Diels - Alder reactions of epoxybutene derivatives and subsequent synthetic manipulations of the cycloadducts

Article abstract of DOI:10.1021/op010219d

Diels - Alder reactions between cyclopentadiene, cyclohexadiene, and a number of epoxybutene derivatives are reported. The endo diastereomer from the Diels - Alder reaction of cyclopentadiene with 2,5-dihydrofuran was functionalized by additional oxidative transformations.

Full text of DOI:10.1021/op010219d

Organic Process Research & Development 2001, 5, 514−518
Diels-Alder Reactions of Epoxybutene Derivatives and Subsequent Synthetic
Manipulations of the Cycloadducts
Marion A. Franks,† John A. Hyatt,‡ and Mark E. Welker*,†
Department of Chemistry, Wake Forest UniVersity, Winston-Salem, North Carolina 27109, U.S.A., and
Eastman Chemical Company, P.O. Box 1972, Kingsport, Tennessee 37662, U.S.A.
Abstract:
1,3-dioxolan-2-one (vinyl ethylene carbonate or VEC) (2c)
produced only small amounts of Diels-Alder cycloadducts
(3). However, the simple change of switching to the use of
Ace Glass Pressure tubes as the reaction vessel produced a
number of Diels-Alder cycloadducts. (Table 1). These tubes
can be used to produce gram quantities of these cycloadducts.
Two of these synthetic preparations were then scaled up
further. Cycloadduct (3a) was produced on 120 g scale
through the use of a steel autoclave (750 mL) equipped with
a glass liner. Use of the glass liner was critical to the success
of this reaction. Vinyl ethylene carbonate was considerably
more reactive than 2a as a dienophile, and the VEC/
cyclopentadiene cycloadduct (3c) was synthesized on a 70
g scale using standard laboratory glassware under reflux at
atmospheric pressure.
Diels-Alder reactions between cyclopentadiene, cyclohexadiene,
and a number of epoxybutene derivatives are reported. The
endo diastereomer from the Diels-Alder reaction of cyclopen-
tadiene with 2,5-dihydrofuran was functionalized by additional
oxidative transformations.
Introduction
3,4-Epoxy-1-butene (2a) is a synthetically interesting
small molecule in that each of the four carbons is part of a
reactive functional group and they all have significantly
different reactivities. Epoxybutene is now commercially
available on a multikilogram scale, and a variety of its
derivatives are also available from Eastman for possible use
as fine, specialty, or commodity chemicals. The ready access
to large quantities of this alkenyl epoxide, coupled with the
fact that Diels-Alder adducts of the derivatives with cyclic
dienes might prove useful as ring-opening metathesis po-
lymerization (ROMP) monomers,1 prompted us to investigate
Diels-Alder reactions of epoxybutene derivatives with
several dienes. While the Diels-Alder reaction between
epoxybutene and hexachlorocyclopentadiene is mentioned
in the patent literature,2 there has been no prior systematic
study of Diels-Alder reactions of this compound and its
derivatives. The alkenes studied here were not classical
Diels-Alder dienophiles because the alkene was not sub-
stituted with a strong electron-withdrawing group. As such,
they would be expected to be sluggish dienophiles in Diels-
Alder reactions, possibly requiring more forcing reaction
conditions used for other dienes3 and dienophiles4 of low
reactivity.
Endo/exo cycloadduct diastereomer ratios could be de-
1
termined in all cases by analysis of their H NMR spectra.
Since this analysis was complicated by the existence of
stereogenic centers in some of the racemic dienophiles we
used, we chose to initiate analysis of the diastereoselectivity
of these cycloadditions by looking at the cyclopentadiene/
Results and Discussion
Initial attempts to effect thermal Diels-Alder reactions
between cyclopentadiene and epoxide (2a) as well as 4-vinyl-
1
2,5-dihydrofuran cycloadducts (3i). H NMR analyses of
related cyclopentadiene Diels-Alder cycloadducts proved
useful for determining diagnostic resonances in the endo and
exo diastereomers reported in Table 1.5 The exo and endo
cycloadducts for the reaction of cyclopentadiene with dim-
ethyl maleate (4, 5), the endo cycloadduct for the reaction
of cyclopentadiene with maleic anhydride (6), as well as the
† Department of Chemistry, Wake Forest University, Winston-Salem, NC,
27109. E-mail: welker@wfu.edu.
‡ Eastman Chemical Company, P.O. Box 1972, Kingsport, TN 37662.
