Regioselective synthesis of oxepin- and oxocin-annulated 2-quinolones

Article abstract of DOI:10.1055/s-2005-861786

A synthetic strategy based on tandem Claisen rearrangement and ring-closing metathesis was developed for the regioselective synthesis of some hitherto unknown oxepin- and oxocin-annulated 2-quinolones. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2005-861786

PAPER
403
Regioselective Synthesis of Oxepin- and Oxocin-Annulated 2-Quinolones
Synthesis of
O
h
xepin- and
O
i
xocin-
t
Annula
a
ted 2-Quin
l
olones K. Chattopadhyay,* Rajat Dey, Suman Biswas
Department of Chemistry, University of Kalyani, Kalyani-741235, India
Fax +91(33)25828282; E-mail: skchatto@yahoo.com
Received 16 June 2004; revised 28 October 2004
allyl bromide,
acetone, K2CO3,
reflux, 12 h
Abstract: A synthetic strategy based on tandem Claisen rearrange-
HO
O
ment and ring-closing metathesis was developed for the regioselec-
tive synthesis of some hitherto unknown oxepin- and oxocin-
annulated 2-quinolones.
79%
N
O
N
O
Me
Key words: Claisen rearrangement, ring-closing metathesis, qui-
Me
2
nolones, oxepin, oxocin
1
Br
( )n
Various quinolone derivatives are known1 to display in-
teresting biological properties ranging from microbial ac-
tivity to cytotoxicity. For this and other reasons interest in
the synthesis of new quinolone derivatives continues to
increase.2 Of particular interest have been3 the furo- and
pyranoquinolones because of their structural similarities
with the photoactive furo- and pyranocoumarins. Other
heterocyclic ring-fused quinolone derivatives have also
been prepared. On the other hand, very little information
is available about medium ring oxacycle-fused quinolone
derivatives which may, in part, be due to lack of general
methods for the synthesis of such ring systems.4 In recent
years ring-closing metathesis (RCM) has emerged5,6 as a
valuable tool for the construction of various carbocyclic
and heterocyclic ring systems of varying size and com-
plexity. Recently, we have described7 a new methodology
based on tandem Claisen rearrangement8 and ring-closing
metathesis reaction for the synthesis of oxepin- and oxo-
cin-annulated coumarin derivatives and other systems of
interest. Herein, we wish to report an analogous applica-
tion of the said methodology for the synthesis of some
hitherto unknown oxepin- and oxocin-fused quinolones.
Thus, starting from 6-hydroxy-N-methyl-2-quinolone3c
(1), the corresponding allyl ether 2 (Scheme 1) was easily
prepared by straightforward alkylation with allyl bromide.
Claisen rearrangement of the allyl ether 2 in refluxing
N,N-diethylaniline neatly provided the rearranged phenol
3 in good yield. Further alkylation of the latter with allyl
bromide in refluxing acetone in the presence of anhydrous
potassium carbonate afforded 5-allyl-6-allyloxy-N-meth-
ylquinolin-2-one (4) in high yield. Similarly, reaction of 3
with 4-bromobut-1-ene under analogous conditions pro-
vided the butenyl ether 5. Ring-closing metathesis of the
dienes 4 and 5 with the Grubbs’ catalyst, bis(tricyclohex-
ylphosphine)benzylideneruthenium(IV) dichloride, under
our previously developed conditions7a neatly provided the
acetone, K2CO3,
reflux
PhNEt2,
reflux, 10 h
HO
81%, 84%
69%
N
O
Me
3
( )n
Grubbs' catalyst,
CH2Cl2, r.t.
RO
O
N
O
72%, 75%
N
O
Me
Me
6, n = 1
7, n = 2
4, R = CH2-CH=CH2
5, R = CH2-CH2-CH=CH2
Scheme 1
angularly fused oxepinoquinolone 6 and the oxocinoqui-
nolone 7, respectively, in good yield.
