Anionic ring opening of norbornenes fused to heterocycles

Article abstract of DOI:10.1016/j.tet.2004.08.038

The 2-hydroxy and 2-oxo derivatives of 1,2,3,4-tetrahydro-1,4- methanophenazine were prepared and found to evolve in basic media through the opening of their bicyclo[2.2.1]heptene moiety, affording 2,3-dihydro-1H- cyclopenta[b]quinoxaline derivatives with

Full text of DOI:10.1016/j.tet.2004.08.038

Tetrahedron 60 (2004) 10343–10352
Anionic ring opening of norbornenes fused to heterocycles
†
Antonio R. Hergueta, Carmen Lopez, Xerardo Garcıa-Mera and Franco Fernandez
*
´
´
´
´ ´
Departamento de Quımica Organica, Facultade de Farmacia, Universidade de Santiago de Compostela,
E-15782 Santiago de Compostela, Spain
Received 29 July 2004; accepted 17 August 2004
Available online 21 September 2004
´
Dedicated to Professor Jose L. Soto, on the occasion of his retirement
Abstract—The 2-hydroxy and 2-oxo derivatives of 1,2,3,4-tetrahydro-1,4-methanophenazine were prepared and found to evolve in basic
media through the opening of their bicyclo[2.2.1]heptene moiety, affording 2,3-dihydro-1H-cyclopenta[b]quinoxaline derivatives with two-
carbon 1-substituents that depend on the starting compound. In the case of 2-hydroxy starting compounds, ring-opening occurs regardless of
the orientation of the hydroxyl group, and in methanolic solution is spontaneous, though slow, even in the absence of added base (at least in
the case of the endo derivative). It is presumably favoured by the steric strain of the heteroaryl-fused bicyclo[2.2.1]heptene moiety, and is
hypothesized to involve the base-promoted formation of anionic intermediates that are stabilized by the p-deficient nature of the quinoxaline
system.
q 2004 Elsevier Ltd. All rights reserved.
1. Introduction
(sometimes incidental) and/or their spectroscopic proper-
ties,26–42 there have also been studies of their chemistry,
including work on electrophilic addition reactions;43–46
aromatic substitution in the heterocyclic moiety;47 the
regiochemistry of their di-p-methane photorearrange-
ment;48,49 the relationship between their basicity and
internal strain;50 and their behaviour as dienophiles in
Diels–Alder reactions.51 Of particular interest is the
participation of the heterocyclic moiety as neighbouring
group in the solvolysis of diverse sulfonates,52–54 in the
acidic opening of an epoxide ring previously formed on
the norbornene moiety55 and in electrophilic
additions,43–46 and the influence of the electronic p-
richness or p-deficiency of that moiety on p-facial
selectivity in the latter reactions.56,57
Though first reported over 40 years ago, molecules
consisting of an aromatic heterocycle fused to norbornene
or norbornadiene have only more recently attracted
attention. Relatively simple derivatives of compounds of
this kind have been proposed for storage of light energy,1,2
while more complex derivatives have been developed as
initiators of photochemical polymerization,3,4 as com-
ponents of holographic recording media,5–8 as ligands
forming part of models for the study of long-range electron
transfer between chelated metal centres,9,10 and as the
monomers of self-assembling dimeric capsules11,12 or of
molecular cavities and ribbons.13,14 In the pharmacological
field, compounds of this type have been prepared in pursuit
of virucidal or virustatic agents,15 antiulcer agents,16 brain
acetylcholinesterase inhibitors,17–19 serotonin antagonists,20
central nervous system stimulants,21–23 dihydrofolate
reductase inhibitors,24 and mGluR1 antagonists.25
If the heterocyclic moiety is p-deficient the norbornene
moiety can behave quite differently from carbocyclic or
non-condensed analogues. For example, subjecting diols 1
to the conditions of Swern’s reaction does not afford the
corresponding diketones 2, but instead 63–75% yields of
alcohols 3 as the only isolatable products.58 Here we
report that the norbornene moiety of 1a and of other
oxygenated 1,2,3,4-tetrahydro-1,4-methanophenazine
derivatives (4 and 5) also opens very readily in basic
media, a finding that as far as we know has no precedent
in the literature except for a preliminary report of ours
concerning 1a.59
Although much of the relevant literature, especially the
older papers, merely describes their preparation
Keywords: Quinoxaline-fused norbornene; Ring opening; Anionic inter-
mediates; Basic medium.
* Corresponding author. Tel.: C34-981-563-100; fax: C34-981-594-912;
e-mail: qofranco@usc.es
† Present address: Tripos Receptor Research Ltd, Bude-Stratton Business
Park, Bude-Cornwall EX23 8LY, England.
0040–4020/$ - see front matter q 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2004.08.038

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tenes occurs almost exclusively at the exo face,62 11–13
were virtually monoepimeric at positions 2 and 3, and
oxidation of both 5-epimers of 13 took place easily to afford
monoketone 14, which upon treatment with selenium
dioxide gave the a-diketone 15. Finally, condensation of
15 with ortho-phenylenediamine yielded the dibenzoate 16.
Because of the likelihood of rearrangements of Wagner–
Meerwein type due to its norbornene moiety, the conversion
of 16 to 1a was attempted by basic rather than acid
hydrolysis. Initial attempts gave only intractable mixtures or
unaltered starting material, but the mildest conditions
compatible with effective saponification of the benzoate
groups (0.9 M KOH in MeOH/H2O, rt, 12 h) afforded a
crude product that upon flash chromatography on silica gel
gave a 66% yield of a dark green solid. This product
underwent alteration when left standing in solution, but IR,
1
MS and H and 13C NMR data obtained immediately after
purification were compatible with its being the enediol 17.
This identification was confirmed by single-crystal X-ray
crystallography of the stable diacetylated derivative 18
(Fig. 1),63 which was obtained by acetylation of 17 with
Ac2O/pyridine.
It may be assumed that the first step in the conversion of 16
to 17 is the desired hydrolysis to 1a; this is supported by the
fact that a sample of 1a prepared by an independent route,58
was transformed into 17 in very similar yield when
subjected to the same basic conditions as 16. A plausible
account of subsequent steps is shown in Scheme 2. Under
the basic working conditions, diol 1a will be in equilibrium
with its monoalkoxide, which because of the stress in the
bridged ring system must be highly susceptible to ring
Our interest in 1a originated from the wish to obtain diacid 6
and diol 7 for the synthesis of carbocyclic analogues of
nucleosides with phthalazine-fused carbocycles; after
several unsuccessful attempts to obtain 6 and 7 through
oxidative cleavage of the double bond in 9,60 we hoped that
mild treatment of 1a (e.g., with periodic acid) would result
in oxidative cleavage leading to dialdehyde 8, which would
then be oxidized to 6 or reduced to 7 in situ.61 Since it was
planned to use 1a on more than one occasion in exploring
its oxidative cleavage under diverse conditions, the finding
that it tended to decompose when stored at rt led us to
prepare compound 16 as a stable derivative that could
presumably be easily converted to 1a immediately before
use. In the event, we found that the basic conditions used for
conversion of 16 into 1a caused the opening of its
norbornene moiety.
