Synthesis of stable derivatives of cycloprop-2-ene carboxylic acid

Article abstract of DOI:10.1021/jo800042w

(Chemical Equation Presented) Large-scale syntheses of 3-(cycloprop-2-en-1- oyl)oxazolidinones from acetylene and ethyl diazoacetate are described. Unlike other cyclopropenes that bear a single substitutent at C-3, these compounds are stable to long-term storage. Although the cyclopropene derivatives are unusually stable, they are reactive toward cyclic and acyclic dienes in stereoselective Diels-Alder reactions.

Full text of DOI:10.1021/jo800042w

SCHEME 1. Synthesis of
3-(Cycloprop-2-en-1-oyl)oxazolidinones
Synthesis of Stable Derivatives of
Cycloprop-2-ene Carboxylic Acid
Ni Yan, Xiaozhong Liu, Mahesh K. Pallerla, and
Joseph M. Fox*
Brown Laboratories, Department of Chemistry and
Biochemistry, UniVersity of Delaware,
Newark, Delaware 19716
jmfox@udel.edu
ReceiVed January 8, 2008
Large-scale syntheses of 3-(cycloprop-2-en-1-oyl)oxazoli-
dinones from acetylene and ethyl diazoacetate are described.
Unlike other cyclopropenes that bear a single substitutent at
C-3, these compounds are stable to long-term storage.
Although the cyclopropene derivatives are unusually stable,
they are reactive toward cyclic and acyclic dienes in
stereoselective Diels-Alder reactions.
propenes with a single substituent at their sp3 centers has been
limited by their instability. Thus, 3-methylcyclopropene is
extremely unstable, whereas 3,3-dimethylcyclopropene is quite
stable at room temperature.4 Although cycloprop-2-ene car-
boxylates (1) are more stable than 3-alkylcyclopropenes, their
long-term storage is also not practical.3a Herein, we describe
scalable syntheses of 3-(cycloprop-2-en-1-oyl)oxazolidinone
derivatives 2-4: crystalline derivatives of cycloprop-2-ene
carboxylic acid that are stable over long periods (Figure 1).
Although derivatives 2-4 are unusually stable, they are reactive
dienophiles that undergo Diels-Alder reactions with high
stereoselectivity.
The Rh-catalyzed reaction of R-diazo esters with alkynes is
an exceptionally useful and operationally simple method for the
preparation of cycloprop-2-ene carboxylates1ssubstances that
are useful building blocks for a number of strain-assisted
transformations.2 In theory, the Rh-catalyzed reaction of acety-
lene with ethyl diazoacetate should provide a particularly
inexpensive route to ethyl cycloprop-2-ene carboxylate (1a).3
Compound 1a and derivatives might serve as useful tools for
diastereoselective synthesis. However, the usefulness of cyclo-
Several preparations of cycloprop-2-ene carboxylates have
been described in the literature.3 In an important study, Baldwin
and Villerica compared several routes to cycloprop-2-ene-1-
carboxylates and described a scalable, Rh-catalyzed procedure
for the preparation of methyl cycloprop-2-ene carboxylate (1b).3a
Despite the considerable merits of the procedure, there were
two limitations that detracted from the preparative utility: the
need to prepare methyl diazoacetate (which has been reported
to “detonate with extreme violence”5) and the modest thermal
stability of cyclopropenes of structure 1. Methyl cycloprop-2-
ene-1-carboxylate (1b) is stable in the refrigerator for several
days.3a However, our own experience with 1a suggests that
storage over longer periods is not practical. Furthermore, because
(1) (a) Baird, M. S. In Carbocyclic Three-Membered Ring Compounds, 4th
ed.; de Meijere, A., Ed.; Georg Thieme Verlag: Stuttgart, 1996; Vol. E17d, pp
2695-2744. (b) Petiniot, N.; Anciaux, A. J.; Noels, A. F.; Hubert, A. J.; Teyssie´,
P. Tetrahedron Lett. 1978, 19, 1239. (c) Liao, L.-a.; Zhang, F.; Yan, N.; Golen,
J. A.; Fox, J. M. Tetrahedron 2004, 60, 1803. and references therein.
(2) Selected reviews to the reaction chemistry of cyclopropenes: (a) Rubin,
M.; Rubina, M.; Gevorgyan, V. Chem. ReV. 2007, 107, 3117. (b) Rubin, M.;
Rubina, M.; Gevorgyan, V. Synthesis 2006, 1221. (c) Halton, B.; Banwell, M. G.