(1) (a) Wu, Z.; Benedicto, A. D.; Grubb, R. H. Macromolecules 1993, 26, 4975.
(b) Tallarizo, J. A.; Bonitatebus, P. J.; Snapper, M. L. J. Am. Chem. Soc.
1997, 119, 7157. (c) For a recent review on olefin metathesis see: Grubbs,
R. H.; Chang, S. Tetrahedron 1998, 54, 4413.
1
3f diastereomers are shown below. Two sets of H NMR
resonances, H7s/7a and H2,3, are most diagnostic of these
stereoisomers (Table 2). The H2,3 protons in the exo
diastereomer (4) are significantly shielded compared to the
(2) (a) Thomas, C. E. U.S. Patent 2,340,908, 1944. (b) Ladd, E. C. U.S. Patent
2,616,899, 1952. (c) Whitworth, C. J.; Zutty, N. L. U.S. Patent 3,277,036,
1966. (d) Reding, F. P.; Starcher, P. S.; Wise, E. W. U.S. Patent 3,494,897,
1970. (e) 5-Oxiranylnorbornene is mentioned in Res. Discl. 1992, 810, 34301
with no reference to its method of preparation.
(3) For an example, see: Dauben, W. G.; Kessel, C. R.; Takemura, K. H. J.
Am. Chem. Soc. 1980, 102, 6893.
(4) For an example, see: Jurczak, J.; Tkacz, M.; Synthesis 1979, 42.
(5) (a) Nelson, W. L.; Freemen, D. S.; Sankar, R.; J. Org. Chem. 1975, 40,
3658. (b) Arnold, D. R.; Trecker, D. J.; Whipple, E. B. J. Am. Chem. Soc.
1965, 87, 2596.
514
•
Vol. 5, No. 5, 2001 / Organic Process Research & Development
10.1021/op010219d CCC: $20.00 © 2001 American Chemical Society and The Royal Society of Chemistry
Published on Web 08/16/2001

Table 1. Thermal Diels-Alder reactions of cyclopentadiene with epoxybutene derivatives
entry
R1
R2
R3
cmpd
yield (%)
endo:exo
cmpd
1
2
3
4
5
6
7
8
9
H
H
H
H
H
H
H
H
R2 ) R3 ) -O-
2a
2b
2c
2d
2e
2f
2g
2h
2i
65
60
95
61
28
10
28
39
87
1.56:1
1.21:1
1.18:1
1.51:1
1.24:1
1.65:1
2.42:1
1.30:1
2.39:1
3a
3b
3c
3d
3e
3f
3g
3h
3i
R2 ) R3 ) -O-C(Me)2-O-
R2 ) R3) -O-C(O)-O-
OH
OAc
OH
H
OBz
OAc
OH
OH
OAc
OMe
2,5-dihydrofuran
Table 2. Proton NMR chemical shifts of endo and exo
diastereomers
diastereomers in low isolated yield. Isoprene proved equally
unreactive as a diene.
H1,4
H2,3
H5,6
H7a
H7s
3.12
2.62
6.22
1.50
2.14
3.10
3.23
6.15
1.37
1.37
3.50
3.56
6.29
1.55
1.77
2.89
2.86
6.21
1.44
1.53
2.67
2.26
6.16
1.31
1.83
Organic
[5.2.1.0]-dec-8-ene
Transformations
of
endo-4-Oxa-tricyclo
The endo and exo diastereomers (3i) of the cyclopenta-
diene/2,5-dihydrofuran cycloadduct could be separated on a
several gram scale using flash silica chromatography. Since
several grams of the endo diastereomer (3i endo) could be
obtained easily, we decided to investigate some additional
organic transformations of this compound. Treatment of 3i
endo with basic KMnO4 yielded the expected diol (7) (64%)
and treatment with MCPBA yielded the epoxide (8)(79%).
These reactions appear to go with complete diastereoselec-
tivity and addition of the oxygens to the exo face of 3i endo
was expected by analogy to other electrophilic additions to
norbornenes which had been reported previously.6
H2,3 protons in the endo diastereomer (5). The endo cycload-
duct of cyclopentadiene with maleic anhydride (6) is similar
to the dimethyl maleate endo cycloadduct, that is, H7s and
H7a close in chemical shift and H2,3 above 3 ppm. Since the
H7s/H7a protons in these molecules are typically easily
discernible, the ratios of H7s/H7a integrals for the endo and
exo isomers were used to calculate diastereomer ratios.
