Swern oxidation of bicyclo[2.2.1]hept-5-ene-2,3-diol and its pyrazine-fused derivatives: An improved synthesis of bicyclo[2.2.1]hept-5-ene-2,3-dione and an unexpected ring-opening reaction

Article abstract of DOI:10.3390/50901062

An improved synthesis of bicyclo[2.2.1]hept-5-ene-2,3-dione by Swern oxidation of bicyclo[2.2.1]hept-5-ene-2,3-diol, and an unexpected ring-opening reaction by the Swern oxidation of pyrazine-fused congeners are described.

Full text of DOI:10.3390/50901062

Molecules 2000, 5, 1062-1067
molecules
ISSN 1420-3049
© 2000 by MDPI
http://www.mdpi.org
Swern Oxidation of Bicyclo[2.2.1]hept-5-ene-2,3-diol and
Its Pyrazine-fused Derivatives: An Improved Synthesis of
Bicyclo[2.2.1]hept-5-ene-2,3-dione and An Unexpected Ring-
Opening Reaction
Tomoshige Kobayashi* and Sayuri Kobayashi
Department of Chemistry, Faculty of Science, Shinshu University, Matsumoto 390-8621, Japan
Tel.: (263) 37-2470, Fax: (263) 37-2470, E-mail: tkobaya@gipac.shinshu-u.ac.jp
Received: 14 August 2000 / Accepted: 6 September 2000 / Published: 9 September 2000
Abstract: An improved synthesis of bicyclo[2.2.1]hept-5-ene-2,3-dione by Swern oxidation of
bicyclo[2.2.1]hept-5-ene-2,3-diol, and an unexpected ring-opening reaction by the Swern oxida-
tion of pyrazine-fused congeners are described.
Keywords: Swern oxidation, vicinal cis-diol, a -diketone, ring-opening, norbornene, pyrazine.
Introduction
Bicyclo[2.2.1]heptane skeletons have been a useful building block for the construction of molecular archi-
tectures with a concavity [1]. In the course of our studies to synthesize a host molecule utilizing a negative
electrostatic potential filed of pyrazine rings, a general method to prepare norobornene-2,3-dione and its py-
razine-fused derivatives was required. We describe here an improved synthesis of bicyclo[2.2.1]hept-5-ene-
2,3-dione (3) by Swern oxidation of bicyclo[2.2.1]hept-5-ene-2,3-diol (6). We also report that a similar
Swern oxidation reaction of pyrazine-fused congeners 10 and 11 was found to undergo an unexpected rring-
opening reaction.
Results and Discussion
Previously, bicyclo[2.2.1]hept-5-ene-2,3-dione (3) was prepared by the Diels-Alder reaction of cyclo-
pentadiene with dichlorovinylene carbonate (1) giving the adduct 2, followed by hydrolysis [2]. Dichlorovinyl-
ene carbonate (1) can be prepared by the reductive dechlorination reaction of tetrachloroethylene carbonate
[3]. However, the synthesis of tetrachloroethylene carbonate is troublesome because the use of a large amount
of chlorine gas is required [3]. Furthermore, we could not reproduce the reported yield of the Diels-Alder re-

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Molecules 2000, 5
action of 1 with cyclopentadiene: the adduct 2 was obtained only in 40-50% yields whereas 65-70% yields
were claimed in the literature [3]. Thus, we report here an improved synthesis of 1 starting from more readily
available vinylene carbonate (4) [4].
Bicyclo[2.2.1]hept-5-ene-2,3-diol (6) was prepared by the Diels-Alder reaction of vinylene carbonate (4)
and cyclopentadiene followed by the hydrolysis as described in the literature [5]. The total yield for the two
steps was 78%. The Swern oxidation of 6 with dimethyl sulfoxide and oxalyl chloride provided 3 in 61%
yield. A similar Swern oxidation by the use of trifluoroacetic anhydride instead of oxalyl chloride increased the
yield of 3 to 73%. The overall yield of 3 from 4 was 57% yield, which is much higher than that from 1 (38%
by our hands).
Cl
O
O
Cl
Cl
O
O
O
O
Cl
O
1
2
3
O
O
O
O
O
OH
OH
O
O
4
5
6
Scheme 1.
We next tried to apply the Swern oxidation to prepare pyrazine-fused norbornenediones 14. 5,6,7,8-
Tetrahydro-5,8-methanoquinoxaline-6-exo,7-exo-diol (10) was prepared in 90% yield by the oxidation of
pyrazine-fused norbornadiene 7 [6] with osmium tetroxide in the presence of N-methylmorpholine N-oxide. A
similar oxidation of 8 [6] provided 1,2,3,4-tetrahydro-1,4-methanophenazine-2-exo,3-exo-diol (11) in 89%
yield. However, treatment of the dicyanopyrazine-fused norbornadiene 9 [6] with osmium tetroxide resulted in
the recovery of 9. The electron-deficient pyrazine ring with cyano substituents would retard the oxidation at
the remote olefinic moiety [7].
When the exo-cis diol 10 was treated with dimethyl sulfoxide and trifluoroacetic anhydride, (6,7-dihydro-
5H-cyclopentapyrazin-5-yl)methanol (12) was obtained in 75% yield. A similar treatment of 11 provided
(2,3-dihydro-1H-cyclopenta[b]quinolin-1-yl)methanol (13) in 63% yield. The Swern oxidation of 11 by the
use of oxalyl chloride instead of trifluoroacetic anhydride also produced 13 in 63% yield. We could observe
no evidence for the formations of expected a -diketones 14. When we were monitoring the reaction by TLC,
a spot initially formed on the TLC plate was disappeared after the work-up with aqueous sodium hydroxide
solution. Unfortunately, our attempts to isolate the intermediate corresponding to this spot were unsuccessful.