On the other hand, attempted alkylation of 4-hydroxy-N-
methylquinolone9 (8) with allyl bromide under a range of
conditions led only to the O,C-diallylated product 9
(Scheme 2) and the C,C- diallylated product 10 as a sepa-
rable mixture. A similar observation has been made10 in
the alkylation of 8 with propargyl bromide. However, for-
mation of 9 from 8 in a single step was an advantageous
outcome since it could be directly utilized in the subse-
quent step. Ring-closing metathesis (RCM) of the O,C-
diallylated product 9 smoothly provided the oxepinoqui-
nolone derivative 11. Similarly, the C,C-diallylated prod-
uct 10 also underwent smooth RCM to give the spiro-
quinolone derivative 12 in good yield.
Several naturally occurring benzo-fused oxepin and oxo-
cin derivatives have recently been found11 to have inter-
esting biological activities and therefore many synthetic
studies12 have been reported along this direction. The
hitherto unknown quinolone-fused oxepin and oxocin de-
rivatives reported here may prove to be of biological inter-
est.
SYNTHESIS 2005, No. 3, pp 0403–0406
x
x
.
x
x
.2
0
0
5
Advanced online publication: 18.01.2005
DOI: 10.1055/s-2005-861786; Art ID: T06804SS
© Georg Thieme Verlag Stuttgart · New York

404
S. K. Chattopadhyay et al.
PAPER
122.1 (d, C-3), 119.6 (d, Ar), 117.8 (d, Ar), 115.3 (d, Ar), 111.5
(t, =CH2), 69.1 (t, OCH2), 29.3 (q, NCH3).
O
Anal. Calcd for C13H13NO2 (215.25): C, 72.54; H, 6.09; N, 6.51.
Found: C, 72.22; H, 5.91; N, 6.33.
allyl bromide,
acetone, K2CO3,
reflux, 12 h
OH
N
O
Me
9 (36%)
5-Allyl-6-hydroxy-N-methylquinolin-2-one (3)
A solution of the allyl ether 2 (1.15g, 5.34 mmol) in N,N-diethyl-
aniline (8 mL) was refluxed for 10 h and then allowed to come to
r.t. It was then poured into ice-cold 4 N HCl (20 mL) and the aque-
ous solution was then extracted with CH2Cl2 (2 × 50 mL). The com-
bined organic extracts were washed successively with 5% aq
NaHCO3 solution (2 × 20 mL), H2O (2 × 20 mL) and brine (20
mL). It was then dried (Na2SO4), filtered and the filtrate was con-
centrated in vacuo to leave the crude product which on chromatog-
raphy (silica gel, EtOAc–petroleum ether, 1:1) provided the product
3 as a colorless solid (0.8 g, 69%); mp 232–234 °C (EtOH).
60%
O
N
+
O
Me
8
N
O
Me
10 (24%)
O
Grubbs' catalyst, CH2Cl2,
r.t., 6 h
IR (KBr): 3462, 3058, 1646, 1579, 1566, 1404, 1297, 838, 808
cm–1.
9
69%
1H NMR (300 MHz, DMSO-d6): d = 9.49 (s, 1 H, OH), 8.09 (d, 1
H, J = 9.1 Hz, H-4), 7.29 (d, 1 H, J = 8.6 Hz, H-8), 7.18 (d, 1 H,
J = 8.7 Hz, H-7), 6.57 (d, 1 H, J = 9.3 Hz, H-3), 5.95–5.90 (m, 1 H,
CH=CH2), 4.97–4.86 (m, 2 H, CH=CH2), 3.63–3.57 (overlapped, 5
H, NCH3 + CH2CH=CH2).
N
O
Me
11
O
Grubbs' catalyst, CH2Cl2,
r.t., 10 h
Anal. Calcd for C13H13NO2 (215.25): C, 72.54; H, 6.09; N, 6.51.
Found: C, 72.31; H, 5.86; N, 6.28.
