Reactions of 2-(methoxyimino)benzen-1-ones with α-alkylethoxycarbonylmethylene(triphenyl)phosphoranes

Article abstract of DOI:10.1016/S0040-4020(01)00942-5

The title 2-(methoxyimino)benzen-1-ones react with α-alkylethoxycarbonylmethylene(triphenyl)phosphoranes to give 2H-[b][1,4]benzoxazine derivatives along with benzoxazole and indole derivatives. Reaction mechanisms to explain the formation of products obt

Full text of DOI:10.1016/S0040-4020(01)00942-5

TETRAHEDRON
Pergamon
Tetrahedron 57 +2001) 9469±9474
Reactions of 2-ꢀmethoxyimino)benzen-1-ones with
a-alkylethoxycarbonylmethyleneꢀtriphenyl)phosphoranes
p
Demetrios N. Nicolaides, Daman R. Gautam, Konstantinos E. Litinas, Christos Manouras
and Konstantina C. Fylaktakidou
Laboratory of Organic Chemistry, University of Thessaloniki, Thessaloniki 54006, Greece
Received 5 June 2001; revised 3 September 2001; accepted 20 September 2001
AbstractÐThe title 2-+methoxyimino)benzen-1-ones react with a-alkylethoxycarbonylmethylene+triphenyl)phosphoranes to give
2H-[b][1,4]benzoxazine derivatives along with benzoxazole and indole derivatives. Reaction mechanisms to explain the formation of
products obtained are suggested. q 2001 Elsevier Science Ltd. All rights reserved.
1. Introduction
described above are further transformed to fused hetero-
cyclic systems.
Relatively little work has been reported on the reaction of
phosphorus ylides with o-quinone mono imine derivatives.
It is of interest that the reaction of N-phenyl-3,5-di-tert-
butyl-1,2-benzoquinone monohydrazone with ylides
1
We have reported earlier that acenaphthylene-1,2-quinone
monoxime reacts with some phosphorus mono-ylides in a
normal Wittig way, while with a bis-ylide, an additional
`Wittig type' reaction between the imine group and the
second ylide group is also observed. We also reported
Ph
1,4-benzoxazine-2-one derivatives via an initial attack of
the ylide to the hydrazone group.
3
PvCHCOR +RˆOMe, OEt) afforded indazole and
6
that 10-+methoxyimino)phenanthren-9-one 10 reacts
with ylides Ph PvCHAr, 23 and Ph PvCHCOPh
2
3
4
2. Results and discussion
3
3
via an initial Wittig monoole®nation. In a similar way,
-+methoxyimino)-4-methylchromene-2,8-dione 1 reacts
7
The work detailed in this paper involves reactions of the title
ylides 2a±c with O-methyl-monoximes 1, 10 and 20, which
lead to unexpected and interesting products. The reactions
studied and the products obtained are depicted in Schemes
1±5. Treatment of monoxime 1 with an equimolar amount
with ylide 23, while with ylides Ph PvCHR +RˆAr,
3
±
d]oxazol-8-ones. Generally, the o-quinone methide
CH±C,) affords 2-R substituted [1]benzopyrano[7,8-
5
imines that are initially formed by Wittig ole®nation
Scheme 1.
Keywords: O-methyl-o-Quinonemonoxime; phosphoranes; benzoxazine; coumarines.
Corresponding author. Tel.: 130-31-997801; fax: 130-31-997679; e-mail: nicol@chem.auth.gr
p
0040±4020/01/$ - see front matter q 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020+01)00942-5

9470
D. N. Nicolaides et al. / Tetrahedron 57 '2001) 9469±9474
Scheme 2.
of ethyl 2-+triphenylphosphoranylidene)butanoate 2a in
boiling dichloromethane for 24 h gave ethyl 2,7-dimethyl-
described by us in a previous study on reactions of several
phosphines with compound 1.
7
9
-oxo-2,9-dihydrochromeno[8,7-b][1,4]oxazine-3-carboxy-
late 3a +25%), and 7-anilino-8-hydroxy-4-methyl-2H-
chromen-2-one 4 +15%) +Scheme 1).