2. Results and discussion
Compound 16 was obtained as shown in Scheme 1. A
commercially available racemic mixture of endo and exo
norbornenyl acetates (10) was dihydroxylated to 11, and
benzoylation followed by selective hydrolysis of the acetate
afforded 13. Since dihydroxylation of bicyclo[2.2.1]hep-
Figure 1. ORTEP plot of the molecular structure of 18 in the solid state.
Scheme 1. Reagents and conditions: (a) OsO4/NMNO/Me2CO–H2O, 40 8C, 18 h; (b) BzCl/Py, rt, 24 h; (c) K2CO3/MeOH, rt, 30 min; (d) CrO3$Py/DCM, rt,
6 h; (e) SeO2/xylene, 140 8C, 24 h; (f) o-(C6H4)(NH2)2/ZnCl2/THF, 66 8C, 18 h; (g) 0.9 M KOH/MeOH–H2O, rt, 12 h; (h) Ac2O/Py, rt, 14 h.

A. R. Hergueta et al. / Tetrahedron 60 (2004) 10343–10352
10345
Scheme 2. Suggested mechanism for the formation of 17 from 1a.
Scheme 3. Reagents and conditions: (a) DMSO-TFAA/DCM/TEA, K78 8C, 3 h; (b) o-(C6H4)(NH2)2/ZnCl2/THF, 66 8C, 4.5 h; (c) 0.7 M Na2CO3/MeOH, rt,
2 h.
opening. The resulting carbanion 19 will be stabilized by its
charge being formally located on the carbon a to position 3
of the p-deficient quinoxaline system, and following
protonation of this carbon the resulting a-hydroxyaldehyde
20 will be susceptible to base-catalyzed isomerization to the
a-hydroxyketone 22 via the enediol 21 (a well-known
conversion in sugar chemistry). Finally, isomerization of 22
to the enediol 17 will be favoured by the exocyclic C]C
bond of the latter being conjugated with the aromatic
quinoxaline system.
As there appear to be no published precedents for the above
anionically driven ring-opening of a bicyclo[2.2.1]heptene
derivative, we began to explore its scope using the
structurally simpler monoalcohols 4a (endo) and 4b (exo),
Figure 2. ORTEP plot of the molecular structure of 24a in the solid state.
which were prepared as shown in Scheme 3 by Swern
oxidation of 11 to the mixture of epimeric diketones 23,
followed by condensation of 23 with ortho-phenylenedia-
mine, chromatographic separation of the resulting mixture
of diastereomeric methanophenazines 24, and mild hydroly-
sis of 24a and 24b (0.7 M Na2CO3 in methanol, rt, 2 h). The
identity of 24a (the major isomer) was confirmed by X-ray
crystallographic analysis of a single crystal (Fig. 2).63
Hydrolysis of 24a or 24b under more severe conditions
(longer reaction times, or use of 1 M KOH instead of 0.7 M
Na2CO3) afforded a mixture including a product with
spectroscopic data compatible with its being aldehyde 25 (in
particular, a substituted cycloalkyl acetaldehyde was
1
indicated by a strong IR band at 1722 cmK1, H NMR
signal at 9.88 ppm, and 13C NMR signals at 201.03 and
47.52 ppm). Starting from 24a, the greatest yield of 25 was
obtained by simply maintaining the conditions used to
Scheme 4. Reagents and conditions: (a) 0.7 M Na2CO3/MeOH, rt, 2 h; (b)
obtain 4a for 6 h instead of 2 h (Scheme 4); this gave an
approximately 71% yield of a product shown by H NMR
data to be 25, in a sample enriched to a 90% content, as
0.7 M Na2CO3/MeOH, rt, 6 h; (c) AgNO3/NH4OH, rt, 3 h; (d) MeOH/TsOH,
65 8C, 3.5 h; (e) NaBH4/EtOH, rt, 15 h; (f) Ac2O/Py, rt, 18 h; (g) 0.5 M
Na2CO3/NaBH4/EtOH, rt, 18 h.
1

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A. R. Hergueta et al. / Tetrahedron 60 (2004) 10343–10352
estimated by 1H NMR. Since this product tended to undergo
alteration during work-up,64 it was converted to more stable
forms by Tollens oxidation to acid 28 and NaBH4 reduction
to alcohol 26, which were then further converted into the
methyl ester 29 and the acetate 27, respectively (Scheme 4).
Compounds 26–29 all had spectra in keeping with the
proposed structures, and that of 26 was confirmed by X-ray
crystallography of a single crystal (Fig. 3).63 If both Na2CO3
and NaBH4 are included in the reaction medium, 4a is
transformed into 25 and 25 into 26 in a tandem process with
an overall yield of 63%, as against an estimated 54% if 25 is
first isolated.
Scheme 6. Preparation of 5 from 4a and suggested mechanism for the
rearrangement of 5 to 26 in basic media. Reagents and conditions: (a)
CrO3$Py/DCM, 0 8C, 6 h; (b) 1 M NaOH/H2O, rt, 14 h; (c) H3OC/pH 4.
tetrahydro-1,4-methanophenazine, affording 2,3-dihydro-
1H-cyclopenta[b]quinoxaline derivatives with two-carbon
1-substituents that depend on the starting compound. Ring-
opening occurs regardless of the orientation of the hydroxyl
group in the case of 2-hydroxy starting compounds, and in
methanolic solution is spontaneous, though slow, even in
the absence of added base (at least in the case of the 2-endo-
hydroxy or 2-oxo derivatives). It is presumably favoured by
the steric strain of the heteroaryl-fused bicyclo[2.2.1]hep-
tene moiety, and may involve the base-promoted formation
of anionic intermediates that are stabilized by the p-
deficient nature of the quinoxaline system. Although there
have been several reports of Wagner–Meerwein and ring-
opening processes involving cationic intermediates which
are undergone by benzene-fused65–69 or heteroarene-
fused44–46,54,55 bicyclo[2.2.1]heptenes, the reactions
described here are as far as we know the first examples of
base-promoted ring-opening involving a carbanion
intermediate.
Figure 3. ORTEP plot of the molecular structure of 26 in the solid state.
The formation of 25 from 4a (or, similarly, from 4b) may be
attributed to the mechanism shown in Scheme 5, which is
exactly analogous to the first part of that shown in Scheme 2
for the conversion of 1a into 17. At rt it occurs even in
methanol without added base (being detectable by 1H NMR
after 48 h), possibly being autocatalysed by the basic centres
of the tetrahydrophenazine alcohol (although solid 4a can be
stored at 5 8C for several weeks without any alteration
1
detectable by H NMR). The acetylated precursors 24 are
perfectly stable in methanol at rt.