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Molecules 2000, 5
H
s
H
a
CH OH
2
R
R
N
N
N
N
R
OH
OH
R
R
R
N
N
7 R = H
8 R-R = CH=CH-CH=CH
12 R = H
13 R-R = CH=CH-CH=CH
10 R = H
11 R-R = CH=CH-CH=CH
9 R = CN
N
N
R
O
O
R
14
Scheme 2.
A plausible mechanism for the present reaction was illustrated in Scheme 3. The initially formed sulfonium
ion 15 would undergo the C-C bond cleavage by the abstraction of hydroxyl proton with triethylamine, and
the intramolecular Cannizzaro reaction under alkaline conditions followed by decarboxylation could give the
products 12 and 13.
NEt
H
3
CHO
CHO
CH OH
2
N
R
O
O
R
R
N
N
R
R
N
N
OH
R
SMe
2
N
COOH
15
16
17
CO
2
12, 13
Scheme 3.
However, the Cannizzaro reaction is well recognized to proceed for aldehydes with no a -hydrogen [8].
Furthermore, the Swern oxidations of vicinal diols 18 [9], 19 [10] and 20 [11] have all been reported to give
the corresponding a -diketones, as did the oxidation reaction of 6. Thus, from our results we did not obtain
evidence to discriminate between those reaction pathways and other potential mechanisms for the present re-
action might be considered.
OH
OH
OH
OH
OH
OH
18
19
20
Scheme 4.

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Molecules 2000, 5
Conclusion
We have presented a facile route for the synthesis of the norbornenedione 3 and an unusual ring-opening
reaction by Swern oxidation of the pyrazine-fused norbornenediols 10 and 11.
Experimental
General
All the melting points were determined with a Yanagimoto hot-stage apparatus. IR spectra were obtained
1
with a JEOL Diamond-20 spectrometer. NMR spectra were recorded either with JEOL JNM-LA400 ( H:
13
400 MHz; C: 100 MHz) spectrometer using TMS as internal standard. J-Values are given in Hz. Assign-
1
13
ments of the H and C signals are based on DEPT, H-H COSY, and C-H COSY measurements. Mass
spectra were measured with a Shimadzu GCMS-QP1000EX spectrometer operating in the electron impact
mode (70eV). High-resolution mass spectra (HR-MS) were taken with a JEOL JMS-SX102A spectrometer
operating in the FAB+ method. Elemental analyses were performed with a Perkin-Elmer Model 240 appara-
tus. Solvents were dried and purified by standard methods. Yields are based on isolated products with suffi-
cient purity.
Bicyclo[2.2.1]hept-5-ene-2,3-dione (3)
Trifluoroacetic anhydride (35.92 g, 171 mmol) was added dropwise over 40 min to a solution of dimethyl
sulfoxide (14.79 g, 189 mmol) in dichloromethane (100 mL) cooled with a dry ice-acetone bath. To this solu-
tion was added a solution of bicyclo[2.2.1]hept-5-ene-2-endo,3-endo-diol (6) (7.50 g, 60 mmol) in dichlo-
romethane (30 mL) over 10 min. The mixture was further stirred at -78°C for 2 h. Triethylamine (31.98 g,
316 mmol) was added to the solution. The mixture was stirred for 3 h and allowed to warm up to room tem-
perature. 2M Hydrochloric acid was added and the product was extracted with dichloromethane. The organic
phase was dried with sodium sulfate. After removal of the solvent, the resulting yellow oil was distilled under
vacuum to give 3 (5.31 g, 73%) as a yellow oil which solidified after cooling: bp 129°C (10 Torr); mp 40°C
1
(lit [3] mp 43°C) ; H NMR (CDCl ) d=2.49 (1H, d, J=11, 7-H), 3.00 (1H, dt, J=11 and 2, 7-H), 3.32
3
(2H, m, 1-H and 4-H), 6.51 (2H, br s, 5-H and 6-H); 13C NMR (CDCl ) d=43.6 (C-7), 51.4 (C-1 and C-
3
-1
+
4), 137.7 (C-5 and C-6), 195.6 (C-2 and C-3); IR (KBr) 1765 cm ; MS m/z 122 (9; M ), 95 (16; M -
C2H3), 66 (100, C5H6).
A similar reaction of 6 (0.65 g, 5.8 mmol) with dimethyl sulfoxide (1.19 g, 15 mmol) and oxalyl chloride
(1.65 g, 13 mmol), followed by the addition of triethylamine (2.70 g, 27 mmol) provided 3 (0.43 g, 61%).
5,6,7,8-Tetrahydro-5,8-methanoquinoxaline-6-exo,-7-exo-diol (10)
To a solution of osmium tetroxide (1 mg, 0.004 mmol) and N-methylmorpholine N-oxide (246 mg, 2.1
mmol) in a mixture of acetone ( 5 mL) and water (10 mL) was added the norbornadiene-fused pyrazine 7
(100 mg, 0.7 mmol) and the mixture was stirred at room temperature for 68 h. Sodium sulfite (3 mg, 0.03
mmol) and florisil (0.5 g) was added to the reaction mixture and insoluble materials were filtered through celite.