A similar nucleophilic attack of 2a to the carbonyl oxygen
of 1 could afford the isomer 1,4-benzoxazine 9a through the
intermediates 7a, 8a. The recorded spectral data, and
1
The formation of benzoxazine derivative 3a can be
explained by the mechanism suggested in Scheme 2.
Nucleophilic attack of the ylide on the oxime nitrogen
could give the corresponding betaine intermediate 5a.
Triphenylphosphine elimination from 5a, followed by
methanol elimination from the intermediate 6a formed can
especially the H NMR spectrum of the product in question,
which exhibited a doublet for protons of the 2-methyl
substituent and a quartet for the vicinal methine proton,
are in good agreement with the structure 3a.
The reaction of 1 with slight excess +10%) of ylide 2b in
re¯uxing dichloromethane for 24 h gave the similar
products ethyl 7-methyl-2-phenyl-9-oxo-2,9-dihydro-
chromeno[8,7-b][1,4]oxazine-3-carboxylate 3b +34%) and
4 +21%). When monoxime 1 was treated with ylide 2c,
5
afford product 3a. The known compound 4 is obviously
formed via a nucleophilic attack of the triphenylphosphine,
generated in situ through the formation of 3a, to the car-
bonyl oxygen of the quinoid part of compound 1, as
Scheme 3.

D. N. Nicolaides et al. / Tetrahedron 57 '2001) 9469±9474
9471
Scheme 4.
under similar conditions, only compound 4 +21%) and its
known O-methyl derivative +11%) were isolated from the
complicated reaction mixture. Efforts for detection or
separation of the expected product 3c from the eluted
fractions were unsuccessful.
benzene for 10 days gave the expected ethyl 2-methyl-2H-
phenanthro[9,10-b][1,4]oxazine-3-carboxylate 11a in 10%
yield +Scheme 3). When a mixture of monoxime 10 and
ylide 2b in benzene was heated under re¯ux for 24 h, no
reaction took place as it was indicated by TLC examination
of the reaction mixture. The solvent was evaporated and the
melted mixture was heated at 1408C for 1.5 h to give ethyl
7
Treatment of monoxime 10 with ylide 2a in re¯uxing
Scheme 5.

9472
D. N. Nicolaides et al. / Tetrahedron 57 '2001) 9469±9474
2
1
-phenyl-2H-phenanthro[9,10-b][1,4]oxazine-3-carboxylate
1b +5%), along with 2-phenylphenanthro[9,10-
hydro-4H-benzo[7,8]chromeno[6,5-d][1,3]oxazole 22 +21%)
were obtained +Scheme 5).
d][1,3]oxazole 12 +29%), identical to that previously
obtained from the reaction of 10 with toluene as well as
We also studied the reaction of 20I1II with ylide 23 in tolu-
ene solution, under re¯ux, which afforded ethyl 6,6-
dimethyl-5,6-dihydro-4H-benzo[7,8]chromeno[6,5-d][1,3]-
oxazole-2-carboxylate 25 in 15% yield, obviously via an
initial formation of ethyl 1-methoxy-6,6-dimethyl-1,2,5,6-
tetrahydro-4H-benzo[7,8]chromeno[6,5-d][1,3]oxazole-2-
carboxylate ,824, followed by methanol elimination
8
±10
with several benzyl derivatives. Obviously, compound
2 is formed by a similar attack of the benzyl carbon
1
atom of 2b, directly or after its previous hydrolysis
to ethyl 3-phenylpropionate, to the imine nitrogen of
1
8
±10
0.
5
Treatment of monoxime 10 with ylide 2c in re¯uxing
benzene for 4 h gave a complicated mixture of products
from which only the unexpected 3-methyl-2H-phenanthro-
+Scheme 5).