In The Chemistry of the Cyclopropyl Group; Patai, S., Rappoport, Z., Eds.; Wiley:
Chichester, 1987; pp 1224-1339. (d) Baird, M. S. Top. Curr. Chem. 1988, 144,
137. (e) Nakamura, M.; Isobe, H.; Nakamura, E. Chem. ReV. 2003, 103, 1295.
(f) Fox, J. M.; Yan, N. Curr. Org. Chem. 2004, 9, 719. (g) Marek, I.; Simaan,
S.; Masarwa, A. Angew. Chem., Int. Ed. 2007, 46, 7364. (h) Chuprakov, S.;
Malyshev, D. A.; Trofimov, A.; Gevorgyan, V. J. Am. Chem. Soc. 2007, 129,
14868. and references therein.
(3) For preparations of alkyl cycloprop-2-ene carboxylates: (a) Baldwin, J. E.;
Villarica, K. A. J. Org. Chem. 1995, 60, 186. (b) Shapiro, E. A.; Kalinin, A. V.;
Nefedov, O. M. Org. Prep. Proc. Int. 1992, 24, 517. (c) Doering, W. V. E.;
Laber, G.; Vonderwahl, R.; Chamberlain, N. F.; Williams, R. B. J. Am. Chem.
Soc. 1956, 78, 5448. (d) Myhre, P. C.; Maxey, C. T.; Bebout, D. C.; Swedberg,
S. H.; Petersen, B. L. J. Org. Chem. 1990, 55, 3417. (e) Sachs, R. K.; Kass,
S. R. J. Am. Chem. Soc. 1994, 116, 783. (f) Kimura, K.; Horie, S.; Minato, I.;
Odaira, Y. Chem. Lett. 1973, 1209.
(4) Closs, G. L.; Closs, L. E.; Bo¨ll, W. A. J. Am. Chem. Soc. 1963, 85,
3796.
(5) Searle, N. E. In Organic Syntheses; Wiley & Sons; New York, 1963;
Collect. Vol. IV, pp 424-426.
10.1021/jo800042w CCC: $40.75
Published on Web 05/02/2008
2008 American Chemical Society
J. Org. Chem. 2008, 73, 4283–4286 4283

SCHEME 2. Stereoselective Diels-Alder Reactions of 3
FIGURE 1. Derivatives of cycloprop-2-ene carboxylic acid.
of its volatility, it is difficult to completely isolate 1a free from
solvent (CH2Cl2).
In earlier studies from our group on the resolution and kinetic
resolution of cyclopropenes,1c,6 we noted that the N-acyloxazo-
lidinones of cycloprop-2-ene carboxylic acids were stable solids
with long shelf-lives. We anticipated that cyclopropenes 2-4
would also be stable, and accordingly we set out to develop
the synthesis and reaction chemistry of these derivatives.
Cyclopropenes 2-4 can be prepared from acetylene and ethyl
diazoacetate as shown in Scheme 1. The preparation of ethyl
cycloprop-2-ene carboxylate (1a) mirrored Baldwin’s synthesis
of 1b,3a with the exception that 1a was not purified. Instead,
the solution of crude 1a was filtered through a bed of silica gel
and directly combined with KOH/MeOH to give acid 5 in 47%
yield (based on ethyl diazoacetate). Carboxylic acid 5 is a
hydroscopic white solid7 that can be isolated in pure form. The
stability of 5 is comparable to that of 1b: it is stable over short
periods but decomposes within 1 week when stored at freezer
temperatures (-20 °C). In one instance, 5 decomposed exo-
thermically and with the evolution of gas (presumably CO2).
