calcd for
(s), 1107 (s), 780 (m). UV–vis (CH3CN, nm): l
(lg 3): 335 (3.84),
max
290 (4.26), 240 (4.42), 229 (4.48). MS (EI, 70 eV): m/z (%)¼326 (Mþ,
67), 268 ([MꢂCH(CH3)2]þ, 15), 239 ([MꢂCO2CH(CH3)2)]þ, 100), 211
(16), 196 (7), 133 (8), 43 ([CH(CH3)2)]þ, 95). HRMS (FT-ICR) calcd for
C
19H20NO4 ([Mþ1]þ): 326.13868; found: 326.13826.
C
16H13NO4 ([M]þ): 283.0845; found: 283.0845ꢃ2 ppm.
3.2.6. Ethyl 2-(4-aza-8-isopropylxanthon-3-yl)acetate (4f)
3.2.3. Isopropyl 2-(4-azaxanthon-3-yl)acetate (4c)
Starting with 3-cyano-6-isopropylchromone 1d (145 mg,
0.68 mmol), Me3SiOTf (196 mg, 0.16 mL, 0.88 mmol), 2a (242 mg,
0.88 mmol), CH2Cl2 (20 mL), EtOH (25 mL) and triethylamine
(526 mg, 0.72 mL, 5.20 mmol), 4f was isolated as a yellow solid
(91 mg, 41%), mp¼140 ꢀC. 1H NMR (300 MHz, CDCl3): d¼1.28 (m,
9H, CH3), 3.12 (sept, 1H, CH(CH3)2), 3.98 (s, 2H, CH2), 4.22 (q,
3J¼7.2 Hz, OCH2CH3), 7.45 (d, 3J¼7.9 Hz, 1H, Ar), 7.53 (d, 3J¼8.6 Hz,
1H, Ar), 7.66 (dd, 3J¼8.6 Hz, 4J¼2.3 Hz, 1H, Ar), 8.15 (d, 4J¼2.3 Hz,
1H, Ar), 8.70 (d, 3J¼7.9 Hz, 1H, Ar). 13C NMR (DEPT, 75.5 MHz,
CDCl3): d¼14.2 (OCH2CH3), 23.9 (CH(CH3)2), 33.7 (CH(CH3)2), 44.2
(CH2), 61.5 (OCH2CH3), 115.3 (C), 118.4, 121.3 (CH), 121.4 (C), 123.5,
134.6, 138.0 (CH), 145.6, 154.1, 159.9, 160.0 (C), 169.4 (C]O, ester),
177.6 (C]O, ketone). IR (KBr, cmꢂ1): ~n¼3428 (m), 3340 (m), 3190
(m), 2962 (m), 2933 (m), 1724 (m), 1666 (s), 1623 (s), 1616 (s), 1536
(s), 1459 (s), 1329 (m), 1266 (m), 1227 (m), 1156 (m), 1095 (m), 1034
(m), 808 (w). UV–vis (CH3CN, nm): lmax (lg 3): 334 (3.79), 291
(4.08), 280 (3.99), 248 (4.39). GC–MS (EI, 70 eV): m/z (%)¼325 (M,
46), 310 (100), 267 (11), 238 (23). HRMS (EI, 70 eV) calcd for
Starting with 3-cyanochromone (1a) (130 mg, 0.76 mmol),
Me3SiOTf (219 mg, 0.18 mL, 0.98 mmol), 2c (285 mg, 0.98 mmol),
CH2Cl2 (10 mL), EtOH (20 mL) and triethylamine (506 mg, 0.69 mL,
5.00 mmol), 4c was isolated as a yellow solid (76 mg, 42%),
mp¼148 ꢀC. 1H NMR (300 MHz, DMSO-d6): d¼1.22 (d, 3J¼6.3 Hz,
6H, CH3), 4.02 (s, 2H, CH2), 4.96 (sept, 3J¼6.3 Hz, 1H, OCH(CH3)2),
7.55 (m, 2H, Ar), 7.73 (dd, 3J¼8.6 Hz, 4J¼1.1 Hz, 1H, Ar), 7.90 (m, 1H,
Ar), 8.15 (dd, 3J¼8.0 Hz, 4J¼1.6 Hz, 1H, Ar), 8.58 (d, 3J¼7.9 Hz, 1H,
Ar). 13C NMR (DEPT, 75.5 MHz, DMSO-d6): d¼21.5 (CH3), 43.5 (CH2),
68.2 (OCH(CH3)2), 114.7 (C), 118.4 (CH), 121.1 (C), 122.1, 124.9, 126.0,
136.0, 137.3 (CH), 155.1, 159.2, 160.6 (C), 168.9 (C]O, ester), 176.57
(C]O, ketone). IR (KBr, cmꢂ1): ~n¼3436 (m), 2984 (m), 2962 (m),
1722 (s), 1672 (s),1615 (s), 1583 (m),1563 (s),1465 (s),1400 (s),1323
(m), 1206 (s), 1109 (s), 954 (w), 766 (s), 749 (m). UV–vis (CH3CN,
nm): lmax (lg 3): 332 (3.95), 285 (4.22), 227 (4.46). MS (EI, 70 eV):
m/z (%)¼297 (Mþ, 75), 238 ([MꢂOCH(CH3)2]þ, 100), 182 (25), 155
(5), 127 (7), 43 ([CH(CH3)2]þ, 40). Anal. Calcd (%) for C17H15NO4: C,
68.68; H, 5.09; N, 4.71. Found: C, 68.60; H, 5.30; N, 4.58.
C19H19NO4: 325.1314; found: 325.1314ꢃ2 ppm.
3.2.4. Ethyl 2-(4-aza-8-methylxanthon-3-yl)acetate (4d)
3.2.7. Ethyl 2-(4-aza-8-chloroxanthon-3-yl)acetate (4g)
Starting with 3-cyano-6-methylchromone (1b) (152 mg,
0.82 mmol), Me3SiOTf (238 mg, 0.19 mL, 1.07 mmol), 2a (294 mg,
1.07 mmol), CH2Cl2 (16 mL), EtOH (20 mL) and triethylamine
(536 mg, 0.73 mL, 5.30 mmol), 4d was isolated as a yellow solid
(97 mg, 40%), mp¼128 ꢀC. 1H NMR (300 MHz, DMSO-d6): d¼1.21
(t, 3J¼7.1 Hz, 3H, OCH2CH3), 2.52 (s, 3H, CH3), 4.04 (s, 2H, CH2), 4.14
(q, 3J¼7.1 Hz, 2H, OCH2CH3), 7.57 (d, 3J¼7.9 Hz, 1H, Ar), 7.63 (d,
3J¼8.5 Hz, 1H, Ar), 7.74 (dd, 3J¼8.5 Hz, 4J¼2.5 Hz, 1H, Ar), 7.96 (d,
4J¼1.5 Hz, 1H, Ar), 8.61 (d, 3J¼7.9 Hz, 1H, Ar). 13C NMR (APT,
75.5 MHz, DMSO-d6): d¼14.1 (OCH2CH3), 20.4 (CH3), 43.3 (CH2),
60.8 (OCH2), 114.7 (C), 118.3 (CH), 120.8 (C), 122.1, 125.3 (CH), 134.5
(C), 137.1, 137.5 (CH), 153.4, 159.3, 160.5 (C), 169.5 (C]O, ester),
176.58 (C]O, ketone). IR (KBr, cmꢂ1): ~n¼3439 (m), 2979 (s), 2935
(s), 1727 (s), 1670 (s), 1616 (s), 1587 (s), 1490 (s), 1432 (s), 1394 (s),
1371 (s), 1340 (s), 1305 (s), 1278 (s), 1203 (s), 1173 (s), 1144 (m),
1108 (m), 1028 (s), 998 (w), 882 (w), 814 (m), 783 (m). UV–vis
Starting with 6-chloro-3-cyanochromone (1e) (148 mg,
0.72 mmol), Me3SiOTf (209 mg, 0.17 mL, 0.94 mmol), 2a (258 mg,
0.94 mmol), CH2Cl2 (16 mL), EtOH (20 mL) and triethylamine
(476 mg, 0.65 mL, 4.70 mmol), 4g was isolated as a yellow solid
(85 mg, 37%), mp¼118 ꢀC. 1H NMR (300 MHz, DMSO-d6): d¼1.21 (t,
3J¼7.2 Hz, 3H, OCH2CH3), 4.05 (s, 2H, CH2), 4.13 (q, 3J¼7.2 Hz, 2H,
OCH2CH3), 7.61 (d, 3J¼7.9 Hz,1H, Ar), 7.80 (d, 3J¼8.9 Hz,1H, Ar), 7.96
(dd, 3J¼8.9 Hz, 4J¼2.6 Hz, 1H, Ar), 8.10 (d, 4J¼2.6 Hz, 1H, Ar), 8.62 (d,
3J¼6.9 Hz, 1H, Ar). 13C NMR (APT, 75.5 MHz, DMSO-d6): d¼13.9
(CH3), 43.2 (CH2), 60.6 (OCH2), 114.4 (C), 120.8 (CH), 122.2 (C), 122.3,
124.7 (CH), 129.0 (C), 135.5, 137.3 (CH), 153.7, 160. 0, 160.8 (C), 169.1
(C]O, ester), 175.6 (C]O, ketone). IR (KBr, cmꢂ1): ~n¼2978 (m),
2931 (m), 1727 (s), 1673 (s), 1610 (s), 1559 (m), 1472 (s), 1434 (s),
1395 (s), 1338 (m), 1258 (s), 1210 (s), 1186 (s), 1108 (m), 1027 (m),
839 (w), 784 (w). UV–vis (CH3CN, nm): lmax (lg 3): 334 (3.85), 292
(4.11), 230 (4.45). MS (EI, 70 eV): m/z (%)¼319 (Mþ, 37Cl, 21), 317
(Mþ, 35Cl, 67), 272 (19), 245 (100), 216 (21),189 (5),153 (7), 126 (10),
64 (12).
