One-pot synthesis of isoindolo[2,1-a]quinolin-11-ones by cyclocondensation of 3-hydroxy-2-arylisoindol-1-ones with 1,3-dicarbonyls

Article abstract of DOI:10.1055/s-0028-1087955

Isoindolo[2,1-a]quinolin-11-ones have been synthesized by one-pot reaction of 3-hydroxy-2-arylisoindol-1-ones with 1,3-dicarbonyls via coupling of N-acyliminium ion intermediates with 1,3-dicarbonyls and subsequent intramolecular Friedel-Crafts reactions

Full text of DOI:10.1055/s-0028-1087955

LETTER
843
One-Pot Synthesis of Isoindolo[2,1-a]quinolin-11-ones by Cyclocondensation
of 3-Hydroxy-2-arylisoindol-1-ones with 1,3-Dicarbonyls
S
ynthesis of Isoind
u
olo[2,1-
a
]qu
e
inolin-11-o
h
nes ua Zhou, Lingfeng Qian, Wei Zhang*
State Key Laboratory of Applied Organic Chemistry, Lanzhou University, Lanzhou 730000, P. R. of China
Fax +86(931)8625657; E-mail: zhangwei6275@lzu.edu.cn
Received 20 September 2008
Ph3P=CHCO2Et2g,1a to produce isoindolo[2,1-a]quino-
line-5,11-diones.
Abstract: Isoindolo[2,1-a]quinolin-11-ones have been synthesized
by one-pot reaction of 3-hydroxy-2-arylisoindol-1-ones with 1,3-
dicarbonyls via coupling of N-acyliminium ion intermediates with
1,3-dicarbonyls and subsequent intramolecular Friedel–Crafts reac-
tions catalyzed by H3PO4–P2O5 or H3PO4–H2SO4.
As a part of our research program directed towards the
synthesis of polycyclic heterocycles, we recently reported
the synthesis of 5-aryl-5,6,6a,12-tetrahydroisoindolo[2,1-
a]quinolin-11-ones and 5-aryl-3a,9a-dihydropyrrolo[2,1-
a]quinolin-1-ones by the [4+2] reactions of N-acylimini-
um ions produced from 3-hydroxy-2-arylisoindol-1-ones
with styrenes.4 We report herein a concise and efficient
synthesis of 6-ethoxycarbonyl- or 6-acyl-subsituted
6a,11-dihydroisoindolo[2,1-a]quinolin-11-ones by a one-
pot reaction of 3-hydroxy-2-aryl-isoindol-1-ones and 1,3-
dicarbonyls via the coupling of N-acyliminium ions pro-
duced from 3-hydroxy-2-aryl-isoindol-1-ones with 1,3-
dicarbonyls and subsequent intramolecular Friedel–Crafts
reactions catalyzed by acids. Although the coupling of N-
acyliminium ions produced from 5-hydroxypyrrolidin-2-
ones and 4-hydroxy[1,3]benzoxazin-2-ones with 1,3-di-
carbonyls had been reported,5 but no similar work has
been found in literature for 3-hydroxy-2-arylisoindol-1-
ones. Only the condensation of 3-methoxy-2-phenylisoin-
dol-1-ones with acetaldehyde to form 5,6,6a,11-tetrahy-
dro-5-trifluoroacetoxyisoindolo[2,1-a]quinolin-11-one
was reported recently.6 Therefore, this is the first report of
Key words: 2,3-dihydro-3-hydroxy-2-arylisoindol-1-one, 1,3-di-
carbonyls, 6a,11-dihydroisoindolo[2,1-a]quinolin-11-ones, N-acyl-
iminium ions, Friedel–Crafts reaction
Isoindolo[2,1-a]quinolines are a class of molecules that
possess a wide range of biological activities. For exam-
ples, 6-aminomethylisoindolo[2,1-a]quinolin-5,11-diones,
analogues of berberine alkaloids, show protective effects
against N2-induced hypoxia and are used for prophylactic
and therapeutic treatment of senile dementia, angina pec-
toris, myocardial infarction, and emotional disorder
caused by stroke and cerebral infarction;1a,b trihydroxy-