Accordingly, it is recommended that 5 be handled in solution
and not as a neat material.
The well-defined faces of 3-substituted cyclopropenes make
them excellent candidates for diastereoselective synthesis. To
illustrate the synthetic utility of 3-(cycloprop-2-en-1-oyl)ox-
azolidinones, the Diels-Alder10 reactions in Scheme 2 were
carried out. Thus, 3 reacts with cyclopentadiene and 1,3-
cyclohexadiene to give 6 and 7 in 95% and 93% yields,
respectively. Similarly, compound 3 reacts with (E)-1,3-octa-
diene to give 8 in 64% yield. The cyclopropene controls the
endo selectivity11 of the cycloadditions to provide the Diels-Alder
adducts as single diastereomers. The stereochemical assignments
for the structures of 6-8 were based on X-ray analysis of 6
and 7, NOE analysis of 8, and correlation with literature
precedents.10 Methanolysis of 7 under Sm(OTf)3-catalyzed
conditions12 proceeded uneventfully to give 9 in 99% yield.
In summary, scalable syntheses of 3-(cycloprop-2-en-1-
oyl)oxazolidinones (2-4) from acetylene and ethyl diazoacetate
have been described. Unlike other cyclopropenes that bear only
a single substituent at C-3, these derivatives are stable to long-
term storage. Although these cyclopropenes are stable, they
participate smoothly in diastereoselective Diels-Alder reactions.
We anticipate that these readily accessible cyclopropene deriva-
tives will find broad utility in stereoselective synthesis.
The reaction of (S)-4-phenyloxazolidinone with the anhydride
from pivaloyl chloride and 5 gave acyloxazolidinone 2 in 90%
yield.8 Importantly, 7.9 g of 2 can be prepared from 10 mL of
ethyl diazoacetate. Compounds 3 and 4 can be prepared in
analogous fashion (Scheme 1). For the preparations of 3 and 4,
1-adamantoyl chloride was used in place of pivaloyl chloride
because the former is a crystalline solid that is more conve-
niently handled in small-scale preparations.9
The crystalline derivatives 2-4 can be handled at rt without
special precaution and are stable over much longer periods than
1 or 5. The stability was quantified for 2: a sample was measured
to be >92% pure (1H NMR) after storage in a freezer (-20
°C) for 2 years. In solution, compound 2 decomposes only
slowly when heated. Thus, a sample of 2 in DMSO-d6 was
1
heated to 80 °C and monitored by H NMR spectroscopy, and
Experimental Section
after 1, 3, and 12 h, the compound was measured to be 89%,
83%, and 50% pure, respectively. In the DSC of 2 there is a
large broad endothermic transition (210 J/g) at 118-119 °C
that corresponds to the melting point. There is also a small,
sharp exothermic transition (48 J/g) at 269 °C that may
correspond to decomposition. Because the heat flow associated
with the exotherm is small, these data suggest that 2 would not
require any unusual safety precautions. Although the stabilities
of 3 and 4 were not quantified, these derivatives are also stable
for months when stored in the freezer.
Cycloprop-2-ene carboxylic Acid (5). A flame-dried 1 L round
bottomed flask containing Rh2(OAc)4 (120 mg, 0.271 mmol) in 800
(10) For reviews on Diels-Alder reactions of cyclopropenes, see ref 2b–d.
For Diels-Alder reactions of cycloprop-2-ene carboxylates, see ref 3b and: (a)
Paulini, K.; Reissig, H. U. J. Prakt. Chem. Chem. Z. 1995, 337, 55. (b) Tomilov,
Y. V.; Shapiro, E. A.; Protopopova, M. N.; Ioffe, A. I.; Dolgii, I. E.; Nefedov,
O. M. Bull. Acad. Sci. USSR., DiV. Chem. Sci. 1985, 34, 576. (c) Shapiro, E. A.;
Lun’kova, G. V.; Nefedov, A. O.; Dolgii, I. E.; Nefedov, O. M. Bull. Acad. Sci.