10
72 %
N
O
Me
5-Allyl-6-allyloxy-N-methylquinolin-2-one (4)
12
A mixture of the phenol 3 (0.25 g, 1.16 mmol), anhyd K2CO3
(0.30g, 2.14 mmol) and allyl bromide (0.3 g, 2.5 mmol) in anhyd ac-
etone (5 mL) was refluxed under stirring for 12 h. The reaction mix-
ture was then allowed to cool, filtered and the filtrate was
concentrated in vacuo. The resulting mass was extracted with
EtOAc (2 × 20 mL) and the combined organic extracts were
washed successively with 10% aq NaOH (2 × 10 mL), H2O (20
mL) and brine (20 mL). It was then dried (Na2SO4), filtered and the
filtrate was concentrated in vacuo to leave the crude product which
on chromatography (silica gel, EtOAc–petroleum ether, 1:3) pro-
vided the product 4 as a colorless solid (0.24 g, 81%); mp 53–54 °C
(petroleum ether).
Scheme 2
Melting points were determined in open capillaries and are uncor-
rected. IR spectra were obtained on a Perkin Elmer 1600 FTIR spec-
trometer. 1H NMR and 13C NMR spectra were recorded on a Bruker
DRX-300 spectrometer in CDCl3 or DMSO-d6 and referenced to the
solvent signal. Low-resolution mass spectra were recorded on a
JEOL-JMS 600 instrument at an ionizing potential of 70 eV. Mi-
croanalyses were performed on a Perkin-Elmer 204B elemental an-
alyzer. Petroleum ether refers to the fraction boiling in the range 60–
80 °C. Silica gel used was purchased from Spectrochem India Lim-
ited.
IR (KBr): 1655, 1614, 1584, 1569, 1456, 1267, 984, 833 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.87 (d, 1 H, J = 9.8 Hz, H-4),
7.26–7.18 (m, 2 H, Ar-H), 6.73 (d, 1 H, J = 9.8 Hz, H-3), 6.11–5.91
(m, 2 H, 2 × CH=CH2), 5.42 (d, 1 H, J = 17.3 Hz, =CH2), 5.28 (dd,
1 H, J = 10.5, 1.0 Hz, =CH2), 5.03 (d, 1 H, J = 10.0 Hz, =CH2), 4.92
(d, 1 H, J = 17.1 Hz, =CH2), 4.61–4.59 (m, 2 H, OCH2), 3.75 (d, 2
H, J = 5.6 Hz, 5-CH2), 3.71(s, 3 H, NCH3).
13C NMR (75 MHz, CDCl3): d = 161.5 (s, C-2), 151.1 (s, C-6),
136.5 (d, C-4), 135.6 (d, CH=CH2), 135.3 (s, Ar), 133.2 (d,
CH=CH2), 125.2 (s, Ar), 121.8 (d, C-3), 120.2 (s, Ar), 117.2 (d, Ar),
116.5 (t, =CH2), 115.6 (d, Ar), 113.0 (t, =CH2), 70.0 (t, OCH2), 29.5
(q, NCH3), 29.0 (t, ArCH2).
6-Allyloxy-N-methylquinolin-2-one (2)
A mixture of 6-hydroxy-N-methylquinoline-2-one (1.50 g, 8.56
mmol), anhyd K2CO3 (2.20 g, 15.9 mmol) and allyl bromide (2.21
g, 18.2 mmol) in anhyd acetone (30 mL) was refluxed under stirring
for 12 h. The reaction mixture was then allowed to cool, filtered and
the filtrate was concentrated in vacuo. The resulting mass was ex-
tracted with EtOAc (2 × 50 mL) and the organic extract was washed
successively with 10% aq NaOH (2 × 25 mL), H2O (25 mL) and
brine (20 mL). It was then dried (Na2SO4), filtered and the filtrate
was concentrated in vacuo to leave the crude product, which was
purified by column chromatography (silica gel, 25% EtOAc in pe-
troleum ether); colorless solid (1.44 g, 79%); mp 87–88 °C
(EtOAc–petroleum ether).