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Molecules 2000, 5
Aqueous sodium hydroxide solution was added to the filtrate and products were extracted with dichlo-
romethane (6 ´ 20 mL). The combined organic phases were dried over sodium sulfate. After removal of the
solvent, the residue was purified by column chromatography (silica gel, ethyl acetate), and the resulting solid
1
was recrystallized from chloroform to give 10 (112 mg, 90%) as a white solid: mp 186-187°C; H NMR
(CDCl ) d=2.17 (1H, dm, J=14, 9-Hs), 3.00 (1H, dt, J=14 and 2, 9-Ha), 3.45 (2H, t, J=2, 5-H and 8-H),
3
3.99 (2H, br s, 6-H and 7-H), 4.15 (2H, s, OH, disappeared by D O addition), 8.16 (2H, s, 2-H and 3-H);
2
13C NMR (CDCl ) d=41.2 (C-5 and C-8), 51.4 (C-9), 69.7 (C-2 and C-3), 141.7 (C-6 and C-7), 161.1
3
-1
(C-4a and C-8a); IR (KBr) 3490, 3097, 1365, 1160 cm ; MS m/z 178 (33; M+), 149 (31; M - CHO), 119
(100, M - 2CHO - H). Anal. Found: C, 60.52; H, 5.96; N, 15.67%. Calcd for C H10N2O2: C, 60.66; H,
9
5.66; N, 15.72%.
1,2,3,4-Tetrahydro-1,4-methanophenazine-2-exo,3-exo-diol (11)
By a similar procedure as described for 10, the norbornadiene-fused quinoxaline 8 (349 mg, 1.8 mmol)
provided 11 (366 mg, 89%) as a white solid after recrystallization from chloroform: mp 183-184°C; 1H NMR
(CDCl ) d=2.23 (1H, dm, J=11, 11-Hs), 2.65 (1H, d, J=11, 11-Ha), 3.58 (2H, s, 1-H and 4-H), 3.77 (2H,
3
s, OH, disappeared by D2O addition), 4.14 (2H, s, 2-H and 3-H), 7.70 (2H, m, 7-H and 8-H), 8.00 (2H, m,
13
6-H and 9-H); C NMR (CDCl ) d=39.0 (C-1 and C-4), 51.3 (C-11), 76.3 (C-2 and C-3), 128.7 (C-7
3
and C-8), 129.4 (C-6 and C-9), 141.4 (C-5a and C-9a), 160.8 (C-4a and C-10a); IR (KBr) 3430, 3074,
-1
1076 cm ; MS m/z 228 (59; M+), 199 (31; M - CHO), 169 (100, M - 2CHO - H). Anal. Found: C, 68.41;
H, 5.30; N, 12.27%. Calcd for C13H12N2O2: C, 68.68, H, 5.21; N, 12.01%.
The Swern Oxidation of 10
To a cooled (-78°C) solution of dimethyl sulfoxide (125 mg, 1.6 mmol) in dichloromethane (10 mL) was
added trifluoroacetic anhydride (315 mg, 1.5 mmol) over 5 min. A solution of 10 (89 mg, 0.5 mmol) in a 1:1
mixture (5 mL) of dichloromethane and dimethyl sulfoxide was added over 10 min and the mixture was stirred
at -78°C for 3 h. Triethylamine (268 mg, 2.7 mmol) was introduced to the solution. The mixture was stirred at
-78°C for 1.5 h and allowed to warm up to room temperature. Aqueous sodium hydroxide solution was
added and the product was extracted with dichloromethane (6 ´ 20 mL). The combined organic phase was
washed with water and dried over sodium sulfate. After removal of the solvent, the residue was separated by
column chromatography (silica gel, ethyl acetate) to give (6,7-dihydro-5H-cyclopentapyrazin-5-yl)methanol
1
(12) (56 mg, 75%) as a colorless liquid: H NMR (CDCl ) d=1.98 (1H, ddd, J=19, 11 and 9, 6-H), 2.37
3
(1H, ddd, J=19, 8 and 6, 6-H), 3.07 (2H, dd, J=9 and 6, 7-H), 3.43 (1H, m, 5-H), 3.80-4.01 (3H, m,
13
CH2OH and OH), 8.24 (1H, br s, 2-H or 3-H), 8.30 (1H, br s, 3-H or 2-H); C NMR (CDCl ) d=24.2
3
(C-6), 30.8 (C-7), 45.1 (C-5), 64.9 (CH2OH), 141.6 (C-2 or C-3), 142.7 (C-3 or C-2), 159.9, 160.2; IR
-1
+
(KBr) 3347, 2946, 1388, 1160 cm ; MS m/z 150 (2; M ), 119 (100, M - CH2OH). HR-MS (FAB+)
found: 151.0899 (M + 1). Calcd for C8H10N2O: 151.0872 (M + 1).
The Swern Oxidation of 11
By a similar procedure as described for the oxidation of 10, the norbornadiene-fused quinoxaline 11 (114
mg, 0.5 mmol) provided (2,3-dihydro-1H-cyclopenta[b]quinolin-1-yl)methanol (13) (58 mg, 63%) as a white