USSR., DiV. Chem. Sci. 1981, 30, 2097. (d) Lind, H.; Deutschman, A. J., Jr. J.
Org. Chem. 1967, 32, 326. (e) Lou, Y.; Horikawa, M.; Kloster, R. A.; Hawryluk,
N. A.; Corey, E. J. J. Am. Chem. Soc. 2004, 126, 8916. For other, recent examples
of Diels-Alder reactions of cyclopropenes, see: (f) Orugunty, R. S.; Wright,
D. L.; Battiste, M. A.; Helmich, R. J.; Abboud, K. J. Org. Chem. 2004, 69, 406.
(g) Al Dulayymi, J. R.; Baird, M. S.; Hussain, H. H.; Alhourani, B. J.;
Alhabashna, A. Y.; Coles, S. J.; Hursthouse, M. B. Tetrahedron Lett. 2000, 41,
4205.
(6) Liao, L.-a.; Zhang, F.; Dmitrenko, O.; Bach, R. D.; Fox, J. M. J. Am.
Chem. Soc. 2004, 126, 4490.
(7) For a prior synthesis of cycloprop-2-ene carboxylic acid, see: (a) Nefedov,
O. M.; Dolgij, I. E.; Okonnischnikova, G. P.; Schwedova, I. B. Angew. Chem.,
Int. Ed. Engl. 1972, 11, 929. For syntheses of 2-silyl derivatives of cycloprop-
2-ene carboxylic acid, see also: (b) Maier, G.; Hoppe, M.; Reisenauer, H. P.;
Kru¨ger, C. Angew. Chem., Int. Ed. Engl. 1982, 21, 437. (c) Kohn, D. W.; Chen,
P. J. Am. Chem. Soc. 1993, 115, 2844.
(11) For recent theoretical studies on the endo selectivity of cyclopropene
Diels-Alder reactions, see: (a) Xidos, J. D.; Gosse, T. L.; Burke, E. D.; Poirer,
R. A.; Burnell, D. J. J. Am. Chem. Soc. 2001, 123, 5482. (b) Imade, M.; Hirao,
H.; Omoto, K.; Fujimoto, H. J. Org. Chem. 1999, 64, 6697. (c) Sodupe, M.;
Rios, R.; Branchadell, V.; Nicholas, T.; Oliva, A.; Dannenberg, J. J. J. Am. Chem.
Soc. 1997, 119, 4232.
(8) Ho, G.-J.; Mathre, D. J. J. Org. Chem. 1995, 60, 2271. (b) Ager, D. J.;
Allen, D. R.; Schaad, D. R. Synthesis 1996, 1283.
(9) Compound 3 was also prepared in similar yield with the modification
that pivaloyl chloride was used in place of 1-adamantoyl chloride.
(12) Ortiz, A.; Quintero, L.; Herna´ndez, H.; Maldonado, S.; Mendoza, G.;
Berne´z, S. Tetrahedron Lett. 2003, 44, 1129.
