Biradicals/zwitterions from thermolysis of enyne-isocyanates. Application to the synthesis of 2(1H)-pyridones, benzofuro[3,2-c]pyridin-1(2H)-ones, 2,5-dihydro-1H-pyrido[4,3,-b]indol-1-ones, and related compounds

Article abstract of DOI:10.1021/jo049716t

Thermolysis of benzannulated enyne-isocyanates 13 and enyne-isocyanates 36 and 37 promoted the cycloaromatization reactions to generate in situ O,4-didehydro-2-hydroxyquinolines and O,4-didehydro-2-hydroxypyridines, respectively, as reactive intermediates. These cycloaromatized intermediates could be captured either as biradicals and/or as zwitterions depending on the nature of the substituent at the alkynyl terminus. The intermediate derived from cycloaromatization of 13a bearing a phenyl substituent could be regarded as biradical 14, which then abstracts hydrogen atoms from γ-terpinene leading to 2(1H)-quinolinone 15. Alternatively, the same intermediate could also be regarded as zwitterion 14′, which then undergoes an initial hydride abstraction from γ-terpinene followed by protonation to produce 15. The presence of a 2-phenylethyl substituent in 13b and 37a or a 2-methylphenyl substituent in 37b also allowed the resulting intermediates to be captured intramolecularly either as biradicals or as zwitterions, producing 2(1H)-quinolinone 19, 2(1H)-pyridone 39, and benzopyranopyridine 43, respectively. On the other hand, with a 2-methoxyphenyl, a 2-(dimethylamino) phenyl, or a 3-methoxypropyl substituent, the chemical behavior of the cycloaromatized adduct could be best accounted for in terms of a zwitterionic intermediate leading to benzofuro [3,2-c]quinolin-6(5H)-one (20), 5,11-dihydro-11-methyl-6H-indolo-[3,2-c]quinolin-6-one (25), benzofuro[3,2-c]pyridin-1(2H)-one 44, 2,5-dihydro-2,5-dimethyl-1H-pyrido-[4,3-b] indol-1-one 46, and related compounds. Interestingly, thermolysis of 37f bearing a 2-(methoxymethyl)phenyl substituent at the alkynyl terminus produced the unexpected benzopyranopyridine 56 as the major product in a process involving the cleavage of the bond between the methoxyl oxygen and the adjacent methylene carbon. The efficiency and selectivity of the cycloaromatization reaction could also be enhanced by the introduction of 1.1 to 10 equiv of dimethylphenylsilyl chloride to the reaction mixture to capture the resulting zwitterion.

Full text of DOI:10.1021/jo049716t

Bir a d ica ls/Zw itter ion s fr om Th er m olysis of En yn e-Isocya n a tes.
Ap p lica tion to th e Syn th esis of 2(1H)-P yr id on es,
Ben zofu r o[3,2-c]p yr id in -1(2H)-on es,
2,5-Dih yd r o-1H-p yr id o[4,3-b]in d ol-1-on es, a n d Rela ted Com p ou n d s
Hongbin Li, Hua Yang, J effrey L. Petersen,† and Kung K. Wang*
Department of Chemistry, West Virginia University, Morgantown, West Virginia 26506-6045
kung.wang@mail.wvu.edu
Received February 18, 2004
Thermolysis of benzannulated enyne-isocyanates 13 and enyne-isocyanates 36 and 37 promoted
the cycloaromatization reactions to generate in situ O,4-didehydro-2-hydroxyquinolines and O,4-
didehydro-2-hydroxypyridines, respectively, as reactive intermediates. These cycloaromatized
intermediates could be captured either as biradicals and/or as zwitterions depending on the nature
of the substituent at the alkynyl terminus. The intermediate derived from cycloaromatization of
13a bearing a phenyl substituent could be regarded as biradical 14, which then abstracts hydrogen
atoms from γ-terpinene leading to 2(1H)-quinolinone 15. Alternatively, the same intermediate could
also be regarded as zwitterion 14′, which then undergoes an initial hydride abstraction from
γ-terpinene followed by protonation to produce 15. The presence of a 2-phenylethyl substituent in
13b and 37a or a 2-methylphenyl substituent in 37b also allowed the resulting intermediates to
be captured intramolecularly either as biradicals or as zwitterions, producing 2(1H)-quinolinone
19, 2(1H)-pyridone 39, and benzopyranopyridine 43, respectively. On the other hand, with a
2-methoxyphenyl, a 2-(dimethylamino)phenyl, or a 3-methoxypropyl substituent, the chemical
behavior of the cycloaromatized adduct could be best accounted for in terms of a zwitterionic
intermediate leading to benzofuro[3,2-c]quinolin-6(5H)-one (20), 5,11-dihydro-11-methyl-6H-indolo-
[3,2-c]quinolin-6-one (25), benzofuro[3,2-c]pyridin-1(2H)-one 44, 2,5-dihydro-2,5-dimethyl-1H-pyrido-
[4,3-b]indol-1-one 46, and related compounds. Interestingly, thermolysis of 37f bearing a 2-(meth-
oxymethyl)phenyl substituent at the alkynyl terminus produced the unexpected benzopyranopyridine
56 as the major product in a process involving the cleavage of the bond between the methoxyl
oxygen and the adjacent methylene carbon. The efficiency and selectivity of the cycloaromatization
reaction could also be enhanced by the introduction of 1.1 to 10 equiv of dimethylphenylsilyl chloride
to the reaction mixture to capture the resulting zwitterion.
In tr od u ction
different mode of cyclization of enyne-allenes involving
the formation of a bond between the C2 and the C6
carbon atoms leading to the five-membered-ring fulvene
biradicals (Schmittel cyclization) has also been reported.4
In general, enyne-allenes having an aryl substituent or
a sterically demanding group, such as tert-butyl or
trimethylsilyl, at the alkynyl terminus prefer the Schmit-
tel cyclization pathway.
The use of unsaturated compounds to generate biradi-
cals has received considerable attention.1 In the cases
that contain only carbon atoms in the conjugated system,
the Bergman cyclization reaction of (Z)-3-hexene-1,5-
diynes (enediynes) to 1,4-didehydrobenzene biradicals2
and the Myers-Saito cyclization reaction of (Z)-1,2,4-
heptatrien-6-ynes (enyne-allenes) to R,3-didehydrotolu-
ene3 biradicals have been investigated extensively. A
(3) (a) Myers, A. G.; Kuo, E. Y.; Finney, N. S. J . Am. Chem. Soc.
1989, 111, 8057-8059. (b) Myers, A. G.; Dragovich, P. S. J . Am. Chem.
Soc. 1989, 111, 9130-9132. (c) Nagata, R.; Yamanaka, H.; Okazaki,
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Yamanaka, H.; Murahashi, E.; Saito, I. Tetrahedron Lett. 1990, 31,
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M.; Steffen, J .-P.; Maywald, M.; Engels, B.; Helten, H.; Musch, P. J .
Chem. Soc., Perkin Trans. 2 2001, 1331-1339.
* To whom correspondence should be addressed. Phone: (304) 293-
3068, ext 6441. Fax: (304) 293-4904.