4. Experimental
4.1. General
Melting points are uncorrected and were determined in a
Reichert Kofler Thermopan or in capillary tubes in a Bu¨chi
apparatus. 1H NMR spectra (300 MHz) and 13C NMR
spectra (75 MHz) were recorded using TMS as internal
reference (chemical shifts in d values, J in Hz). Micro-
analyses were performed by the Microanalysis Service of
the University of Santiago. Crystallographic data were
obtained with a MACH3 Enraf Nonius diffractometer. Flash
chromatography was performed on silica gel (230–240
mesh) and analytical TLC on pre-coated silica gel plates
(F254, 0.25 mm) and spots were examined with UV light
and sulfuric acid/anisaldehyde spray.
Scheme 5. Suggested mechanism for the formation of 25 from 4a.
Finally, we also performed the ring-opening reaction on
ketone 5, which was easily obtained by oxidation of 4a with
CrO3. In basic medium, 5 was converted to the acid 28 by a
mechanism hypothesized as starting by the nucleophilic
attack of the base to the carbonyl carbon and otherwise
being analogous to those proposed above (Scheme 6). Under
appropriate conditions, the reaction could be used prepara-
tively, though spontaneous partial transformation of 5 into
28 in chloroform-d CDCl3/methanol-d3 CD3OD solution
was also observed (1H NMR) after 3 days at rt.
4.1.1. (G)-(5-exo,6-exo)-5,6-Dihydroxybicyclo[2.2.1]-
hept-2-yl acetate (mixture of 2-endo and 2-exo) (11). A
solution of commercial (G)-5-norbornen-2-yl acetate
(10.0 g, 65.8 mmol) in 4:1 acetone/water (140 mL) was
heated to 40 8C, N-methylmorpholine N-oxide (8.50 g,
72.5 mmol) was added, and 5 min later this mixture was
treated with 2 mL of a commercial solution of OsO4 (4 wt%
in water), which caused it to turn brown almost
3. Conclusion
Basic media promote the opening of the bicyclo[2.2.1]hep-
tene moiety of 2-hydroxy and 2-oxo derivatives of 1,2,3,4-

A. R. Hergueta et al. / Tetrahedron 60 (2004) 10343–10352
10347
immediately. The stirred, heated mixture was monitored by
TLC, and after 18 h the reaction was deemed complete. The
acetone was removed under reduced pressure, the remaining
aqueous solution was extracted with AcOEt, the resulting
organic extract was dried (Na2SO4), the solvent was
removed, and the crude residue was purified by column
chromatography with 1:1 (v/v) hexane/EtOAc as eluent,
affording a yellowish oil composed of a mixture of diols 11
(11.6 g, 95%) in approximate endo/exo ratio 78:22 (as
determined by 1H NMR). This oil solidified spontaneously.
IR (KBr) n: 3385 (OH), 1731 (CO), 1377, 1248, 1147,
942 cmK1. EIMS m/z (%): 168 (4), 126 (79), 79 (100), 70
(79), 67 (55), 58 (81). 1H NMR and 13C NMR for the major
isomer (2-endo) were in accordance with the literature.70
[2H, m, 2!(40-H)], 7.29–7.23 [4H, m, 2!(30,50-H2)], 5.79
(1H, d, JZ6.0 Hz, 6-H), 5.27 (1H, d, JZ6.0 Hz, 5-H), 4.39
(1H, dt, JZ10.3, 4.1 Hz, 2-exo-H), 2.62 (1H, d, JZ3.4 Hz,
1-H), 2.49 (1H, d, JZ4.1 Hz, 4-H), 2.25–2.12 (2H, m, 3-
exo-HC7-HH), 1.71 (1H, b s, D2O exchang., OH), 1.47
(1H, d, JZ10.8 Hz, 7-HH), 1.46 (1H, dt, JZ13.8, 3.4 Hz, 3-
endo-H). 13C NMR and DEPT (CDCl3) d: 166.1 (CO), 166.0
(CO), 133.2 (CH), 130.4 (C), 130.0 (CH), 125.6 (CH), 77.1
(CH), 72.3 (CH), 70.3 (CH), 48.2 (CH), 42.6 (CH), 35.1
(CH2), 33.7 (CH2). HRMS calcd for C21H20O5: 352.1311.
Found: 352.1304.
4.1.4. (G)-(exo,exo)-5,6-Dibenzoyloxybicyclo[2.2.1]hep-
tan-2-one (14). A solution of 13 (3.86 g, 11.0 mmol) in
CH2Cl2 (100 mL) was added during 15 min to a stirred
mixture of pyridine (11 mL), CH2Cl2 (110 mL) and CrO3
(6.63 g, 66.3 mmol) kept at 0 8C, and stirring was continued
for 6 h. The mixture was then filtered through celite and
evaporated to dryness under reduced pressure. Purification
of the resulting residue by silica gel column chromatog-
raphy with 7:3 (v/v) hexane/EtOAc as eluent afforded 14
(2.99 g, 78%) as a white solid. An analytical sample was
obtained by recrystallization from cyclohexane. Mp 141–
142 8C. IR (KBr) n: 1751 (CO), 1726 (CO), 1651, 1600,
1558, 1548, 1508, 1315, 1287, 708 cmK1. EIMS m/z (%):
350 (MC, 0.5), 323 (3), 322 (14), 228 (3), 186 (14), 106 (8),
105 (100), 79 (4), 78 (4), 77 (60), 76 (3), 51 (13). 1H NMR
(CDCl3) d: 7.90–7.82 [4H, m, 2!(20,60-H2)], 7.55–7.45
[2H, m, 2!(40-H)], 7.33–7.22 [4H, m, 2!(30,50-H2)], 5.37
(2H, virtual s, 5-HC6-H), 3.01 (1H, d, JZ3.8 Hz, 4-H),
2.96 (1H, s, 1-H), 2.58 (1H, d, JZ11.1 Hz, 7-HH), 2.30 (1H,
dd, JZ18.6, 5.3 Hz, 3-exo-H), 2.16 (1H, dd, JZ18.6,
4.2 Hz, 3-endo-H), 1.95 (1H,d, JZ11.1 Hz, 7-HH). 13C
NMR and DEPT (CDCl3) d: 212.4 (CO), 165.8 (CO), 165.5
(CO), 133.62 (CH), 133.56 (CH), 130.1 (CH), 130.0 (CH),
129.8 (C), 129.7 (C), 128.7 (CH), 128.6 (CH), 75.6 (CH),
71.6 (CH), 56.3 (CH), 41.7 (CH2), 41.2 (CH), 34.0 (CH2).
Anal. Calcd for C21H18O5 (350.36): C, 71.99; H, 5.18.
Found: C, 71.72; H, 5.28.