4284 J. Org. Chem. Vol. 73, No. 11, 2008

mL of CH2Cl2 was cooled by a bath of ice-water. The flask was
swept with N2. The N2 was then turned off, and the solution was
sparged for 30 min with acetylene gas [acetone was removed from
the acetylene by first it passing through two cold traps (-60 to
-65 °C)]. Ethyl diazoacetate (Aldrich, contains 15% CH2Cl2, 10
mL, 9.2 g, 81 mmol) was added over the course of 5 h via syringe
pump at 0 °C. The color of the mixture was dark green while ethyl
diazoacetate was added. In some runs, the reaction color turned
yellow or light red during the last hour of the addition, but this did
not affect the yield significantly. After the addition of ethyl
diazoacetate was complete, the acetylene was turned off, and the
mixture was sparged with N2 for about 20 min followed by filtration
through a short silica gel plug to remove the Rh2(OAc)4. Without
removal of solvent, the light yellow filtrate was transferred to a 2
L round bottomed flask. The flask was cooled by an ice bath, and
methanol (800 mL) was added. After the mixture had cooled, 200
mL of aqueous KOH (1.8 M) was added dropwise, and the
homogeneous yellow mixture was allowed to stir overnight under
N2 atmosphere. The progress of the reaction was monitored
periodically by TLC analysis to ensure that the hydrolysis was
complete. The mixture was then concentrated on the rotary
evaporator (at rt) to remove the organic solvents. To the resulting
aqueous solution was added methyl tert-butyl ether (300 mL), and
the mixture was cooled by an ice bath. Aqueous HCl solution (3
M) was added dropwise until the aqueous phase was rendered acidic
(pH ∼3), and solid NaCl was added until the aqueous layer was
saturated. The aqueous layer was extracted twice with 300 mL
portions of methyl tert-butyl ether. The combined organics were
dried over MgSO4, filtered, and concentrated until the total volume
was ∼50 mL. The residue was subjected to rapid flash chroma-
tography on a short silica gel column (3 in. high × 3 in. diameter)
using MTBE as the eluent. Solvent removal gave 3.2 g (38 mmol,
47%) of compound 5 as a white solid, mp 40-41 °C (the previously
reported7a mp was much higher: 147-148 °C). In some cases, 5
was obtained as an oil that was spectroscopically pure.
was immediately partitioned between 300 mL of CH2Cl2 and 100
mL water. The aqueous layer was extracted twice with 100 mL
portions of CH2Cl2, and the combined organics were dried
(Na2SO4), filtered, and concentrated. The residue was chromato-
graphed on a column of silica gel (8 in. high × 1.5 in. diameter).
The initial eluent was 3:1 methylene chloride/hexane, followed by
elution with 10:10:1 CH2Cl2/hexane/ethyl acetate. The yield of 2
was 7.90 g (34.3 mmol, 90%). Compound 2 is a white solid: mp
1
118-119 °C; [R]D +140.0 (c 1.00, THF); H NMR (CDCl3, 400
MHz) δ 7.38-7.31 (m, 5H), 6.79 (dd, J ) 0.6, 1.3 Hz, 1H), 6.74
(dd, J ) 0.6, 1.4 Hz, 1H), 5.43 (dd, J ) 3.9, 8.7 Hz, 1H), 4.71
(app t, J ) 8.8 Hz, 1H), 4.30 (dd, J ) 3.9, 8.9 Hz, 1H), 3.52 (app
t, J ) 1.4 Hz, 1H); 13C NMR (CDCl3, 90 MHz) δ 175.9 (C), 154.2
(C), 139.1 (C), 129.1 (CH), 128.6 (CH), 126.1 (CH), 101.9 (CH),
101.7 (CH), 70.2 (CH2), 58.0 (CH), 17.1 (CH); IR (neat, cm-1):
1758, 1698, 1660, 1364, 1323, 1240, 1205, 1181, 1083, 1066, 1036,
985, 762, 734, 701, 644, 623; HRMS-CI (M + H) m/z calcd for
C13H12NO3 230.0844, found 230.0806.