2,5 -Dihydrofuran (2i) cyclized with cyclopentadiene in
high chemical yield, 87%, (Table 1, entry 9) as a 2.39:1
mixture of diastereomers. The major diastereomer was
1
determined to be the endo diastereomer (3i endo) by H
NMR analysis as described above. Endo/exo ratios for the
other cycloadducts listed in Table 1 were determined
analogously. Dienophiles containing stereogenic centers were
used as racemic mixtures. In general, epoxybutene derived
dienophiles where the oxygen dienophile substituents (Table
1, entries 1-3, 9), were part of a ring provided Diels-Alder
cycloadducts in the highest chemical yields.
Conclusions
Diels-Alder cycloadducts from reactions of cyclopenta-
diene with epoxybutene derivatives have been prepared in
batch sizes of 1-100 g. One of the diastereomerically pure
cycloadducts, endo-4-oxa-tricyclo[5.2.1.0]-dec-8-ene (3i endo),
was subsequently oxidized to a diol and an epoxide.
Epoxybutene (2a) is too reactive to be used as a possible
substrate for Lewis acid-catalyzed Diels-Alder reactions.
We made a number of attempts to improve endo/exo ratios
by Lewis acid catalysis of the cyclopentadiene/VEC (2c)
Diels-Alder reaction. A variety of aluminum, boron, and
titanium containing Lewis acids were tried in CH2Cl2 and
toluene over temperature ranges from -78 to 40 °C. In no
case did we observe more than trace amounts of Diels-Alder
cycloadducts (3).
As expected, these epoxybutene derivatives were less
reactive with cyclohexadiene. The reaction of 2a with
cyclohexadiene required a temperature of 210 °C for 72 h
to generate small amounts of product. Cyclohexadiene also
reacted with VEC to provide a 1:1 mixture of endo/exo
Experimental Section
General Methods. Nuclear magnetic resonance (NMR)
spectra were obtained on a Bruker AVANCE 300 or 500
MHz FT NMR. All absorptions are expressed in parts per
million using residual protonated solvent as the reference.
Infrared (IR) spectra were obtained using a Perkin-Elmer
1620 FTIR. Elemental analyses were performed by Atlantic
Microlab Inc. of Norcross, Georgia. Melting points were
obtained on a Mel Temp apparatus and are reported uncor-
(6) (a) Ogino, T.; Mochizuki, K. Chem. Lett. 1979, 443. (b) Uozumi, Y.; Lee,
S. Y.; Hayashi, T. Tetrahedron Lett. 1992, 33, 7185. (c) Culberson, C. F.;
Seward, J. H.; Wilder, P., Jr. J. Am. Chem. Soc. 1960, 82, 2541.
Vol. 5, No. 5, 2001 / Organic Process Research & Development
•
515

rected. Alumina (80-200) mesh was purchased from Fisher
Scientific and deactivated with a 90:10 by volume acetone-
water mixture. Flash silica gel was purchased from Universal
Scientific Inc. All dienophiles were used as received from
Eastman Chemical Company.
above. The excess 2,2-dimethyl-4-ethenyl-1,3-dioxolane
(7.97 g) was removed using vacuum distillation (30 °C, 11
mmHg). The product was further purified by bulb-to-bulb
distillation yielding a clear liquid (1.39 g, 7.16 mmol, 58%)
1
at 120 °C (7 mmHg). H NMR (300 MHz, CDCl3) major
2-Bicyclo[2.2.1]hept-5-en-2-yl oxirane (3a). A thick-
walled, high-pressure tube was charged with freshly cracked
cyclopentadiene (0.821 g, 12.42 mmol) and epoxybutene
(8.21 g, 117.40 mmol). The contents were degassed by
bubbling nitrogen through the solution for 5 min. The tube
was equipped with a magnetic stirring bar and fitted with a
Teflon screw cap. The reaction tube was placed into an oil
bath (170 °C) for 66 h and then cooled to room temperature.