4.1.2. (G)-(5-exo,6-exo)-5,6-Dibenzoyloxybicyclo[2.2.1]-
hept-2-yl acetate (mixture of 2-endo and 2-exo) (12).
Benzoyl chloride (8 mL, 68 mmol) was slowly added to a
solution of 11 (5.00 g, 26.8 mmol) in dry pyridine (37 mL)
at 0 8C, and the mixture was stirred at rt for 24 h and then
placed in an ice-bath, brought to pH 8 with 2 N NaOH, and
extracted with EtOAc (2!150 mL). The pooled organic
extracts were washed several times with water and dried
(Na2SO4), the solvent was removed under reduced pressure,
and the residue was purified by silica gel column
chromatography using 5:1 (v/v) hexane/EtOAc as eluent,
which afforded the ester mixture 12 as a low melting solid
(8.05 g, 76%) in approximate endo/exo ratio 4:1 (as
1
determined by H NMR). IR (KBr) n: 1738, 1719, 1708,
1651, 1615, 1558, 1540, 1456, 1239, 1026, 712 cmK1
.
EIMS m/z (%): 394 (MC, 1), 335 (7), 289 (11), 272 (4), 186
(6), 106 (7), 105 (100), 78 (3), 77 (42), 76 (2), 51 (9). Major
1
isomer (2-endo): H NMR (CDCl3) d: 7.89–7.81 [4H, m,
2!(20,60-H2)], 7.51–7.43 [2H, m, 2!(40-H)], 7.31–7.21
[4H, m, 2!(30,5prime;-H2)], 5.64 (1H, dd, JZ5.9, 1.4 Hz,
6-H), 5.26 (1H, dd, JZ5.9, 1.3 Hz, 5-H), 5.12–5.08 (1H,
m, 2-exo-H), 2.81 (1H, d, JZ3.4 Hz, 1-H), 2.52 (1H, d,
JZ4.7 Hz, 4-H), 2.25–2.17 (2H, m, 3-exo-HC7-HH), 2.13
(3H, s, CH3), 2.07–2.03 (1H, m, 7-HH), 1.28–1.21 (1H, m,
3-endo-H). 13C NMR and DEPT (CDCl3) d: 171.4 (CO),
165.9 (CO), 133.3 (CH), 130.2 (C), 129.98 (CH), 129.97
(C), 128.6 (CH), 128.5 (CH), 76.6 (CH), 72.3 (CH), 72.1
(CH), 45.8 (CH), 42.0 (CH), 33.4 (CH2), 33.0 (CH2), 21.5
(CH3). HRMS calcd for C23H22O6: 394.1416. Found:
394.1409.
4.1.5. (exo,exo)-5,6-Dibenzoyloxybicyclo[2.2.1]heptane-
2,3-dione (15). A mixture of 14 (1.95 g, 5.56 mmol),
SeO2 (0.61 g, 5.56 mmol) and xylenes (6 mL) was refluxed
for 24 h, vacuum-filtered through celite, and condensed to
dryness under reduced pressure. Purification of the resulting
residue by silica gel column chromatography with 4:1 (v/v)
hexane/EtOAc as eluent afforded 15$H2O as a white solid
(1.59 g, 74%). An analytical sample was obtained by
recrystallization from EtOAc–hexane. Mp 109–110 8C. IR
(KBr) n: 3423, 1777, 1723, 1600, 1450, 1279, 1114,
713 cmK1. Anal. Calcd for C21H16O6$H2O (382.36): C,
65.96; H, 4.74. Found: C, 66.21; H, 4.57.
4.1.3. (G)-(5-exo,6-exo)-5,6-Dibenzoyloxybicyclo[2.2.1]-
heptan-2-ol (mixture of 2-endo and 2-exo) (13). Solid
K2CO3 (1.43 g, 10.3 mmol) was added to a solution of 12
(8.16 g, 20.7 mmol) in MeOH (120 mL), and the mixture
was successively stirred at rt for 30 min, diluted with EtOAc
(500 mL), washed with saturated NH4Cl solution followed
by water, and dried (Na2SO4). The organic solvents were
removed under reduced pressure, and the residue was
purified by silica gel column chromatography using 1:1
(v/v) hexane/EtOAc as eluent, which afforded the alcohol
mixture 13 (6.71 g, 92%) as a waxy solid in approximate
endo/exo ratio 4:1, as determined by 1H NMR. IR (KBr) n:
3505 (OH), 1720 (CO), 1651, 1540, 1455, 1286, 1123, 1025,
707 cmK1. EIMS m/z (%): 352 (0.5, MC), 335 (7), 289 (11),
247 (2), 230 (9), 186 (5), 136 (4), 125 (11), 108 (4), 106 (7),
105 (100), 77 (42), 51 (9). Major isomer (2-endo): 1H NMR
(CDCl3) d: 7.89–7.84 [4H, m, 2!(20,60-H2)], 7.49–7.44
4.1.6. (exo,exo)-1,2,3,4-Tetrahydro-1,4-methanophena-
zine-2,3-diyl dibenzoate (16). A mixture of 15$H2O
(1.45 g, 3.79 mmol), o-phenylenediamine (1.10 g,
10.5 mmol) and the zinc catalyst ZnCl2[C6H5CH(NH2)-
CH3]2 (10 mg) in dry THF (33 mL) was refluxed for 18 h.
The solvent was then evaporated off, and chromatographic
purification of the resulting crude product with 7:3 (v/v)
hexane/EtOAc as eluent afforded 16 (1.31 g, 79%) as a
white solid. An analytical sample was obtained by
recrystallization from EtOAc–hexane. Mp 194–195 8C. IR

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A. R. Hergueta et al. / Tetrahedron 60 (2004) 10343–10352
(KBr) n: 1731, 1716, 1600, 1276, 1120, 1072, 971, 760,
708 cmK1. EIMS m/z (%): 437 (14, MC1), 436 (47, MC),
331 (16), 209 (11), 181 (8), 169 (11), 105 (100), 77 (24). 1H
NMR (CDCl3) d: 8.06 (2H, dd, JZ6.3, 3.3 Hz, 6-HC9-H),
7.90 [4H, d, JZ8.0 Hz, 2!(20,60-H2)], 7.73 (2H, dd,
JZ6.2, 3.5 Hz, 7-HC8-H), 7.50 [2H, t, JZ7.3 Hz, 2!(40-
H)], 7.28 [4H, t, JZ7.7 Hz, 2!(30,50-H2)], 5.48 (2H, s, 2-
HC3-H), 3.87 (2H,s, 1-HC4-H), 2.96 (1H, d, JZ10.3 Hz,
7-HH), 2.44 (1H, d, JZ10.3 Hz, 7-HH). 13C NMR and
DEPT (CDCl3) d: 165.6 (CO), 159.9 (C), 142.4 (C), 133.6
(CH), 130.1 (CH), 129.9 (CH), 129.8 (C), 129.6 (CH), 128.7
(CH), 73.3 (CH), 50.1 (CH), 42.0 (CH2). Anal. Calcd for
C27H20N2O4 (436.47): C, 74.30; H, 4.62; N, 6.42. Found: C,
74.11; H, 4.71; N 6.29.