† To whom correspondence concerning the X-ray structures should
be addressed. Phone: (304) 293-3435, ext 6423. Fax: (304) 293-4904.
E-mail: jeffrey.petersen@mail.wvu.edu.
(1) (a) Nicolaou, K. C.; Dai, W.-M. Angew. Chem., Int. Ed. Engl.
1991, 30, 1387-1416. (b) Maier, M. E. Synlett 1995, 13-26. (c) Wang,
K. K. Chem. Rev. 1996, 96, 207-222. (d) Saito, I.; Nakatani, K. Bull.
Chem. Soc. J pn. 1996, 69, 3007-3019. (e) Grissom, J . W.; Gunawar-
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6518.
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10.1021/jo049716t CCC: $27.50 © 2004 American Chemical Society
Published on Web 05/28/2004
4500
J . Org. Chem. 2004, 69, 4500-4508

Biradicals/ Zwitterions from Enyne-Isocyanates
SCHEME 1
SCHEME 3
stantially higher temperatures (80-138 °C) were needed
to promote the cyclization reactions of the benzannulated
enyne-carbodiimides 5.11 In addition, with the only
exception of R ) H, cyclization gave exclusively the
putative indole biradicals 9 (R ) Me, Pr, Ph, t-Bu, or Me3-
Si) via the C2-C6 cyclization pathway.11a However, it is
possible to redirect the reaction toward the C2-C7
pathway by incorporating the central carbon-carbon
double bond of the enyne-carbodiimide system in a five-
membered ring as depicted in 10 to form the pyridine
biradical 11 (Scheme 3).11e As in the enyne-ketene
system, under certain reaction conditions, the chemical
behavior of biradical 11 could be best described in terms
of zwitterion 11′.
Our continued interest in the development of new
conjugated systems for the thermal generation of biradi-
cals/zwitterions and the use of these reactive intermedi-
ates for synthetic applications led us to investigate the
enyne-isocyanate system. Several interesting features
of this system and new synthetic pathways to the
derivatives of 2(1H)-pyridone, benzofuro[3,2-c]pyridin-
1(2H)-one,12 2,5-dihydro-1H-pyrido[4,3-b]indol-1-one,13 and
related compounds were discovered.
SCHEME 2
The Moore cyclization reaction of enyne-ketene 1
having an oxygen atom in the conjugated system pro-
duces biradical 2 bearing an aryl radical center and a
phenoxyl radical center (Scheme 1).5 Under certain
reaction conditions, the chemical behavior of biradical 2
could be best accounted for by regarding it as zwitterion
2′. Examples of the C2-C6 cyclization reaction of the
enyne-ketene system having a phenyl substituent or
other radical-stabilizing groups at the alkynyl terminus
to form the fulvene biradical 3 were also observed.5a,c
The conjugated systems bearing other heteroatoms
have also been employed to generate biradicals. A case
containing a sulfur atom was observed.6 Recently, a
potential aza-Bergman route from 3-aza-3-hexene-1,5-
diynes and a related heterocyclic analogue to 2,5-dide-
hydropyridine biradicals were reported.7 Examples in-
volving the enallene-nitrile8 and the enallene-isonitrile9
systems have also been investigated. The benzannulated
enyne-ketenimines 4 were also found to undergo the C2-
C7 cyclization reaction to form the quinoline biradicals 6
(R ) H or Pr) and/or the C2-C6 cyclization reaction to
form the putative indole biradicals 7 (R ) Pr, Ph, t-Bu,
or Me3Si) (Scheme 2).10 These cyclization reactions oc-
curred readily under mild thermal conditions ranging
from ambient temperature to 80 °C. In contrast, sub-
Resu lts a n d Discu ssion
The benzannulated enyne-isocyanate 13a (R ) Ph)
was previously synthesized as the precursor of an enyne-
carbodiimide.11a Alternatively, it could also be efficiently
synthesized by treatment of 2-(phenylethynyl)aniline
(12a ), derived from the palladium-catalyzed cross-
coupling reaction between 2-iodoaniline and phenyl-
acetylene,10a with triphosgene (Scheme 4) in 81% yield
(Table 1). However, 13a did not show any propensity to
undergo cyclization in the presence of an excess of
γ-terpinene under refluxing benzene (80 °C) for 4 h. This
is in sharp contrast to the benzannulated enyne-keten-
imine 4a (R ) Ph, X ) CPh2) and the benzannulated
enyne-carbodiimide 5a (R ) Ph, X ) NPh), which
underwent facile C2-C6 cyclizations to generate 7a (R )
Ph, X ) CPh2) at ambient temperature10a and 9a (R )
Ph, X ) NPh) under refluxing benzene,11a respectively.
Heating 13a under refluxing 1,2-dichlorobenzene at 180
°C for 24 h also failed to promote the cyclization reaction.
It was necessary to heat 13a in the presence of an excess
of γ-terpinene in 1,2-dichlorobenzene in a sealed glass
(5) (a) Karlsson, J . O.; Nguyen, N. V.; Foland, L. D.; Moore, H. W.
J . Am. Chem. Soc. 1985, 107, 3392-3393. (b) Moore, H. W.; Chow, K.;
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H. W. J . Am. Chem. Soc. 1989, 111, 975-989. (d) Chow, K.; Nguyen,
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16, 1081-1084.
J . Org. Chem, Vol. 69, No. 13, 2004 4501

Li et al.
SCHEME 4
SCHEME 5
SCHEME 6
TABLE 1. Syn th esis of th e Ben za n n u la ted
En yn e-Isocya n a tes 13
R
12 (yield, %)
13 (yield, %)
phenyl
2-phenylethyl
2-methoxyphenyl
2-(dimethylamino)phenyl
3-methoxypropyl
12a (89)
12b (90)
12c (89)
12d (89)
12e (83)
13a (81)
13b (74)
13c (88)
13d (72)
13e (75)
zene (180 °C) for 14 days produced 19 in only 27% yield.
The ability of the phenyl substituent to capture the aryl
radical/cationic center was also observed previously in
the enyne-ketene5e,f and the enyne-carbodiimide11e
systems.
tube at 230 °C for 24 h to produce 3-phenyl-2(1H)-
quinolinone (15)14 in 47% yield along with a small amount
of the chlorinated adduct 1615 (6%). Presumably, the C2-
C7 cyclization reaction of 13a occurred to generate the
quinoline biradical/zwitterion 14/14′. Hydrogen atom
abstractions from γ-terpinene by biradical 14 then pro-
duced 15. Alternatively, an initial hydride abstraction
from γ-terpinene by zwitterion 14′ followed by protona-
tion could also lead to 15. The chloro substituent in 16
presumably came from 1,2-dichlorobenzene. However, the
reaction pathway that allowed the acquisition of the
chloro substituent remained to be investigated. The
preference for 13a to undergo the C2-C7 cyclization
reaction is also dramatically different from those of 4a
and 5a , which favor the C2-C6 cyclization pathway. The
reason for such a change is not clear at the present time.