3-(Cycloprop-2-en-1-oyl)-3H-benzooxazol-2-one (3). A flame-
dried 100 mL round bottomed flask containing 513 (84 mg, 1.0
mmol) and 20 mL of THF was chilled by a cold bath at -25 to
-30 °C (dry ice/30% ethanol in ethylene glycol). The mixture was
allowed to stir under nitrogen atmosphere. Distilled triethylamine
(0.36 g, 0.50 mL, 3.5 mmol) and 1-adamantoyl chloride9 (238 mg,
1.2 mmol) were added sequentially, and stirring at -25 to -30 °C
was continued for 1 h. LiCl (0.21 g, 5.0 mmol) was added. After
5 min, 2-benzoxazolinone (203 mg, 1.50 mmol), and 4-dimethy-
laminopyridine (13 mg, 0.10 mmol) were added. The reaction
mixture was allowed to stir overnight, during which time the dry
ice in the bath dissipated, and the mixture had gradually warmed
to rt. The solvents were removed at rt under reduced pressure, and
the residue was immediately partitioned between 20 mL of CH2Cl2
and 20 mL of water. The aqueous layer was extracted twice with
20 mL portions of CH2Cl2, and the combined organics were dried
(Na2SO4), filtered, and concentrated. The residue was chromato-
graphed on silica gel. The eluent was 1:3:6 CH2Cl2/ethyl acetate/
hexane. The yield of 3 was 161 mg (0.80 mmol, 80%). Compound
NOTE: In one case, pure 5 decomposed exothermically and with
the release of gas (presumably CO2). To avoid this decomposition,
it is recommended that 5 should not be evaporated to dryness after
the final chromatography. Rather, it is advised that solvent be
removed until the concentration of 5 in MTBE is an ∼30% solution
by weight (i.e., ∼9 g total weight). The yield of 5 can be estimated
1
3 is a white solid: mp 82-83 °C; H NMR (CDCl3, 400 MHz) δ
8.01-7.99 (m, 1H), 7.24-7.19 (m, 3H), 6.92 (d, J ) 0.6 Hz, 1H),
3.63 (t, J ) 1.4 Hz, 1H); 13C NMR (CDCl3, 100 MHz) δ 175.7
(C), 151.8 (C), 142.2 (C), 128.1 (C), 125.1 (CH), 124.7 (CH), 115.9
(CH), 109.7 (CH), 101.6 (CH), 17.9 (CH); IR (neat, cm-1) 1787,
1704, 1669, 1477, 1467, 1248, 1138, 754, 698, 605; HRMS-CI (M
+ H) m/z calcd for C11H8NO3 202.0504, found 202.0497.
1
by analyzing the H NMR spectrum of the MTBE solution. We
have handled solutions of 5 many times without event. MTBE
solutions of 5 can be used directly for the preparations of 2-4.
1
Spectral properties of pure 5: H NMR (CDCl3, 400 MHz) δ
Synthesis of 3-(Cycloprop-2-en-1-oyl)oxazolidinone (4). A
flame-dried 100 mL round-bottomed flask containing 513 (84 mg,
1.0 mmol) and 20 mL of THF was chilled by a cold bath at -25
to -30 °C (dry ice/30% ethanol in ethylene glycol). The mixture
was allowed to stir under nitrogen atmosphere. Distilled triethy-
lamine (0.36 g, 0.50 mL, 3.5 mmol), 1-adamantoyl chloride9 (238
mg, 1.2 mmol) were added sequentially, and stirring at -25 to -30
°C was continued for 1 h. LiCl (0.21 g, 5.0 mmol) was added. A
solution of oxazolidinone (131 mg, 1.50 mmol) in THF (2.0 mL)
was prepared in the glovebox, and after 5 min, the oxazolidinone
solution and 4-dimethylaminopyridine (13 mg, 0.10 mmol) were
sequentially added. The reaction mixture was allowed to stir
overnight, during which time the dry ice in the bath dissipated and
the mixture gradually warmed to rt. The solvents were removed at
rt under reduced pressure, and the residue was immediately
partitioned between 20 mL of CH2Cl2 and 20 mL water. The
aqueous layer was extracted twice with 20 mL portions of CH2Cl2,
and the combined organics were dried (Na2SO4), filtered, and
concentrated. The residue was chromatographed on silica gel. The
eluent was 1:3:6 CH2Cl2/ethyl acetate/hexane. The yield of 4 was
115 mg (0.752 mmol, 75%). Compound 4 is a semisolid: 1H NMR
(CDCl3, 400 MHz) δ 6.82 (d, J ) 1.3 Hz, 2H), 4.30 (t, J ) 8.2
Hz, 2H), 4.03 (t, J ) 8.1 Hz, 2H), 3.51 (t, J ) 1.3 Hz, 1H); 13C
NMR (CDCl3, 100 MHz) δ 176.5 (CH), 154.0 (CH), 101.8 (CH),
62.3 (CH2), 43.0 (CH2), 16.6 (CH); IR (neat, cm-1) 1742, 1700,
11.43 (br s, 1H), 6.92 (s, 2H), 2.21 (s, 1H); 13C NMR (CDCl3, 100
MHz) δ 182.5 (C), 103.0 (CH), 16.5 (CH); IR (neat, cm-1) 2973
(br), 1694, 1659, 1650, 1416, 1323, 1280, 1238, 1093, 978, 897,
697; HRMS-CI (M+) m/z calcd for C4H4O2 84.0211, found 84.0207.