(CH3CN, nm): l
(lg 3): 334 (3.86), 290 (4.23), 240 (4.39), 229
max
(4.46). MS (EI, 70 eV): m/z (%)¼297 (Mþ, 84), 252 ([MꢂOCH2CH3]þ,

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M.A. Rashid et al. / Tetrahedron 64 (2008) 5416–5425
3.2.8. Ethyl 2-(4-aza-6,8-dichloroxanthon-3-yl)acetate (4h)
1H, Ar), 12.66 (s, 1H, OH). 13C NMR (DEPT, 75.5 MHz, CDCl3): d¼15.5
(CH3), 96.1 (C–CN), 106.2 (CN), 116.7 (C), 117.9 (CH), 119.5 (C), 125.0,
125.7 (CH), 127.5 (C), 132.1 (CH), 135.3 (C), 143.8 (CH), 150.3, 164.7,
165.0 (C). IR (KBr, cmꢂ1): ~n¼3420 (w), 2970 (w), 2830 (w), 2212 (s),
1684 (s), 1600 (s), 1459 (s), 1412 (m), 1388 (m), 1326 (m), 1262 (s),
1219 (m),1170 (s),1147 (s),1112 (s), 811 (m), 764 (s), 666 (m). UV–vis
(CH3CN, nm):lmax (lg 3): 350 (3.81), 338 (3.34), 311 (4.02), 299 (3.95),
288 (3.96), 254 (4.48), 206 (4.52). Fluorescence (CH3CN, nm): Flmax
(lEx): 489 (345). MS (EI, 70 eV): m/z (%)¼251 (Mþ,100), 222 (18),194
(14),177 (8),140 (10), 71 (6). Anal. Calcd (%) for C15H9NO3 (250.7): C,
71.98; H, 3.61; N, 5.60. Found: C, 71.71; H, 4.20; N, 5.70. In a second
fraction, 4k was detected, which could not be isolated in pure form.
Signals of 4k in the mixture with 5a: 1H NMR (300 MHz, CDCl3):
d¼2.47 (s, 3H, CH3), 3.76 (s, 3H, OMe), 3.82 (s, 2H, CH2), 7.38 (m, 2H,
Ar), 7.76 (m, 2H, Ar), 8.47 (s,1H, Ar). MS (EI, 70 eV): m/z (%)¼283 (Mþ,
72), 268 (38), 251 (223, 100), 224 (21), 197 (14), 121 (12).
Starting with 6,8-dichloro-3-cyanochromone (1f) (162 mg,
0.67 mmol), Me3SiOTf (194 mg, 0.16 mL, 0.87 mmol), 2a (239 mg,
0.87 mmol), CH2Cl2 (15 mL), EtOH (20 mL) and triethylamine
(365 mg, 0.50 mL, 3.60 mmol), 4h was isolated as a yellow solid
(113 mg, 48%), mp¼155 ꢀC. 1H NMR (300 MHz, DMSO-d6): d¼1.31
(t, 3J¼7.1 Hz, 3H, OCH2CH3), 3.74 (s, 2H, CH2), 4.30 (q, 3J¼7.1 Hz, 2H,
OCH2CH3), 6.92 (dd, 3J¼6.9 Hz, 4J¼2.2 Hz, 1H, Ar), 7.64 (dd,
3J¼6.9 Hz, 4J¼2.1 Hz, 1H, Ar), 7.87 (d, 4J¼2.6 Hz, 1H, Ar), 8.06 (d,
4J¼2.6 Hz, 1H, Ar). 13C NMR (DEPT, 75.5 MHz, DMSO-d6): d¼13.9
(CH3), 55.2 (CH2), 62.3 (OCH2), 113.9, 121.9 (CH), 122.1 (C), 123.3
(CH), 124.8, 129.5 (C), 133.3 (CH), 147.8, 155.1, 156.2, 160.8 (C), 164.9
(C]O, ester), 173.4 (C]O, ketone). IR (KBr, cmꢂ1): ~n¼3423 (m),
3352 (s), 3260 (m), 3134 (m), 1724 (s), 1675 (s), 1613 (s), 1572 (s),
1543 (s), 1512 (s), 1459 (s), 1387 (m), 1323 (m), 1293 (s), 1243 (s),
1176 (s), 1021 (m), 858 (m), 777 (m), 707 (m). UV–vis (CH3CN, nm):
l
(lg 3): 431 (2.85), 271 (4.19), 221 (3.80). MS (EI, 70 eV): m/z
max
(%)¼356 ([M]þ, [2ꢁ37Cl], 3), 354 ([M]þ, [37Cl], [35Cl], 11), 352 ([M]þ,
[2ꢁ35Cl], 22), 307 (12), 279 (16), 258 (22), 224 (74), 189 (77), 149
(100), 122 (83), 97 (11), 69 (14).
3.2.12. Ethyl 2-(7-chloro-3-methyl-5-oxo-5H-chromeno[2,3-b]-
pyrid-2-yl)acetate (4l)
Starting with6-chlorocyanochromone (1e)(150 mg, 0.60 mmol),
2e (288 mg, 0.78 mmol), Me3SiOTf (0.14 mL, 0.78 mmol) and NEt3
(0.16 mL, 1.20 mmol), 4l was isolated as a colourless solid (98 mg,
41%), mp¼190 ꢀC. 1H NMR (250 MHz, CDCl3): d¼1.27 (t, 3H,
3J¼7.1 Hz, CH3), 2.46 (s, 3H, CH3), 3.99 (s, 2H, CH2), 4.28 (q, 2H, 3J¼
6.9 Hz, OCH2CH3), 7.55 (d, 1H, 3J¼8.9 Hz, ArH), 7.71 (dd, 1H,
3J¼7.91 Hz, 4J¼2.5 Hz, ArH), 8.26 (d, 1H, 4J¼2.5 Hz, ArH), 8.46 (s, 1H,
ArH). 13C NMR (62 MHz, CDCl3): d¼14.1, 18.1 (CH3), 42.3, 61.4 (CH2),
115.6 (C), 120.2 (CH), 122.5 (2C, C), 125.9 (CH), 130.0 (C), 135.5, 138.1
(CH), (C), 154.0, 157.1, 159.5 (C), 169.0, 176.5 (C]O). IR (neat, cmꢂ1):
~n¼3092 (w), 2977 (m), 2921 (w),1724 (s),1667 (s),1603 (m),1439 (s),
1270 (s), 1180 (s), 843 (s), 788 (m). GC–MS (EI, 70 eV): m/z (%)¼333
(Mþ, 37Cl, 27), 331 (Mþ, 35Cl, 87), 285 (70), 257 (100), 230 (29), 194
3.2.9. Ethyl 2-(4-aza-8-bromoxanthon-3-yl)acetate (4i)
Starting with 6-bromo-3-cyanochromone (1g) (170 mg,
0.68 mmol), Me3SiOTf (196 mg, 0.16 mL, 0.88 mmol), 2a (243 mg,
0.88 mmol), CH2Cl2 (15 mL), EtOH (20 mL) and triethylamine
(455 mg, 0.62 mL, 4.50 mmol), 4i was isolated as a yellow solid
(84 mg, 34%), mp¼127 ꢀC. 1H NMR (300 MHz, CDCl3): d¼1.26 (t,
3J¼7.1 Hz, 3H, OCH2CH3), 3.98 (s, 2H, CH2), 4.22 (q, 3J¼7.1 Hz, 2H,
OCH2CH3), 7.44 (d, 3J¼7.9 Hz,1H, Ar), 7.45 (d, 3J¼8.5 Hz,1H, Ar), 7.57
(dd, 3J¼8.5 Hz, 4J¼2.2 Hz,1H, Ar), 8.08 (d, 4J¼2.2 Hz,1H, Ar), 8.67 (d,
3J¼7.9 Hz, 1H, Ar). 13C NMR (75.5 MHz, CDCl3): d¼14.2 (CH3), 20.9,
44.1 (CH2), 61.5 (OCH2), 115.3 (C), 118.3 (CH), 121.3 (C), 121.3, 126.0
(CH), 134.7 (C), 136.9, 137.9 (CH), 153.9, 159.9, 160.0 (C), 169.4 (C]O,
ester), 177.44 (C]O, ketone). IR (KBr, cmꢂ1): ~n¼2981 (m), 2934 (m),
1728 (s),1669 (s),1614 (s),1409 (m),1433 (s),1397 (s),1339 (m),1305
(m),1278 (m),1206 (s),1174 (s),1137 (m),1029 (m), 816 (m), 782 (m).
UV–vis (CH3CN, nm): lmax (lg 3): 335 (3.89), 290 (4.28), 240 (4.44),
228 (4.51). MS (EI, 70 eV): m/z (%)¼363 (Mþ, 81Br, 2), 361 (Mþ, 79Br,
3), 252/250 (10/12), 225 (100), 196 (34), 148 (23), 86 (32).
(4), 126 (15), 63 (10). HRMS (ESI) calcd for C18H16NO4Cl (Mþþ
331.06059; found: 331.060408.
,
35Cl):
3.2.13. Ethyl 2-(4-aza-2-ethylxanthon-3-yl)acetate (4m) and 10-
cyano-8-ethyl-7-hydroxydibenzo[b,d]pyran-6-one (5b)
Starting with 1a (171 mg, 1.0 mmol), Me3SiOTf (289 mg,
1.3 mmol) and 1f (393 mg, 1.3 mmol), 4m (53 mg, 17%) was isolated
as a yellow solid and 5b was isolated as a colourless solid (90 mg,
34%). The synthesis of 5b has been previously reported.10
3.2.10. Isopropyl 2-(4-aza-8-bromoxanthon-3-yl)acetate (4j)
Starting with 6-bromo-3-cyanochromone (1g) (162 mg,
0.65 mmol), Me3SiOTf (187 mg, 0.15 mL, 0.84 mmol), 2c (242 mg,
0.84 mmol), CH2Cl2 (15 mL), EtOH (20 mL) and triethylamine
(425 mg, 0.58 mL, 4.20 mmol), 4j was isolated as a yellow solid
(66 mg, 32%), mp¼128 ꢀC. 1H NMR (300 MHz, CDCl3): d¼1.35 (d,
3J¼6.3 Hz, 6H, CH(CH3)2), 3.96 (s, 2H, CH2), 5.09 (sept, 3J¼6.3 Hz,1H,
CH(CH3)2), 7.48 (m, 2H, Ar), 7.83 (dd, 3J¼8.9 Hz, 4J¼2.6 Hz, 1H, Ar),
8.39 (d, 4J¼2.4 Hz,1H, Ar), 8.65 (d, 3J¼7.9 Hz,1H, Ar).13C NMR (DEPT,
75.5 MHz, CDCl3): d¼21.8 (OCH(CH3)2), 44.4 (CH2), 69.2
(OCH(CH3)2),115.0,117.9 (C),120.4,121.9 (CH),122.9 (C),129.2,137.9,
138.4 (CH), 154.4, 159.4, 160.8 (C), 168.8 (C]O, ester), 176.1 (C]O,
ketone). IR (KBr, cmꢂ1): ~n¼2931 (m), 2249 (m), 1650 (m), 1492 (s),
1458 (s),1423 (m),1403 (s), 752 (s). MS (EI, 70 eV): m/z (%)¼377 (Mþ,
81Br, 33), 375 (Mþ, 79Br, 34), 319/317 ([MꢂOiPr]þ, 6/6), 292/290
Compound 4m: mp¼125 ꢀC.1H NMR (300 MHz, CDCl3): d¼1.25 (t,
3J¼8.9 Hz, 3H, CH2CH3), 1.33 (t, 3J¼7.5 Hz, 3H, OCH2CH3), 2.80 (q,
3J¼8.9 Hz, 2H, CH2CH3), 4.02 (s, 2H, CH2), 4.21 (q, 3J¼7.5 Hz, 2H,
OCH2CH3), 7.42 (m, 1H, Ar), 7.61 (dd, 3J¼8.8 Hz, 4J¼0.6 Hz, 1H, Ar),
7.76 (m,1H, Ar), 8.32(dd, 3J¼8.0 Hz, 4J¼1.7 Hz,1H, Ar), 8.53(s,1H, Ar).