Anal. Calcd for C16H17NO2 (255.32): C, 75.27; H, 6.71; N, 5.48.
Found: C, 74.91; H, 6.46; N, 5.29.
IR (KBr): 1651, 1583, 1250, 854, 816 cm–1.
5-Allylbut-6-enyloxy-N-methylquinolin-2-one (5)
A mixture of the phenol 3 (0.25 g, 1.16 mmol), anhyd K2CO3 (0.40
g, 2.80 mmol) and 4-bromobut-1-ene (0.53 g, 3.9 mmol) in anhyd
acetone (10 mL) was refluxed under stirring for 20 h. The reaction
mixture was then allowed to cool, filtered and the filtrate was con-
centrated in vacuo. The resulting mass was extracted with EtOAc
(2 × 20 mL) and the combined organic extracts were washed suc-
cessively with 10% aq NaOH (2 × 10 mL), H2O (20 mL) and brine
(20 mL). It was then dried (Na2SO4), filtered and the filtrate was
concentrated in vacuo to leave the crude product which on chroma-
1H NMR (300 MHz, CDCl3): d = 7.59 (d, 1 H, J = 9.5 Hz, H-4),
7.29 (d, 1 H, J = 9.2 Hz, H-8), 7.20 (dd, 1 H, J = 9.2, 2.7 Hz, H-7),
7.01 (d, 1 H, J = 2.7 Hz, H-5), 6.71 (d, 1 H, J = 9.5 Hz, H-3), 6.12–
6.01 (m, 1 H, CH=CH2), 5.44 (dd, 1 H, J = 17.3, 1.4 Hz, =CH2),
5.32 (dd, 1 H, J = 10.5, 1.3 Hz, =CH2), 4.6 (d, 2 H, J = 5.2 Hz,
OCH2), 3.7 (s, 3 H, NCH3).
13C NMR (75 MHz, CDCl3): d = 161.7 (s, C-2), 153.5 (s, C-6),
138.4 (s, Ar), 138.2 (d, C-4), 134.5 (s, Ar), 132.8 (d, CH=CH2),
Synthesis 2005, No. 3, 403–406 © Thieme Stuttgart · New York

PAPER
Synthesis of Oxepin- and Oxocin-Annulated 2-Quinolones
405
tography (silica gel, EtOAc–petroleum ether, 1:3) provided the
product 5 as a colorless solid (0.21 g, 84%); mp 65–66 °C (EtOAc–
petroleum ether).
Anal. Calcd for C16H17NO2 (255.32): C, 75.27; H, 6.71; N, 5.49.
Found: C, 75.44; H, 6.89; N, 5.31.
Ring-Closing Metathesis; General Procedure
IR (KBr): 1658, 1615, 1585, 1570, 1456, 1269 cm–1.
A solution of the appropriate diene 4,5,9 or 10 (0.2 mmol) and
Grubbs’ catalyst (5 mol%) in anhyd and degassed CH2Cl2 (25 mL)
was stirred under argon at r.t. until the starting material was con-
sumed (6–24 h). The reaction mixture was then concentrated and
chromatographed.
1H NMR (300 MHz, CDCl3): d = 7.92 (d, 1 H, J = 9.91 Hz, H-4),
7.34–7.28 (m, 2 H, ArH), 6.94 (d, 1 H, J = 9.80 Hz, H-3), 6.10–5.88
(m, 2 H, 2 × CH=CH2), 5.46 (d, 1 H, J = 17.41 Hz, =CH2), 5.20–
5.12 (m, 2 H, =CH2), 4.92 (dd, 1 H, J = 1.3, 17.1 Hz, =CH2), 4.45
(t, 2 H, J = 6.6 Hz, OCH2), 3.79 (d, 2 H, J = 5.8 Hz, ArCH2), 3.70
(s, 3 H, NCH3), 2.59–2.51 (m, 2 H, OCH2CH2).