4(S)-3-(Cycloprop-2-en-1-oyl)-4-phenyloxazolidinone (2). A
flame-dried 1 L round bottomed flask containing a solution of 513
(3.2 g, 38 mmol) in 800 mL of THF was chilled by a cold bath
that was maintained between -25 and -30 °C (dry ice/30% ethanol
in ethylene glycol). The mixture was allowed to stir under nitrogen
atmosphere. Distilled triethylamine (14.1 g, 19.4 mL, 139 mmol)
and pivaloyl chloride (7.0 g, 7.1 mL, 58 mmol) were added
sequentially, and stirring at -25 to -30 °C was continued for 2 h,
during which time a large volume of a white solid (Et3N · HCl)
precipitated. LiCl (7.0 g, 170 mmol) was added, and after 10 min,
(S)-4-phenyloxazolidinone (11.2 g, 69 mmol) and 4-dimethylami-
nopyridine (500 mg, 4.10 mmol) were added. The reaction mixture
was allowed to stir for 20 h, during which time the dry ice in the
bath dissipated and the mixture gradually warmed to rt. The mixture
was then filtered on a Buchner funnel to remove precipitated
Et3N·HCl, and the precipitate was rinsed with additional THF. The
solvents were removed under reduced pressure at rt, and the residue
(13) For the preparations of 2-4, similar yields were obtained when 5 was
added as neat material or as a ∼30% wt solution in MTBE.
J. Org. Chem. Vol. 73, No. 11, 2008 4285

1651, 1364, 1323; HRMS-CI (M + H) m/z calcd for C7H8NO3
154.0504, found 154.0505.
cm-1) 1791, 1711, 1481, 1319, 1278, 1137, 1027, 748, 710; HRMS-
CI(NH3) m/z [M + H] calcd for C17H16NO3 282.1130, found
282.1134.
General Procedure for Diels-Alder Reactions. A 3 dram vial
containing a stirbar was sequentially charged with the indicated
amounts of CH2Cl2, diene, and 3. The reaction mixture was allowed
to stir at rt for the indicated time. The mixture was then concentrated
under reduced pressure, and the crude residue was purified on a
column of silica gel (2% ethyl acetate in hexanes was the eluent).
3-[rel-(1R,2R,6R,7R)-2-Butylbicyclo[4.1.0]hept-3-ene-7-carbo-
nyl]-3H-benzooxazol-2-one (8). The general procedure was fol-
lowed using CH2Cl2 (0.2 mL), (E)-1,3-octadiene (54 mg, 0.49
mmol), and 3 (11 mg, 0.055 mmol) and the mixture allowed to stir
for 12 h. Obtained was 11 mg (0.35 mmol, 64%) of 8 as a colorless
solid. A minor impurity that could not be removed by chromatog-
raphy was detected at 1.9 ppm in the 1H NMR spectrum: mp 95-97
°C; 1H NMR (CDCl3, 400 MHz) δ 7.96-7.94 (m, 1H), 7.18-7.13
(m, 3H), 5.41 (m, 1H), 5.34 (m, 1H), 3.21 (m, 1H), 2.39-2.36 (m,
3H), 2.07 (m, 2H), 1.37-1.23 (m, 7H), 0.79 (t, J ) 7.4 Hz, 3H);
13C NMR (CDCl3, 100 MHz) δ 173.4 (C), 151.8 (C), 141.9 (C),
128.3 (CH), 128.2 (C), 125.0 (CH), 124.6 (CH), 122.3 (CH), 116.0
(CH), 109.7 (CH), 35.2 (CH2), 31.9 (CH), 31.8 (CH), 29.1 (CH2),
26.1 (CH), 23.2 (CH2), 22.7 (CH2), 20.9 (CH), 14.0 (CH3); IR (neat,
cm-1) 1792, 1699, 1479, 1315, 1251, 1141, 1040, 751, 699; HRMS-
CI(NH3) m/z [M + H] calcd for C19H22NO3 312.1600, found
312.1590.