isoindolo[2,1-a]quinolin-5,11-diones show inhibitory ac-
tivities against bacterial DNA-gyrase and human
topoisomerase II.1c Considering the important pharmaco-
logical properties displayed by the isoindolo[2,1-a]quino-
line core, several synthetic approaches have been
developed2a–2f and reviewed,3 for example, N-acylation of
4-(2′-furyl)-4-(N-aryl)aminobutenes with maleic anhy-
dride, subsequent intramolecular Diels–Alder reaction
with the furan moiety, and dehydration to afford the
5,6,6a,12-tetrahydroisoindolo[2,1-a]quinolin-11-one-10-
carboxylic acids;2a,b the Suzuki–Miyaura coupling of
2-chloroquinoline with 2-formylphenylboronic acid and
nucleophilic cyclization to produce 5,6,6a,12-tetrahydro-
isoindolo[2,1-a]quinolin-11-one;2c lithium bistrimethylsi-
lylamide (LBTSA)2d or sodium hydride2e catalyzed
intramolecular aldol condensation of 2-(phthalimidin-3-
yl)acetophenone and thermal dehydration; one-pot con-
densation of substituted 2-amino-2-methoxyacetophe-
nones with phthalic anhydrides in refluxing toluene in the
presence of triethylamine to give isoindolo[2,1-a]quino-
line-5,11-diones;1b intramolecular Friedel–Crafts reaction
of 2-aryl-3-carboxymethyl isoindol-1-ones prepared from
the reaction of the 2-aryl-3-hydroxyisoindol-1-ones with
1-methoxy-1-trimethylsilyloxyethene in the presence of
titanium(IV) chloride2f or from Wittig reaction of N-
acyliminium ion from 3-hydroxyphenylisoindolones with
a
one-pot synthesis of 6a,11-dihydroisoindolo[2,1-
a]quinolin-11-ones from 3-hydroxy-2-arylisoindol-1-
ones and 1,3-dicarbonyls (Scheme 1).
N-Acyliminium ions are known as important, reactive
species in organic synthesis for the construction of
carbon–carbon bonds.5–7 The reactions of N-acyliminium
ions generated from 5-ethoxypyrrolidin-2-ones or 5-ace-
toxypyrrolidin-2-ones with ethyl acetoacetate under the
catalysis of NbCl5 or AlCl3 afforded coupling product eth-
yl 2-(2-oxo-pyrrolidin-2-on-5-yl)acetoacetate in high
yields.5a,b We found the reaction of N-acyliminium ion
generated from 3-hydroxy-2-phenylisoindol-1-ones (1a)
with ethyl acetoacetate (2a) could also proceed quickly
under the catalysis of BF3·OEt2, TFA, PTSA, or H3PO4 to
afford the coupling product ethyl 2-(1-oxo-2-arylisoindol-
3-yl)acetoacetate (4) in high yields, but no further
Friedel–Crafts reaction between aryl group and carbonyl
group took place. Only when P2O5 (method A) or H2SO4
(method B) was added to the above solutions, the coupling
product ethyl 2-(1-oxo-2-arylisoindol-3-yl)acetoacetate
could be converted into the cyclization product 6-ethoxy-
carbonyl-6a,11-dihydroisoindolo[2,1-a]quinolin-11-one
(3a) smoothly (Scheme 2).
SYNLETT 2009, No. 5, pp 0843–0847
x
x.
x
x.
2
0
0
9
Advanced online publication: 26.02.2009
DOI: 10.1055/s-0028-1087955; Art ID: W14608ST
© Georg Thieme Verlag Stuttgart · New York

844
Y. Zhou et al.
LETTER
O
O
O
O
N
X
H3PO4–P2O5
R1
R2
N
X
+
or
H3PO4–H2SO4
O
R2
OH
R1
3a–k
2a–d
1a–e
Scheme 1 Reactions of 3-hydroxy-2-arylisoindol-1-ones with 1,3-dicarbonyls
O
O
O
BF3⋅OEt2
N
N
O
O
or TFA
P2O5
N
+
Me
OEt
O
O
or H3PO4
r.t.
or H2SO4
r.t.