13C NMR (75 MHz, CDCl3): d = 162.0 (s, C-2), 151.9 (s, C-6),
136.5 (d, C-4), 135.6 (d, CH=CH2), 135.4 (s, Ar), 134.8 (d,
CH=CH2), 125.7 (s, Ar), 122.3 (d, C-3), 120.7 (s, Ar), 117.5 (d, Ar),
116.6 (t, =CH2), 115.9 (t, =CH2), 113.5 (d, Ar), 69.1 (t, OCH2), 34.3
(t, OCCH2), 30.0 (q, NCH3), 29.5 (t, 5-CH2).
4-Methyl-3,4,8,11-tetrahydrooxepino[3,2-f]quinolin-3-one (6)
The reaction was complete in 18 h. The product was eluted with
30% EtOAc in petroleum ether; yield: 72%: mp 147–149 °C
(EtOAc–petroleum ether).
IR (KBr): 1651, 1586, 1457, 1241, 1057, 829, 632 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.96 (d, 1 H, J = 9.9 Hz, H-1),
7.34 (d, 1 H, J = 9.1 Hz, H-5), 7.22 (d, 1 H, J = 9.0 Hz, H-6), 6.77
(d, 1 H, J = 9.9 Hz, H-2), 5.92–5.87 (m, 1 H, H-9), 5.49 (d, 1 H,
J = 10.8 Hz, H-10), 4.62 (s, 2 H, H-8), 3.76 (s, 2 H, H-11), 3.72 (s,
3 H, NCH3).
13C NMR (75 MHz, CDCl3): d = 161.6 (s, C-3), 153.3 (s, OCarom),
137.2 (s, Ar), 134.4 (s, Ar), 134.2 (d, C-1), 128.1 (d, C-9), 124.7 (d,
C-10), 124.5 (d, Ar), 121.6 (d, C-2), 118.1 (s, Ar), 113.3 (d, Ar),
71.4 (t, C-8), 29.8 (q, NCH3), 24.4 (t, C-11).
Anal. Calcd for C17H19NO2 (269.34): C, 75.81; H, 7.11; N, 5.20.
Found: C, 75.59; H, 6.96; N, 5.39.
3-Allyl-4-allyloxy-N-methylquinolin-2-one (9) and 3,3-Diallyl-
1-methylquinoline-2,4-(1H,3H)-dione (10)
A mixture of 4-hydroxy-N-methylquinoline-2-one13 (0.34 g, 1.94
mmol), anhyd K2CO3 (0.51 g, 3.6 mmol) and allyl bromide (0.51 g,
4.12 mmol) in anhyd acetone (10 mL) was refluxed under stirring
for 12 h. The reaction mixture was then allowed to cool, filtered and
the filtrate was concentrated in vacuo. The resulting mass was ex-
tracted with EtOAc (2 × 50 mL) and the combined organic extracts
were washed successively with 10% aq NaOH (10%, 2 × 25 mL),
H2O (25 mL) and brine (20 mL). It was then dried (Na2SO4), filtered
and the filtrate was concentrated in vacuo to leave the crude product
which on flash chromatography over silica gel (petroleum ether)
provided the C,C-diallylated product 10 as a viscous liquid (0.12 g,
24%).
MS (EI): m/z (%) = 227 (42), 212 (100).
Anal. Calcd for C14H13NO2 (227.26): C, 73.99; H, 5.76; N, 6.16.
Found: C, 73.71; H, 5.49; N, 6.34.
4-Methyl-3,8,9,12-tetrahydro-4H-oxocino[3,2-f]quinolin-3-one
(7)
The reaction was complete in 24 h. The product was eluted with
25% EtOAc in petroleum ether and was obtained as a viscous liq-
uid; yield: 75%.
10
IR (neat): 1659, 1595, 1440, 1345, 780 cm–1.