Several other enyne-isocyanates were likewise syn-
thesized from 2-iodoaniline (Table 1). Thermolysis of 13b
bearing a properly situated phenyl substituent at 230 °C
in a sealed glass tube allowed the resulting aryl radical/
cationic center in 17/17′ to be captured by the phenyl
substituent to form 18/18′. A subsequent prototropic
rearrangement then furnished 7,8-dihydrobenzo[k]phenan-
thridin-6(5H)-one (19)15,16 in 81% yield (Scheme 5). Again,
it was necessary to conduct the reaction at 230 °C for 24
h. Thermolysis of 13b under refluxing 1,2-dichloroben-
Thermolysis of 13c having a 2-methoxyphenyl sub-
stituent at the alkynyl terminus under refluxing 1,2-
dichlorobenzene for 21 days produced benzofuro[3,2-
c]quinolin-6(5H)-one (20)17a-c in 11% yield and the
N-methylated adduct 2117d-f in 9% yield (Scheme 6). The
yield of 20 was improved to 53% when thermolysis was
conducted in the presence of 1.1 equiv of dimethylphen-
ylsilyl chloride. Dimethylphenylsilyl chloride instead of
trimethylsilyl chloride was selected as the silylating
agent because of its relatively high boiling point. Heating
13c in the presence of 1.1 equiv of dimethylphenylsilyl
chloride in 1,2-dichlorobenzene in a sealed glass tube at
230 °C for 24 h further improved the yield of 20 to 68%
along with 6% of 21. The formation of 20 and 21 could
be best accounted for by regarding the initial formed O,4-
didehydro-2-hydroxyquinoline biradical 22 as zwitterion
22′ (Scheme 7). The carbocationic center in 22′ was
captured by the methoxyl group to give the oxonium ion
in 23. Subsequent hydrolysis of 23 then afforded 20. It
is worth noting that methylation of 23 or the correspond-
ing demethylated anion occurred on the nitrogen to
furnish 21. The reactive methyl group of the oxonium
(16) (a) Paramasivam, K.; Pamasamy, K.; Shanmugam, P. Synthesis
1977, 768-770. (b) Veeramani, K.; Paramasivam, K.; Ramakrishna-
subramanian, S.; Shanmugam, P. Synthesis 1978, 855-857. (c) Cap-
pelli, A.; Anzini, M.; Vomero, S.; Canullo, L.; Mennuni, L.; Makovec,
F.; Doucet, E.; Hamon, M.; Menziani, M. C.; De Benedetti, P. G.; Bruni,
G.; Romeo, M. R.; Giorgi, G.; Donati, A. J . Med. Chem. 1999, 42, 1556-
1575.
(14) (a) Ferna´ndez, M.; de la Cuesta, E.; Avendan˜o, C. Synthesis
1995, 1362-1364. (b) Cheon, S. H.; Lee, J . Y.; Chung, B.-H.; Choi,
B.-G.; Cho, W.-J .; Kim, T. S. Arch. Pharmacal Res. 1999, 22, 179-
183. (c) Huang, L.-J .; Hsieh, M.-C.; Teng, C.-M.; Lee, K.-H.; Kuo, S.-
C. Bioorg. Med. Chem. 1998, 6, 1657-1662.
(15) Structure was established by X-ray structure analysis.
4502 J . Org. Chem., Vol. 69, No. 13, 2004

Biradicals/ Zwitterions from Enyne-Isocyanates
SCHEME 7
SCHEME 9
SCHEME 8
SCHEME 10
ion in 23 is presumably the source of the methyl group
for methylation intermolecularly. The chemical behavior
of 22 as zwitterion 22 is reminiscent of what were
observed previously in the enyne-ketene,5 the enyne-
carbodiimide,11e and the enallene-isonitrile9 systems.
The favorable effect by either trimethylsilyl chloride or
dimethylphenylsilyl chloride was also observed previ-
ously in several examples of the enyne-ketene5b and the
enyne-carbodiimide11e systems. Presumably, the oxygen-
centered anion in 23 was captured by dimethylphenylsilyl
chloride to form 24, enhancing the efficiency and selectiv-
ity of the cycloaromatization reaction.
TABLE 2. Syn th esis of En yn e-Isocya n a tes 36 a n d 37
32/33
34/35
36/37
R
(yield, %) (yield, %) (yield, %)
3-methoxypropyl
32 (91)
34 (87)
36 (82)
2-phenylethyl
2-methylphenyl
2-methoxyphenyl
2-(dimethylamino)phenyl
3-methoxypropyl
33a (98)
33b (90)
33c (92)
33d (91)
33e (97)
33f (93)
35a (92)
35b (96)
35c (92)
35d (85)
35e (86)
35f (89)
37a (86)
37b (91)
37c (84)
37d (87)
37e (89)
37f (91)
2-(methoxymethyl)phenyl
The use of 13d bearing a 2-(dimethylamino)phenyl
group at the alkynyl terminus for thermolysis in the
presence of 1.1 equiv of dimethylphenylsilyl chloride at
230 °C for 24 h furnished 5,11-dihydro-11-methyl-6H-
indolo[3,2-c]quinolin-6-one (25)15,18 in 59% yield and
5,11-dihydro-5,11-dimethyl-6H-indolo[3,2-c]quinolin-6-
one (26) in 24% yield (Scheme 8). In the presence of 10
equiv of dimethylphenylsilyl chloride, 25 and 26 were
isolated in 82% and 6% yields, respectively.
10 equiv of dimethylphenylsilyl chloride at 230 °C, the
N-methylated adduct 29 was produced.
Enyne-isocyanate 36 (R ) 3-methoxypropyl) having
the central carbon-carbon double bond incorporated in
the cyclohexenyl ring was synthesized from 3019 as
outlined in Scheme 10. The palladium-catalyzed cross-
coupling reaction between 30 and 5-methoxy-1-pentyne
produced carboxylic ester 32, which was then hydrolyzed
to give the corresponding carboxylic acid 34 (Table 2).
Treatment of 34 with diphenyl phosphorazidate20 (DPPA)
then furnished enyne-isocyanate 36. Enyne-isocyanates
37 bearing a cyclopentenyl ring were likewise synthesized
from 3119 as reported previously.11e
Interestingly, when 13e was subjected to thermolysis
at 180 °C for 14 days, 2(1H)-quinolinone 27 and the
corresponding O-methylated adduct 28 were obtained
(Scheme 9). On the other hand, in the presence of 1.1 or
Enyne-isocyanates 36 and 37 appeared to be more
reactive than the benzannulated derivatives. Thermolysis
(17) (a) Kawase, Y.; Yamaguchi, S.; Morita, M.; Uesugi, T. Bull.
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J . Org. Chem, Vol. 69, No. 13, 2004 4503

Li et al.
SCHEME 11
SCHEME 12
SCHEME 13
of 36 in the presence of 1.1 equiv of dimethylphenylsilyl
chloride under refluxing 1,2-dichlorobenzene at 180 °C
for 36 h was sufficient to produce 2(1H)-pyridone 3815
(eq 1). However, unlike 13e, the N-methylated adduct of
38 was not detected.
SCHEME 14
The chemical behavior of 37a closely resembles that
of the benzannulated analogue 13b in producing 3915 in
98% yield (eq 2) except that heating at 180 °C for 3 h
was also sufficient to promote the cyclization reaction.