[9,10-b][1,4]oxazine-2-one 15 +15%) and ethyl 1H-di-
benzo[e,g]indole-3-carboxylate 18 +21%) were isolated
3. Experimental
+
Scheme 4). The expected [1,4]oxazine derivative 11c
RˆH) was not detected in the eluted fractions. We believe
3
.1. General
+
that, like in the case of formation of compounds 3a±b and
1
Mps are uncorrected and were measured on a Ko¯er hot-
stage apparatus. IR spectra were obtained with a Perkin±
Elmer 1310 spectrophotometer. H NMR spectra were
1a±b, the phenoxy betaine 13 is initially formed +Scheme
), from which, via a further lactonization with the ethoxy-
1
4
carbonyl group, product 15 is obtained. Obviously, the
presence of the less bulky methyl substituent in the inter-
mediate 13 favors an appropriate con®guration for its
further lactonization to product 15. On the other hand,
Wittig ole®nation of the carbonyl group of monoxime 10,
followed by full aromatization of the intermediate 16
formed, through an ene reaction, to hydroxylamine
derivative 17, intramolecular Michael addition of amine to
a,b-unsaturated ester in 17 and ®nally methanol
elimination could account for the formation of compound
recorded with CDCl as a solvent on a Bruker 300 AM
3
1
3
300 MHz) with SiMe as the internal standard. C NMR
+
4
were obtained at 75.5 MHz on a Bruker 300 AM spectro-
meter in CDCl3 solutions with SiMe4 as the internal
reference. Mass Spectra were determined on a VG-250
spectrometer with ionization energy maintained at 70 eV
under Electron Impact +EI) conditions or on an IONSPEC
mass spectrometer under Electronspray Ionization +ESI)
conditions. High-resolution mass spectra +HRMS) were
obtained on an IONSPEC mass spectrometer under Matrix
Assisted Laser Desorption Ionization Fourier Transform
Mass Spectrometry +MALDI-FTMS) conditions with 2,5-
dihydroxybenzoic acid +DHB) as the matrix. Earlier
reported procedures were used for the preparation of
1
8 +Scheme 4).
We also prepared 2,2-dimethyl-3,4-dihydro-2H-benzo[h]-
chromene-5,6-dione 6-+O-metyl-oxime) 20 from b-lapa-
chone 19 [as a mixture of +Z-) and +E-) isomers 20 and
1
1
8
11
I
compound 1 and 19.
2
0II] +Scheme 5). Efforts for further separation of the
mixture by column chromatography gave ®rst the isomer
0 , while later fractions gave the isomer 20 . Different
solutions of each isomer transformed gradually to mixtures
of isomers. The structure of 20 can be suggested due to
expected favored attack of the O-methylhydroxylamine to
the more electrophilic 6-carbonyl carbon, because of the
action of the pyran oxygen and was further supported by
NOE experiments +interactions between the protons of
3.1.1. Reaction of 1 with ylide 2a. A solution of 1 +0.219 g,
1 mmol) and 2a +0.376 g, 1 mmol) in dichloromethane
+10 ml) was re¯uxed for 24 h. The solvent was evaporated
under reduced pressure and the residue was separated by
column chromatography +silica gel, hexane/ethyl acetate
15:10). The fraction eluted ®rst afforded compound 4
+39 mg, 15%), mp 213±2158C +dichloromethane/hexane)
2
I
II
5
+Lit. 214±2168C). The fraction eluted next gave colorless
needles of compound 3a +76 mg, 25%), mp 182±1848C
±
OCH group and the 7-H and not between the protons of
3
1
this group with 4-H). The H NMR spectrum of 20I
exhibited a singlet at d 1.41 [6H, C+CH ) ], a triplet at d