13C NMR (DEPT, 75.5 MHz, CDCl3): d¼14.0 (OCH2CH3),14.2 (CH2CH3),
24.5 (CH2CH3), 41.8 (CH2), 61.4 (OCH2CH3),115.6 (C),118.5 (CH),121.6
(C), 124.5, 126.9, 135.4 (CH), 135.9 (C), 136.4 (CH), 155.8, 158.1, 158.6
(C), 169.4 (CO, ester), 177.7 (C]O, ketone). IR (KBr, cmꢂ1): ~n¼3390
(m),3150(m),2984(m), 2932(m),1733 (s),1663(s),1612 (s),1561(s),
1471 (s),1424 (s),1316 (s),1266 (s),1229 (m),1184 (m),1149 (s),1119
(s),1028 (m), 909 (w), 734 (m). UV–vis (CH3CN, nm): lmax (lg 3): 339
(3.93), 289 (4.09), 229 (4.47). MS (EI, 70 eV): m/z (%)¼311 (Mþ, 100),
265 (42), 237 (97), 210 (15),175 (13),153 (12), 86 (19), 57 (76). HRMS
(EI) calcd for C18H17NO4 (Mþ): 311.1158; found: 311.1158ꢃ2 ppm.
Compound 5b: mp¼183 ꢀC. 1H NMR (300 MHz, CDCl3): d¼1.30 (t,
3J¼7.2 Hz, 3H, CH2CH3), 2.78 (q, 3J¼7.2 Hz, 2H, CH2CH3), 7.45 (m, 2H,
Ar), 7.60 (m, 1H, Ar), 7.88 (s, 1H, Ar), 9.19 (dd, 3J¼2.3 Hz, 4J¼1.4 Hz,
1H, Ar), 12.71 (s, 1H, OH). 13C NMR (DEPT, 75.5 MHz, CDCl3): d¼13.0
(CH3), 22.5 (CH2), 96.3, 106.3, 116.8 (C), 117.9 (CH), 119.8 (C), 125.1,
125.8, 132.2 (CH), 133.2, 135.3 (C), 142.3 (CH), 150.3, 164.2, 165.2 (C).
IR (KBr, cmꢂ1): ~n¼3150 (w), 2971 (w), 2939 (w), 2877 (w), 2219 (m),
1675 (s), 1600 (s), 1459 (s), 1440 (m), 1422 (s), 1361 (w), 1338
(m), 1316 (m), 1273 (s), 1250 (m), 1221 (m), 1169 (s), 1155 (m), 1115
(m), 817 (s), 796 (m), 764 (s). UV–vis (CH3CN, nm): lmax (lg 3): 383
([MꢂCO2 Pr]þ, 34/36), 266 (33), 251 (54),182 (7),121 (15), 86 (9), 43
i
(iPrþ, 100). HRMS (EI) calcd for C17H14BrNO4 (Mþ, 79Br): 375.0106;
found: 375.0106ꢃ2 ppm.
3.2.11. Methyl 2-(4-aza-2-methylxanthon-3-yl)acetate (4k) and
10-cyano-7-hydroxy-8-methyldibenzo[b,d]pyran-6-one (5a)
Starting with 1a (171 mg, 1.0 mmol), Me3SiOTf (289 mg,
1.3 mmol) and 2d (357 mg, 1.3 mmol), 5a (85 mg, 34%) was isolated
asayellowsolid, mp¼238 ꢀC. Thesynthesisof5ahasbeenpreviously
reported.10 1H NMR (300 MHz, CDCl3): d¼2.38 (s, 3H, CH3), 7.44 (m,
2H, Ar), 7.61 (m,1H, Ar), 7.87 (s,1H, Ar), 9.18 (dd, 3J¼2.3 Hz, 4J¼1.4 Hz,

M.A. Rashid et al. / Tetrahedron 64 (2008) 5416–5425
5421
(3.11), 351 (3.78), 338 (3.79), 311 (3.97), 300 (3.92), 289 (3.93), 255
(4.45), 208 (4.44). MS (EI, 70 eV): m/z (%)¼265 (Mþ, 64), 251 (94),
211 (3), 58 (7), 32 (23). HRMS (EI) calcd for C16H11NO3 (Mþ):
265.0739; found: 265.0739ꢃ2 ppm.
isolated as a colourless solid, mp¼132 ꢀC. The synthesis of 5d has
been previously reported.10 1H NMR (300 MHz, CDCl3): d¼0.98 (t,
3J¼7.3 Hz, 3H, CH3), 1.42 (m, 2H, CH2), 1.65 (m, 2H, CH2), 2.74 (t,
3J¼7.6 Hz, 2H, ArCH2), 7.39–7.47 (br m, 2H, Ar), 7.60 (m, 1H, Ar), 7.84
(s,1H, Ar), 9.15 (dd, 3J¼8.3 Hz, 4J¼1.4 Hz,1H, Ar),12.67 (s,1H, OH).13
C
3.2.14. Ethyl 2-(7-chloro-3-ethyl-5-oxo-5H-chromeno[2,3-b]pyrid-
2-yl)acetate (4n)
NMR (DEPT, 75.5 MHz, CDCl3): d¼13.9 (CH3), 22.5, 29.0, 30.9 (CH2),
96.2,106.3,116.7 (C),117.9 (CH),119.7 (C),125.0,125.7 (CH),132.0 (C),
132.2 (CH), 135.2 (C), 143.1 (CH), 150.3, 164.5, 165.1 (C). IR (KBr,
cmꢂ1):~n¼3126 (w), 2958 (w), 2929 (w), 2866 (w), 2219 (m),1679 (s),
1602 (s),1458 (s),1414 (s),1352 (m),1326 (s),1268 (s),1213 (m),1169
(s), 1114 (m), 805 (m), 791 (m), 765 (s), 739 (m), 668 (m). UV–vis
(CH3CN, nm): lmax (lg 3): 351 (3.86), 339 (3.88), 311 (4.04), 299
(3.95), 289 (3.96), 255 (4.50), 207 (4.53). Fluorescence (CH3CN, nm):
Flmax (lEx): 479 (345). MS (EI, 70 eV): m/z (%)¼293 (Mþ, 100), 250
(26), 222 (3), 210 (3), 164 (79), 161 (18), 70 (3). HRMS (EI) calcd for
Starting with 6-chlorocyanochromone (1e) (150 mg, 0.60 mmol),
1,3-bis(silyl enol ether) 2f (305 mg, 0.78 mmol), Me3SiOTf (0.14 mL,
0.78 mmol) and NEt3 (0.16 mL, 1.20 mmol), 4n was isolated as
a highly viscous yellowish oil (150 mg, 46%). 1H NMR (250 MHz,
CDCl3): d¼1.25 (t, 3H, 3J¼7.3 Hz, CH3), 1.33 (t, 3H, 3J¼7.5 Hz, CH3),
2.81 (q, 2H, 3J¼6.9 Hz, CH2CH3), 4.00 (s, 2H, CH2), 4.20 (q, 2H,
3J¼7.1 Hz, OCH2CH3), 7.55 (d, 1H, 3J¼8.9 Hz, ArH), 7.70 (dd, 1H,
3J¼7.91 Hz, 4J¼1.5 Hz, ArH), 8.28 (d, 1H, 4J¼2.5 Hz, ArH), 8.51 (s, 1H,
ArH). 13C NMR (62 MHz, CDCl3): d¼13.9, 14.1 (CH3), 29.6, 41.7, 61.4
(CH2),115.2 (C),120.2 (CH),122.5 (C),125.9(CH),130.0(C),135.5 (CH),
136.3 (C), 136.4 (CH), 154.0, 157.2, 159.0 (C), 169.2, 176.5 (C]O). IR
(neat, cmꢂ1):~n¼2956 (w), 2921 (m), 2935 (w),1726 (s),1699 (s),1583
(m), 1428 (s), 1180 (s), 1024 (s), 789 (s), 710 (m). GC–MS (EI, 70 eV):
m/z (%)¼347 (Mþ, 37Cl, 24), 345 (Mþ, 35Cl), 299 (34), 271 (100), 257
(29), 208 (4),139(15), 63(10). HRMS(ESI) calcd for C18H16NO4Cl (Mþ,
35Cl): 345.0764; found: 345.07626.
C
18H15NO3 (Mþ): 293.1052; found: 293.1052ꢃ2 ppm.
3.2.18. Ethyl 2-(3-heptyl-5-oxo-5H-chromeno[2,3-b]pyrid-2-
yl)acetate (4r)
Starting with 1a (343 mg, 2.0 mmol), 2i (967 mg, 2.61 mmol),
Me3SiOTf (0.47 mL, 2.61 mmol) and NEt3 (1.4 mL, 10.0 mmol), 4r
was isolated as a colourless solid (195 mg, 25%), mp¼117 ꢀC. 1H
NMR (250 MHz, CDCl3): d¼0.86 (t, 3J¼6.7 Hz, 3H, CH2CH3), 1.25 (t,
3J¼7.2 Hz, 3H, CH2CH3), 1.34 (m, 8H, CH2CH2C4H8CH3), 1.66 (m, 2H,
CH2CH2C5H11), 2.72 (t, 3J¼8.0 Hz, 2H, CH2C6H13), 3.99 (s, 2H,
CH2COO), 4.19 (q, 3J¼7.16 Hz, 2H, OCH2CH3), 7.39 (m,1H, Ar), 7.56 (d,
3J¼8.5 Hz, 1H, Ar), 7.74 (ddd, 3J¼8.7 Hz, 4J¼1.7 Hz, 1H, Ar), 8.28 (dd,
3J¼1.5, 8.0 Hz, 1H, Ar), 8.47 (s, 1H, Ar). 13C NMR (250 MHz, CDCl3):
d¼14.0 (CH3), 14.1 (CH3), 22.6, 29.0, 29.3, 30.0, 31.5, 31.7, 41.7 (CH2),
61.4 (OCH2CH3), 115.4 (C), 118.4 (CH), 121.6 (C), 124.4, 126.6 (CH),
134.8 (C), 135.4, 137.1 (CH), 155.7, 158.0, 158.6, 169.4 (C), 177.6
(C]O). IR (KBr, cmꢂ1): ~n¼3453 (br, w), 3051 (w), 2976 (m), 2951
(m), 2922 (s), 2849 (m), 1733 (s), 1669 (s), 1613 (s), 1560 (w), 1447
(s), 1428 (s), 1367 (m), 1340 (m), 1320 (m), 1277 (m), 1231 (m), 1205
(m), 1176 (m), 1115 (m), 1035 (m), 961 (w), 943 (w), 875 (w), 764
(m). MS (EI, 70 eV): m/z (%)¼381 (Mþ, 12), 294 (100), 336 (8), 310
(79), 264 (29), 236 (84), 224 (61). HRMS (EI) calcd for C23H27NO4
(Mþ): 381.19346; found: 381.19345.