However, heating 37a at 132 °C under refluxing chlo-
robenzene for 10 h resulted in only ca. 65% completion
of reaction.
SCHEME 15
Biradical/zwitterion 40/40′, generated from thermolysis
of 37b at 180 °C for 48 h, underwent a 1,5-hydrogen/
hydride shift to form 41/41′, which could also be regarded
as o-quinodimethane 41′′ (Scheme 11). A subsequent
rotation around the central carbon-carbon bond of 41/
41′ could give 42 for an electrocyclic reaction to produce
43.15 Such a cascade sequence was also observed previ-
ously in the enyne-allene,21 the enyne-ketene,5d and the
enyne-carbodiimide11e systems. Thermolysis of 37c at
132 °C for 36 h furnished 4415 and 45 in 10% and 52%
yields, respectively (Scheme 12). In the presence of 1.1
equiv of dimethylphenylsilyl chloride, 44 was produced
exclusively. Similarly, cyclization of 37d led to 4615 and
4715 in 38% and 28% yields, respectively, and in the
presence of 1.1 equiv of dimethylphenylsilyl chloride, 4815
in 75% yield (Scheme 13).
In addition to the cyclized products 49-51, a small
amount of 52 was isolated from thermolysis of 37e
(Scheme 14). Presumably, the initially formed zwitterion
53 or its methylated derivative was attacked by a second
molecule of 53 or its demethylated derivative as depicted
(21) Liu, B.; Wang, K. K.; Petersen, J . L. J . Org. Chem. 1996, 61,
8503-8507.
4504 J . Org. Chem., Vol. 69, No. 13, 2004

Biradicals/ Zwitterions from Enyne-Isocyanates
SCHEME 16
dimethylphenylsilyl chloride, 56 was also produced ex-
clusively in 76% yield.
Con clu sion s
Thermolysis of enyne-isocyanates and the benzannu-
lated analogues was successful in promoting the cy-
cloaromatization reactions to generate O,4-didehydro-2-
hydroxypyridines and O,4-didehydro-2-hydroxyquinolines
as biradicals/zwitterions for subsequent synthetic ap-
plications. The presence of two reactive centers in the
same molecule simultaneously provided many pathways
for intramolecular decay to produce heteroaromatic
compounds. A variety of 2(1H)-pyridones, 2(1H)-quino-
linones, benzopyranopyridines, benzofuro[3,2-c]quinolin-
6(5H)-ones,17 5,11-dihydro-11-methyl-6H-indolo[3,2-c]-
quinolin-6-ones,18 benzofuro[3,2-c]pyridin-1(2H)-ones,12
2,5-dihydro-5-methyl-1H-pyrido[4,3-b]indol-1-ones,13 and
related compounds were thus synthesized. Many deriva-
tives of these heteroaromatic compounds were found to
possess interesting biological activities. Compared to
other conjugated systems, such as enyne-allene, enyne-
ketene, enyne-ketenimine, enyne-carbodiimide, and
enallene-isonitrile, the cycloaromatization reactions of
enyne-isocyanates appear to require higher tempera-
tures and are more in favor of the C2-C7 cyclization
pathway.
SCHEME 17
Exp er im en ta l Section
2-(4-P h en yl-1-bu tyn yl)a n ilin e (12b). The following pro-
cedure is representative for the preparation of anilines 12. To
a mixture of 2-iodoaniline (1.095 g, 5.0 mmol), triethylamine
(0.84 mL, 6.0 mmol), Pd(PPh3)2Cl2 (0.105 g, 0.15 mmol), and
copper(I) iodide (0.049 g, 0.26 mmol) in 30 mL of DMF was
added slowly a solution of 4-phenyl-1-butyne (0.710 g, 5.5
mmol) in 5 mL of DMF. After 2 h of stirring at room
temperature, 50 mL of a saturated aqueous ammonium
chloride solution and 50 mL of diethyl ether were added. The
organic layer was separated, and the aqueous layer was back
extracted with diethyl ether. The combined organic layers were
washed with brine and water, dried over sodium sulfate, and
concentrated. Purification of the residue by flash column
chromatography (silica gel/50% diethyl ether in hexanes)
afforded 0.997 g of 12b (4.5 mmol, 90%) as a light yellow
in Scheme 15 leading to 52. In the presence of 1.1 equiv
of dimethylphenylsilyl chloride, 49 was produced exclu-
sively in 89% yield.
1
liquid: IR (neat) 3467, 3358, 749 cm-1; H δ 7.37-7.21 (6 H,
m), 7.08 (1 H, ddd, J ) 8.5, 7.7, 1.6 Hz), 6.69-6.63 (2 H, m),
3.93 (2 H, br s), 2.95 (2 H, t, J ) 7.0 Hz), 2.81 (2 H, t, J ) 7.0
Hz); 13C δ 147.7, 140.5, 131.9, 128.9, 128.5, 128.4, 126.3, 117.6,
114.0, 108.5, 94.6, 77.9, 35.0, 21.6.
Surprisingly, thermolysis of 37f at 180 °C for 5 h
furnished 55 and the unexpected benzopyranopyridine
5615 (Scheme 16). As observed in the case of 40, a 1,5-
hydrogen shift of the initially formed biradical 57 could
form 58, which could also be regarded as o-quin-
odimethane 58′ (Scheme 17). A subsequent rotation
around the central carbon-carbon bond of 58 could give
59 for an electrocyclic reaction to produce 55. Alterna-
tively, the carbocationic center in 57′ could be captured
by the methoxyl oxygen to form 60. The cleavage of the
bond between the oxonium oxygen and the adjacent
methylene carbon could lead to o-quinodimethane 61,
which could also be regarded as biradical 61′. Rotation
around the central carbon-carbon bond of 61′ could give
62, which in turn could undergo an electrocyclic reaction
to account for the formation of the unexpected 56.
Thermolysis of 37f at 150 °C for 20 h produced 56
exclusively in 59% yield. In the presence of 1.1 equiv of
En yn e-Isocya n a te 13b. The following procedure is rep-
resentative for the preparation of the benzannulated enyne-
isocyanates 13 from anilines 12. To a solution of 0.104 g of
triphosgene (0.35 mmol) in 15 mL of anhydrous benzene was
added a mixture of 0.208 g of aniline 12b (0.94 mmol) and
0.28 mL of triethylamine (2.0 mmol) in 10 mL of benzene under
a nitrogen atmosphere at room temperature. After 6 h of
stirring, the white precipitate of triethylamine hydrochloride
was removed by filtration, and the filtrate was concentrated
in vacuo. Purification of the residue by flash column chroma-
tography (silica gel/20% diethyl ether in hexanes) afforded
0.172 g of 13b (0.70 mmol, 74%) as a pale yellow liquid: IR
1
(neat) 2252, 755, 699 cm-1; H δ 7.40-7.25 (6 H, m), 7.21 (1
H, dd, J ) 7.7, 1.6 Hz), 7.12 (1 H, td, J ) 7.5, 1.4 Hz), 7.03 (1
H, dd, J ) 7.8, 1.1 Hz), 3.00 (2 H, t, J ) 7.5 Hz), 2.81 (2 H, t,
J ) 7.2 Hz); 13C δ 140.4, 135.2, 132.1, 128.7, 128.4, 127.4,
126.3, 125.2, 123.4, 121.3, 98.6, 76.9, 34.5, 21.8; MS m/z 247
(M+), 218, 156, 91.