C17H16N2O4 (312.33): C, 65.38; H, 5.16; N, 8.97. Found: C,
65.17; H, 5.23; N 8.84.
4.1.9. (G)-5,6-Dioxobicyclo[2.2.1]hept-2-yl acetate (mix-
ture of endo and exo) (23). Dry DMSO (7 mL) was added
very slowly to a solution of dry trifluoroacetic anhydride
(12.3 mL, 88.1 mmol) in dry CH2Cl2 (52 mL) at K78 8C
(internal temperature), and the mixture was stirred for
10 min, treated with a solution of the acetate mixture 11
(5.75 g, 30.9 mmol) in CH2Cl2 (15 mL), stirred at K78 8C
for 2.5 h, treated with Et3N (23 mL), stirred at K78 8C for a
further 3 h, allowed to reach 0 8C, transferred to an ice-bath,
acidified with 3 M HCl, and extracted with CH2Cl2 (2!
120 mL). The pooled extracts were washed with brine and
dried (Na2SO4), and the solvent was removed under reduced
pressure, leaving the acetate mixture 23 as a dark, viscous
oil (4.03 g). Crude product was used directly in the next
synthetic step. A small sample (0.53 g) was resolved by
silica gel column chromatography with 7:1 (v/v) hexane/
EtOAc as eluent into the two epimers of 23, isolated as clear
oils.
4.1.7. E-1-(2,3-Dihydro-1H-cyclopenta[b]quinoxalin-1-
ylidene)-1,2-ethanediol (17). 1 N KOH (20 mL) was
added to a solution of 16 (1.25 g, 2.86 mmol) in MeOH
(3 mL), and the mixture was stirred at rt for 12 h, brought to
pH 8 with 1 N HCl, concentrated under reduced pressure,
and extracted with CH2Cl2 (2!20 mL). The pooled extracts
were washed with saturated NaCl solution and dried
(Na2SO4), and the solvent was removed under reduced
pressure. The purification of the resulting residue by flash
chromatography with 10:1 (v/v) EtOAc/MeOH as eluent
afforded 17 as a deep green solid (0.43 g, 66%), solutions of
which changed with time from fluorescent green to black.
The best samples were obtained by rapid recrystallization
from EtOAc–hexane. The product obtained by chromato-
graphy was used directly to obtain its diacetylated
derivative. IR (KBr) n: 3434, 3318, 1644, 1610, 1580,
1558, 1232, 1068, 901, 770, 600 cmK1. EIMS m/z (%): 228
(32, MC), 197 (71), 170 (41), 169 (61), 168 (26), 58 (100),
52 (2). 1H NMR (CDCl3) d: 10.32 (1H, b s, D2O exchang.,
1-OH), 7.55 (1H, dt, JZ7.9, 1.2 Hz), 7.32 (1H, dt, JZ7.7,
1.3 Hz), 7.18 (1H, dt, JZ7.7, 1.3 Hz), 7.04 (1H, dt, JZ7.9,
1.2 Hz), 4.34 (2H, s, CH2O), 3.49 (1H, b s, D2O exchang., 2-
OH), 3.06–3.02 (2H, m), 2.81–2.77 (2H, m). 13C NMR and
DEPT (CDCl3) d: 194.6 (C), 171.1 (C), 143.3 (C), 136.5
(C), 129.6 (CH), 129.3 (C), 128.6 (CH), 124.7 (CH), 115.8
(CH), 105.9 (C), 65.7 (CH2), 30.2 (CH2), 22.7 (CH2).
Compound endo-23. IR (NaCl) n: 1747 (CO), 1407, 1244,
1046 cmK1. 1H NMR (CDCl3) d: 5.39 (1H, ddd, JZ9.5, 5.5,
3.5 Hz, 2-exo-H), 3.37 (1H, dd, JZ5.1, 1.2 Hz, m, 1-H),
3.06 (1H, d, JZ5.1 Hz, 4-H), 2.65 (1H ddd, JZ14.7, 9.9,
5.1 Hz, 3-exo-H), 2.30–1.98 (2H, m, 7-H2), 1.97 (3H, s,
CH3), 1.72 (1H, dt, JZ14.7, 3.0 Hz, 3-endo-H).
Compound exo-23. IR (NaCl) n: 1740 (CO), 1376, 1230,
1057 cmK1. 1H NMR (CDCl3) d: 4.87 (1H, d, JZ6.9 Hz, 2-
endo-H), 2.79–2.76 (1H, m, 1-H), 2.09–1.99 (1H, m, 4-H),
2.03 (3H, s, CH3), 1.89–1.70 (2H, m, 7-H2), 1.14–1.04 (1H,
m, 3-exo-H), 0.89–0.82 (1H, m, 3-endo-H).
4.1.10. (G)-endo- and (G)-exo-1,2,3,4-Tetrahydro-1,4-
methanophenazin-2-yl acetates (24a and 24b). o-Phenyl-
enediamine (2.70 g, 25.0 mmol) and the zinc catalyst
ZnCl2[C6H5CH(NH2)CH3]2 (10 mg) were added to a
solution of the crude product of the previous reaction
(3.50 g) in dry THF (80 mL), and the mixture was refluxed
for 4.5 h. The solvent was then removed under reduced
pressure, and fractionation of the residue by column
chromatography, first with 7:3 (v/v) hexane/EtOAc as
eluent which afforded the minor isomer 24b (0.37 g) and
then with 4:6 (v/v) hexane/EtOAc to isolate the major
isomer, 24a (1.47 g) (joint yield from mixture 11, 27%).
Analytical samples of both isomers were obtained by
recrystallization from EtOAc/hexane.
4.1.8. E-1-(2,3-Dihydro-1H-cyclopenta[b]quinoxalin-1-
ylidene)ethane-1,2-diyl diacetate (18). Acetic anhydride
(5 mL) was slowly added to a solution of 17 (0.30 g,
1.31 mmol) in dry pyridine (5 mL), and the mixture was
stirred at rt for 14 h. The solvent and excess reagent were
removed under reduced pressure, and purification of the
residue by silica gel column chromatography with 1:1 (v/v)
EtOAc/hexane as eluent afforded 18 as a white solid (0.35 g,
85%). An analytical sample was obtained by recrystalliza-
tion from EtOAc–hexane. Mp 136–137 8C. IR (KBr) n:
Compound 24a. White solid, mp 131–132 8C. IR (KBr) n:
1730 (CO), K339, 1114, 769 cmK1. EIMS m/z (%): 254
(47, MC), 212 (64), 184 (76), 183 (100), 181 (29), 169 (31),
1758, 1736, 1437, 1375, 1230, 1170, 1102, 1017, 803 cmK1
.