O
R2
OH
OEt Me
R1
3a
1a
2a
4a
Scheme 2 Two-step synthesis of 3a
After comparison of the experimental results from differ-
ent catalysts and solvents, H3PO4–P2O5 or H3PO4–H2SO4
mixture was selected as a catalyst for the reactions of 3-
hydroxy-2-arylisoindol-1-ones (1a–e) with 1,3-dicarbon-
yls including ethyl acetoacetate (2a), acetoacetone (2b),
and benzoylacetone (2c) as well as monocarbonyl com-
pound cyclohexanone (2d).8 The results of the reactions
are summarized in Table 1. All these reactions afforded
isoindolo[2,1-a]quinolin-11-ones as the main products
1
which were fully characterized by H NMR, 13C NMR,
and MS and the structure of 3c was further confirmed by
X-ray crystal structure as depicted in Figure 1.9
In comparison of the reactions of 1a–e with 2a, it could be
noticed that the reaction rate of 1b with 2a was faster than
that of 1a with 2a, and the yield of product 3b was higher
than that of 3a; while the reaction rate of 1c with 2a was
much slower than that of 1a with 2a, and the yield of prod-
uct 3c was relatively lower. These results could be as-
cribed to the activating effect of methyl group and the
deactivating effect of chlorine atom. But in the case of 1d,
the yield of 3d was decreased because 1d could undergo
self-condensation in acidic medium. In contrast to 1a–d,
no cyclization product was obtained from the reaction of
1e with 2a (Scheme 3), only the decarboxylation product
5 was separated from the reaction mixture after prolonged
stirring. Obviously, the deactivating effect of nitro group
resisted the intramolecular Friedel–Crafts reaction.
Figure 1 The X-ray crystal structure (ORTEP drawing) of 3c
Another difference in the reaction outcome was found in
the reaction of 1a,b with 2b under different reaction con-
ditions. The main products produced in H3PO4–P2O5 me-
dium at room temperature were the normal cyclization
products 3e and 3f, but in the presence of H3PO4–H2SO4
at 60 °C deacetylation and reduction products 6a and 6b
appeared as main products (Scheme 4). We were unable
to rationalize the mechanism of their formation.
Besides of the 1,3-dicarbonyls, cyclohexanone (2d) could
also react with 1a,b under similar conditions to give the
isoindolo[2,1-a]quinolin-11-ones as shown in Scheme 5.
O
O
O
O
N
NO2
H3PO4–H2SO4
60 °C, 4 h
+
N
NO2
Me
OEt
O
OH
2a
5
1e
Me
Scheme 3 Reaction of 1e with 2a in H3PO4–H2SO4 under heating
Synlett 2009, No. 5, 843–847 © Thieme Stuttgart · New York

LETTER
Synthesis of Isoindolo[2,1-a]quinolin-11-ones
845
Table 1 The Reactions of 3-Hydroxy-2-arylisoindol-1-ones with 1,3-Dicarbonyls Catalyzed by Acids
Entry
Reactant
Method
Time (h)
Temp (°C) Product
Yield (%)c
X
R1
R2
1
2
1a
1a
1a
1b
1c
1d
1e
1a
1a
1a
1a
1b
1b
1a
1a
1b
1c
1a
1b
H
2a
2a
2a
2a
2a
2a
2a
2b
2b
2b
2b
2b
2b
2c
2c
2c
2c
2d
2d
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Ph
OEt
OEt
OEt
OEt
OEt
OEt
OEt
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Aa
A
Bb
A
A
A
B
24
12
16
8
r.t.
60
r.t.
60
60
60
60
r.t
3a
85
H
3a
78
3
H
3a
75
4
Me
Cl
MeO
NO2
H
3b
93
5
32
12
4
3c
76
6
3d
45
7
5
90
8
A
A
B
34
4
3e
83
9
H
60
r.t
3e + 6a
3e + 6a
6a
62 + 8
28 + 37
78
10
11
12
13
14
15
16
17
18
19
H
24
2
H
B
60
60
60
60
60
r.t.
60
60
60
Me
Me
H
A
B
1.5
0.5
2
3f
82
6b
67
A
B
3g
81
H
Ph
1
3g
75
Me
Cl
H
Ph
A
A
A
A
12
32
12
6
3h
84
Ph
3i
78
cyclohexanone
cyclohexanone
3j
63
Me
3k
78
a H3PO4–P2O5 as catalyst.
b H3PO4–H2SO4 as catalyst.
c Isolation yields based on 1a–e.
O
N
X
H3PO4–P2O5
r.t.