IR (neat): 1694, 1659, 1602, 1473, 1362, 1302, 924, 763 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.96 (d, 1 H, J = 9.9 Hz, H-1),
7.34 (d, 1 H, J = 9.1 Hz, H-5), 7.31 (d, 1 H, J = 9.3 Hz, H-6), 6.77(d,
1 H, J = 9.9 Hz, H-2), 6.04–5.89 (m, 1 H, H-11), 5.71–5.63 (m, 1 H,
H-10), 4.05 (t, 2 H, J = 4.4 Hz, H-8), 3.72 (s, 5 H, NCH3 + H-12),
2.61–2.56 (m, 2 H, H-9).
13C NMR (75 MHz, CDCl3): d = 167.8 (s, C-3), 154.0 (s, OCarom),
138.2 (s, Ar), 135.8 (d, C-1), 132.4 (d, C-10), 128.8 (d, C-11), 126.0
(s, NCarom), 125.8 (d, C-2), 121.7 (d, Ar), 121.2 (s), 113.2 (d, Ar),
72.2 (t, C-8), 33.4 (t, C-9), 29.6 (q, NCH3), 25.6(t, C-12).
1H NMR (300 MHz, CDCl3): d = 8.01 (d, 1 H, J = 7.8 Hz, H-5),
7.62 (dt, 1 H, J = 1.4, 8.1 Hz, H-6/7), 7.19–7.13 (m, 2 H, Ar-H),
5.60–5.46 (m, 2 H, 2 × CH=CH2), 5.02 (d, 2 H, J = 17 Hz, =CH2),
4.92 (d, 2 H, J = 10.1 Hz, =CH2), 3.46 (s, 3 H, NCH3), 2.80–2.68
(m, 4 H, 2 × CH2CH=CH2).
13C NMR (75 MHz, CDCl3): d = 196.3 (s, C-4), 172.0 (s, C-2),
143.2 (s, Ar), 136.1 (d, Ar), 131.9 (d, CH=CH2), 127.5 (d, Ar),
122.9 (d, Ar), 120.7 (s, Ar), 118.9 (t, CH=CH2), 114.7 (d, Ar), 61.4
(s, C-3), 42.8 (t, CH2CH=CH2), 29.3 (q, NCH3).
MS (EI): m/z (%) = 241 (100), 213 (16.7), 187 (22.8).
Anal. Calcd for C16H17NO2 (255.32): C, 75.27; H, 6.71; N, 5.49.
Found: C, 74.94; H, 6.49; N, 5.20.
Anal. Calcd for C15H15NO2 (241.29): C, 74.67; H, 6.26; N, 5.80.
Found: C, 74.79; H, 6.40; N, 6.04.
Further elution with 5% EtOAc in petroleum ether provided the
O,C-diallylated product 9 as a viscous liquid (0.18 g, 36%).
7-Methyl-2,5,6,7-tetrahydrooxepino[3,2-c]quinolin-6-one (11)
The reaction was complete in 6 h. The product was eluted with 5%
EtOAc in petroleum ether and was obtained as a colorless solid;
yield: 69%; mp 118–119 °C (EtOAc–petroleum ether).
9
IR (neat): 1640, 1596, 1464, 1232, 756 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.84 (d, 1 H, J = 7.9 Hz, H-5),
7.56 (t, 1 H, J = 7.6 Hz, H-6/7), 7.37 (d, 1 H, J = 8.5 Hz, H-8), 7.26
(t, 1 H, J = 9.1 Hz, H-6/7), 6.21–5.98 (m, 2 H, 2 × CH=CH2), 5.49
(d, 1 H, J = 17.1 Hz, =CH2), 5.33 (d, 1 H, J = 10.4 Hz, =CH2), 5.10
(d, 1 H, J = 16.9 Hz, =CH2), 5.03 (d, 1 H, J = 9.8 Hz, =CH2), 4.54
(d, 2 H, J = 5.4 Hz, OCH2), 3.74 (s, 3 H, NCH3), 3.47–3.32 (m, 2 H,
3-CH2).
