Synthesis and highly selective Diels-Alder cycloadditions of the new dienes N-substituted 2,3,5,6-tetrahydrobenzoxazol-2-ones

Article abstract of DOI:10.1016/S0040-4020(02)01536-3

The synthesis of the new dienes N-substituted 2,3,4,5-tetrahydrobenzoxazol-2-ones 8a-8c is described, through a one-step convergent process from 1,2-cyclohexanedione (7a) and the corresponding isocyanates 2a-2c. The presence of electron-donor substituents in the aryl ring of the isocyanate gave rise to the exclusive formation of the captodative olefins 10. Diene 8a proved to be reactive and stereoselective in Diels-Alder additions with a cyclic olefin. The reaction with acetylenic dienophiles yielded the 2,3-dihydrobenzoxazol-2-ones 21 and 24, as the products of sequential [4+2] cycloaddition and retro-Diels-Alder reactions. Methyl vinyl ketone (22) underwent regio- and stereoselective tandem Diels-Alder and Michael additions to give propellane 29a. Evidence of an endo π-pyramidalization of the central double bond of adduct 19 would rationalize the exo stereoselection in the formation of 29a. The regioselectivity in these reactions has been rationalized in terms of FMO theory by ab initio calculations.

Full text of DOI:10.1016/S0040-4020(02)01536-3

Tetrahedron 59 (2003) 481–492
Synthesis and highly selective Diels–Alder cycloadditions of the
new dienes N-substituted 2,3,5,6-tetrahydrobenzoxazol-2-ones
†
Rafael Martınez, Hugo A. Jimenez-Vazquez, Francisco Delgado and Joaquın Tamariz
*
´
´
´
´
´ ´ ´ ´
Departamento de Quımica Organica, Escuela Nacional de Ciencias Biologicas, Instituto Politecnico Nacional,
´
Prol. Carpio y Plan de Ayala, 11340 Mexico, D.F., Mexico
Received 29 August 2002; revised 28 November 2002; accepted 28 November 2002
Abstract—The synthesis of the new dienes N-substituted 2,3,4,5-tetrahydrobenzoxazol-2-ones 8a–8c is described, through a one-step
convergent process from 1,2-cyclohexanedione (7a) and the corresponding isocyanates 2a–2c. The presence of electron-donor substituents
in the aryl ring of the isocyanate gave rise to the exclusive formation of the captodative olefins 10. Diene 8a proved to be reactive and
stereoselective in Diels–Alder additions with a cyclic olefin. The reaction with acetylenic dienophiles yielded the 2,3-dihydrobenzoxazol-2-
ones 21 and 24, as the products of sequential [4þ2] cycloaddition and retro-Diels–Alder reactions. Methyl vinyl ketone (22) underwent
regio- and stereoselective tandem Diels–Alder and Michael additions to give propellane 29a. Evidence of an endo p-pyramidalization of the
central double bond of adduct 19 would rationalize the exo stereoselection in the formation of 29a. The regioselectivity in these reactions has
been rationalized in terms of FMO theory by ab initio calculations. q 2003 Elsevier Science Ltd. All rights reserved.
1. Introduction
The presence of the methyl group enhanced the reactivity
and regioselectivity of the Diels–Alder reaction with
unsymmetrical olefins. It was noteworthy that a high endo
stereoselectivity was also observed. When the symmetric
a-diketone 1c was used, a mixture of 5-(4Z,5Z)/6-(4E,5Z)
isomers was isolated, being isomer 6 the major component.6
The presence of the E methyl group in the diene moiety of
the latter had a significant impact on the stereoselectivity
and regioselectivity in the addition toward diverse
dienophiles.
1,3-Conjugated cyclic dienes have been widely used as
privileged molecular systems for evaluating the stereo-
specificity, the endo/exo stereoselectivity, and p-facial
control, among other features, in Diels–Alder cyclo-
additions.1 In particular, heteroatom-substituted 1,3-cyclo-
hexadienes have been found to improve the reactivity,
stereoselectivity, and regioselectivity of intermolecular
[4þ2] cycloadditions.2 This advantageous behavior has
allowed their use as attractive and efficient synthons in
organic synthesis.3
The synthesis of this kind of 2-oxazolidinone dienes
containing the conjugated diene inside a five- or six-
membered ring would provide new insight about the factors
that control not only the stereo- and regioselectivity in
Diels–Alder additions of cyclic dienes, but also the
performance of our method for diene formation. Therefore,
We have described a highly convergent synthesis of the
novel N-substituted outer-ring dienes of 2-oxazolidinones 3
(Scheme 1).4 The use of the unsymmetrical a-diketone 1b
led to the regio- and stereoselective formation of dienes 4.5
Scheme 1.
Keywords: Tetrahydrobenzoxazol-2-ones; dienes; Diels–Alder; p-pyramidalization; Michael addition; propellanes.
*
Corresponding author. Tel.: þ5255-5729630062411; fax: þ5255-5396-3503; e-mail: jtamariz@woodward.encb.ipn.mx
†
´ ´ ´ ´
Present address: Programa de Simulacion Molecular, Instituto Mexicano del Petroleo, Eje Lazaro Cardenas 152, 07730 Mexico, D.F., Mexico.
0040–4020/03/$ - see front matter q 2003 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020(02)01536-3