EIMS m/z (%): 312 (7, MC), 253 (35), 213 (23), 211 (29),
195 (12), 61 (100), 59 (12), 43 (82), 42 (82), 42 (29), 41
(39), 33 (17), 28 (87), 19 (49), 17 (76). 1H NMR (CDCl3) d:
8.07–8.03 (1H, m), 8.00–7.97 (1H, m), 7.73–7.67 (2H, m),
5.76 (2H, s, CH2O), 3.27–3.22 (2H, m), 2.96–2.90 (2H, m),
2.27 (3H, s, CH3), 2.11 (3H, s, CH3). 13C NMR and DEPT
(CDCl3) d: 171.2 (CO), 168.5 (CO), 162.5 (C), 152.6 (C),
145.2 (C), 142.1 (C), 142.0 (C), 131.0 (C), 130.3 (CH),
130.2 (CH), 129.7 (CH), 128.9 (CH), 60.7 (CH2), 29.3
(CH2), 24.6 (CH2), 21.3 (CH3), 21.1 (CH3). Anal. Calcd for
168 (69), 76 (9). H NMR (CDCl3) d: 8.07–8.01 (2H, m,
1
6-HC9-H), 7.71–7.68 (2H, m, 7-HC8-H), 5.62 (1H, ddd,
JZ9.4, 4.5, 3.1 Hz, 2-exo-H), 3.86 (1H, dd, JZ4.5, 1.4 Hz,
1-H), 3.58 (1H, d, JZ3.3 Hz, 4-H), 2.71 (1H, ddd, JZ13.6,
9.5, 4.5 Hz, 3-exo-H), 2.16 (1H, dm, JZ10.5 Hz, 11-HH),
2.06 (1H, dm, JZ10.5 Hz, 11-HH), 1.82 (3H, s, CH3), 1.43
(1H, dt, JZ13.6, 3.2 Hz, 3-endo-H). 13C NMR and DEPT
(CDCl3) d: 171.2 (CO), 163.4 (C), 159.8 (C), 142.1 (C),
142.0 (C), 129.4 (CH), 129.3 (CH), 129.2 (CH), 129.0 (CH),
73.2 (CH), 48.6 (CH), 44.4 (CH2), 43.9 (CH), 35.2 (CH2),

A. R. Hergueta et al. / Tetrahedron 60 (2004) 10343–10352
10349
21.2 (CH3). Anal. Calcd for C15H14N2O2 (254.29): C, 70.85;
H, 5.55; N, 11.02. Found: C, 70.68; H, 5.63; N 10.84.
pH 8 with saturated NaHCO3 solution, and extracted with
EtOAc (2!10 mL). The pooled organic extracts were dried
(Na2SO4), the solvent was removed under reduced pressure,
and purification of the residue by silica gel column
chromatography with 7:3 (v/v) EtOAc/hexane as eluent
afforded 26 as a clear oil that subsequently crystallized
(50 mg; overall yield with regard to 24a, 51%). An
analytical sample was obtained by recrystallization from
EtOAc/hexane. Mp 80–81 8C. IR (KBr) n: 3284 (OH), 1375,
1323, 1145, 1057, 774 cmK1. EIMS m/z (%): 214 (13, MC),
184 (23), 183 (38), 182 (17), 181 (29), 168 (100), 102 (27),
89 (15), 77 (29), 76 (29), 75 (23), 63 (15), 51 (17), 50 (21),
39 (13), 31 (22). 1H NMR (CDCl3) d: 8.04–8.00 (2H, m, 5-
HC8-H), 7.72–7.68 (2H, m, 6-HC7-H), 5.12 (1H, b s, D2O
exchang., OH), 3.99 (2H, t, JZ6.8 Hz, CH2O), 3.49–3.43
(1H, m, 1-H), 3.22–3.17 (2H, m, 3-H2), 2.61–2.54 (1H, m,
1-CHH), 2.10–1.90 (3H, m, 1-CHHC2-H2). 13C NMR and
DEPT (CDCl3) d: 162.4 (C), 161.2 (C), 142.1 (C), 140.8
(C), 129.6 (CH), 129.5 (CH), 129.1 (CH), 128.8 (CH), 62.7
(CH2), 44.6 (CH), 36.5 (CH2), 31.8 (CH2), 30.1 (CH2).
Anal. Calcd for C13H14N2O (214.27): C, 72.87; H, 6.59; N,
13.07. Found: C, 72.69; H, 6.70; N 13.00.
Compound 24b. White solid, mp 83–84 8C. IR (KBr) n:
1
1731 (CO), 1460, 1033, 762 cmK1. H NMR (CDCl3) d:
7.77–7.71 (2H, m, 6-HC9-H), 7.41–7.38 (2H, m, 7-HC8-
H), 4.74–4.76 (1H, m, 2-endo-H), 3.46 (1H, s, 1-H), 3.37
(1H, d, JZ2.8 Hz, 4-H), 2.12 (1H, d, JZ10.0 Hz, 11-HH),
1.97 (1H, d, JZ10.0 Hz, 11-HH), 1.88 (3H, s, CH3), 1.91–
1.80 (2H, m, 3-H2). 13C NMR and DEPT (CDCl3) d: 170.2
(CO), 163.8 (C), 159.7 (C), 141.4 (C), 141.3 (C), 129.1
(CH), 129.0 (CH), 128.9 (CH), 128.7 (CH), 73.8 (CH), 50.1
(CH), 43.5 (CH), 42.8 (CH2), 36.5 (CH2), 21.2 (CH3). Anal.
Calcd for C15H14N2O2 (254.29): C, 70.85; H, 5.55; N,
11.02. Found: C, 70.74; H, 5.62; N, 10.87.
4.1.11. (G)-endo-1,2,3,4-Tetrahydro-1,4-methanophena-
zin-2-ol (4a). Na2CO3 (2.00 g, 18.86 mmol) was added to a
solution of 24a (1.00 g, 3.93 mmol) in MeOH (25 mL), and
the mixture was stirred vigorously for 2 h. The MeOH was
then removed under reduced pressure, and the residue was
taken into water (50 mL) and extracted with EtOAc (2!
100 mL). The pooled organic extracts were dried (Na2SO4),
the solvent was removed under reduced pressure, and
purification of the solid residue by silica gel column
chromatography with 10:1 (v/v) EtOAc/hexane as eluent
afforded 4a as a white solid (0.77 g, 92%). An analytical
sample was obtained by recrystallization from EtOAc/
hexane. Mp 171–172 8C. IR (KBr) n: 3208 (OH), 1510,
1465, 1367, 1343, 1309, 1288, 1235, 1202, 1183, 1134,
1118, 1076, 1054, 941, 767 cmK1. EIMS m/z (%): 212 (41,
MC), 183 (100), 169 (32), 167 (49), 102 (16), 76 (10), 50
(b) Alternatively, a solution of alcohol 4a (100 mg,
0.47 mmol), Na2CO3 (98 mg, 0.92 mmol) and NaBH4
(35 mg, 0.92 mmol) in EtOH (2 mL) was stirred at rt for
18 h, diluted with water (5 mL) and extracted with EtOAc
(2!10 mL). Work-up and purification as in method (a)
afforded a product (64 mg, 63%) with characteristics
identical to those of 26 prepared as above.