13C NMR (75 MHz, CDCl3): d = 163.6 (s, C-2), 159.7 (s, C-4),
139.1 (d, CH=CH2), 135.7 (d, CH=CH2), 132.9 (s, Ar), 132.0 (d,
Ar), 130.3 (d, Ar), 123.6 (d, Ar), 121.9 (d, Ar), 119.1 (s, C-3), 118.0
(s, Ar), 115.4 (t, =CH2), 114.1 (t, =CH2), 75.1 (t, OCH2), 29.7 (q,
NCH3), 29.6 (t, 3-CH2).
IR (KBr): 1652, 1601, 1473, 1355, 779 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.94 (d, 1 H, J = 7.9 Hz, H-8),
7.59–7.51 (m, 1 H, H-11), 7.33–7.29 (m, 1 H, H-10), 7.25–7.20 (m,
1 H, H-9), 6.14–6.07 (m, 1 H, H-3), 5.92–5.85 (m, 1 H, H-4), 4.82
(d, 2 H, J = 4.7, H-2), 3.81 (overlapped 5 H, NCH3 + CH2C=C).
13C NMR (75 MHz, CDCl3): d = 163.2 (s, C-6), 159.4 (s, OC=C),
138.6 (s, Ar), 131.4 (d, C-3), 130.1 (d, C-4), 126.6 (d, Ar), 126.3 (d,
Ar), 124.4 (d, Ar), 123.6 (d, Ar), 122.1 (s, OC=C), 119.1 (s, Ar),
71.1 (t, C-2), 29.7 (q, NCH3), 25.2 (t, C-5).
MS (EI): m/z (%) = 227 (86), 212 (41), 175 (31), 147 (100).
Synthesis 2005, No. 3, 403–406 © Thieme Stuttgart · New York

406
S. K. Chattopadhyay et al.
PAPER
(3) (a) Yang, Z.-Y.; Xia, Y.; Xia, P.; Brossi, A.; Lee, K.-H.
Anal. Calcd for C14H13NO2 (227.26): C, 73.99; H, 5.76; N, 6.16.
Found: C, 74.28; H, 5.92; N, 6.31.
Tetrahedron Lett. 1999, 40, 4505. (b) Ye, J.-H.; Ling, K.-
Q.; Zhang, Y.; Li, N.; Xu, J.-H. J. Chem. Soc., Perkin Trans.
1 1999, 2017. (c) Majumdar, K. C.; Ghosh, S. K.; Biswas, P.
Monatsh. Chem. 2000, 31, 967.
Compound 12
The reaction was complete in 10 h. The product was eluted with
10% EtOAc in petroleum ether and was obtained as a colorless sol-
id; yield: 72%; mp 119–120 °C (CH2Cl2–petroleum ether).
IR (KBr): 1690, 1652, 1601, 1472, 1416, 1354, 780 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.99 (dd, 1 H, J = 6.6, 1.5 Hz, H-
5), 7.64 (dt, 1 H, J = 7.5, 1.7 Hz, H-6/7), 7.21–7.16 (m, 2 H, Ar),
5.64 (s, 2 H, CH=CH), 3.48 (s, 3 H, NCH3), 3.02 (s, 4 H, CH2C=C).
13C NMR (75 MHz, CDCl3): d = 195.4 (s, C-4), 173.7 (s, C-2),
143.3 (s, Ar), 135.7 (d, Ar), 128.3 (d, CH=CH), 127.2 (d, Ar), 123.0
(d, Ar), 120.3 (s, Ar), 114.8 (d, Ar), 61.6 (s, C-3), 42.9 (t, CH2C=C),
30.0 (q, NCH3).
(4) Yet, L. Chem. Rev. 2000, 100, 2963.