J . Org. Chem, Vol. 69, No. 13, 2004 4505

Li et al.
3-P h en yl-2-(1H )-q u in olin on e (15)14 a n d 4-Ch lor o-3-
p h en yl-2-(1H)-qu in olin on e (16). A solution of 13a (0.038 g,
0.17 mmol) and γ-terpinene (0.48 g, 3.4 mmol) in 2 mL of 1,2-
dichlorobenzene in a sealed glass tube was heated at 230 °C
for 24 h. The solvent was removed in vacuo, and the residue
was purified by flash column chromatography (silica gel/25%
ethyl acetate in methylene chloride) to afford 0.018 g of 15
(0.081 mmol, 47%) as white crystals and 0.0025 g (6%) of 16
as a solid. 15: mp 230-231 °C (lit.14a mp 234 °C); IR 3446,
1659, 753, 696 cm-1; 1H δ 11.7 (1 H, br s), 7.92 (1 H, s), 7.84-
7.79 (2 H, m), 7.61 (1 H, dd, J ) 7.9, 1.0 Hz), 7.53-7.41 (4 H,
m), 7.37 (1 H, d, J ) 8.2 Hz), 7.23 (1 H, t, J ) 7.2 Hz); 13C δ
163.1, 138.5, 138.0, 136.2, 132.4, 130.3, 128.9, 128.3, 128.2,
127.8, 122.7, 120.3, 115.5. 16: 1H δ 11.4 (1 H, s), 8.05 (1 H, d,
J ) 7.4 Hz), 7.55-7.44 (6 H, m), 7.32 (1 H, t, J ) 7.4 Hz), 7.26
(1 H, d, J ) 7.6 Hz). The structure of 16 was established by
X-ray structure analysis.
25 (0.44 mmol, 82%) and 0.008 g of 26 (0.03 mmol, 6%). 25:
mp 335 °C dec with melting (lit.18a mp 323-326 °C); IR 3500,
1648 cm-1; 1H δ 9.88 (1 H, br s), 8.58 (1 H, d, J ) 7.4 Hz), 8.36
(1 H, d, J ) 8.4 Hz), 7.58-7.46 (4 H, m), 7.41 (1 H, ddd, J )
8.1, 6.4, 1.5 Hz), 7.33 (1 H, ddd, J ) 8.4, 6.9, 1.5 Hz), 4.33 (3
H, s); 13C (4% MeOH-d4 in CDCl3) δ 161.0, 140.8, 139.6, 137.6,
128.8, 124.5, 123.6, 122.4, 122.1, 121.8, 121.7, 116.9, 113.3,
109.0, 107.4, 33.3; MS m/z 248 (M+), 232, 207. The structure
of 25 was established by X-ray structure analysis. 26: mp
207-208 °C; IR 1648, 744 cm-1 1H δ 8.56 (1 H, d, J ) 7.4
;
Hz), 8.30 (1 H, d, J ) 8.2 Hz), 7.57 (1 H, ddd, J ) 8.5, 6.6, 1.5
Hz), 7.48 (1 H, d, J ) 7.9 Hz), 7.43-7.27 (4 H, m), 4.17 (3 H,
s), 3.80 (3 H, s); 13C (4% MeOH-d4 in CDCl3) δ 160.0, 139.6,
139.2, 138.9, 128.8, 124.4, 124.2, 122.9, 122.2, 121.8, 121.3,
115.6, 114.4, 108.9, 107.6, 33.5, 29.0; MS m/z 262 (M+), 248,
233, 207.
Eth yl 2-(5-Meth oxy-1-pen tyn yl)-1-cycloh exen ecar boxyl-
a te (32). To a mixture of enol triflate 3019 (0.40 g, 1.32 mmol),
N,N-diisopropylethylamine (0.23 mL, 1.32 mmol), Pd(PPh3)2-
Cl2 (0.027 g, 0.040 mmol), and copper(I) iodide (0.013 g, 0.066
mmol) in 5 mL of DMF was added slowly a solution of
5-methoxy-1-pentyne22 (0.13 g, 1.32 mmol) in 2 mL of DMF.
After 2 h of stirring at room temperature, 10 mL of a saturated
aqueous ammonium chloride solution and 10 mL of diethyl
ether were added. The organic layer was separated, and the
aqueous layer was back extracted with diethyl ether. The
combined organic layers were washed with brine and water,
dried over sodium sulfate, and concentrated. Purification of
the residue by flash column chromatography (silica gel/ 50%
diethyl ether in hexanes, Rf 0.45) afforded 0.30 g of 32 (1.2
mmol, 91%) as a yellow liquid: IR (neat) 2214, 1719, 1696
cm-1; 1H δ 4.21 (2 H, quartet, J ) 7.2 Hz), 3.48 (2 H, t, J ) 6.4
Hz), 3.34 (3 H, s), 2.47 (2 H, t, J ) 6.9 Hz), 2.38-2.26 (4 H,
m), 1.81 (2 H, quintet, J ) 6.6 Hz), 1.65-1.58 (4 H, m), 1.30
(3 H, t, J ) 7.2 Hz); 13C δ 167.2, 133.3, 128.4, 96.8, 80.9, 71.2,
60.3, 58.6, 32.7, 28.7, 26.1, 21.8, 21.7, 16.6, 14.3; MS m/z 250
(M+), 235, 222, 205, 192, 177, 164.
7,8-Dih yd r oben zo[k]p h en a n th r id in -6(5H)-on e (19).16
A
solution of 13b (0.186 g, 0.75 mmol) in 10 mL of 1,2-
dichlorobenzene was heated under reflux for 14 days. The
solvent was removed in vacuo, and the residue was purified
by column chromatography to afford 0.050 g of 19 (0.20 mmol,
27%) as brown crystals. Similarly, a solution of 13b (0.100 g,
0.40 mmol) in 2 mL of 1,2-dichlorobenzene in a sealed glass
tube was heated at 230 °C for 24 h to afford 0.081 g of 19 (0.33
mmol, 81%): mp 245-246 °C (lit.16a mp 250-252 °C); IR 3430,
1
1646, 755 cm-1; H δ 12.04 (1 H, br s), 8.18 (1 H, d, J ) 8.2
Hz), 7.90-7.85 (1 H, m), 7.52-7.50 (2 H, m), 7.44-7.33 (3 H,
m), 7.27-7.21 (1 H, m), 2.94-2.81 (4 H, m); 13C δ 163.4, 142.6,
140.3, 138.1, 131.8, 129.4, 129.3, 129.0, 128.3, 128.2, 126.2,
126.0, 122.2, 117.9, 116.9, 28.4, 21.9. The structure of 19 was
established by X-ray structure analysis.