+ethyl acetate/hexane); IR +Nujol):
n
1725, 1705,
2
1
1
3
2
1617 cm ; H NMR d 1.43 +3H, d, Jˆ6.4 Hz, 2-CH ),
3
2
.55 +2H, probably 4-H), a singlet at d 4.26 +3H, ±OCH3)
1.44 +3H, t, Jˆ7.6 Hz, CH CH ±), 2.44 +3H, s, 7-CH ),
3
2
3
and peaks at d 7.81 +dd, 1H, probably 10-H), 8.03 +dd, 1H,
probably 7-H), while the spectrum of the isomer 20II
exhibited absorptions at d 1.42, 2.56, 4.31, 7.89 and 8.63
for the analogous protons, respectively. The absorptions of
the other protons in the recorded spectra of both isomers in
4.46 +2H, q, Jˆ7.6 Hz, CH CH ±), 5.53 +1H, q, Jˆ
3
2
6.4 Hz, 2-H), 6.34 +1H, s, 8-H), 7.25 +1H, d, Jˆ8.9 Hz),
1
3
7.49 +1H, d, Jˆ8.9 Hz); C NMR d 14.2, 16.7, 18.8,
62.7, 68.1, 116.1, 116.7, 122.3, 123.9, 133.1, 133.6, 149.5,
152.0, 158.3, 159.6, 167.8; MS +EI): m/z 301 +M , 37%),
1
1
question are almost coincident. On the other hand, the H
NMR spectrum of quinone 19 showed a doublet for 7-H at d
286 +12), 229 +21), 228 +100), 199 +17); Anal. Calcd for
C H NO : C, 63.78; H, 5.02; N, 4.65. Found: C, 63.55;
H, 4.95; N, 4.80.
1
6
15
5
8
.06 +d, Jˆ8.0 Hz). On the basis of these data, we can
conclude the structure of 6-+O-methyl oxime) instead of
the 5-isomer for 20 and 20 with the +Z-) and +E-) con-
I
II
3.1.2. Reaction of 1 with ylide 2b. A solution of
compounds 1 +0.219 g, 1 mmol) and 2b +0.482g,
1.1 mmol) in dichloromethane +10 ml) was re¯uxed for
24 h. The solvent was evaporated under reduced pressure
and the residue was subjected to column chromatography
+silica gel, hexane/ethyl acetate 3:1). The fraction eluted
®
compound 20 120 and ylide 2b +18% excess) was heated
guration, respectively. When a melted mixture of
I
II
at 1408C for 10 min, ethyl 7,7-dimethyl-3-phenyl-6,7-di-
hydro-3H,5H-benzo[7,8]chromeno[5,6-b][1,4]oxazine-2-
carboxylate 21 +20%) and 6,6-dimethyl-2-phenyl-5,6-di-

D. N. Nicolaides et al. / Tetrahedron 57 '2001) 9469±9474
9473
1
®rst afforded compound 4 +55 mg, 21%), identical to that
obtained above. The fraction eluted next gave light yellow
HRMS
C H NO Na m/z 404.1260, found m/z 404.1257.
+MALDI-FTMS):
+M1Na)
calcd
for
2
5
19
3
needles of compound 3b +0.124 g, 34%), mp 197±1988C
+
ethyl acetate/hexane); IR +Nujol):
n
1725, 1710,
3.1.6. Reaction of 10with ylide 2c. A solution of 10
+0.522 g, 2.2 mmol) and 2c +0.797 g, 2.2 mmol) in dry
benzene +15 ml) was re¯uxed for 4 days. The solvent was
removed in a rotary evaporator and the residue was
subjected to column chromatography +silica gel, hexane/
ethyl acetate 10:1). The fractions of two bands were
collected. The fractions of the faster eluted band were
mixed and subjected again to column chromatography
+silica gel, hexane/ethyl acetate 30:1) to give yellow crystals
of compound +blue ¯uorescence in short wave UV) 15
2
1 1
1
620 cm ; H NMR d 1.38 +3H, t, Jˆ7.1 Hz, CH CH ±
3
2
)
, 2.40 +3H, s, 7-CH ), 4.42+ 2H , q, Jˆ7.1 Hz, CH CH ±),
3
3
2
6
7
1
1
1
.30 +1H, s, 8-H), 6.45 +1H, s, 2-H), 7.23 +1H, d, Jˆ8.5 Hz),
1
3
.28±7.40 +5H, m), 7.53 +1H, d, Jˆ8.5 Hz); C NMR d
4.1, 18.8, 62.8, 72.3, 116.1, 116.9, 122.4, 123.9, 127.4,
28.9, 129.6, 133.4, 134.1, 134.7, 142.5, 151.9, 154.1,
1
59.5, 162.4; MS +EI): m/z 363 +M , 11%), 291 +23), 290
+
52), 267 +10); Anal. Calcd for C H NO : C, 69.41; H,
21 17 5
4
.72; N, 3.86. Found: C, 69.51; H, 4.68; N, 3.79.