(5) For recent reviews, see: (a) Trnka, T. M.; Grubbs, R. H. Acc.
Chem. Res. 2001, 34, 18. (b) Fürstner, A. Angew. Chem. Int.
Ed. 2000, 39, 3012. (c) Blechert, S.; Connon, S. Angew.
Chem. Int. Ed. 2003, 42, 1900. (d) Poulsen, C. S.; Madsen,
R. Synthesis 2003, 1.
(6) For some recent applications of RCM reaction in medium
ring oxacycle formation, see: (a) Mamouni, R.; Soukri, M.;
Lazar, S.; Akssira, M.; Guillaumet, G. Tetrahedron Lett.
2004, 45, 2631. (b) Van Otterlo, W. A. L.; Pathak, R.; de
Koning, C. B. Synlett 2003, 1859. (c) Pain, C.; Celanire, S.;
Guillaumet, G.; Joseph, B. Synlett 2003, 2089.
MS (EI): m/z (%) = 227 (100), 212 (49), 198 (42).
(7) (a) Chattopadhyay, S. K.; Maity, S.; Panja, S. Tetrahedron
Lett. 2002, 43, 7781. (b) Chattopadhyay, S. K.; Paul, B. K.;
Maity, S. Chem. Lett. 2003, 32, 1190.
Anal. Calcd for C14H13NO2 (227.26): C, 73.99; H, 5.76; N, 6.16.
Found: C, 74.17; H, 5.88; N, 6.27.
(8) For some recent reviews on Claisen rearrangement, see:
(a) Nubbemeyer, U. Synthesis 2003, 961. (b) Castro, A. M.
M. Chem. Rev. 2004, 104, 2939. (c) Blechert, S. Synthesis
1989, 71.
Acknowledgment
Financial assistance from CSIR, New Delhi (Grant No. 01/1676/00/
EMR-II) is gratefully acknowledged.
(9) Chamberlin, T. R.; Grundon, M. F. Tetrahedron Lett. 1967,
3547.
(10) (a) Rao, S. V.; Darbarwar, M. Synthesis 1989, 139. (b)Rao,
S. V.; Darbarwar, M. Synth. Commun. 1989, 19, 2713.
(11) (a) Macias, F. A.; Varela, R. M.; Torres, A.; Molinillo, J. M.
G. Tetrahedron Lett. 1999, 40, 4725. (b) Macias, F. A.;
Molinillo, J. M. G.; Varela, R. M.; Torres, A.; Fronzek, F. R.
J. Org. Chem. 1994, 59, 8261.
(12) (a) Stefinovic, M.; Snieckus, V. J. Org. Chem. 1998, 63,
2808. (b) Kishuku, H.; Shindo, M.; Shishido, K. Chem.
Commun. 2003, 350. (c) Sabui, S. K.; Venkateswaran, R. V.
Tetrahedron Lett. 2004, 45, 983.
References
(1) (a) Abd, E.; Hisham, A. Pharmazie 1997, 52, 28. (b) Sun,
H. B.; Qing, F. L.; Chen, X. F. Synthesis 1997, 1249.
(c) Nevile, C. F.; Grundon, M. F.; Ramchandran, V. N.;
Reisch, G.; Reisch, J. J. Chem. Soc., Perkin Trans. 1 1991,
2261.
(2) (a) Staubitz, A.; Dohle, W.; Knochel, P. Synthesis 2003,
233. (b) Lee, Y. R.; Kweon, H. I.; Koh, W. S.; Min, K. R.;
Kim, Y.; Lee, S. H. Synthesis 2001, 1851. (c) Ullrich, T.;
Girard, F. Tetrahedron Lett. 2003, 44, 4207.
(13) Lutz, R. E.; Codington, J. F.; Rowlett, R. J.; Deinet, A. J.;
Bailey, P. S. J. Am. Chem. Soc. 1946, 68, 1810.
Synthesis 2005, No. 3, 403–406 © Thieme Stuttgart · New York