O
Me
O
N
O
O
X
+
3e X = H
3f X = Me
Me
Me
OH
O
N
1a X = H
1b X = Me
2b
H3PO4–H2SO4
60 °C
X
Me
6a X = H
6b X = Me
Scheme 4 Reactions of 1a,b with 2b under two different conditions
Synlett 2009, No. 5, 843–847 © Thieme Stuttgart · New York

846
Y. Zhou et al.
LETTER
O
O
O
N
X
H3PO4–P2O5
60 °C
N
X
+
OH
1a X = H
1b X = Me
2d
3j X = H
3k X = Me
Scheme 5 Reactions of 1a,b with cyclohexanone (2d)
OH
O
O
O
OEt
H3PO4
2a
+
N
N
OH
1a
O
N
O
O
– H2O
N
N
+
OH
O
O
O
OH
OEt
3a
OEt
OEt
Scheme 6 Plausible mechanism for the formation of 3a
Podlogar, B. L.; Ohemeng, K. A. Bioorg. Med. Chem. 1998,
6, 735. (c) Goto, G.; Ishihara, Y. JP 02042078, 1990;
Application: JP 88-193656 19880802.
According to the above results, a plausible mechanism for
the formation of isoindolo[2,1-a]quinolin-11-ones was
proposed (Scheme 6). The reaction was initiated by the
formation of an N-acyliminium intermediate which was
then attached by the nuclephilic 1,3-dicarbonyl com-
pounds. Subsequent intramolecular Friedel–Crafts reac-
tion between the protected aniline with the ketone
afforded the isoindolo[2,1-a]quinolin-11-one derivative.
(2) (a) Kouznetsov, V. V.; Cruz, U. M.; Zubkov, F. I.; Nikitina,
E. V. Synthesis 2007, 375. (b) Zubkov, F. I.; Boltukhina,
E. V.; Turchin, K. F.; Borisov, R. S.; Varlamov, A. V.
Tetrahedron 2005, 61, 4099. (c) Mamane, V.; Fort, Y.
Tetrahedron Lett. 2006, 47, 2337. (d) Hamersak, Z.; Litvic,
M.; Sepac, D.; Lesac, A.; Raza, Z.; Sunjic, V. Synthesis
2002, 2174. (e) Kim, G.; Keum, G. Heterocycles 1997, 45,
1979. (f) Epsztajn, J.; Jozwiak, A.; Koluda, P.; Sadokierska,
I.; Wilkowska, I. D. Tetrahedron 2000, 56, 4837.
(g) Epsztajn, J.; Grzelak, R.; Jozwiak, A. Synthesis 1996,
1212. (h) Kumar, P.; Dinesh, C. U.; Pandey, B. Tetrahedron
Lett. 1994, 35, 9229.
In summary, an efficient methodology for the synthesis of
isoindolo[2,1-a]quinolin-11-ones has been developed. To
our best knowledge, this is the first report for the synthesis
of these compounds via a one-pot, two-step reaction of N-
acyliminium ions with 1,3-dicarbonyls under the catalysis
of H3PO4–P2O5 or H3PO4–H2SO4. Further investigations
of synthetic application of this strategy were under way.
(3) Bonnett, R.; North, S. A. Adv. Heterocycl. Chem. 1981, 29,
341.
(4) (a) Zhang, W.; Zhen, A.; Liu, Z.; Yang, L.; Liu, Z. L.
Tetrahedron Lett. 2005, 46, 5691. (b) Zhang, W.; Huang,
L.; Wang, J. Synthesis 2006, 2053.
(5) (a) Kleber, C.; Andrade, Z.; Matos, R. A. F. Synlett 2003,
1189. (b) Kraus, G. A.; Neuenschwander, K. Tetrahedron
Lett. 1980, 21, 3841.
Supporting Information for this article is available online at
http://www.thieme-connect.com/ejournals/toc/synlett.
(6) Lübbers, T.; Angehrn, P.; Gmünder, H.; Herzig, S. Bioorg.
Med. Chem. Lett. 2007, 17, 4708.
Acknowledgment
(7) (a) Maryanoff, B. E.; Zhang, H. C.; Cohen, J. H.; Turchi,
I. J.; Maryanoff, C. A. Chem. Rev. 2004, 104, 1431.
(b) Speckamp, W. N.; Hiemstra, H. Tetrahedron 1985, 41,
4367.
We thank the National Natural Science Foundation of China
(20872056) for financial support.
(8) Typical Experimental Procedure
References and Notes
Method A
(1) (a) Ishihara, Y.; Kiyota, Y.; Goto, G. Chem. Pharm. Bull.