Ben zofu r o[3,2-c]qu in olin -6(5H)-on e (20)17a-c a n d 5-Me-
th ylben zofu r o[3,2-c]qu in olin -6(5H)-on e (21).17d-f A solu-
tion of 13c (0.095 g, 0.38 mmol) in 4 mL of 1,2-dichlorobenzene
was heated under reflux for 21 days. The solvent was removed
in vacuo, and the residue was purified by column chromatog-
raphy to afford 0.010 g of 20 (0.043 mmol, 11%) as a light
brown solid and 0.009 g of 21 (0.036 mmol, 9%) as a white
solid. Similarly, a solution of 13c (0.150 g, 0.6 mmol) and
dimethylphenylsilyl chloride (0.113 g, 0.66 mmol) in 6 mL of
1,2-dichlorobenzene was heated under reflux for 21 days to
afford 0.076 g of 20 (0.32 mmol, 53%). Thermolysis of a solution
of 13c (0.050 g, 0.2 mmol) and dimethylphenylsilyl chloride
(0.036 g, 0.21 mmol) in 2 mL of 1,2-dichlorobenzene in a sealed
glass tube at 230 °C for 24 h produced 0.032 g of 20 (0.14 mmol,
68%) and 0.003 g of 21 (0.012 mmol, 6%). 20: mp 294-295 °C
2-(5-Meth oxy-1-pen tyn yl)-1-cycloh exen ecar boxylic Acid
(34). A mixture of 1.2 g of 32 (4.8 mmol) in 10 mL of
1,2-dimethoxyethane and 10 mL of a 1 M aqueous lithium
hydroxide solution was stirred at room temperature for 36 h.
Then 1,2-dimethoxyethane was removed in vacuo, and 10 mL
of water was introduced. The solution was extracted with
diethyl ether (3 × 10 mL), and the diethyl ether extracts were
discarded. The aqueous solution was cooled in an ice-water
bath, acidified with cold 10% sulfuric acid, and then extracted
with Et2O (3 × 30 mL). The combined diethyl ether layers were
dried over sodium sulfate and concentrated in vacuo to give
0.93 g of 34 (4.19 mmol, 87%) as a colorless liquid: IR (neat)
1
(lit.17a mp 294-296 °C); IR 1685, 736 cm-1; H (DMSO-d6) δ
12.01 (1 H, br s), 8.10 (1 H, dd, J ) 6.9, 2.0 Hz), 8.05 (1 H, d,
J ) 7.9 Hz), 7.84 (1 H, dd, J ) 7.1, 1.4 Hz), 7.61 (1 H, ddd, J
) 8.4, 7.1, 1.3 Hz), 7.54-7.44 (3 H, m), 7.33 (1 H, td, J ) 7.5,
0.9 Hz); 13C (DMSO-d6) δ 159.1, 157.9, 154.8, 138.4, 130.9,
126.3, 124.7, 123.8, 122.5, 121.3, 121.2, 116.2, 111.8, 110.7,
110.0. 21: mp 201-202 °C (lit.17d mp 202-204 °C); IR 1660,
742 cm-1; 1H δ 8.32-8.27 (1 H, m), 8.17 (1 H, dd, J ) 7.7, 1.4
Hz), 7.68-7.61 (2 H, m), 7.50 (1 H, d, J ) 8.9 Hz), 7.47-7.41
1
3300-2600 (br), 2241, 1690 cm-1; H δ 3.49 (2 H, t, J ) 6.2
Hz), 3.34 (3 H, s), 2.51 (2 H, t, J ) 6.9 Hz), 2.38-2.30 (4 H,
m), 1.82 (2 H, quintet, J ) 6.6 Hz), 1.67-1.60 (4 H, m); 13C δ
170.4, 132.7, 131.0, 100.4, 80.8, 71.0, 58.6, 33.1, 28.4, 25.9, 21.7,
16.6; MS m/z 222 (M+), 190, 177.
En yn e-Isocya n a te 36. To a solution of 0.42 g of 34 (1.89
mmol) in 15 mL of anhydrous benzene was added a solution
of 0.29 mL of triethylamine (2.1 mmol) and 0.51 g of DPPA
(1.85 mmol) in 2 mL of benzene. After 6 h of stirring at room
temperature, the reaction mixture was then washed with brine
and water, dried over sodium sulfate, and concentrated.
Purification of the residue by flash column chromatography
(silica gel/5% diethyl ether in hexanes, Rf 0.28) afforded 0.33
g of 36 (1.51 mmol, 82%) as a colorless liquid: IR (neat) 2248,
(2 H, m), 7.37 (1 H, ddd, J ) 8.0, 6.9, 1.1 Hz), 3.85 (3 H, s); 13
C
δ 159.6, 157.3, 155.4, 139.3, 130.7, 126.1, 124.6, 124.4, 122.3,
122.2, 115.1, 112.8, 111.3, 110.3, 29.2.
5,11-Dih yd r o-11-m et h yl-6H -in d olo[3,2-c]q u in olin -6-
on e (25)18 a n d 5,11-Dih yd r o-5,11-d im eth yl-6H-in d olo[3,2-
c]qu in olin -6-on e (26). A solution of 13d (0.050 g, 0.19 mmol)
and dimethylphenylsilyl chloride (0.036 g, 0.21 mmol) in 2.5
mL of 1,2-dichlorobenzene in a sealed glass tube was heated
at 230 °C for 24 h. The solvent was removed in vacuo, and the
residue was purified by flash column chromatography (silica
gel/20% ethanol in methylene chloride, Rf 0.55) to afford 0.028
g of 25 (0.11 mmol, 59%) as a white solid and 0.012 g of 26
(0.046 mmol, 24%) as a yellow solid. Similarly, a solution of
13d (0.139 g, 0.53 mmol) and dimethylphenylsilyl chloride
(0.92 g, 5.3 mmol) in 2.5 mL of 1,2-dichlorobenzene in a sealed
glass tube was heated at 230 °C for 24 h to afford 0.108 g of
1
1458, 1120 cm-1; H δ 3.48 (2 H, t, J ) 6.2 Hz), 3.34 (3 H, s),
2.47 (2 H, t, J ) 6.9 Hz), 2.21-2.08 (4 H, m), 1.82 (2 H, quintet,
(22) (a) Mu¨ller, P.; Gra¨nicher, C. Helv. Chim. Acta 1995, 78, 129-
144. (b) J ackson, W. R.; Perlmutter, P.; Smallridge, A. J . Aust. J . Chem.
1988, 41, 251-261.
(23) Larock, R. C.; Harrison, L. W. J . Am. Chem. Soc. 1984, 106,
4218-4227.
(24) Brandsma, L.; Hommes, H.; Verkruijsse, H. D.; de J ong, R. L.
P. Recl. Trav. Chim. Pays-Bas 1985, 104, 226-230.
4506 J . Org. Chem., Vol. 69, No. 13, 2004

Biradicals/ Zwitterions from Enyne-Isocyanates
J ) 6.9 Hz), 1.70-1.53 (4 H, m); 13C (C6D6) δ 133.9, 115.1,
98.3, 79.8, 71.8, 59.0, 30.3, 30.1, 29.8, 22.9, 22.5, 17.4; MS m/z
219 (M+), 204, 187, 158.
2,5-Dih yd r o-2,5-d im e t h yl-1H -p yr id o[4,3-b]in d ol-1-
on e 46 a n d 1-Meth oxy-5-m eth yl-5H-p yr id o[4,3-b]in d ole
47. A solution of 0.282 g of 37d (1.12 mmol) in 5 mL of 1,2-
dichlorobenzene was heated under reflux at 180 °C for 5 h.