+85 mg, 15%), mp 224±2268C +ethyl acetate/hexane); IR
+Nujol) n 1725, 1615 cm ; H NMR d 2.70 +3H, s,
2
1 1
3
1
.1.3. Reaction of 1 with ylide 2c. A solution of compounds
+0.548 g, 2.5 mmol) and 2c +0.906 g, 2.5 mmol) in dry
3-CH ), 7.67±7.79 +4H, m), 8.44 +1H, d, Jˆ7.8 Hz),
3
1
3
dichloromethane +15 ml) was heated under re¯ux for 32h,
the solvent was removed in a rotary evaporator and the
residue was subjected to column chromatography
+silica gel, hexane/ethyl acetate 2:1) to give, after the elution
of triphenylphosphine +19 mg), 7-anilino-8-methoxy-4-
methyl-2H-chromen-2-one +74 mg, 11%), mp 142±
1
fraction eluted next gave compound 4 +137 mg, 21%),
identical to that obtained above from the reaction between
1
8.59±8.66 +2H, m), 8.80 +1H, d, Jˆ8.1 Hz); C NMR d
21.4, 122.5, 122.7, 122.9, 123.0, 123.6, 123.7, 127.1,
127.6, 127.9, 128.2, 128.5, 129.2, 131.5, 153.8, 153.9,
1
158.0; HRMS +MALDI-FTMS): +M1H) calcd for
C H NO m/z 262.0867, found m/z: 262.0863.
1
7
12
2
7
448C +ethyl acetate/hexane) +Lit. mp 143±1458C). The
The fraction of the band eluted next from the original
column were also mixed and subjected to a new column
chromatography +silica gel, hexane/ethyl acetate 4:1) to
give colorless needles of compound 18 +133 mg, 21%),
mp 218±2208C +ethyl acetate/hexane); IR +Nujol): n
and ylides 2a and 2b.
2
1
1
3
.1.4. Reaction of 10with ylide 2a. A solution of 10
0.237 g, 1 mmol) and 2a +0.376 g, 1 mmol) in benzene
3320, 1720, 1625 cm ; H NMR d 1.46 +3H, t, Jˆ
+
+
7.0 Hz, CH CH ±), 4.44 +2H, q, Jˆ7.0 Hz, CH CH ±),
3
2
3
2
10 ml) was re¯uxed for 10 days. The solvent was evapo-
7.57±7.69 +4H, m), 7.94±8.00 +2H, m), 8.68±8.75 +2H,
1
3
rated under reduced pressure and the residue was subjected
to column chromatography +silica gel, hexane/ethyl acetate
16:1) to give orange prisms of compound 11a +32mg, 10%),
mp 82±848C +ethyl acetate/hexane); IR +KBr): n 1702,
1
1
m), 9.32+1H, brs, NH), 9.73 +1H, d, Jˆ8.4 Hz); C NMR
d 14.5, 60.2, 112.9, 119.4, 123.0, 123.9, 125.0, 125.6, 126.7,
126.9, 127.0, 127.5, 128.0, 129.0, 129.5, 135.5, 138.1,
147.7, 165.7; MS +EI): m/z 289 +100%), 261 +29),
244 +40), 214 +18), 189 +65); Anal. Calcd for C H NO :
2
1
1
602cm ; H NMR d 1.43 +3H, d, Jˆ6.8 Hz, 2-CH ),
3
19 15
2
.48 +3H, t, Jˆ7.1 Hz, CH CH ±), 4.47 +2H, q, Jˆ7.1 Hz,
C, 78.87; H, 5.23; N, 4.84. Found: C, 78.93; H, 5.27; N,
4.83.