3.2.15. Ethyl 2-(3-ethyl-7,8-dimethyl-5-oxo-5H-chromeno[2,3-b]-
pyrid-2-yl)acetate (4o)
Starting with 6,7-dimethylcyanochromone (1h) (150 mg,
0.75 mmol), 1,3-bis(silyl enol ether) 2f (302 mg, 0.97 mmol),
Me3SiOTf (0.17 mL, 0.97 mmol) and NEt3 (0.20 mL, 1.5 mmol), 4o
was isolated as a colourless solid (100 mg, 38%), mp¼149 ꢀC.1H NMR
(250 MHz, CDCl3): d¼1.25 (t, 3H, 3J¼7.1 Hz, CH3), 1.34 (t, 3H,
3J¼7.5 Hz, CH3), 2.37 (s, 3H, CH3), 2.42 (s, 3H, CH3), 2.79 (q, 2H,
3J¼7.4 Hz, CH2CH3), 4.0 (s, 2H, CH2), 4.21 (q, 2H, 3J¼7.2 Hz, OCH2CH3),
7.34 (s,1H, ArH), 8.00 (s,1H, ArH), 8.51 (s,1H, ArH).13C NMR (62 MHz,
CDCl3): d¼14.0, 14.1, 19.2, 20.6 (CH3), 24.4, 41.7, 61.3 (CH2), 115.6 (C),
118.5 (CH), 119.4 (C), 126.2 (CH), 133.7, 135.5 (C), 136.3 (CH), 146.2,
154.2, 157.9, 158.0 (C), 169.4, 177.4 (C]O). IR (neat, cmꢂ1): ~n¼2970
(w), 2921 (m), 2856 (w),1727 (s),1663 (s),1607 (m),1425 (s),1181 (s),
1158 (s), 1026 (s), 789 (s), 739 (m). GC–MS (EI, 70 eV): m/z (%)¼339
(Mþ, 96), 293 (61), 265 (100), 250 (16), 222 (7), 1194 (15), 91 (10).
HRMS (ESI) calcd for C20H21NO4 [M]þ: 339.14651; found: 339.14641.
3.2.19. Ethyl 2-(7-chloro-3-heptyl-5-oxo-5H-chromeno[2,3-b]-
pyrid-2-yl)acetate (4s)
Starting with 3-chloro-3-cyanochromone 1e (150 mg,
0.7 mmol), 2i (340 mg, 0.91 mmol), Me3SiOTf (0.21 mL, 0.91 mmol)
and NEt3 (0.45 mL, 3.5 mmol), 4s was isolated as a colourless solid
(110 mg, 38%), mp¼146 ꢀC. 1H NMR (250 MHz, CDCl3): d¼0.86 (t,
3J¼6.7 Hz, 3H, CH2CH3), 1.25 (t, 3J¼7.1 Hz, 3H, CH2CH3), 1.35 (m, 8H,
CH2CH2C4H8CH3), 1.66 (m, 2H, CH2CH2C5H11), 2.72 (t, 3J¼8.0 Hz, 2H,
CH2C6H13), 3.99 (s, 2H, CH2COO), 4.19 (q, 3J¼7.16 Hz, 2H, OCH2CH3),
7.53 (d, 3J¼8.8 Hz, 1H, Ar), 7.68 (dd, 4J¼2.6 Hz, 3J¼8.9 Hz, 1H, Ar),
8.25 (d, 3J¼2.5 Hz, 1H, Ar), 8.46 (s, 1H, Ar). 13C NMR (250 MHz,
CDCl3): d¼14.0, 14.1 (CH3), 22.6, 29.0, 29.4, 30.0, 31.5, 31.7, 41.8
(CH2), 61.4 (OCH2CH3), 115.1 (C), 120.2 (CH), 122.5 (C), 126.0 (CH),
130.3, 135.2 (C), 135.5, 137.2 (CH), 154.1, 157.8, 159.1, 169.3 (C), 176.6
(C]O). IR (ATR, cmꢂ1): ~n¼2923 (br, w), 1730 (m), 1667 (s), 1556 (w),
1431 (s), 1337 (m), 1314 (w), 1271 (m), 1173 (m), 1089 (m), 968 (w),
891 (w), 791 (m), 712 (m), 578 (m), 542 (w). MS (EI, 70 eV): m/z
(%)¼417 (Mþ, 37Cl, 4), 415 (Mþ, 35Cl, 13), 328 (100), 370 (8), 344 (61),
298 (25), 270 (64), 207 (7). HRMS (EI) calcd for C23H26ClNO4 (Mþ,
35Cl): 415.155487; found: 415.15449.
3.2.16. 10-Cyano-7-hydroxy-8-n-propyldibenzo[b,d]pyran-
6-one (5c)
Starting with 1a (205 mg, 1.2 mmol), Me3SiOTf (347 mg,
0.28 mL, 1.56 mmol) and 2g (428 mg, 1.56 mmol), 5c (124 mg, 37%)
was isolated as a yellow solid, mp¼172 ꢀC. The synthesis of 5c has
been previously reported.10 1H NMR (300 MHz, CDCl3): d¼1.01 (t,
3J¼7.4 Hz, 3H, CH3), 1.69 (m, 2H, CH2CH3), 2.74 (t, 3J¼7.3 Hz, 2H,
ArCH2), 7.45 (m, 2H, Ar), 7.61 (m, 1H, Ar), 7.86 (s, 1H, Ar), 9.20 (dd,
3J¼8.1 Hz, 4J¼1.3 Hz, 1H, Ar), 12.69 (s, 1H, Ar). 13C NMR (DEPT,
75.5 MHz, CDCl3): d¼13.8 (CH3), 21.9 (CH2CH3), 31.2 (ArCH2), 96.1,
106.2, 116.6 (C), 117.8 (CH), 119.6 (C), 124.9, 125.7 (CH), 131.7 (C),
132.1 (CH), 135.2 (C), 143.1 (CH), 150.2, 164.5, 165.0 (C). IR (KBr,
cmꢂ1): ~n¼3434 (m), 2961 (m), 2875 (m), 2219 (m), 1678 (s), 1602
(s), 1459 (s), 1416 (s), 1357 (m), 1325 (s), 1270 (s), 1224 (m), 1168 (s),
1115 (m), 814 (m), 791 (w), 761 (m). UV–vis (CH3CN, nm): l
max
(lg 3): 351 (3.83), 339 (3.86), 311 (4.03), 299 (3.96), 289 (3.96), 255
(4.48), 208 (4.47). MS (EI, 70 eV): m/z (%)¼279 (Mþ, 43), 264 (12),
250 (100), 222 (4), 206 (2), 164 (4), 139 (5), 77 (50), 43 (4). HRMS
(EI) calcd for C17H13NO3 (Mþ): 279.0895; found: 279.0895ꢃ2 ppm.
3.2.20. Methyl 2-(3-allyl-5-oxo-5H-chromeno[2,3-b]pyrid-2-yl)-
acetate (4t)
3.2.17. 8-n-Butyl-10-cyano-7-hydroxydibenzo[b,d]pyran-
6-one (5d)
Starting with 1a (257 mg, 1.5 mmol), Me3SiOTf (433 mg,
1.95 mmol) and 2h (645 mg, 1.95 mmol), 5d (185 mg, 42%) was
Starting with 3-cyanochromone (1a) (400 mg, 2.33 mmol), 2j
(917 mg, 3.0 mmol), Me3SiOTf (0.54 mL, 3.0 mmol) and NEt3
(0.6 mL, 4.66 mmol), 4t was isolated as a colourless solid (275 mg,
38%), mp¼124 ꢀC. 1H NMR (CDCl3, 250 MHz): d¼3.48 (d, 3J¼6.1 Hz,

5422
M.A. Rashid et al. / Tetrahedron 64 (2008) 5416–5425
2H, CH2CHCH2), 3.68 (s, 3H, OCH3), 3.96 (s, 2H, CH2), 4.98–5.16 (m,
2H, CHCH2), 5.86–5.96 (m, 1H, CHCH2), 7.32–7.38 (m, 1H, ArH), 7.53
(dd, 3J¼8.5 Hz, 4J¼0.6 Hz, 1H, ArH), 7.67–7.74 (m, 1H, ArH), 8.23 (dd,
3J¼7.8 Hz, 4J¼1.5 Hz, 1H, ArH), 8.44 (s, 1H, ArH). 13C NMR (75 MHz,
CDCl3): d¼35.8, 41.5 (CH2), 52.4 (CH3), 115.5 (C), 117.8 (CH2), 118.4
(CH), 121.5 (C), 124.5, 126.6 (CH), 132.0 (C), 134.5, 135.5, 138.1 (CH),
155.6, 158.3, 158.8 (C), 169.6, 177.4 (C]O). IR (KBr, cmꢂ1): ~n¼3065
(w), 2995 (w), 2841 (w), 1738 (s), 1668 (s), 1609 (s), 1559 (m), 1429
(s), 1344 (s), 1269 (m), 1190 (s), 1165 (m), 997 (m), 916 (w), 766 (s),
670 (w). GC–MS (EI, 70 eV): m/z (%)¼309 (Mþ, 85), 278 (11), 249
(100), 236 (35), 220 (16), 191 (5), 152 (5), 124 (6), 77 (8), 51 (3). Anal.
Calcd (%) for C18H15NO4: C, 69.89; H, 4.89; N, 4.53. Found: C, 6980;
H, 4.97; N, 4.30.
(m),1600 (s),1597 (s),1548 (m),1467 (s),1442 (m),1412 (s),1314 (m),
1271 (s),1253 (s),1216 (s),1150 (s),1069 (s), 793 (m), 755 (s), 615 (m).
GC–MS (EI, 70 eV): m/z (%)¼359 (Mþ, 100), 327 (Mþ, 70), 298 (17),
285 (5), 256 (5), 228 (4),150 (7). HRMS (EI) calcd for C22H17O4N (Mþ):
359.114605; found: 359.11521.