The yellow solution was transferred to a 10 mL conical
reaction vial, and epoxybutene (4.66 g, 66.49 mmol) was
distilled from the solution at 63 °C. The conical reaction
vial was then connected to a micro spinning band distillation
apparatus. The distillation yielded a clear product (1.11 g,
8.15 mmol, 65%) at 75 °C (11 mmHg). The product
contained 97% of the expected cycloadduct and 3% of
dicyclopentadiene impurity. A second spinning band distil-
lation at 75 °C (11 mmHg) can be performed to yield
analytically pure material if desired. Diagnostic NMR
diastereomer: 0.27 (ddd, J ) 11.49, 4.50, 4.40 Hz, 1H), 1.19
(m, 1H), 1.41 (s, 3H), 1.54 (s, 3H), 1.95 (m, 1H), 2.10 (m,
1H), 2.40 (s, 1H), 3.51 (m, 1H), 3.91 (m, 1H), 6.07 (m, 1H),
6.11 (m, 1H). 13C NMR (125 MHz, CDCl3) 26.25 (C4′),
27.41 (C5′), 31.30 (C3), 42.63 (C2), 43.86 (C4), 49.35 (C7),
45.85 (C1), 69.28 (C2′), 79.97 (C1′), 133.48 (C5), 137.36
(C6). Anal. Calcd. For C12H18O2 C, 74.19; H, 9.34. Found:
C, 74.36; H, 9.30. HRMS for C12H18O2 m/z Calcd: 194.1307.
Found: 194.1307.
4-Bicyclo[2.2.1]hept-5′-en-2′-yl-1,3-dioxolan-2-one (3c).
A thick-walled, high-pressure tube was charged with freshly
cracked cyclopentadiene (0.411 g, 6.21 mmol) and 4-ethenyl-
1,3 dioxolan-2-one (5.59 g, 48.99 mmol). The contents were
degassed then heated at 138 °C for 48 h. The tube was then
cooled to -78 °C to relieve any pressure from the possible
formation of CO2. The yellow solution was transferred to a
round-bottom flask and cooled to -78 °C, and excess
4-ethenyl-1,3 dioxolan-2-one (3.78 g, 33.13 mmol) was
removed by trituration with petroleum ether. The remaining
product was a white solid (1.12 g, 5.55 mmol, 84%); mp )
32 °C; diagnostic NMR resonances from the major product
diastereomer: 1H NMR (300 MHz, CDCl3) 0.53 (ddd, J )
11.69, 4.50, 4.40 Hz, 1H), 1.08 (t, J ) 3.6 Hz, 1H), 1.45
(m, 1H), 1.77 (dt, J ) 5.6, 3.8 Hz, 1H), 2.31 (m, 1H), 2.82
(bs, 1H), 2.85 (bs, 1H), 5.97 (m, 1H) 6.16 (m, 1H). 13C NMR
(125 MHz, CDCl3) 31.30 (C3), 43.81 (C2), 43.86 (C4), 50.17
(C7), 45.85 (C1), 69.30 (C2′), 80.50 (C1′), 132.92 (C5),
138.77 (C6). IR (NaCl) 3060.20, 2966.21, 2872.24, 1801.51,
1478.96, 1366.77, 1337.37, 1260.91, 1166.93, 1067.06 cm-1.
Anal. Calcd for C10H12O3 C, 66.65; H, 6.71; Found: C,
66.65; H, 6.76.
Scale-Up Preparation of 3c. A 300 mL three-necked
flask was equipped with thermometer, reflux condenser,
magnetic stirrer, and argon atmosphere and was charged with
vinyl ethylene carbonate (57 g, 0.50 mol), dicyclopentadiene
(37 g, 0.28 mol, 12% excess), and tert-butylhydroquinone
(0.10 g). The mixture was stirred under reflux for 2 h, during
which time the pot temperature climbed from 160 to 220
°C. The heating was removed, and the cooled batch was
sampled. Gas chromatographic analysis (DB-5 capillary
column, 75 to 275 °C @ 15 °C/min) indicated that the
reaction was about 65% complete. After standing under argon
overnight at 25 °C, the mixture was reheated to 200-220
°C for 3 h, after which time GC analysis indicated more
than 95% consumption of the vinylethylene carbonate. The
flask was fitted with a short-path distillation head, and the
material was distilled at 0.3 mmHg. A forerun of 16 g, bp
to 125 °C, was discarded. Product was then obtained (67.7
g, 0.38 mol, 75% based on vinylethylene carbonate) bp 128-
148 °C/0.3 mmHg. GC analysis disclosed the presence of at
least three isomers. The product solidified upon standing in
the refrigerator, but all attempts to separate the isomers by
crystallization or column chromatography failed to provide
1
resonances from the major product diastereomer: H NMR
(300 MHz, CDCl3, δ) 0.70 (ddd, J ) 11.63, 4.41, 4.43 Hz,
1H), 1.18 (m, 1H), 1.35 (m, 1H), 1.77 (dt, J ) 11.28, 3.80
Hz, 1H), 2.62 (m, 1H), 2.80 (bs, 2H), 5.95 (dd, J ) 2.9, 2.7
Hz, 1H) 6.13 (dd, J ) 3.1, 2.4 Hz, 1H). 13C NMR (125 MHz,
CDCl3, δ) 28.88 (C3), 30.22 (C2), 45.27 (C4), 47.53 (C1),
50.10 (C7), 55.10 (C1′), 56.07 (C2′), 132.60 (C5), 137.28
(C6). IR (NaCl) 2964.07, 2871.50, 2448.21, 1730.81, 1455.03,
1234.22, 1196.62, 1079.94, 1049.09, 1023.05 cm-1. Anal.