3
2
CH CH ±), 5.68 +1H, q, Jˆ6.8 Hz, 2-H), 7.57±7.76
3
2
1
3
+
NMR d 14.2, 15.4, 62.1, 67.6, 122.3, 122.8, 123.5, 125.0,
4H, m), 8.33 +1H, d, Jˆ7.8 Hz), 8.57±8.68 +3H, m);
C
3.1.7. Preparation of 2,2-dimethyl-3,4-dihydro-2H-
benzo[h]chromene-5,6-dione-6-ꢀO-methyloxime) 20I1II.
1
1
1
25.4, 125.8, 126.8, 127.2, 127.5, 128.5, 128.9, 129.6,
1
39.0, 149.7, 157.0, 166.2; MS +EI): m/z 319 +M ,
00%), 304 +23), 290 +7); HRMS +MALDI-FTMS):
A solution of b-lapachone 19 +0.588 g, 2.43 mmol) and
methoxylamine hydrochloride +0.203 g, 2.43 mmol) in
methanol +50 ml) was stirred at room temperature for
14 h, until full consumption of quinone. The solvent was
evaporated in a rotary evaporator and the residue was
subjected to column chromatography +silica gel, hexane/
ethyl acetate 5:1). The fractions eluted ®rst gave the isomer
1
+
M1H) calcd for C H NO m/z 320.1281, found m/z
3
2
0
18
3
20.1289.
3
.1.5. Reaction of 10with yield 2b. A melted mixture of
compounds 10 +0.225 g, 0.95 mmol) and 2b +0.416 g,
.95 mmol) was heated at 1408C for 1.5 h and then
0
20 as a yellow oil +0.174 g, 26%), while the last fractions
I
subjected to column chromatography +silica gel, hexane/
ethyl acetate 5:1 to give from the faster moving band
compound 12 +81 mg, 29%), mp 204±2058C +dichloro-
methane/hexane) Lit. mp 205±2068C. The fractions eluted
next were further separated by column chromatography
gave the isomer 20 +0.256 g, 39%) as yellow crystals, mp
II
80±828C +ethyl ether).
1
1
21 1
Compound 20 : IR +Nujol): n 1625, 1605, 1580 cm ; H
I
NMR d 1.41 [6H, s, 2-+CH ) ], 1.80 +2H, t, Jˆ6.4 Hz), 2.55
3
2
+
of compound 11b +18 mg, 5%), mp 129±1318C +ethyl
silica gel, hexane/ethyl acetate 20:1) to give yellow crystals
+2H, t, Jˆ6.4 Hz), 4.26 +3H, s, CH O±), 7.36±7.45 +2H, m),
3
7.81 +1H, dd, Jˆ1.7, 7.4 Hz), 8.03 +1H, dd, Jˆ1.5, 7.6 Hz);
2
1
1
13
C NMR d 16.2, 26.7, 31.9, 65.4, 77.8, 112.1, 123.0, 123.7,
129.0, 129.5, 129.7, 130.8, 142.9, 160.0, 177.6; MS +ESI):
acetate/hexane); IR +Nujol): n 1705 cm ; H NMR d
.45 +3H, t, Jˆ7.6 Hz, CH CH ±), 4.46 +2H, q, Jˆ7.6 Hz,
1
CH CH ±), 6.63 +1H, s), 7.20±7.28 +3H, m) 7.35±7.40 +2H,
3
2
1
m/z 272 for +M1H) ; Anal. Calcd for C H NO : C, 70.83;
H, 6.32; N, 5.16. Found: C, 70.72; H, 6.35; N, 5.10.