3.2.24. Ethyl 2-[3-(4-chlorophenyl)-5-oxo-5H-chromeno[2,3-b]-
pyrid-2-yl]acetate (4x)
Starting with 1a (256 mg, 1.5 mmol), 2m (723 mg, 1.95 mmol),
Me3SiOTf (0.36 mL, 1.95 mmol) and NEt3 (0.45 mL, 3.0 mmol), 4x
was isolated as a colourless solid (284 mg, 50%), mp¼182 ꢀC. 1H
NMR (CDCl3, 250 MHz): d¼3.78 (s, 3H, CH3), 4.52 (s, 2H, CH2), 7.06–
7.17 (m, 4H, ArH), 7.30 (m, 1H, ArH), 7.45 (m, 1H, ArH), 7.61 (m, 1H,
ArH), 8.13 (dd, 3J¼7.8 Hz, 4J¼1.4 Hz, 1H, Ar–H), 9.06 (s, 1H, ArH). 13
C
3.2.21. Methyl 2-(3-allyl-7-chloro-5-oxo-5H-chromeno[2,3-b]-
pyrid-2-yl)acetate (4u)
NMR (62 MHz, CDCl3): d¼41.8 (CH3), 52.6 (CH2), 114.5 (C), 118.6
(CH), 121.6, 123.0 (C), 125.8, 126.8 (CH), 128.5, 130.6 (2C, CH), 132.4
(C), 135.9 (CH), 136.5 (C), 141.3 (CH), 155.5, 160.5, 165.1 (C), 167.2,
177.3 (C]O). IR (KBr, cmꢂ1): ~n¼3076 (w), 3048 (w), 2952 (w), 2918
(w), 1729 (s), 1664 (s), 1613 (m), 1600 (s), 1547 (m), 1492 (w), 1483
(s), 1414 (s), 1338 (w), 1310 (m), 1271 (s), 1247 (s), 1216 (s), 1139 (m),
1065 (m), 943 (m), 765 (s). GC–MS (EI, 70 eV): m/z (%)¼381 (Mþ,
37Cl, 34), 379 (Mþ, 35Cl, 100), 347 (46), 320 (15), 312 (59), 284 (13),
256 (14), 228 (9). HRMS (EI) calcd for C21H14O4NCl (Mþ, 35Cl):
379.06059; found: 379.06052.
Starting with 1e (200 mg, 0.97 mmol), 2j (380 mg, 1.26 mmol),
Me3SiOTf (0.22 mL, 1.26 mmol) and NEt3 (0.27 mL, 1.94 mmol), 4u
was isolated as a colourless solid (100 mg, 30%), mp¼177 ꢀC. 1H
NMR (CDCl3, 250 MHz): d¼3.64 (d, 3J¼6.3 Hz, 2H, CH2CHCH2), 3.84
(s, 3H, OCH3), 4.12 (s, 2H, CH2), 5.14–5.34 (m, 2H, CHCH2), 5.98–6.12
(m, 1H, CHCH2), 7.65 (d, 3J¼8.9 Hz, 1H, ArH), 7.81 (dd, 3J¼8.5 Hz,
4J¼2.5 Hz, 1H, ArH), 8.36 (d, 4J¼2.3 Hz, 1H, ArH), 8.59 (s, 1H, ArH).
13C NMR (75 MHz, CDCl3): d¼35.8, 41.5 (CH2), 52.4 (CH3), 115.2 (C),
117.9 (CH2), 120.0 (CH), 122.5 (C), 126.0 (CH), 130.4, 132.4 (C), 134.3,
135.6, 138.1 (CH), 154.0, 158.2, 159.2 (C), 169.5, 176.4 (C]O). IR (KBr,
cmꢂ1): ~n¼3052 (w), 2999 (w), 2950 (w), 1738 (s), 1667 (s), 1608 (s),
1475 (s), 1348 (s), 1311 (m), 1272 (s), 1169 (s), 1137 (m), 1000 (m),
639 (w). GC–MS (EI, 70 eV): m/z (%)¼345 (Mþ, 37Cl, 20), 343 (Mþ,
35Cl, 60), 285 (37Cl, 43), 283 (35Cl, 100), 270 (29), 248 (10), 219 (7),
178 (10), 149 (13), 97 (19), 69 (55), 57 (50). Anal. Calcd (%) for
3.2.25. Methyl 2-[7-chloro-3-(2-methoxyphenyl)-5-oxo-5H-
chromeno[2,3-b]pyrid-2-yl]acetate (4y)
Starting with 1e (200 mg, 0.97 mmol), 2n (465 mg, 1.26 mmol),
Me3SiOTf (0.22 mL, 1.26 mmol) and NEt3 (0.27 mL, 1.94 mmol), 4y
was isolated as a colourless solid (144 mg, 40%), mp¼172 ꢀC. 1H
NMR (CDCl3, 250 MHz): d¼3.55 (s, 3H, OCH3), 3.68 (s, 3H, OCH3),
3.79 (s, 2H, CH2), 6.91–7.02 (m, 2H, ArH), 7.15 (dd, 3J¼7.4 Hz,
4J¼1.8 Hz, 1H, ArH), 7.33–7.39 (m, 1H, ArH), 7.49 (d, 3J¼8.8 Hz, 1H,
ArH), 7.64 (dd, 3J¼8.8 Hz, 4J¼2.5 Hz, 1H, ArH), 8.19 (d, 4J¼2.3 Hz, 1H,
ArH), 8.45 (s, 1H, ArH). 13C NMR (62 MHz, CDCl3): d¼42.2 (CH2),
52.1, 52.3 (CH3), 110.8 (CH), 114.9 (C), 120.2, 121.0 (CH), 122.5, 125.5
(C), 125.9, 130.4, 131.3 (CH), 132.8 (C), 135.5, 139.0 (CH), 154.0, 156.2,
158.7, 159.6 (C), 169.8, 176.4 (C]O). IR (KBr, cmꢂ1): ~n¼3067 (w),
2985 (w), 2939 (w), 1727 (s), 1662 (s), 1597 (s), 1471 (s), 1432 (s),
1309 (m), 1259 (s), 1025 (m), 828 (m), 631 (w), 538 (w). GC–MS (EI,
70 eV): m/z (%)¼411 (Mþ, 37Cl, 8), 409 (Mþ, 35Cl, 26), 338 (37Cl, 27),
336 (35Cl, 100), 306 (9), 243 (2), 168 (3), 97 (10), 83 (13), 71 (11), 69
C
18H14ClNO4: C, 62.89; H, 4.10; N, 4.07. Found: C, 62.86; H, 4.31; N,
3.60.
3.2.22. Ethyl 2-(5-oxo-3-phenyl-5H-chromeno[2,3-b]pyrid-2-yl)-
acetate (4v)
Starting with 3-cyanochromone 1a (256 mg, 1.5 mmol), 2k
(656 mg, 1.95 mmol), Me3SiOTf (0.35 mL, 1.95 mmol) and Et3N
(0.45 mL, 3.0 mmol), 4v was isolated as a colourless solid (320 mg,
62%), mp¼152 ꢀC. 1H NMR (CDCl3, 250 MHz): d¼3.85 (s, 3H, CH3),
4.65 (s, 2H, CH2), 7.11–7.27 (m, 5H, ArH), 7.38 (m, 2H, ArH), 7.54 (m,
1H, ArH), 7.72 (m, 1H, 7-H), 8.21 (dd, 3J¼7.9 Hz, 4J¼1.5 Hz, 1H,
Ar–H), 9.13 (s, 1H, ArH). 13C NMR (62 MHz, CDCl3): d¼42.5 (CH3),
52.6 (CH2), 114.3 (C), 118.6 (CH), 121.6, 123.2 (C), 125.1, 126.5, 126.8
(CH), 128.4, 129.2 (2C, CH), 135.9 (CH), 138.1 (C), 141.1 (CH), 155.5,
160.5, 165.1 (C), 167.7, 176.8 (C]O). IR (neat, cmꢂ1): ~n¼3048 (w),
3061 (w), 3028 (w), 3007 (w), 2948 (w), 2929 (w),1725 (s), 1669 (s),
1595 (s), 1547 (m), 1466 (s), 1413 (s), 1314 (m), 1270 (s), 1214 (s),
1069 (m), 968 (m), 765 (s), 742 (s), 690 (s). GC–MS (EI, 70 eV): m/z
(%)¼345 (Mþ, 100), 313 (56), 286 (28), 256 (8), 228 (12). HRMS (EI)
calcd for C21H15O4N (Mþ, 35Cl): 345.09956; found: 345.09971.
(20), 57 (21), 44 (25). HRMS (EI) calcd for C22H16ClNO5 (Mþþ
409.07189; found: 409.07115.
,
35Cl):
3.2.26. Methyl 2-[7-methyl-3-(2-methoxyphenyl)-5-oxo-5H-
chromeno[2,3-b]pyrid-2-yl]acetate (4z)
Starting with 1b (200 mg, 1.08 mmol), 2n (516 mg, 1.4 mmol),
Me3SiOTf (0.25 mL, 1.4 mmol) and NEt3 (0.3 mL, 2.16 mmol), 4z was
isolated as a colourless solid (134 mg, 32%), mp¼165 ꢀC. 1H NMR
(CDCl3, 250 MHz): d¼2.41 (s, 3H, CH3), 3.54 (s, 3H, OCH3), 3.68 (s, 3H,
OCH3), 3.78 (s, 2H, CH2), 6.90–7.01 (m, 2H, ArH), 7.15 (dd, 3J¼7.4 Hz,
4J¼1.7 Hz, 1H, ArH), 7.32–7.39 (m, 1H, ArH), 7.43–7.53 (m, 2H, ArH),
8.02 (s,1H, ArH), 8.46 (s,1H, ArH). 13C NMR (62 MHz, CDCl3): d¼20.8
(CH3), 42.0 (CH2), 52.0, 52.3 (CH3), 110.7 (CH), 115.2 (C), 118.2, 120.9
(CH), 121.3, 125.8 (C), 126.0, 130.2, 131.4 (CH), 132.2, 134.4 (C), 136.7,
138.9 (CH),153.9,156.2,159.0 (C),169.9,177.6 (C]O). IR (KBr, cmꢂ1):
~n¼3058 (w), 3046 (w), 2923 (w),1742 (s),1655 (s),1488 (s), 1432 (s),
1253 (m), 1147 (s), 1020 (s), 834 (m), 794 (m), 630 (w), 542 (w). GC–
MS (EI, 70 eV): m/z (%)¼389 (Mþ, 35), 357 (9), 316 (100), 286 (11),
149 (8),111 (18), 97 (32), 83 (41), 57 (65), 44 (90). HRMS (EI) calcd for
3.2.23. Methyl 2-[3-(4-methylphenyl)-5-oxo-5H-chromeno[2,3-b]-
pyrid-2-yl]acetate (4w)
Starting with 1a (0.256 mg, 1.5 mmol), Me3SiOTf (219 mg,
0.18 mL, 0.98 mmol), CH2Cl2 (13.5 mL) and 1,3-bis(trimethyl-
silyloxy)-1,3-butadiene 2l (0.683 mg, 0.98 mmol), 4w was isolated
as a yellow solid (333 mg, 63%), mp¼173–174 ꢀC. 1H NMR (CDCl3,
250 MHz): d¼2.23 (s, 3H, CH3), 3.85 (s, 3H, CH3), 4.60 (s, 2H, CH2),
6.98 (d, J¼7.8 Hz, 2H, ArH), 7.15 (d, 2H, ArH), 7.33–7.39 (m, 1H, ArH),
7.53 (d, J¼7.87 Hz,1H, ArH), 7.67–7.74 (m,1H, ArH), 8.20 (m,1H, ArH),
9.10 (s,1H, ArH). 13C NMR (62 MHz, CDCl3): d¼21.0 (CH3), 42.1 (CH2),
52.5 (OCH3), 114.3 (C), 118.6 (CH), 121.6, 123.2 (C), 125.1, 126.8 (CH),
129.0 (2C, CH), 129.1 (2C, CH), 135.0 (C), 135.8 (CH), 136.1 (C), 141.1
(CH), 155.6, 160.5, 165.3 (C), 168.0, 176.8 (C]O). IR (KBr, cmꢂ1):
~n¼3084 (w), 3058 (w), 3009 (w), 2948 (w), 1720 (s), 1671 (s), 1613
C
23H19NO5 [M]þ: 389.12597; found: 389.12577.