Calcd for C9H12O C, 79.37; H, 8.88. Found: C, 79.50; H,
8.84.
Scale-Up Preparation of 3a. A 750-ml steel autoclave
equipped with a glass liner was charged with epoxybutene
(175 g, 200 mL, 2.50 mol) and dicyclopentadiene (DCPD)
(79 g, 80 mL, 0.60 mol). The autoclave was sealed, purged
with nitrogen, and agitated at 185 °C for 48 h. After cooling
the contents were discharged as a yellow-orange liquid which
was analyzed by gas chromatography and immediately
distilled through a 10-in. Vigreaux column. GC analysis
(DB-5 capillary column, 30-200 °C @ 10 °C/min) disclosed
the presence of residual epoxybutene, a trace of dicyclopen-
tadiene, two diastereomeric product peaks, and four minor
high-boiling byproducts. Distillation to a head temperature
of 67-70 deg/760 mmHg provided unreacted epoxybutene
(85 g, 49%). The pressure was then gradually lowered and
a product cut (colorless liquid, 117.0 g, 0.86 mol) was taken
at 73-75 °C/10-12 mmHg (72% yield based on DCPD
charged, 68% based on epoxybutene consumed). This
material was identical by spectroscopic comparison to the
material (3a) reported above.
4-Bicyclo[2.2.1]hept-5′-2′-yl-2,2-dimethyl-1,3-dioxo-
lane (3b). A thick-walled, high-pressure tube was charged
with freshly cracked cyclopentadiene (0.821 g, 12.42 mmol)
and 2,2-dimethyl-4-ethenyl-1,3-dioxolane (10 g, 78 mmol).
The contents were degassed, heated, and cooled as described
516
•
Vol. 5, No. 5, 2001 / Organic Process Research & Development

useful resolution. This material was identical by spectro-
scopic comparison to 3c reported above.
(C2), 43.32 (C4), 45.38 (C1), 49.44 (C7), 66.31 (C2′), 76.89
(C1′), 132.75 (C5), 137.49 (C6). IR (NaCl) 3443.29, 3411.47,
3030.60, 2967.92, 2942.85, 2870.54, 2395.17, 933.38 cm-1.
Anal. Calcd for C9H14O2 C, 70.10; H, 9.15. Found: C, 69.05;
H, 9.17.
2-Bicyclo[2.2.1]hept-5′-en-2′-yl-2-benzyloxyethanol (3d).
A thick-walled, high-pressure tube was charged with freshly
cracked cyclopentadiene (0.841 g, 12.72 mmol) and 2-benz-
yloxy-3-buten-1-ol (9.06 g, 50.92 mmol). The contents were
degassed, heated, and cooled as described above. The
solution was transferred to a round-bottom flask, and the
excess butenol (3.48 g) was removed using vacuum distil-
lation (105 °C, 5 mmHg) followed by the product (1.924 g,
7.88 mmol, 62%) at 189 °C (1 mmHg). Diagnostic NMR
2-Bicyclo[2.2.1]hept-5-en-2-yl ethanol (3g). A thick-
walled, high-pressure tube was charged with freshly cracked
cyclopentadiene (0.821 g, 12.42 mmol) and 3-butenol (8.84
g, 122.65 mmol). The contents were degassed, heated, and
cooled as described above. The solution was transferred to
a 10 mL conical reaction vial, and excess 3-butenol (8.06 g,
111.83 mmol) was distilled at 113 °C. Subsequent spinning
band distillation yielded a clear product (0.421 g, 3.05 mmol,
28%) at 62 °C (7 mmHg). Diagnostic NMR resonances for
the major diastereomer: 1H NMR (300 MHz, CDCl3) 0.52
(dt, J ) 11.22, 4.10, 4.00 Hz, 1H), 1.21 (d, J ) 8.05 Hz,
1H), 1.32 (m, 2H), 1.37 (m, 1H), 1.86 (dt, J ) 12.20, 2.72
Hz, 1H), 2.07 (m, 1H), 2.26 (s, 1H), 2.76 (br, 2H), 3.59 (t,
J ) 6.95 Hz, 2H), 6.10 (m, 1H), 6.13 (m, 1H).13C NMR
(125 MHz, CDCl3) 32.34 (C3), 35.34 (C2), 42.84 (C1′),
45.89 (C4), 49.72 (C1), 49.93 (C7), 62.42 (C2′), 132.64 (C5),
137.52 (C6). IR (NaCl) 3507.14, 3011.32, 2964.07, 2940.93,
2869.57, 1047.16, 1006.66, 936.27 cm-1. HRMS (m/z) Calcd
for C9H14O 138.1045; found 138.1049.