1990, 38, 3024. (b) Sui, Z.; Altom, J.; Nguyen, V. N.;
Fernandez, J.; Bernstein, J. I.; Hiliard, J. J.; Barrett, J. F.;
To a stirred mixture of 3-hydroxy-2-phenylisoindol-1-one
(1a, 1.0 mmol), ethyl acetoacetate (2b, 1.2 mmol) and
H3PO4 (2 mL), P2O5 (2 g) was added at one portion at r.t.
After the solid was dissolved completely the mixture was
stirred at r.t. or heated at 60 °C for 6–24 h (TLC control). The
Synlett 2009, No. 5, 843–847 © Thieme Stuttgart · New York

LETTER
reaction was quenched by crashed ice and the solution was
Synthesis of Isoindolo[2,1-a]quinolin-11-ones
847
134.7 (C), 136.8 (C), 140.1 (C), 166.5 (CO), 196.9 (CO).
MS: m/z (%) = 351 (37) [M+], 350 (14), 336 (25), 246 (79),
105 (100), 77 (89). Anal. Calcd (%) for C24H17NO2: C,
82.03; H, 4.88; N, 3.99 Found: C, 81.94; H, 4.84; N, 4.07.
Compound 3j: colorless needles; 131–132 °C. 1H NMR (300
MHz, CDCl3): d = 1.49–1.75 (m, 2 H), 1.81–1.85 (m, 2 H),
2.16–2.31 (m, 2 H), 2.54–2.62 (m, 2 H), 5.40 (s, 1 H, NCH),
7.22 (t, 1 H, J = 8.7 Hz), 7.30–7.35 (m, 2 H), 7.49–7.61 (m,
2 H), 7.67 (d, 1 H, J = 7.8 Hz), 7.95 (d, 1 H, J = 6.5 Hz), 8.05
(d, 1 H, J = 6.9 Hz). 13C NMR (75 MHz CDCl3): d = 22.0
(CH2), 22.2 (CH2), 22.4 (CH2), 27.5 (CH2), 60.8 (NCH),
121.3 (CH), 122.7 (CH), 124.0 (CH), 124.7 (CH), 127.3
(CH), 127.6 (C), 128.4 (CH), 129.2 (C), 130.4 (C), 131.5
(CH), 132.4 (C), 133.6 (C), 141.2 (C), 165.6 (NCO). MS
(EI): m/z (%) = 287 (86) [M+], 286 (67), 270 (4), 258 (100),
232 (10), 216 (11). Anal. Calcd (%) for C20H17NO: C, 83.60;
H, 5.96; N, 4.87 Found: C, 83.67; H, 6.02; N, 4.74.
Compound 5: colorless needles; 172–174 °C. 1H NMR (300
MHz CDCl3): d = 2.20 (s, 3 H, CH3), 2.73 (dd, 1 H, J = 18.6,
9.6 Hz, CHH), 3.15 (dd, 1 H, J = 18.0, 2.4 Hz, CHH), 5.83
(dd, 1 H, J = 9.6, 2.4 Hz CH), 7.49 (d, 1 H, J = 7.5 Hz, C-5),
7.64 (t, 1 H, J = 7.2 Hz, ArH), 7.55 (t, 1 H, J = 7.2 Hz, ArH),
7.88 (d, 2 H, J = 8.7 Hz, H-2′), 7.92 (d, 1 H, J = 7.8 Hz, H-
7), 8.30 (d, 2 H, J = 9.0 Hz, H-3′). 13C NMR (75 MHz,
CDCl3): d = 30.7 (CH3), 46.2 (CH2), 55.7 (C-3), 121.2 (2 C),
122.8 (CH), 124.5 (CH), 124.9 (2 C), 129.1 (CH), 130.1 (C),
133.3 (CH), 142.6 (C), 143.8 (C), 144.8 (C), 167.1 (NCO),
205.6 (CO). MS (EI): m/z (%) = 310 (11) [M+], 293 (10), 281
(7), 267 (27), 253 (44), 234 (18), 43 (100). Anal. Calcd (%)
for C17H14N2O4: C, 65.80; H, 4.55; N, 9.03 Found: C, 65.75;
H, 4.62; N, 9.02.
Compound 6b: mixture of cis- and trans-isomers (30:70).