4.1.14. 2-(2,3-Dihydro-1H-cyclopenta[b]quinoxalin-1-
yl)ethyl acetate (27). Alcohol 26 (25 mg, 0.12 mmol) was
dissolved in a mixture of dry pyridine (1 mL) and Ac2O
(1 mL), and this solution was stirred at rt for 18 h, poured
over crushed ice (5 g), stirred for 1 h more, and extracted
with EtOAc (2!5 mL). The pooled extracts were washed
successively with 2 N HCl (5 mL) and brine, and dried
(Na2SO4). Removal of the solvent under reduced pressure
then left 27 as a colourless oil (23 mg, 77%). IR (NaCl) n:
1
(11). H NMR (CDCl3) d: 8.03–7.99 (2H, m, 6-HC9-H),
7.70–7.63 (2H, m, 7-HC8-H), 5.00 (1H, ddd, JZ9.4, 4.3,
3.4 Hz, 2-exo-H), 3.96 (1H, b s, D2O exchang., OH), 3.62–
3.54 (2H, m, 1-HC4-H), 2.67 (1H, ddd, JZ13.3, 9.2,
4.4 Hz, 3-exo-H), 2.09 (1H, dm, JZ10.3 Hz, 11-HH), 2.00
(1H, d, JZ10.3 Hz, 11-HH), 1.37 (1H, dt, JZ13.3, 3.1 Hz,
3-endo-H). 13C NMR and DEPT (CDCl3) d: 164.2 (C),
160.6 (C), 142.1 (C), 141.5 (C), 129.4 (CH), 129.1 (CH),
129.0 (CH), 128.8 (CH), 71.3 (CH), 51.3 (CH), 44.5 (CH2),
44.4 (CH), 37.1 (CH2). Anal. Calcd for C13H12N2O
(212.25): C, 73.56; H, 5.70; N, 13.20. Found: C, 73.38; H,
5.77; N 13.04.
1736 (CO), 1653, 1497, 1459, 1366, 1241, 1120, 764 cmK1
.
EIMS m/z (%): 256 (19, MC), 213 (14), 196 (99), 186 (23),
185 (20), 184 (22), 183 (79), 181 (48), 168 (100), 142 (14),
129 (21), 115 (19), 103 (18), 102 (47), 90 (14), 89 (33), 78
(14), 77 (37), 76 (37), 75 (31), 63 (17), 51 (16), 50 (21), 43
1
(21), 42 (60), 41 (19), 39 (17). H NMR (CDCl3) d: 8.01–
4.1.12. (G)-exo-1,2,3,4-Tetrahydro-1,4-methanophena-
zin-2-ol (4b). Compound 4b was obtained from 24b in the
same way as 4a from 24a. Yield 93%. Mp 154–155 8C. IR
(KBr) n: 3262, 1541, 1512, 1452, 1440, 1401, 1360, 1329,
1307, 1283, 1241, 1227, 1196, 1166, 1154, 1125, 1082,
7.95 (2H, m, 5-HC8-H), 7.66–7.61 (2H, m, 6-HC7-H),
4.35 (2H, t, JZ6.6 Hz, CH2O), 3.40–3.31 (1H, m, 1-H),
3.17–3.08 (2H, m, 3-H2), 2.59–2.43 (2H, m, 1-CH2), 2.02
(3H, s, CH3), 1.97–1.84 (2H, m, 2-H2). 13C NMR and DEPT
(CDCl3) d: 171. 5 (CO), 162.3 (C), 160.6 (C), 142.1 (C),
142.1 (C), 129.4 (CH), 129.3 (CH), 129.14 (CH), 129.10
(CH), 63.0 (CH2), 41.1 (CH), 32.7 (CH2), 31.4 (CH2), 29.0
(CH2), 21.4 (CH3). HRMS calcd for C15H16N2O2:
256.1212. Found: 256.1218.
1053, 1019, 972, 959, 916, 902, 839, 772, 717, 677 cmK1
.
1H NMR (CDCl3) d: 7.99–7.96 (2H, m, 6-HC9-H), 7.69–
7.65 (2H, m, 7-HC8-H), 4.34 (1H, d, JZ4.9 Hz, 2-endo-H),
3.60–3.57 (2H, m, 1-HC4-H), 2.52 (1H, d, JZ10.0 Hz, 11-
HH), 2.20 (1H, d, JZ10.0 Hz, 11-HH), 2.14–2.00 (2H, m,
3-H2). Anal. Calcd for C13H12N2O (212.25): C, 73.56; H,
5.70; N, 13.20. Found: C, 73.31; H, 5.83; N 13.12.
4.1.15. (2,3-Dihydro-1H-cyclopenta[b]quinoxalin-1-yl)
acetic acid (28). Acetate 24a (240 mg, 0.94 mmol) was
treated and worked up as in the preparation of 4a except that
reaction was prolonged for 6 h. Chromatography of the
crude product with 10:1 (v/v) EtOAc/hexane as eluent,
afforded a dark slurry (159 mg) that consisted very
predominantly of 25 (90% as determined by 1H NMR;
4.1.13. 2-(2,3-Dihydro-1H-cyclopenta[b]quinoxalin-1-
yl)etanol (26). (a) NaBH4 (17 mg, 0.45 mmol) was added
to a solution of 25 (77 mg of the chromatographed material)
in EtOH (4 mL), and the mixture was successively stirred at
rt for 14 h, treated with 1 N HCl (1 mL), brought to about

10350
A. R. Hergueta et al. / Tetrahedron 60 (2004) 10343–10352
estimated yield in 25, 71%). This material was used directly
in subsequent transformations.