3.2.27. Methyl 2-(4-aza-2-methoxyxanthon-3-yl)acetate (4aa)
Starting with 1a (171 mg, 1.0 mmol), Me3SiOTf (289 mg,
1.3 mmol) and 2o (377 mg, 1.3 mmol), 4aa (92 mg, 31%) was

M.A. Rashid et al. / Tetrahedron 64 (2008) 5416–5425
5423
isolated as a yellow solid. 1H NMR (300 MHz, CDCl3): d¼3.74 (s, 3H,
3.2.31. Methyl 2-[7,9-dichloro-3-(4-methylphenoxy)-5-oxo-5H-
chromeno[2,3-b]pyrid-2-yl]acetate (4ae)
OCH3), 3.99 (s, 3H, OCH3), 4.03 (s, 2H, CH2), 7.43 (m, 1H, Ar), 7.54 (d,
3J¼8.1 Hz, 1H, Ar), 7.78 (m, 1H, Ar), 8.33 (dd, 3J¼8.2 Hz, 4J¼1.8 Hz,
1H, Ar), 8.06 (s, 1H, Ar). 13C NMR (DEPT, 75.5 MHz, CDCl3): d¼39.1
(CH2), 52.3, 56.5 (OCH3), 115.1 (CH), 115.7 (C), 118.4 (CH), 120.9 (C),
124.4, 126.5, 135.3 (CH), 151.0, 152.1, 153.8, 155.6 (C), 169.7 (C]O,
ester), 177.6 (C]O, ketone). MS (EI, 70 eV): m/z (%)¼299 (Mþ, 100),
267 (28), 240 (41), 210 (46), 171 (12), 120 (13).
Starting with 1f (400 mg, 1.66 mmol), 2r (797 mg, 2.16 mmol),
Me3SiOTf (0.39 mL, 2.16 mmol) and NEt3 (0.6 mL, 4.32 mmol), 4ae
was isolated as a colourless solid (294 mg, 42%), mp¼194 ꢀC. 1H
NMR (CDCl3, 250 MHz): d¼2.31 (s, 3H, CH3), 3.65 (s, 3H, OCH3), 4.09
(s, 2H, CH2), 6.89 (d, 3J¼8.5 Hz, 2H, ArH), 7.14 (d, 3J¼8.1 Hz, 2H, ArH),
7.74 (d, 4J¼2.6 Hz, 1H, ArH), 7.85 (s, 1H, ArH), 8.05 (d, 4J¼2.5 Hz, 1H,
ArH). 13C NMR (62 MHz, CDCl3): d¼20.1 (CH3), 39.3 (CH2), 52.4
(OCH3), 115.5 (C), 119.6 (2C, CH), 121.5 (CH), 122.6 (C), 124.5 (CH),
124.5, 130.0 (C), 130.9 (2C, CH), 135.1 (C), 135.3 (CH), 150.0, 152.1,
152.8, 152.9, 154.0 (C), 169.4, 175.7 (C]O). IR (KBr, cmꢂ1): ~n¼3068
(w), 2964 (w), 2924 (w), 1728 (s), 1666 (s), 1508 (s), 1429 (s), 1396
(s), 1272 (m), 1172 (m), 1016 (m), 787 (m), 718 (w), 527 (w). GC–MS
(EI, 70 eV): m/z (%)¼447 ([M]þ, [2ꢁ37Cl], 7), 445 ([M]þ, [37Cl], [35Cl],
47), 443 ([M]þ, [2ꢁ35Cl], 7, 77), 386 (17), 384 (26), 311 (13), 266 (12),
239 (4), 149 (7), 105 (12), 97 (17), 84 (10), 71 (25), 44 (100). HRMS
(EI) calcd for C22H15Cl2NO5 ([M]þ, [2ꢁ35Cl]): 443.03085; found:
343.03218.
3.2.28. Ethyl 2-(5-oxo-3-phenoxy-5H-chromeno[2,3-b]pyrid-2-yl)-
acetate (4ab)
Starting with 1a (400 mg, 2.62 mmol), 2p (1.25 g, 3.41 mmol),
Me3SiOTf (0.62 mL, 3.41 mmol), NEt3 (0.72 mL, 5.24 mmol), 4ab
was isolated as a colourless solid (595 mg, 66%), mp¼144 ꢀC. 1H
NMR (CDCl3, 250 MHz): d¼1.13 (t, 3J¼7.0 Hz, 3H, CH3), 4.01 (s, 2H,
CH2), 4.09 (q, 3J¼7.0 Hz, 2H, OCH2CH3), 6.98–7.00 (m, 2H, ArH),
7.08–7.15 (m, 1H, ArH), 7.26–7.33 (m, 3H, ArH), 7.49 (dd, 3J¼8.5 Hz,
4J¼0.7 Hz, 1H, ArH), 7.63–7.70 (m, 1H, ArH), 7.95 (s, 1H, ArH), 8.15
(dd, 3J¼8.0 Hz, 4J¼1.4 Hz, 1H, ArH). 13C NMR (62 MHz, CDCl3):
d¼14.1 (CH3), 39.5 (CH2), 61.3 (OCH2),116.1 (C),118.3 (CH),119.2 (2C,
CH), 120.9 (C), 123.1, 124.5, 124.8, 126.5 (CH), 130.2 (2C, CH), 135.5
(CH), 150.6, 152.5, 154.9, 155.5, 155.7 (C), 169.0, 177.1 (C]O). IR (KBr,
cmꢂ1): ~n¼3072 (w), 2985 (w), 2937 (w), 1730 (s), 1664 (s), 1470 (s),
1309 (s), 1220 (s), 1119 (m), 1024 (m), 771 (s), 757 (m), 689 (m), 498
(w). GC–MS (EI, 70 eV): m/z (%)¼375 (Mþ, 100), 302 (10), 282 (12),
254 (88), 177 (44), 153 (13), 127 (54), 91 (10), 51 (7). Anal. Calcd (%)
for C22H17NO5: C, 70.39; H, 4.56; N, 3.73. Found: C, 69.78; H, 4.46; N,
3.55.
3.2.32. Ethyl 2-[5-oxo-3-(phenylsulfanyl)-5H-chromeno-
[2,3-b]pyrid-2-yl]acetate (4af)
Starting with 1a (400 mg, 2.33 mmol), 2s (1.18 g, 3.11 mmol),
Me3SiOTf (0.56 mL, 3.11 mmol) and NEt3 (0.64 mL, 4.66 mmol), 4af
was isolated as a colourless solid (465 mg, 51%), mp¼88 ꢀC. 1H NMR
(CDCl3, 250 MHz): d¼1.30 (t, 3J¼7.1 Hz, 3H, CH3), 4.27 (q, 3J¼7.1 Hz,
2H, OCH2CH3), 4.65 (s, 2H, CH2), 7.04–7.13 (m, 3H, ArH), 7.24–7.32
(m, 3H, ArH), 7.47 (dd, 3J¼8.3 Hz, 4J¼0.6 Hz, 1H, ArH), 7.62–7.69 (m,
1H, ArH), 8.16 (dd, 3J¼7.8 Hz, 4J¼1.5 Hz, 1H, ArH), 9.05 (s, 1H, ArH).
13C NMR (62 MHz, CDCl3): d¼14.1 (CH3), 40.0 (CH2), 62.0 (OCH2),
114.6 (C), 118.6 (CH), 121.6, 123.1 (C), 125.1, 126.7, 127.0 (CH), 128.8
(2C, CH), 131.0 (2C, CH), 134.4, 134.9 (C), 135.9, 141.0 (CH), 155.5,
164.6 (C), 165.4, 176.9 (C]O). IR (KBr, cmꢂ1): ~n¼3074 (w), 2982 (w),
2930 (w), 1725 (s), 1674 (s), 1600 (s), 1551 (m), 1310 (m), 1264 (s),
1159 (m), 765 (m), 689 (m), 528 (w), 508 (w). GC–MS (EI, 70 eV):
m/z (%)¼391 (Mþ, 100), 58 (10), 345 (40), 282 (13), 254 (94), 226
(17), 196 (12), 170 (4), 109 (13), 65 (8). HRMS (EI) calcd for
3.2.29. Ethyl 2-(7,9-dichloro-5-oxo-3-phenoxy-5H-chromeno-
[2,3-b]pyrid-2-yl)acetate (4ac)
Starting with 1f (125 mg, 0.52 mmol), 2p (247 mg, 0.67 mmol),
Me3SiOTf (0.12 mL, 0.67 mmol) and NEt3 (0.14 mL, 1.04 mmol), 4ac
was isolated as a colourless solid (102 mg, 44%), mp¼147 ꢀC. 1H
NMR (CDCl3, 300 MHz): d¼1.17 (t, 3J¼7.0 Hz, 3H, CH3), 4.07 (s, 2H,
CH2), 4.09 (q, 3J¼7.0 Hz, 2H, OCH2CH3), 7.01 (m, 2H, ArH), 7.17 (m,
1H, ArH), 7.35 (m, 2H, ArH), 7.74 (d, 4J¼2.6 Hz, 1H, ArH), 7.90 (s, 1H,
ArH), 8.05 (d, 4J¼2.6 Hz, 1H, ArH). 13C NMR (75 MHz, CDCl3): d¼13.1
(CH3), 38.6 (CH2), 60.4 (OCH2), 114.5 (C), 118.6 (2C, CH), 121.1 (CH),
121.7 (C), 123.5 (CH), 123.6 (C), 124.2 (CH), 129.0 (C), 129.4 (2C, CH),
134.4 (CH), 149.0, 150.6, 152.4, 153.2, 154.3 (C), 167.9, 174.7 (C]O).