1H NMR (300 MHz, CDCl3): d (trans-isomer) = 1.48 (d, 3
H, J = 7.8 Hz, CH3), 1.78 (dt, 1 H, J = 9.3, 3.3 Hz, CHH),
2.30 (dd, 1 H, J = 12.9, 1.2 Hz, CHH), 2.33 (s, 3 H, CH3),
3.18 (t, 1 H, J = 6.6 Hz, CH), 4.78 (d, 1 H, J = 12.3, Hz
NCH), 7.06 (s, 1 H, H-4), 7.11 (d, 1 H, J = 8.4 Hz, H-2),
7.48–7.51 (m, 2 H), 7.57 (d, 1 H, J = 7.5 Hz), 7.92 (d, 1 H,
J = 8.4 Hz), 8.46 (d 1 H, J = 8.1 Hz); d (cis-isomer) = 1.42
(d 3 H, J = 6.9 Hz, CH3), 2.35 (s 3 H, CH3), 2.60 (dt 1 H,
J = 13 5, 1 2 Hz, CHH), 3 21 (t 3 H, J = 6 9 Hz, CH3), 4 70
(dd 1 H, J = 12 3, 2.4 Hz, NCH), 7.11 (d, 1 H, J = 8.4 Hz, H-
2), 7.18 (s, 1 H, H-4), 7.48–7.51 (m, 2 H), 7.59 (d, 1 H,
J = 6.9 Hz), 7.92 (d, 1 H, J = 8.4 Hz), 8.44 (d, 1 H, J = 7.8
Hz). 13C NMR (75 MHz, CDCl3): d (trans-isomer) = 21.0,
24.5, 30.8, 34.8, 54.2 (NCH), 120.1 (CH), 121.7 (CH), 124.1
(CH), 127.6 (CH), 128.3 (CH), 129.6 (CH), 131.0 (C), 131.8
(CH), 132.8 (C), 133.4 (C), 144.6 (C), 165.9 (NCO); d (cis-
isomer) = 20.9, 21.1, 31.4, 37.5, 58.7, 120.0 (CH), 121.7
(CH), 124.1 (CH), 127.6 (CH), 128.4 (CH), 129.6 (CH),
131.0 (C), 131.8 (CH), 132.9 (C), 133.4 (C), 144.6 (C),
165.9 (NCO). MS (EI): m/z = 263 (87) [M+], 248 (100), 232
(16), 220 (17), 115 (25), 77 (38).
extracted with CH2Cl2 (2 × 10 mL).The organic phase was
washed with sat. aq NaHCO3 (10 mL) and H2O, respectively
and dried with anhyd Na2SO4, concentrated at reduced
pressure to furnish the crude products 3a which was purified
by silica gel column chromatography using EtOAc–hexane
(1:9) as eluents and further purified by recrystallization from
EtOH.
Method B
The procedure is similar to method A, only P2O5 was
replaced by H2SO4 (2 mL, 98%) which was added dropwise
into the mixture of 1a (1.0 mmol), 2a (1.2 mmol), and H3PO4
(2 mL).