hexane as eluent afforded 5 as a clear yellowish oil (99 mg,
67%). IR (NaCl) n: 1751 (CO), 1578, 1510, 1463, 1410,
1361, 1303, 1274, 1254, 1216, 1200, 1158, 1111, 1086,
1059, 957, 834, 762, 732, 700 cmK1. EIMS m/z (%): 210
(75, MC), 181 (100), 168 (99), 140 (20), 129 (31), 128 (22),
103 (27), 102 (39), 91 (28), 78 (25), 77 (22), 76 (62), 75
(20), 74 (25), 64 (20), 63 (30), 53 (21), 52 (22), 51 (32), 50
(42), 39 (27). 1H NMR (CDCl3) d: 7.91–7.86 (2H, m, 6-HC
9-H), 7.62–7.56 (2H, m, 7-HC8-H), 3.85–3.82 (2H, m, 1-
HC4-H), 2.66–2.54 (2H, m, 3-exo-HC11-HH), 2.46 (1H,
dd, JZ10.4, 1.2 Hz, 11-HH), 2.16 (1H, dd, JZ17.8, 4.3 Hz,
3-endo-H). 13C NMR and DEPT (CDCl3) d: 208.2 (CO),
163.1 (C), 156.3 (C), 142.1 (C), 141.6 (C), 129.9 (CH),
129.6 (CH), 129.5 (CH), 129.2 (CH), 59.9 (CH), 46.7 (CH2),
42.6 (CH), 40.2 (CH2). HRMS calcd for C13H10N2O:
210.0793. Found: 210.0801.
Compound 25. IR (KBr) n: 1722 (CO) cmK1. EIMS m/z (%):
212 (1, MC), 184 (76), 183 (100, MKCHO), 169 (44), 168
(21), 102 (9), 76 (8), 58 (9). 1H NMR (CDCl3) d: 9.88 (1H, s,
CHO). 13C NMR and DEPT (CDCl3) d: 201.0 (CHO), 161.3
(C), 160.3 (C), 141.93 (C), 141.86 (C), 129.4 (CH), 129.2
(CH), 129.1 (CH), 129.0 (CH), 47.5 (CH2), 38.3 (CH), 31.3
(CH2), 29.3 (CH2).
Minor contaminant: EIMS m/z (%): 424 (7), 213 (44), 212
(23), 184 (33), 183 (100), 181 (32), 169 (100), 168 (47), 129
(7), 102 (10), 77 (11).
A solution of the above product (66 mg) in MeOH (2 mL)
was treated with 3 drops of Tollens’ reagent,71 left for 3 h at
rt (a silver mirror was formed on the wall of the flask),
diluted with water (10 mL), extracted with CHCl3 (5 mL),
brought to pH 5 with formic acid, and finally extracted with
EtOAc (2!5 mL). These last extracts were pooled and
dried (Na2SO4), and the solvent was removed under reduced
pressure, leaving 28 as a yellowish thick paste (40 mg;
yield, 45% with regard to starting 24a). IR (NaCl) n: 3420,
2508, 1718, 1507, 1329, 1192, 770 cmK1. 1H NMR (CDCl3)
d: 8.05–8.00 (2H, m, 5-HC8-H), 7.70–7.67 (2H, m, 6-HC
7-H), 3.82–3.71 (1H, m, 1-H), 3.27–3.17 (3H, m, 1-CHHC
3-H2), 2.77–2.63 (2H, m, 1-CHHC2-HH), 1.98 (1H, dd,
JZ12.9, 9.2 Hz, 2-HH).
1H and 13C NMR spectra obtained after 5 had been left in an
NMR spectrometry tube for 3 days at rt showed signals of 5
and 28 in approximately 1:1 ratio.
Acknowledgements
The authors thank the Xunta de Galicia for finan-
cial support under projects PGIDT01PXI20302PR and
PGIDIT02BTF20305PR.
4.1.16. Methyl (2,3-dihydro-1H-cyclopenta[b]quinoxa-
lin-1-yl)acetate (29). p-Toluenesulfonic acid (5 mg) was
added to a solution of 28 (35 mg, 0.15 mmol) in dry MeOH
(3 mL), and the mixture was refluxed under argon for 3.5 h,
mixed with saturated NaHCO3 solution (5 mL), and
extracted with EtOAc (2!5 mL). The pooled organic
extracts were dried (Na2SO4) and the solvent was removed
under reduced pressure, leaving 29 as a clear oil that
solidified spontaneously (25 mg, 67%). An analytical
sample was obtained by recrystallization from EtOAc/
hexane. Mp 155 8C, dec.). IR (KBr) n: 1732 (CO), 1560,
References and notes
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Chemicals, Inc. JP 60152435, 1985; Chem. Abstr. 1986, 104,
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Chemicals, Inc. JP 60152473, 1985; Chem. Abstr. 1986, 104,
88578u.
3. Toba, Y.; Yasuike, M.; Yamaguchi, T. Toyo Inki Seizo K.K.
Japan. JP 04113361, 1992; Chem. Abstr. 1993, 118, 136244v.
4. Toba, Y.; Yasuike, M.; Yamaguchi, T., Toyo Ink Mfg Co, Ltd,
Japan. JP 04243261, 1992; Chem. Abstr. 1993, 119, 17907z.
5. Yamaguchi, T.; Toba, Y.; Yasuike, M. Toyo Ink Mfg Co.,
Japan. JP 06175564, 1994; Chem. Abstr. 1995, 122, 147529a.
6. Toba, Y.; Yamaguchi, T.; Yasuike, M., Toyo Ink Mfg Co.,
Japan. JP 06195015, 1994; Chem. Abstr. 1995, 122, 147507s.
7. Toba, Y.; Yamaguchi, T.; Yasuike, M., Toyo Ink Mfg Co.,
Japan. JP 06202544, 1994; Chem. Abstr. 1995, 122, 147513r.
8. Yamaguchi, T.; Toba, Y.; Yasuike, M., Toyo Ink Mfg Co.,
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1
1501, 1436, 1369, 1325, 1263, 1196, 1171, 764 cmK1. H
NMR (CDCl3) d: 8.03–7.98 (2H, m, 5-HC8-H), 7.69–7.65
(2H, m, 6-HC7-H), 3.82–3.70 (1H, m, 1-H), 3.74 (3H, s,
CH3), 3.28–3.15 (3H, m, 1-CHHC3-H2), 2.73–2.58 (2H, m,
1-CHHC2-HH), 1.95 (1H, m, JZ12.9, 9.2 Hz, 2-HH). 13C
NMR and DEPT (CDCl3) d: 173.0 (CO), 161.3 (C), 160.5
(C), 142.1 (C), 142.0 (C), 129.4 (CH), 129.3 (CH), 129.2
(CH), 129.1 (CH), 52.2 (CH3), 40.5 (CH), 37.8 (CH2), 31.3
(CH2), 29.2 (CH2). Anal. Calcd for C14H14N2O2 (242.28):
C, 69.41; H, 5.82; N, 11.56. Found: C, 69.28; H, 5.89; N
11.60.
4.1.17. 1,2,3,4-Tetrahydro-1,4-methanophenazin-2-one
(5). To a solution of dry pyridine (0.67 mL, 8.4 mmol) in
CH2Cl2 (7.5 mL) at 0 8C was added CrO3 (0.42 g,
4.2 mmol) followed by a solution of 4a (150 mg,
0.71 mmol) in CH2Cl2 (3.5 mL). The reaction mixture was
left stirring overnight at rt, and was then filtered through
celite. The celite was washed with EtOAc (10 mL), the
pooled filtrates were dried (Na2SO4), and the solvents were
removed under reduced pressure. Purification of the residue
by silica gel column chromatography with 7:3 (v/v) EtOAc/
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