IR (ATR, cmꢂ1): ~n¼3073 (w), 2983 (w), 2916 (w), 1720 (s), 1671 (s),
1423 (s),1225 (s),1192 (s),1120 (m),1024 (m), 991 (m), 802 (m), 785
(s), 692 (m). GC–MS (EI, 70 eV): m/z (%)¼447 ([M]þ, [2ꢁ37Cl],1), 445
([M]þ, [37Cl], [35Cl], 2), 443 ([M]þ, [2ꢁ35Cl], 4), 400 (3), 398 (4), 352
(25), 350 (38), 324 (64), 322 (100), 294 (15), 266 (5), 174 (2), 94 (5),
C
22H17NO4S [M]þ: 391.08738; found: 391.08728.
3.2.33. Ethyl 2-{3-[(4-chlorophenyl)sulfanyl]-7,8-dimethyl-5-oxo-
5H-chromeno[2,3-b]pyrid-2-yl}acetate (4ag)
Starting with 1h (400 mg, 2.0 mmol), 2t (418 mg, 2.6 mmol),
Me3SiOTf (0.46 mL, 2.6 mmol) and NEt3 (0.55 mL, 4.0 mmol), 4ag
was isolated as a colourless solid (515 mg, 56%), mp¼147 ꢀC. 1H
NMR (250 MHz, CDCl3): d¼1.14 (t, 3H, 3J¼7.1 Hz, CH3), 2.09 (s, 3H,
CH3), 2.14 (s, 3H, CH3), 4.10 (q, 2H, 3J¼6.9 Hz, OCH2CH3), 4.43 (s,
2H, CH2), 6.92 (m, 2H, ArH), 7.05 (s, 1H, ArH), 7.09 (m, 2H, ArH),
7.73 (s, 1H, ArH), 8.90 (s, 1H, ArH). 13C NMR (62 MHz, CDCl3):
d¼14.2, 19.2, 20.7 (CH3), 40.1, 60.9 (CH2), 114.8 (C), 118.7 (CH),
119.4, 122.6 (C), 126.4 (CH), 129.0 (2C, CH), 132.3 (2C, CH), 133.1,
133.6, 134.6, 141.1, 147.0, 153.9, 160.0, 164.6 (C), 164.9, 176.5 (C]O).
IR (neat, cmꢂ1): ~n¼3054 (w), 2975 (w), 2895 (w), 1703 (s), 1605 (s),
1463 (m), 1439 (s), 1240 (s), 1162 (s), 833 (s), 793 (m). GC–MS (EI,
70 eV): m/z (%)¼455 (Mþ, 37Cl, 17), 453 (Mþ, 35Cl, 46), 407 (20),
311 (30), 282 (100), 266 (23), 144 (20), 109 (15), 44 (78). HRMS
65 (7). HRMS (EI) calcd for
443.03114; found: 343.03218.
C
22H15Cl2NO5 ([M]þ, [2ꢁ35Cl]):
3.2.30. Methyl 2-[3-(4-chlorophenoxy)-7,8-dimethyl-5-oxo-5H-
chromeno[2,3-b]pyrid-2-yl]acetate (4ad)
Starting with 1h (400 mg, 2.0 mmol), 2q (1.00 g, 2.61 mmol),
Me3SiOTf (0.47 mL, 2.61 mmol) and NEt3 (0.55 mL, 4.0 mmol), 4ad
was isolated as a colourless solid (280 mg, 33%), mp¼155 ꢀC. 1H
NMR (CDCl3, 300 MHz): d¼2.26 (s, 3H, CH3), 2.32 (s, 3H, CH3), 3.61
(s, 3H, OCH3), 3.99 (s, 2H, CH2), 6.91 (d, 3J¼7.5 Hz, 2H, ArH), 7.26 (d,
3J¼7.3 Hz, 2H, ArH), 7.86 (s, 1H, ArH), 7.95 (s, 1H, ArH). 13C NMR
(75 MHz, CDCl3): d¼19.1, 20.6 (CH3), 39.2 (CH2), 52.3 (OCH3), 61.5
(OCH2), 116.3, 118.4 (C), 118.7 (CH), 120.4 (2C, CH), 123.6, 126.1 (CH),
129.9 (C), 130.0 (2C, CH),133.9,146.6,149.9,151.8,153.9,154.0,154.5
(C), 169.5, 176.7 (C]O). IR (ATR, cmꢂ1): ~n¼3051 (w), 2956 (w), 2847
(w), 1730 (s), 1607 (s), 1471 (s), 1410 (s), 1318 (s), 1209 (s), 1145 (s),
1087 (s), 994 (m), 873 (m), 672 (w). GC–MS (EI, 70 eV): m/z (%)¼425
(Mþ, 37Cl, 1), 423 (Mþ, 35Cl, 3), 392 (1), 364 (1), 296 (100), 266 (7),
(ESI) calcd for
453.07890.
C
24H20NO4ClS (Mþ, 35Cl): 453.07961; found:
3.2.34. Ethyl 2-{7-methyl-3-[(4-methylphenyl)sulfanyl]-5-oxo-5H-
chromeno[2,3-b]pyrid-2-yl}acetate (4ah)
Starting with 1b (400 mg, 2.16 mmol), 2u (396 mg, 2.81 mmol),
Me3SiOTf (0.50 mL, 2.81 mmol) and NEt3 (0.60 mL, 4.3 mmol), 4ah
was isolated as a colourless solid (572 mg, 63%), mp¼148 ꢀC. 1H
NMR (250 MHz, CDCl3): d¼1.51 (t, 3H, 3J¼7.2 Hz, CH3), 2.38 (s, 3H,
CH3), 2.58 (s, 3H, CH3), 4.48 (q, 2H, 3J¼7.1 Hz, OCH2CH3), 4.83 (s, 2H,
CH2), 7.15 (d, 2H, 3J¼7.91 Hz, ArH), 7.37 (d, 2H, 3J¼7.6 Hz, ArH), 7.60
238 (4), 127 (1), 99 (2). HRMS (EI) calcd for C23H18ClNO5 (Mþþ
35Cl): 423.08620; found: 423.08680.
,

5424
M.A. Rashid et al. / Tetrahedron 64 (2008) 5416–5425
(d, 1H, 3J¼8.7 Hz, ArH), 7.70 (dd, 1H, 3J¼6.91 Hz, 4J¼2.5 Hz, ArH),
8.21 (d, 1H, 4J¼2.62 Hz, ArH), 9.30 (s, 1H, ArH). 13C NMR (62 MHz,
CDCl3): d¼14.1, 20.8, 21.0 (CH3), 40.6, 61.9 (CH2), 114.5 (C), 118.0
(CH), 121.0, 123.2 (C), 126.1 (CH), 129.6 (2C, CH), 131.0 (C), 131.9 (2C,
CH), 135.2 (C), 137.1 (CH), 137.3 (C), 140.9 (CH), 153.7, 160.1, 164.7 (C),
165.5, 176.8 (C]O). IR (neat, cmꢂ1): ~n¼3075 (w), 2979 (w), 2810
(w), 1731 (s), 1695 (s), 1475 (m), 1339 (s), 1249 (s), 1062 (s), 803 (s),
796 (m). GC–MS (EI, 70 eV): m/z (%)¼419 (Mþ, 91), 404 (5), 373 (21),
268 (100), 240 (17), 210 (21), 105 (11). HRMS (ESI) calcd for
1027 (w), 930 (m), 845 (m), 760 (s), 750 (m), 685 (m). GC–MS (EI,
70 eV): m/z (%)¼297 (Mþ, 0.7), 269 (83), 238 (90),182 (7). HRMS (EI)
calcd for C17H15O4N (Mþ): 297.09956; found: 297.098859.
3.2.38. Ethyl 6-aza-5-oxa-12-oxo-7,9,10,12-tetrahydronaphtacene-
7-carboxylate (4al)
Starting with 1a (240 mg, 1.4 mmol), Me3SiOTf (404 mg,
0.33 mL, 1.82 mmol) and 2y (573 mg, 1.82 mmol), 4al (163 mg, 36%)
was isolated as a yellow solid. 1H NMR (300 MHz, CDCl3): d¼1.29 (t,
3J¼7.1 Hz, 3H, OCH2CH3), 1.92 (m, 2H, CH2), 2.27 (m, 2H, CH2), 2.97
(m, 2H, CH2), 4.04 (t, 3J¼6.1 Hz, 1H, CH), 4.26 (q, 3J¼7.3 Hz, 2H,
OCH2CH3), 7.39 (m, 1H, Ar), 7.57 (dd, 3J¼8.0 Hz, 4J¼1.0 Hz, 1H, Ar),
7.75 (m, 1H, Ar), 8.28 (dd, 3J¼7.9 Hz, 4J¼1.6 Hz, 1H, Ar), 8.43 (s, 1H,
Ar). 13C NMR (DEPT, 75.5 MHz, CDCl3): d¼14.2 (OCH2CH3), 20.0,
26.7, 27.8 (CH2), 48.7 (CH), 61.2 (OCH2CH3), 115.5 (C), 118.5 (CH),
121.5 (C), 124.4, 126.6 (CH), 130.7 (C), 135.5, 137.6 (CH), 155.8, 158.0,
159.6 (C), 173.1 (C]O, ester), 177.6 (C]O, ketone). IR (KBr, cmꢂ1):
~n¼3444 (m), 2980 (m), 2946 (m), 1734 (s), 1663 (s), 1608 (s), 1559
(m), 1471 (s), 1471 (s), 1439 (s), 1415 (s), 1369 (m), 1313 (m), 1264
(m), 1226 (m), 1171 (s), 1063 (m), 1032 (s), 766 (s). UV–vis (CH3CN,
C
24H21NO4S (Mþ)þ: 419.11858; found: 419.11936.