Selected Spectroscopic Data
Compound 3a: colorless needles; mp 124–126 °C. 1H NMR
(300 MHz, CDCl3): d = 1.33 (t, 3 H, J = 7.5 Hz, CH3), 2.21
(s, 3 H, CH3), 4.35 (q, 2 H, J = 7.5 Hz, OCH2), 5.92 (s, 1 H,
H-6a), 7.23 (t, 1 H, J = 7 8 Hz), 7.42–7.60 (m, 5 H), 7.96 (d,
1 H, J = 7.2 Hz H-10), 8.05 (d, 1 H, J = 7 8 Hz H-1). 13
C
NMR (75 MHz, CDCl3): d = 14.2 (CH3), 15.6 (CH3), 58.7
(OCH2), 61.0 (C-6a), 122.0 (CH), 123.7 (CH), 124.3 (CH),
125.0 (CH), 125.2 (CH), 126.8 (C), 127.5 (C), 128.9 (CH),
129.7(CH), 132.0 (C), 132.5 (CH), 133.7 (C), 134.7 (C),
140.7 (C), 166.5 (CO), 166.9 (CO). MS (EI): m/z (%) = 319
(18) [M+], 304 (8), 290 (30), 274 (4), 262 (6), 246 (99), 86
(100). Anal. Calcd (%) for C20H17NO3: C, 75.22; H, 5.37; N
4.39 Found: C, 75.13; H, 5.45; N 4.25.
Compound 3c: colorless needles; mp 151–153 °C. 1H NMR
(300 MHz, CDCl3): d = 1.33 (t, 3 H, J = 7.2 Hz, CH3), 2.17
(s, 3 H, CH3), 4.35 (q, 2 H, J = 7.5 Hz, OCH2), 5.90 (s, 1 H,
H-6a), 7.39 (dd, 1 H, J = 7.5, 1.5 Hz), 7.42 (d, 1 H, J = 1.5
Hz, H-4), 7.52–7.60 (m, 3 H), 7.94 (d, 1 H, J = 7.5 Hz, H-1),
8.00 (d, 1 H, J = 8.1 Hz, H-10). 13C NMR (75 MHz, CDCl3):
d = 14.2 (CH3), 15.6 (CH3), 58.5 (OCH2), 61.2 (C-6a), 123.1
(CH), 123.7 (CH), 124.4 (CH), 125.2 (CH), 128.0 (C), 129.0
(CH), 129.4 (CH), 130.4 (C), 131.7 (C), 132.5 (C), 132.7
(CH), 133.1 (C), 140.5 (C), 166.5 (CO), 166.7 (CO). MS
(EI): m/z (%) = 355 (8) [M + 2+], 353 (25 [M+], 340 (20), 338
(62), 326 (31), 324 (87), 310 (28), 296 (5), 282 (29), 280
(100). Anal. Calcd (%) for C20H18ClNO3: C, 67.90; H, 4.56;
N, 3.96 Found: C, 67.83; H, 4.63; N, 4.07.
Compound 3f: colorless needles; 141–143 °C. 1H NMR (300
MHz, CDCl3): d = 2.09 (s, 3 H, CH3), 2.16 (s, 3 H, CH3),
2.39 (s, 3 H, CH3), 5.80 (s, 1 H, H-6a), 7.23 (s, 1 H, H-4),
7.26 (t, 1 H, J = 6.0 Hz), 7.41 (d, 1 H, J = 7.2 Hz, H-2), 7.50–
7.59 (m, 3 H), 7.95 (d, 2 H, J = 8.7 Hz, H-1, H-10). 13C NMR
(75 MHz, CDCl3): d = 15.6 (CH3), 21.2 (CH3), 32.8 (CH3),
58.5 (C-6a), 121.5 (CH), 123.7 (CH), 124.3 (CH), 125.2
(CH), 127.2 (C), 128.9 (CH), 129.1 (C), 130.1 (CH), 132.1
(C), 132.2 (C), 132.4 (CH), 134.5 (C), 134.8 (C), 140.1 (C),
166.1 (CO), 204.6 (CO). MS (EI): m/z (%) = 303 (16) [M+],
302 (10), 288 (36), 260 (62), 246 (18), 230 (5), 217 (13), 43
(100). Anal. Calcd (%) for C20H17NO2: C, 79.18; H, 5.65; N,
4.62 Found: C, 79.12; H, 5.74; N, 4.55.
(9) (9) Crystal Data for Compound 3c
Compound 3g: colorless needles; 156–158 °C. 1H NMR
(300 MHz, CDCl3): d = 1.94 (s, 3 H, CH3), 6.06 (s, 1 H, H-
6a), 7.22–7.54 (m, 9 H), 7.80 (d, 2 H, J = 7.8 Hz, H-2¢), 7.90
(d, 1 H, J = 6.9 Hz, H-10), 8. 16 (d, 1 H, J = 7.5 Hz, H-1).
13C NMR (75 MHz, CDCl3): d = 16.4 (CH3), 59.2 (C-6a),
121.7 (CH), 124.0 (2 CH), 124.8 (CH), 125.0 (CH), 127.6
(C), 128.7 (CH), 128.9 (2 CH), 129.2 (2 CH), 129.6 (CH),
131.3 (C), 131.7 (C), 131.9 (C), 132.3 (CH), 134.1 (CH),
Formula: C20H16ClNO3; Mr = 353.79 monoclinic;
a = 9.3133(17) Å, b = 7.3351(14) Å, c = 24.716(5) Å,
b = 96.800(3)°; space group P2(1)/n; V = 1676.6(5) Å3;
colorless plates r = 1.402 g cm–3, T = 296(2) K, space group
P2(1)/c Z = 4, m(Mo Ka) = 0.71073 mm–1, cmax = 25.82°,
3217 reflections collected 2045 unique (Rint = 0.1585) which
was used in all calculations. Final wR (F2) = 0.0830 (all
data); CCDC No: 695063
Synlett 2009, No. 5, 843–847 © Thieme Stuttgart · New York

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