3
2
16 17
3
m), 7.55±7.71 +4H, m), 8.37 +1H, d, Jˆ8.9 Hz), 8.56 +1H, d,
Jˆ7.6 Hz) 8.61 +1H, d, Jˆ7.6 Hz), 8.67 +1H, d, Jˆ8.9 Hz);
1
3
21 1
Compound 20 : IR +Nujol): n 1640, 1605, 1580 cm ; H
C NMR d 14.2, 61.4, 71.8, 109.3, 120.9, 122.3, 122.8,
22.9, 123.5, 123.6, 123.7, 125.5, 126.8, 126.9, 127.1,
27.5, 128.1, 128.6, 128.7, 129.0, 139.6, 156.8, 163.4;
II
1
1
NMR d 1.42[6H, s, 2-+CH ) ], 1.80 +2H, t, Jˆ6.4 Hz), 2.56
3
2
+2H, t, Jˆ6.4 Hz), 4.30 +3H, s, CH O±), 7.39±7.49 +2H, m),
3

9474
D. N. Nicolaides et al. / Tetrahedron 57 '2001) 9469±9474
7
.89 +1H, dd, Jˆ2.0, 7.7 Hz), 8.63 +1H, dd, Jˆ2.0, 7.2 Hz);
Jˆ6.4 Hz), 4.58 +2H, q, Jˆ7.6 Hz, ±CH CH ), 7.55 +1H, t,
2
3
1
3
C NMR d 16.5, 26.8, 31.9, 64.8, 78.0, 111.1, 123.7, 126.0,
28.8, 129.8, 130.2, 130.9, 144.8, 160.5, 182.8; MS +ESI):
Jˆ7.6 Hz), 7.66 +1H, t, Jˆ7.6 Hz), 8.31 +1H, d, Jˆ8.2Hz),
1
3
1
m/z 272 for +M1H) , 294 for +M1Na) ; Anal. Calcd for
8.53 +1H, d, Jˆ8.2Hz); C NMR d 14.1, 17.0, 26.5, 31.3,
62.5, 75.8, 101.3, 121.9, 122.7, 124.7, 125.0, 125.3, 127.3,
129.2, 149.1, 150.4, 154.9, 166.0; MS +ESI): m/z 326 for
1
1
C H NO : C, 70.83; H, 6.32; N, 5.16. Found: C, 71.07; H,
1
6
6
17
3
1
1
.30; N, 5.20.
+M1H) , 348 for +M1Na) ; Anal. Calcd for C H NO :
19 19 4
C, 70.14; H, 5.89; N, 4.31. Found: C, 70.32; H, 5.70; N,
4.11.
3
2
.1.8. Reaction of 20I1II with ylide 2b. A melted mixture of
0I1II +0.150 g, 0.553 mmol) and 2b +0.291 g, 0.653 mmol)
was heated at 1408C for 10 min and the reaction mixture
Acknowledgements
was chromatographed +silica gel, hexane/ethyl acetate
20:1). Compound 22 +colorless prisms with blue ¯uores-
cence in short wave UV, 38 mg, 21%) was eluted ®rst, mp
D. R. Gautam extends his sincere thanks to the State
Scholarship Foundation +IKY) of Greece for providing
2
1 1
1
1
68±1698C +hexane); IR +Nujol): n 1572cm ; H NMR d
.49 [6H, s, 2-+CH ) ], 2.00 +2H, t, Jˆ6.4 Hz, 3-H), 3.12
®
nancial support for research in Greece. He also thanks
3
2
the Tribhuvan University, Kathmandu, Nepal for granting
him study leave.
+
2H, t, Jˆ6.4 Hz, 4-H), 7.47±7.55 +4H, m), 7.62+1H, t,
Jˆ7.6 Hz), 8.26±8.32 +3H, m), 8.47 +1H, d, Jˆ7.6 Hz);
1
3
C NMR d 17.4, 26.7, 31.7, 75.2, 101.8, 121.8, 122.6,
23.9, 124.4, 125.4, 126.7, 126.8, 127.2, 127.6, 127.9,
28.8, 129.8, 130.3, 147.7, 160.6; MS+ESI): m/z 330 for
1
1
References
1
1
+M1H) ; HRMS +MALDI-FTMS): +M1H) calcd for
C H NO m/z 330.1488, found m/z 330.1477.