3-(Tricyclo[3.2.1.02,4]oct-6-ene-3-carbonyl)-3H-benzooxazol-
2-one (6). The general procedure was followed using CH2Cl2 (2
mL), cyclopentadiene (330 mg, 4.99 mmol), and 3 (100 mg, 0.498
mmol). The mixture was allowed to stir for 5 min. Obtained were
126 mg (0.471 mmol, 95%) of 6 as a colorless solid. The purity
1
was measured to be greater than 95% by H NMR: mp 129-131
°C; 1H NMR (CDCl3, 400 MHz) δ 7.98-7.96 (m, 1H), 7.23-7.18
(m, 3H), 5.99 (m, 2H), 3.06 (m, 2H), 3.02 (app t, J ) 2.4 Hz, 1H),
2.33 (m, 2H), 1.97 (td, J ) 1.6, 7.2 Hz, 1H), 1.74 (d, J ) 7.2 Hz,
1H); 13C NMR (CDCl3, 100 MHz) δ 170.2 (C), 151.6 (C), 142.0
(C), 132.2 (CH), 128.0 (C), 125.0 (CH), 124.6 (CH), 115.9 (CH),
109.6 (CH), 64.4 (CH2), 43.4 (CH), 32.0 (CH), 26.3 (CH); IR (neat,
cm-1) 1781, 1699, 1477, 1380, 1316, 1278, 1135, 1046, 761, 733,
698; HRMS-CI(NH3) m/z [M + H] calcd for C16H14NO3 268.0974,
found 268.0964.
Acknowledgment. This work was supported by NIH Grant
No. GM068640-01. We thank Glenn P. A. Yap for determina-
tion of the X-ray structures. We thank Andrew DeAngelis and
Vinod Tarwade for experimental assistance, Guotao Luo for
obtaining DSC data, and Daniel Hill and John McCauley for
assistance in DSC interpretation.
3-(Tricyclo[3.2.2.02,4]non-6-ene-3-carbonyl)-3H-benzooxazol-
2-one (7). The general procedure was followed using CH2Cl2 (0.3
mL), cyclohexadiene (400 mg, 4.99 mmol), and 3 (100 mg, 0.498
mmol). The mixture was allowed to stir for 5 h. Obtained was 130
mg (0.462 mmol, 93%) of 7 as a colorless solid. The purity was
Supporting Information Available: Copies of 1H NMR and
13C NMR spectra are provided for new compounds. Charac-
terization details and a procedure for the preparation of 9 are
provided. NOE and 2-D NMR data are provided for 8. DSC
data for 2 and CIF files for 2, 6, and 7 are provided. This
material is available free of charge via the Internet at
http://pubs.acs.org.
1
measured to be greater than 95% by H NMR: mp 129-131 °C;
1H NMR (CDCl3, 400 MHz) δ 7.97-7.96 (m, 1H), 7.22-7.18 (m,
3H), 5.98 (m, 1H), 2.96 (m, 2H), 2.81 (t, J ) 2.8 Hz, 1H), 1.93
(m, 2H), 1.62 (dd, J ) 1.2, 6.8 Hz, 2H), 1.28 (dd, J ) 1.2, 6.8 Hz,
2H); 13C NMR (CDCl3, 100 MHz) δ 172.8 (C), 151.7 (C), 141.9
(C), 129.9 (CH), 128.1 (C), 124.9 (CH), 124.6 (CH), 115.9 (CH),
109.6 (CH), 30.4 (CH), 25.3 (CH), 24.4 (CH2), 18.8 (CH); IR (neat,
JO800042W
4286 J. Org. Chem. Vol. 73, No. 11, 2008