1
resonances for the major diastereomer: H NMR (300 MHz,
CDCl3) 0.53 (ddd, J ) 11.53, 4.70, 4.60 Hz, 1H), 1.29 (d,
J ) 7.4 Hz, 1H), 1.44 (d, J ) 2.0 Hz, 1H), 2.00 (m, 1H),
2.31 (m, 1H), 2.84 (bs, 2H), 5.81 (m, 1H) 6.15 (m, 1H). 13
C
NMR (125 MHz, CDCl3) 29.30 (C3), 42.63 (C2), 44.48 (C4),
44.60 (C1), 49.54 (C7), 62.97 (C2′), 83.89 (C1′), 133.08
(C5), 138.01 (C6). IR (NaCl) 3038.71, 2954.52, 2872.21,
2343.23, 1260.95, 1102.22, 1037.60 cm-1. HRMS for
C16H20O2 m/z Calcd 244.1463. Found 244.1467.
Acetic Acid 2-Acetoxy-1-bicyclo[2.2.1]hept-5-en-2-yl
Ethyl Ester (3e). A thick-walled, high-pressure tube was
charged with freshly cracked cyclopentadiene (0.821 g 12.42
mmol) and 3,4-diacetoxybutene (21.90 g, 127.21 mmol). The
contents were degassed, heated, and cooled as described
above. The yellow solution was transferred to a round-bottom
flask, and excess 3,4-diacetoxybutene (11.83 g, 68.17 mmol)
was distilled from the solution at 60 °C (9 mmHg). Further
purification via bulb-to-bulb distillation yielded a clear
product (0.832 g, 3.49 mmol, 28%) at 180 °C (2 mmHg).
Acetic Acid 2-bicyclo[2.2.1]hept-5-en-2-yl-2-methoxy
Ethyl Ester (3h). A thick-walled, high-pressure tube was
charged with freshly cracked cyclopentadiene (0.821 g, 12.42
mmol) and 1-acetoxy-2-methoxy-3-butene (7.08 g, 48.61
mmol). The contents were degassed, heated, and cooled as
described above. The solution was transferred to a 25 mL
round-bottom flask, and the excess 1-acetoxy-2-methoxy-
3-butene (3.80 g) was removed using vacuum distillation (68
°C, 5 mmHg) followed by the clear product (1.049 g, 5.41
mmol, 40%) at 129 °C (5 mmHg). Diagnostic NMR
1
Diagnostic NMR resonances for the major diastereomer: H
NMR (300 MHz, CDCl3) 0.61 (ddd, J ) 11.66, 4.50, 4.20
Hz, 1H), 1.22 (t, J ) 4.8 Hz, 1H), 1.41(dd, J ) 8.5, 1.8 Hz,
1H), 1.79 (m, 1H), 2.00 (s, 3H), 2.06 (s, 3H), 2.80 (bs, 2H),
3.93 (m, 1H) 4.23 (d, J ) 6.7 Hz, 1H), 4.33 (d, J ) 9.9 Hz,
1H), 4.49 (m, 1H), 5.84 (bs, 1H), 6.15 (bs, 1H). 13C NMR
(125 MHz, CDCl3) 29.41 (C3), 40.21 (C2), 45.55 (C4), 49.17
(C7), 50.17 (C1), 75.59 (C2′), 76.37 (C1′), 132.73 (C5),
138.26 (C6), 170.46 (C3′) 171.13 (C4′). IR (NaCl) 3017.10,
2968.89, 2394.24, 2286.21, 1737.55, 1588.10, 1318.11,
1236.15, 1152.26, 1047.16, 952.66 cm-1. Anal. Calcd for
C14H18O2: C, 65.53; H, 7.61. Found: C, 64.98; H, 7.54.