The solvent was removed in vacuo, and the residue was
purified by flash column chromatography to afford 0.106 g of
46 (0.42 mmol, 38%) as brown crystals and 0.079 g of 47 (0.31
mmol, 28%) as yellow crystals. 46: mp 238-240 °C; IR 1653,
1561, 747, 721 cm-1; 1H δ 8.40 (1 H, dd, J ) 6.6, 1.9 Hz), 7.31
(1 H, td, J ) 7.0, 1.6 Hz), 7.26 (1 H, td, J ) 6.9, 1.6 Hz), 7.20
(1 H, dd, J ) 6.6, 1.6 Hz), 3.70 (3 H, s), 3.50 (3 H, s), 3.05 (2
H, t, J ) 7.4 Hz), 2.81 (2 H, t, J ) 7.7 Hz), 2.13 (2 H, quintet,
J ) 7.5 Hz); 13C δ 160.3, 147.5, 142.7, 138.9, 125.0, 123.3,
121.4, 121.0, 108.1, 105.3, 105.2, 32.0, 31.2, 30.4, 29.7, 22.0;
MS m/z 252 (M+), 251, 236. The structure of 46 was established
by X-ray structure analysis. 47: mp 205-206 °C; IR (KBr)
2,3,4,6,7,8,9,10-Octa h yd r o-5H-p yr a n o[3,2-c]qu in olin -5-
on e (38). A solution of 36 (0.23 g, 1.05 mmol) and dimeth-
ylphenylsilyl chloride (0.20 g, 1.15 mmol) in 10 mL of 1,2-
dichlorobenzene was heated under reflux for 36 h. The solvent
was removed in vacuo, and the residue was purified by column
chromatography to afford 0.19 g of 38 (0.93 mmol, 89%) as a
1
pale yellow solid: mp 261-263 °C; IR 1641, 1128 cm-1; H δ
11.3 (1 H, br), 4.17 (2 H, t, J ) 5.0 Hz), 2.6-2.5 (4 H, m), 2.35
(2 H, t, J ) 5.9 Hz), 1.94 (2 H, quintet, J ) 5.2 Hz), 1.78-1.66
(4 H, m); 13C δ 164.3, 162.4, 139.8, 107.6, 104.4, 66.8, 26.6,
22.1, 21.7, 21.3, 20.6, 18.8. The structure of 38 was established
by X-ray structure analysis.
Ben zoisoqu in olin on e 39. The following procedure is
representative for thermolysis of enyne-isocyanates 37. A
solution of 0.237 g of 37a (1.0 mmol) in 6 mL of 1,2-
dichlorobenzene was heated under reflux for 3 h. The solvent
was removed in vacuo, and the residue was purified by flash
column chromatography (silica gel/50% diethyl ether in hex-
anes) to afford 0.232 g of 39 (0.98 mmol, 98%) as light yellow
crystals: mp 244-245 °C; IR (KBr) 3000-2300 (br), 1643, 764,
1622, 1595, 752 cm-1 1H δ 8.21 (1 H, dd, J ) 6.7, 2.0 Hz),
;
7.42 (1 H, td, J ) 7.6, 1.2 Hz), 7.31-7.25 (2 H, m), 4.20 (3 H,
s), 3.85 (3 H, s), 3.26 (2 H, t, J ) 7.3 Hz), 3.04 (2 H, t, J ) 7.7
Hz), 2.22 (2 H, quintet, J ) 7.5 Hz); 13C δ 159.7, 158.6, 144.6,
139.8, 124.5, 122.1, 121.9, 120.2, 111.1, 108.1, 103.6, 53.2, 34.2,
30.5, 29.0, 23.0; MS m/z 252 (M+), 251, 223. The structure of
47 was established by X-ray structure analysis.
2,5-Dih yd r o-5-m eth yl-1H-p yr id o[4,3-b]in d ol-1-on e 48.
A solution of 37d (0.038 g, 0.15 mmol) and dimethylphenylsilyl
chloride (0.028 g, 0.16 mmol) in 5 mL of 1,2-dichlorobenzene
was heated under reflux for 13 h. The solvent was removed in
vacuo, and the residue was purified by flash column chroma-
tography to afford 0.027 g of 48 (0.11 mmol, 75%) as a white
1
740 cm-1; H δ 13.51 (1 H, br s), 7.74-7.70 (1 H, m), 7.32-
7.28 (3 H, m), 3.12 (2 H, t, J ) 7.1 Hz), 2.99 (2 H, t, J ) 7.5
Hz), 2.82 (4 H, s), 2.15 (2 H, quintet, J ) 7.3 Hz); 13C δ 164.5,
147.6, 143.3, 139.9, 133.2, 129.0, 128.1, 126.9, 126.3, 123.2,
116.7, 32.5, 31.0, 28.8, 23.7, 21.2; MS m/z 237 (M+), 236, 207;
HRMS calcd for C16H15NO 237.1154, found 237.1156. The
structure of 39 was established by X-ray structure analysis.
solid: mp 318 °C dec with melting; IR 3385, 1636, 751 cm-1
;
1H δ 9.35 (1 H, br s), 8.40 (1 H, d, J ) 7.2 Hz), 7.38-7.32 (3 H,
m), 3.95 (3 H, s), 3.25 (2 H, t, J ) 7.2 Hz), 2.96 (2 H, t, J ) 7.7
Hz), 2.29 (2 H, quintet, J ) 7.7 Hz); 13C (4% of MeOH-d4 in
CDCl3) δ 161.3, 146.0, 144.6, 138.9, 124.1, 123.8, 121.3, 120.9,
108.5, 106.5, 105.2, 30.5, 29.1, 22.5. The structure of 48 was
established by X-ray structure analysis.
Ben zop yr a n op yr id in e 43. A solution of 0.178 g of 37b
(0.80 mmol) in 6 mL of 1,2-dichlorobenzene was heated under
reflux for 48 h. The solvent was removed in vacuo, and the
residue was purified by flash column chromatography (silica
gel/50% diethyl ether in hexanes, Rf 0.26) to afford 0.072 g of
43 (0.32 mmol, 40%) as a brown solid. Recrystallization of 43
from CH2Cl2/hexanes gave brown crystals: mp 103-104 °C;
Ben zop yr a n op yr id in es 55 a n d 56. A solution of 0.372 g
of 37f (1.47 mmol) in 6 mL of 1,2-dichlorobenzene was heated
under reflux at 180 °C for 5 h. The solvent was removed in
vacuo, and the residue was purified by flash column chroma-
tography (silica gel/50% diethyl ether and 10% methylene
chloride in hexanes) to afford 0.068 g of 55 (0.27 mmol, 18%)
as a white solid and 0.215 g of 56 (0.85 mmol, 58%) as white
crystals. Similarly, a solution of 0.306 g of 37f (1.21 mmol) in
6 mL of 1,2-dichlorobenzene was heated at 150 °C for 20 h.