3.2.35. Ethyl 2-{7,9-dichloro-3-[(4-methoxyphenyl)sulfanyl]-
5-oxo-5H-chromeno[2,3-b]pyrid-2-yl}acetate (4ai)
Starting with 1f (400 mg, 1.66 mmol), 2v (891 mg, 2.16 mmol),
Me3SiOTf (0.39 mL, 2.16 mmol) and NEt3 (0.6 mL, 4.32 mmol), 4ai
was isolated as a colourless solid (366 mg, 45%), mp¼153 ꢀC. 1H
NMR (CDCl3, 250 MHz): d¼1.28 (t, 3J¼7.0 Hz, 3H, CH3), 3.83 (s, 3H,
OCH3), 4.17 (s, 2H, CH2), 4.23 (q, 3J¼7.1 Hz, 2H, OCH2), 6.91 (d,
3J¼8.9 Hz, 2H, ArH), 7.41 (d, 3J¼8.9 Hz, 2H, ArH), 7.77 (d, 4J¼2.5 Hz,
1H, ArH), 8.06 (d, 4J¼2.5 Hz, 1H, ArH), 8.20 (s, 1H, ArH). 13C NMR
(75 MHz, CDCl3): d¼14.1 (CH3), 42.5 (CH2), 55.4 (OCH3), 61.5
(OCH2), 115.3 (C), 115.6 (2C, CH), 121.5, 123.2 (C), 124.5 (CH), 130.1,
134.8, 135.1 (C), 135.4 (CH), 135.5 (2C, CH), 137.2 (CH), 149.9, 157.3,
159.0, 160.6 (C), 168.7, 175.2 (C]O). IR (KBr, cmꢂ1): ~n¼3070 (w),
2985 (w), 2836 (w), 1727 (s), 1668 (s), 1591 (s), 1413 (s), 1387 (s),
1253 (s), 1176 (s), 1024 (s), 830 (m), 787 (m), 523 (w). GC–MS (EI,
70 eV): m/z (%)¼493 ([M]þ, [2ꢁ37Cl], 7), 491 ([M]þ, [37Cl], [35Cl], 32),
489 ([M]þ, [2ꢁ35Cl], 46), 419 (10), 417 (17), 384 (13), 311 (8), 266 (8),
207 (3), 97 (15), 85 (11), 84 (10), 57 (34), 44 (100). Anal. Calcd (%) for
nm): l
(lg 3): 341 (3.94), 292 (4.10), 232 (4.47). MS (EI, 70 eV):
max
m/z (%)¼323 (Mþ, 98), 250 ([MꢂCO2CH2CH3]þ, 100), 235 (16), 207
(7), 103 (5), 77 (8).
3.2.39. Ethyl 6-aza-9-methyl-5-oxa-12-oxo-7,9,10,12-
tetrahydronaphtacene-7-carboxylate (4am)
Starting with 1a (240 mg,1.4 mmol), Me3SiOTf (404 mg, 0.33 mL,
1.82 mmol) and 2z (573 mg, 1.82 mmol), 4am (145 mg, 32%) was
isolated as a yellow solid.1H NMR (300 MHz, CDCl3, dr¼3:2): d¼1.13,
1.16 (d, 3J¼6.3 Hz, 3H, CH3), 1.37 (m, 1H, CH2, CH2), 1.79–1.91 (m, 1H,
CH2, CH2), 2.20–2.35 (m, 1H, CH2, CH2), 2.72–2.48 (m, 1H, CH, CH),
2.95–3.10 (m, 1H, CH, CH), 3.73, 3.83 (s, 3H, OCH3, OCH3), 4.08–4.15
(m, 1H, CH, CH), 7.38–7.44 (m, 1H, Ar, Ar), 7.59 (d, 3J¼8.4 Hz, 1H, Ar,
Ar), 7.73–7.79 (m,1H, Ar, Ar), 8.28, 8.31 (t, 2J¼2.4 Hz,1H, Ar, Ar), 8.41,
8.45 (s, 1H, Ar, Ar). 13C NMR (DEPT, 75.5 MHz, CDCl3, signals of main
diastereomer): d¼21.2 (CH3), 25.6 (CH), 34.2, 36.1 (CH2), 48.1 (CH),
52.5 (CH3),115.6 (C),118.5 (CH),121.5 (C),124.4,126.7 (CH),130.5 (C),
135.5, 137.1 (CH), 155.8, 159.0, 159.6 (C), 173.8, 177.6 (C]O). IR (KBr,
cmꢂ1): ~n¼3437 (m), 2952 (m), 2926 (m), 1737 (s), 1661 (s), 1609 (s),
1559 (m), 1471 (s), 1418 (s), 1319 (m), 1267 (m), 1223 (m), 1197 (m),
1161 (m), 767 (m). UV–vis (CH3CN, nm): lmax (lg 3): 341 (4.00), 292
(4.14), 232 (4.49). MS (EI, 70 eV): m/z (%)¼323 (Mþ, 28), 208 (34),
248 (43), 108 (7), 120 (100), 106 (34).
C
23H17Cl2NO5S: C, 56.34; H, 3.49; N, 2.86. Found: C, 56.33; H, 3.46;
N, 2.87.
3.2.36. Ethyl 2-{7,9-dichloro-3-[(4-methoxyphenyl)sulfanyl]-
5-oxo-5H-chromeno[2,3-b]pyrid-2-yl}propionate (4aj)
Starting with 1a (256 mg, 1.5 mmol), Me3SiOTf (433 mg,
0.33 mL, 1.95 mmol), 2w (560 mg, 1.95 mmol), CH2Cl2 (13.5 mL),
EtOH (15 mL) and triethylamine (324 mg, 0.44 mL, 3.00 mmol),
4aj was isolated as a yellow oil (149 mg, 34%). 1H NMR (CDCl3,
250 MHz): d¼1.12 (t, J¼7.2 Hz, 3H, CH3), 1.53 (d, J¼7.2 Hz, 3H, CH3),
3.92 (q, J¼7.2 Hz, 1H, CH), 4.04–4.13 (m, 2H, CH2), 7.32 (d, J¼8.0 Hz,
2H, ArH), 7.50 (d, J¼7.7 Hz, 1H, ArH), 7.64–7.70 (m, 1H, ArH), 8.18–
8.21 (dd, J¼1.4, 8.0 Hz,1H, ArH), 8.58 (d, J¼7.8 Hz,1H, ArH). 13C NMR
(62 MHz, CDCl3): d¼14.0, 16.9 (CH3), 48.3 (CH), 61.3 (OCH2), 115.3
(C), 118.4, 119.7 (CH), 121.6 (C), 124.6, 126.6, 135.5, 137.9 (CH), 155.7,
159.8, 165.6 (C), 172.3, 177.3 (C]O). IR (KBr, cmꢂ1): ~n¼3307 (w),
3069 (w), 2980 (m), 2874 (w), 1730 (s), 1662 (s), 1614 (m), 1598 (s),
1559 (m), 1461 (s), 1397 (s), 1318 (w), 1250 (m), 1149 (m), 1107 (m),
1027 (w), 958 (m), 852 (m), 763 (s), 688 (m). GC–MS (EI, 70 eV): m/z
(%)¼297 (Mþ, 18), 252 (5), 225 (35), 224 (100). HRMS (EI) calcd for
Acknowledgements
Financial support from the State of Pakistan (HEC scholarships
for M.A.R. and N.R.), from the State of Mecklenburg-Vorpommern
(scholarships for V.K. and S.M.) and from the DAAD (scholarship for
S.M.) is gratefully acknowledged.
C
17H15O4N (Mþ): 297.09956; found: 297.099255.
3.2.37. Methyl 2-{7,9-dichloro-3-[(4-methoxyphenyl)sulfanyl]-
5-oxo-5H-chromeno[2,3-b]pyrid-2-yl}butyrate (4ak)
References and notes
1. (a) Akira, N.; Toshihira, I.; Kiyoshi, U. J. Med. Chem. 1985, 28, 559; (b) Lo¨we, W.;
Jeske, P. Liebigs Ann. Chem. 1987, 549.
Starting with 1a (256 mg,1.5 mmol), Me3SiOTf (433 mg, 0.33 mL,
1.95 mmol), 2x (560 mg,1.95 mmol), CH2Cl2 (13.5 mL), EtOH(15 mL)
and triethylamine (324 mg, 0.44 mL, 3.00 mmol), 4ak was isolated
as a yellow oil (136 mg, 31%). 1H NMR (CDCl3, 250 MHz): d¼0.88 (t,
J¼7.4 Hz, 3H, CH3), 1.93–2.23 (m, 2H, CH2), 3.46 (s, 3H, CH3), 3.80 (t,
J¼7.7 Hz, 1H, CH), 7.31–7.40 (m, 2H, ArH), 7.52–7.55 (d, J¼7.7 Hz, 1H,
ArH), 7.66–7.73 (m, 1H, ArH), 8.20–8.24 (dd, J¼1.4, 8.0 Hz, 1H, ArH),
8.58 (d, J¼7.8 Hz, 1H, ArH). 13C NMR (62 MHz, CDCl3): d¼12.0 (CH3),
25.5 (CH2), 52.3 (OCH3), 55.7 (CH), 115.4 (C), 118.4, 120.1 (CH), 121.6
(C), 124.6, 126.6, 135.5, 137.9 (CH), 155.6,159.8,164.4 (C), 172.2, 177.3
(C]O). IR (KBr, cmꢂ1): ~n¼3316 (w), 3068 (w), 2966 (m), 2875 (w),
2841 (w), 2705 (w), 1732 (s), 1661 (s), 1613 (m), 1597 (s), 1585 (m),
1599 (m), 1460 (s), 1397 (s), 1350 (w), 1194 (m), 1149 (m), 1103 (m),
2. (a) Ghosh, C. K.; Sinha, R. D. K.; Mukhopadhyay, K. K. J. Chem. Soc., Perkin Trans. 1
1979, 1964; (b) Kubo, K.; Ukawa, K.; Kuzuna, S.; Nohara, A. Chem. Pharm. Bull.
1986, 34, 1108; (c) Zheng, H.; Lin, G.; Weng, L. L. Indian J. Chem. 1998, 37B, 933.
3. (a) Iwasaki, H.; Kume, T.; Yamamoto, Y.; Akiba, K.-Y. Tetrahedron Lett. 1987,
6355; (b) Lee, Y.-G.; Ishimaru, K.; Iwasaki, H.; Ohkata, K.; Akiba, K. J. Org. Chem.
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Beifuss, U.; Tietze, M.; Gehm, H. Synlett 1996, 182.
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6. For a review of domino reactions of 4-(silyloxy)benzopyrylium triflates with
1,3-bis(trimethylsilyloxy)-1,3-butadienes, see: Langer, P. Synlett 2007, 1016.
7. Langer, P.; Appel, B. Tetrahedron Lett. 2003, 5133.

M.A. Rashid et al. / Tetrahedron 64 (2008) 5416–5425
5425
8. For a review of 1,3-bis(trimethylsilyloxy)-1,3-butadienes in general, see: Langer,
P. Synthesis 2002, 441.
9. (a) Chan, T.-H.; Brownbridge, P. J. Am. Chem. Soc. 1980, 102, 3534; (b) Molander,
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11. CCDC-669708 contains all crystallographic details of this publication and is
available free of charge at www.ccdc.cam.ac.uk/conts/retrieving.html or can be
ordered from the following address: Cambridge Crystallographic Data Centre,
12 Union Road, GB-Cambridge CB21EZ; fax: þ44 1223 336 033 or deposit@ccdc.
cam.ac.uk.
10. Appel, B.; Saleh, N. N. R.; Langer, P. Chem.dEur. J. 2006, 12, 1221.