HRMS (m/z) Calcd for C14H18O2: 238.1205, found: 238.1201.
1-Bicyclo[2.2.1]hept-5′-en-2′yl-1,2-ethanediol (3f). A
thick-walled, high-pressure tube was charged with freshly
cracked cyclopentadiene (0.841 g, 12.72 mmol) and 3-buten-
1,2-diol (5.24 g, 59.42 mmol). The contents were degassed,
heated, and cooled as described above. The solution was
transferred to a 25 mL round-bottom flask, and the excess
diol (2.89 g) was removed using vacuum distillation (104
°C, 12 mmHg). The remaining product was purified by bulb-
to-bulb distillation yielding a clear product (0.205 g, 1.33
mmol, 10%) at 160 °C (1 mmHg). Diagnostic NMR
1
resonances for the major diastereomer: H NMR (300 MHz,
CDCl3) 0.54 (ddd, J ) 11.56, 4.52, 4.40 Hz, 1H), 1.16 (m,
1H), 1.36 (m, 1H), 1.71 (dt, J ) 11.70, 3.84 Hz, 1H), 2.01
(s, 3H), 2.14 (m, 1H), 3.33 (s, 3H), 4.27 (dd, J ) 11.23,
3.00 Hz, 1H), 5.90 (m, 1H), 6.15 (m, 1H). 13C NMR (125
MHz, CDCl3) 29.41 (C3), 40.21 (C2), 45.55 (C4), 49.17
(C7), 50.17 (C1), 75.59 (C2′), 76.37 (C1′), 132.73 (C5),
138.26 (C6), 170.46 (OAc), 171.132 (OAc). IR (NaCl)
3009.39, 2966, 2870.54, 2830.04, 1733.70, 1453.10, 1271.83,
1042.34, 968.09 cm-1. Anal. Calcd for C12H18O2 C, 68.55;
H, 8.63. Found: C, 68.60; H, 8.63.
4-Oxa-tricyclo[5.2.1.0]dec-8-ene (3i). A thick-walled,
high-pressure tube was charged with freshly cracked cyclo-
pentadiene (0.821 g 12.42 mmol) and 2,5-dihydrofuran (8.70
g, 124.13 mmol). The contents were degassed, heated, and
cooled as described above. The yellow solution was trans-
ferred to a 10 mL conical reaction vial and 2,5-dihydrofuran
(7.07 g, 100.87 mmol) was distilled from the solution at 64
°C. The conical reaction vial was then connected to a micro
spinning band distillation apparatus to produce a clear
product7 (1.10 g, 8.08 mmol, 65%) at 70 °C (25 mmHg);
mp ) 26 °C. Diagnostic NMR resonances for the major
1
resonances for the major diastereomer: H NMR (300 MHz,
CDCl3) 0.49 (ddd, J ) 11.50, 4.44, 4.40 Hz, 1H), 0.96 (dt,
J ) 4.8, 2.7 Hz, 1H), 1.70 (dd, 1H, J ) 5.4, 3.8 Hz, 1H),
2.04 (m, 2H), 2.79 (bs, 1H), 2.81 (bs, 1H), 6.01 (m, 1H),
6.14 (m, 1H). 13C NMR (125 MHz, CDCl3) 29.75 (C3), 42.56
(7) For a report of the reaction between cyclopentadiene and 2,5-dihydrofuran,
see: Brace, N. O. J. Am. Chem. Soc. 1955, 77, 4157.
Vol. 5, No. 5, 2001 / Organic Process Research & Development
•
517

1
diastereomer: H NMR (300 MHz, CDCl3) 1.41 (d, J ) 8.2
evaporation and high vacuum to yield a viscous liquid (0.739
g, 4.35 mmol, 64%). H NMR (300 MHz, CDCl3) 1.30 (d,
1
Hz, 1H), 1.49 (d, J ) 8.2 Hz, 1H), 2.83 (s, 1H), 2.86 (t, J )
3.35 Hz, 2H), 3.40 (d, J ) 2.2 Hz, 1H), 3.43 (s, 1H), 3.54
(m, 2H,). 13C NMR (125 MHz, CDCl3) 46.19 (C1, C4),
48.33(C7), 53.01(C2, C3), 70.39 (C1′), 135.44 (C5, C6). IR
(NaCl) 3017.10, 2968.89, 2802.08, 1350.89, 1207.22, 1091.51,
998.95 cm-1. Anal. Calcd for C9H12O C, 79.37; H, 8.88.