The solvent was removed in vacuo, and the residue was
purified by flash column chromatography (silica gel/50%
diethyl ether and 10% methylene chloride in hexanes, Rf 0.30)
to afford 0.182 g of 56 (0.72 mmol, 59%) as white crystals.
Heating a solution of 37f (0.021 g, 0.083 mmol) and dimeth-
ylphenylsilyl chloride (0.016 g, 0.090 mmol) in 4 mL of 1,2-
dichlorobenzene under reflux at 180 °C for 13 h produced 0.016
g of 56 (0.063 mmol, 76%). 55: mp 84-86 °C; IR 1607, 1408,
1
IR 1409, 782, 734 cm-1; H δ 7.82 (1 H, s), 7.61 (1 H, d, J )
7.7 Hz), 7.34 (1 H, td, J ) 7.5, 1.4 Hz), 7.26 (1 H, td, J ) 7.4,
1.3 Hz), 7.12 (1 H, d, J ) 7.3 Hz), 5.27 (2 H, s), 2.92 (4 H,
quartet, J ) 7.6 Hz), 2.12 (2 H, quintet, J ) 7.6 Hz); 13C δ
164.4, 160.4, 131.5, 130.5, 129.8, 128.4, 127.8, 127.7, 124.5,
121.7, 114.1, 68.9, 34.0, 30.0, 23.2; MS m/z 223 (M+), 222. Anal.
Calcd for C15H13NO: C, 80.68; H, 5.87; N, 6.28. Found: C,
80.38; H, 5.89; N, 6.23. The structure of 43 was established
by X-ray structure analysis.
Ben zofu r o[3,2-c]p yr id in -1(2H)-on e 44 a n d Ben zofu r o-
[3,2-c]p yr id in e 45. A solution of 0.104 g of 37c (0.44 mmol)
in 6 mL of chlorobenzene was heated under reflux at 132 °C
for 36 h. The solvent was removed in vacuo, and the residue
was purified by flash column chromatography to afford 0.010
g of 44 (0.044 mmol, 10%) as a white solid and 0.054 g of 45
(0.23 mmol, 52%) as a white solid. Similarly, a solution of 37c
(0.095 g, 0.40 mmol) and dimethylphenylsilyl chloride (0.076
g, 0.44 mmol) in 3.5 mL of 1,2-dichlorobenzene was heated
under reflux for 12 h to afford 0.080 g of 44 (0.36 mmol, 90%)
as a white solid. 44: mp 305 °C dec with melting; IR 3421,
1
782, 753 cm-1; H δ 7.97 (1 H, s), 7.78 (1 H, d, J ) 7.9 Hz),
7.47 (1 H, ddd, J ) 7.7, 5.9, 3.0 Hz), 7.41-7.34 (2 H, m), 6.07
(1 H, s), 3.64 (3 H, s), 3.00 (2 H, td, J ) 7.6, 2.6 Hz), 2.96 (2 H,
t, J ) 7.3 Hz), 2.17 (2 H, quintet, J ) 7.6 Hz); 13C δ 164.6,
156.7, 131.9, 129.6, 129.4, 128.6, 127.9, 127.7, 126.4, 121.8,
113.1, 100.2, 56.0, 34.1, 30.1, 23.2; MS m/z 253 (M+), 222. 56:
mp 125-126 °C; IR 1584, 1558, 1080, 795, 748 cm-1; 1H δ 8.19
(1 H, d, J ) 7.9 Hz), 7.34 (1 H, td, J ) 7.5, 1.2 Hz), 7.26 (1 H,
t, J ) 7.0 Hz), 7.16 (1 H, d, J ) 7.3 Hz), 5.15 (2 H, s), 4.01 (3
H, s), 3.12 (2 H, t, J ) 7.3 Hz), 2.92 (2 H, t, J ) 7.7 Hz), 2.12
(2 H, quintet, J ) 7.6 Hz); 13C δ 165.9, 163.1, 162.2, 131.2,
129.0, 128.1, 127.1, 126.3, 124.4, 120.8, 106.0, 69.1, 59.1, 34.3,
29.6, 23.0; MS m/z 253 (M+), 252, 236. The structure of 56 was
established by X-ray structure analysis.
1656, 748 cm-1 1H δ 10.74 (1 H, br s), 8.22-8.16 (1 H, m),
;
7.57-7.51 (1 H, m), 7.42-7.35 (2 H, m), 3.05 (4 H, t, J ) 7.4
Hz), 2.30 (2 H, quintet, J ) 7.4 Hz); 13C (DMSO-d6) δ 160.1,
159.7, 153.8, 150.2, 124.6, 124.1, 123.7, 120.1, 110.9, 106.9,
105.1, 30.9, 26.1, 22.0; MS m/z 225 (M+) 191; HRMS calcd for
C
14H11NO2 225.0790, found 225.0779. The structure of 44 was
established by X-ray structure analysis. 45: recrystallization
from CH2Cl2/hexanes gave brown crystals, mp 115-116 °C;
1
IR 1594, 1067, 748 cm-1; H δ 8.02 (1 H, d, J ) 6.7 Hz), 7.54
(1 H, d, J ) 7.3 Hz), 7.43-7.33 (2 H, m), 4.17 (3 H, s), 3.11 (2
H, t, J ) 7.3 Hz), 3.06 (2 H, t, J ) 7.7 Hz), 2.24 (2 H, quintet,
J ) 7.5 Hz); 13C δ 161.7, 160.1, 159.6, 155.2, 126.0, 123.5,
122.6, 122.1, 113.4, 111.1, 105.5, 53.6, 34.7, 26.8, 23.1; MS m/z
239 (M+), 238, 210.
Ack n ow led gm en t. The financial support of the
National Science Foundation (CHE-9618676) to K.K.W.
is gratefully acknowledged. J .L.P. acknowledges the
support (CHE-9120098) provided by the Chemical In-
J . Org. Chem, Vol. 69, No. 13, 2004 4507

Li et al.
e, 15, 16, 19-21, 25-29, 32, 33e, [[2-(methoxymethyl)phenyl]-
ethynyl]trimethylsilane,23 1-ethynyl-2-(methoxymethyl)ben-
zene,24 33f, 34, 35e,f, 36, 37e,f, 38, 39, 43-52, 55, and 56;
ORTEP drawings of the crystal structures of 16, 19, 25, 38,
39, 43, 44, 46-48, and 56 in PDF format; and X-ray crystal-
lographic data of 16, 19, 25, 38, 39, 43, 44, 46-48, and 56 as
CIF. This material is available free of charge via the Internet
at http://pubs.acs.org.
strumentation Program of the National Science Foun-
dation for the acquisition of a Siemens P4 X-ray
diffractometer in the Department of Chemistry at West
Virginia University.
Su p p or tin g In for m a tion Ava ila ble: Experimental pro-
cedures and spectroscopic data for 12c-e, 13a , 13c-e, 27-
29, 33e, [[2-(methoxymethyl)phenyl]ethynyl]trimethylsilane,
1-ethynyl-2-(methoxymethyl)benzene, 33f, 35e,f, 37e,f, and
49-52; 1H and 13C NMR spectra of compounds 12b-e, 13b-
J O049716T
4508 J . Org. Chem., Vol. 69, No. 13, 2004