1
2
. Papageorgiou, G.; Nicolaides, D. N.; Stephanidou-
Stephanatou, J. Liebigs Ann. Chem. 1989, 397.
2
2
20
2
. Nicolaides, D. N.; Litinas, K. E.; Papageorgiou, G. K.;
Stephanidou-Stephanatou, J. J. Heterocycl. Chem. 1991, 28,
The following fractions afforded compound 21 +46 mg,
2
1
1
2
1
0%), yellow oil; IR +Nujol) n 1723 cm ; H NMR d
.39 +6H, s), 1.49 +3H, t, Jˆ7.1 Hz), 1.86 +2H, t,
1
39.
3
. Nicolaides, D. N.; Awad, R. W.; Papageorgiou, G. K.;
Stephanidou-Stephanatou, J. J. Org. Chem. 1994, 59, 1083.
. Nicolaides, D. N.; Awad, R. W.; Papageorgiou, G. K.;
Stephanidou-Stephanatou, J. Tetrahedron Lett. 1996, 37,
Jˆ6.4 Hz), 2.95 +2H, t, Jˆ6.4 Hz), 4.40 +2H, q,
Jˆ7.1 Hz), 6.45 +1H, s), 7.20±7.30 +3H, m), 7.32±7.40
4
+
3H, m), 7.51 +1H, t, Jˆ7.6 Hz), 8.08 +1H, d, Jˆ7.6 Hz),
1
3
8
6
1
1
.50 +1H, d, Jˆ7.6 Hz); C NMR d 14.2, 16.9, 26.5, 31.7,
1.9, 71.9, 75.6, 105.9, 119.7, 121.5, 121.8, 121.9, 123.9,
26.9, 127.4, 128.6, 128.9, 130.5, 131.0, 136.6, 143.2,
1097.
. Bezergiannidou-Balouctsi, C.; Litinas, K. E.; Malamidou-
Xenikaki, E.; Nicolaides, D. N. Liebigs Ann. Chem. 1993,
5
6
1
43.4, 153.0, 163.7; MS +ESI): m/z 416 for +M1H) , 438
1175.
. Abdou, W. M. Synth. Commun. 1997, 27, 3599.
1
1
for +M1Na) ; HRMS +MALDI-FTMS): +M1H) calcd for
C H NO m/z 416.1856, found m/z 416.1853.
2
6
26
4
7. Nicolaides, D. N.; Awad, R. W.; Litinas, K. E.; Malamidou-
Xenikaki, E. Tetrahedron 1996, 52, 15007.
3
.1.9. Reaction of 20I1II with ylide 23. A solution of
compound 20I1II +67 mg, 0.247 mmol) and ylide 23
86 mg, 0.247 mmol) in dry toluene +2 ml) was re¯uxed
8. Nicolaides, D. N.; Papageorgiou, G. K.; Stephanidou-
Stephanatou, J. Tetrahedron 1989, 45, 4585.
+
9
. Nicolaides, D. N.; Varella, E. A.; Awad, R. W. Tetrahedron
993, 49, 7779.
for 48 h. The solvent was removed in a rotary evaporator
and the residue was subjected to column chromatography
1
10. Nicolaides, D. N.; Awad, R. W.; Varella, E. A. J. Heterocycl.
Chem. 1996, 33, 633.
11. Sun, J. S.; Geiser, A. H.; Frydmann, B. Tetrahedron Lett.
+
compound 25 +12mg, 15%), mp 181±183 8C +hexane); IR
silica gel, hexane/ethyl acetate 6:1) to give colorless
21 1
Nujol): n 1712cm ; H NMR d 1.58 +6H, s), 1.51 +3H,
+
1
998, 39, 8221.
t, Jˆ7.6 Hz, -CH CH ), 2.00 +2H, t, Jˆ6.4 Hz), 3.10 +2H, t,
2
3