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Molecules 2000, 5
solid after recrystallization from hexane: mp 83-84°C; 1H NMR (CDCl ) d=1.97 (1H, ddd, J=18, 13, and 9,
3
2-H), 2.47 (1H, ddd, J=18, 8, and 5, 2-H), 3.02 (1H, s, OH), 3.22 (2H, dd, J=9 and 5, 3-H), 3.58 (1H, m,
1-H), 3.98 (1H, dd, J=11 and 8, CH2OH), 4.09 (1H, dd, J=11 and 5, CH2OH), 7.62 (2H, m), 8.02 (2H,
m); 13C NMR (CDCl ) d=24.3 (C-2), 31.3 (C-3), 45.0 (C-1), 65.1 (CH2OH), 128.7, 128.8, 128.9, 129.1,
3
-1
141.0, 141.9, 160.6, 161.8; IR (KBr) 3241, 2964, 1342 cm ; MS m/z 200 (5; M+), 182 (16, M M - H O
2
), 169 (100, M - CH2OH). HR-MS (FAB+) found: 201.1055 (M + 1). Calcd for C12H12N2O: 201.1028 (M
+ 1).
A similar Swern oxidation of 11 (68 mg, 0.3 mmol) by the use of oxalyl chloride (114 mg, 0.9 mmol) in-
stead of trifluoroacetic anhydride also afforded 13 (38 mg, 63%).
References and Notes
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Chem. 1999, 2741-2749 (and references cited therein).
2. Scharf, H.-D.; Küsters, W. Chem. Ber. 1972, 105, 564-574.
3. Scharf, H.-D.; Pinske, W.; Feilen, M.-H.; Droste, W. Chem.. Ber. 1972, 105, 554-563.
4. Newman, M. S.; Addor, R. W. J. Am. Chem. Soc. 1953, 75, 1263-1264.
5. Newman, M. S.; Addor, R. W. J. Am. Chem. Soc. 1955, 77, 3789-3793.
6. Kobayashi, T.; Miki, K. Bull. Chem. Soc. Jpn. 1998, 71, 1443-1449.
7. Kobayashi, T.; Miki, K.; Nikaeen, B.; Baba, H. Tetrahedron, 1999, 55, 13179-13192.
8. March, J. Advanced Organic Chemistry, 3 rd ed.; John Wiley & Sons: New York, 1985; p. 1117.
9. Russell, R. A.; Harrison, P. A.; Warrener, R. N. Aust. J. Chem. 1984, 37, 1035-1041.
10. Wright, M. W.; Welker, M. E. J. Org. Chem. 1996, 61, 133-141.
11. Christl, M.; Kraft, A. Angew. Chem., Int. Ed. Engl. 1988, 27, 1369-1370.
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