Found C, 79.37; H, 8.89.
J ) 8.4 Hz, 1H), 1.70 (bs, 2H), 1.93 (d, J ) 10.1 Hz, 1H),
2.18 (m, 2H), 2.54 (m, 2H), 3.29 (m, 2H), 3.93 (d, J ) 9.9
Hz, 2H), 4.05 (d, J ) 9.8 Hz, 2H). 13C NMR (125 MHz,
CDCl3) 30.70(C7), 43.57 (C5, C6) 47.79 (C1,C4), 68.69-
(C1′), 70.58 (C2, C3). Anal. Calcd for C9H14O3: C, 63.51;
H, 8.29. Found C, 63.57; H, 8.02.
Organic Transformations of Diasteromerically Pure
endo-4-Oxatricyclo[5.2.1.0]dec-8-ene. Isolation of the Endo
Diastereomer (3i endo). A thick-walled, high-pressure tube
was charged with freshly cracked cyclopentadiene (4.11 g,
62.10 mmol) and 2,5 dihydrofuran (23.5 g, 335.24 mmol).
The contents were degassed, heated, and cooled as described
above. Excess 2,5-dihydrofuran (15.77 g) was removed by
distillation at 80 °C (20 mmHg). Column chromatography
of the remaining material (19:1 petroleum ether/diethyl ether)
yielded 1.70 g of a mixture (1.5:1) of endo/exo cycloadduct,
followed by 3.95 g (40.1%) of endo-4-oxa-tricyclo[5.2.1]-
dec-8-ene (3i endo) identical by spectroscopic comparison
to the material reported above.
4-Oxa-tricyclo[5.2.1.0]decane-8,9-diol (7). A flask was
charged with triethylbenzylammonium chloride (2.34 g,
10.23 mmol), KMnO4 (1.62 g, 10.23 mmol), and CH2Cl2
(20 mL). The flask was cooled to 0 °C. A solution of endo-
4-oxa-tricyclo[5.2.1]dec-8-ene (3i endo) (0.93 g, 6.81 mmol)
in methylene chloride (10 mL) was added to the stirring
solution dropwise over a time period of 50 min while
maintaining the temperature. The solution was stirred until
most of the KMnO4 had reacted (2 h), then treated with 20
mL of 3% NaOH, and stirred for 18 h at 25 °C. The solution
was filtered through Celite to remove the potassium salts,
and the organic layer and the aqueous layer were separated.
The aqueous layer was extracted several times using ether;
the extracts were dried and concentrated using rotary
4-Oxa-tricyclo[5.2.1.0]-8,9-epoxydecane (8). A round-
bottom flask was charged with endo-4-oxa-tricyclo[5.2.1]-
dec-8-ene (3i endo) (0.100 g, 0.735 mmol), NaHCO3 (0.200
g, 2.38 mmol), and dry CH2Cl2 (10 mL). The flask was
placed in an ice bath, and the solution was stirred while
MCPBA (0.256 g, 1.483 mmol) dissolved in dry CH2Cl2 (15
mL) was added dropwise over a period of 20 min. After
stirring (5 h) a white precipitate had formed. The solution
was treated with aqueous Na2CO3 (10 mL) and stirred for
30 min. The aqueous layer was extracted using diethyl ether
and dried using MgSO4. The organic layer was concentrated
using rotary evaporation and further dried under high vacuum
to yield a white solid (0.088 g, 0.58 mmol, 79%); mp )
1
64-65 °C. H NMR (300 MHz, CDCl3) 0.83 (d, J ) 9.7
Hz, 1H), 1.45 (d, J ) 9.7 Hz, 1H), 2.55 (m, 2H), 2.68 (m,
2H), 3.25 (s, 2H), 3.43 (dd, J ) 12.5, 7.5 Hz, 2H), 3.75 (d,
J ) 12.5 Hz, 2H) 13C NMR (125 MHz, CDCl3) 29.91(C7),
40.17 (C5, C6) 46.55 (C1, C4), 49.89 (C2, C3), 68.49 (C1′).
Anal. Calcd for C9H12O2: C, 71.03; H, 7.95. Found: C,
70.48; H, 8.00.
Acknowledgment
We thank Eastman Chemical Company for support of this
research.
Received for review June 8, 2001.
OP010219D
518
•
Vol. 5, No. 5, 2001 / Organic Process Research & Development