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R. Martınez et al. / Tetrahedron 59 (2003) 481–492
482
dehydrating agent. Only the presence of an excess of 2a
leads to the formation of diene 8a (Table 1, entries 1 and 2).
The increase of the reaction time and temperature does not
produce a significant change in favor of the desired diene
(Table 1, entries 2–4). Even though lithium carbonate has
been found to be the optimum dehydrating agent for diene
formation,4 it was interesting to see that molecular sieves
˚
(4 A) improved the yield of diene 8a in particular detriment
of the urea 11a (Table 1, entry 2 vs 5).
Scheme 2.
Under these optimal conditions, derivatives 8b and 8c were
prepared in similar fair yields, and also isolated along with
the corresponding cyclohexenones 10b and 10c,8 and the
carbamoyl ureas 11b and 11c (Table 1). Carbamoyl ureas
(biurets) 11 have been previously reported as by-products in
the preparation of urethanes,9 forming metallacycles with
palladium and indium,10 and they have been prepared by
treating carbanilates with a base.11
we have intended the preparation of dienes 8 and 9 from
a-diketones 7a and 7b with isocyanates 2 (Scheme 2),
assessing the strain caused by the ring size during the
intramolecular cyclization when the 1,3-oxazolidin-2-one
ring is formed.5 An evaluation of the regio- and stereo-
selectivity of the prepared dienes in Diels–Alder additions
toward a series of dienophiles was also carried out, and the
results are described herein.
The isolation of enones 10, which could also be considered
as cyclic captodative olefins,7,12 represents additional
support of the mechanism proposed earlier for the formation
of dienes 3–6, where a carbamate anion intermediate 12a
was postulated (Scheme 4).5,6 The isocyanate undergoes
addition from the base-promoted enolate of 1,2-diketone 7a,
to yield 12a. This may lead to hemiaminal 14 (some
analogous hemiaminals have been isolated and charac-
terized)5 by intramolecular cyclization, which can lose a
molecule of water by the presence of the dehydrating agent
to give the corresponding diene 8. If the intramolecular
cyclization is partially or totally inhibited, the protonation of
12a could take place providing the observed enone 10.
2. Results and discussion
2.1. Synthesis of dienes 8a–8c
When the condensation of a-diketone 7a with isocyanate 2a
was carried out, under similar reaction conditions to those
previously used for the preparation of dienes 3 and 4,
mixtures of three different products were formed (Scheme
3). Table 1 summarizes ratios and yields of the mixtures of
diene 8a,7 enone 10a, and carbamoyl urea 11a obtained
after purification by column chromatography. It is note-
worthy to see that the proportion of the products is mainly
modified by three factors: (a) the number of molecular
equivalents of the isocyanate, (b) temperature, and (c) the
To favor the intramolecular cyclization and the formation of
the diene, we used isocyanates with electron-releasing
Scheme 3.
Table 1. Condensation of 7a with isocyanates 2a–2e
Entrya
2 (mol equiv.)
Dehydrating agentb
T (8C)
t (h)
8 (%)c
10 (%)c
11 (%)c
1
2
3
4
5
6
7
8
9
2a (1.0)
2a (2.6)
2a (2.6)
2a (2.6)
2a (2.6)
2b (2.6)
2c (2.6)
2d (2.6)
2e (2.6)
Li2CO3
Li2CO3
Li2CO3
Li2CO3
Molecular sieves (4A)
Molecular sieves (4A)
Molecular sieves (4A)
Molecular sieves (4A)
˚
Molecular sieves (4A)
25
25
25
50
25
25
25
25
25
12
12
24
12
12
12
12
12
12
0
50
22
23
29
31
30
35
77
82
30
40
37
37
19
24
20
0
26
24
20
40
40
35
0
˚
˚
˚
˚
0
0
a
Dioxane, Et3N (1.94 mol equiv.), under N2 atmosphere.
Li2CO3 (1.2 mol equiv.); 0.3 g of molecular sieves.
After column chromatography and recrystallization.
b
c

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R. Martınez et al. / Tetrahedron 59 (2003) 481–492
483
Scheme 4.
groups in the aromatic ring, 2d and 2e. In principle, the
effect of the substituent R1 in the intermediate 12a should
increase the nucleophilicity of the carbamide, improving
the attack to the carbonyl group to give 14.4 In contrast to
the expected behavior, isocyanates 2d and 2e gave rise to
the enones 10d and 10e, respectively, as single products in
good yields (entries 8 and 9, Table 1). Probably, when the
N-substituent R1 in the isocyanate has a stronger electron-
donating effect, the carbamide species 12a becomes a
stronger basis as well, hence the abstraction of an a-proton
of the enone moiety might be favored, leading to the
conjugate enolate 16 (Scheme 4). This intermediate will
then be unable to undergo intramolecular cyclization to the
hemiaminal 14, and consequently will fail to yield the
wanted diene 8. This hypothesis would support the fact that
no carbamoyl ureas 11 were obtained, since the formation of
11 needs the presence of water in the reaction medium
(generated in the process by dehydration of 14) for
decomposing the isocyanate to the amine R1-NH2.13
Reaction of 3-methyl-1,2-cyclopentanedione (7b) with
p-chloroisocyanate (2b) gives rise exclusively, even under
optimum reaction conditions, to the cyclopentenone 13 in
55% yield (Scheme 4). This suggests again that the
intramolecular cyclization to give the heterocycle is the
cumbersome step and, probably, the rate determining step as
well.5 The structure of 13 was readily established by single-
crystal X-ray diffraction (CH2Cl2/hexane, 1:1) (Fig. 1).14
The conformation of the carbamate moiety was out of the
plane formed by the cyclopentane enone p system, but it
Figure 1. X-Ray structure of compound 13.

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R. Martınez et al. / Tetrahedron 59 (2003) 481–492
484
crystals (CH2Cl2/hexane, 7:3), and its X-ray structure was
obtained (Fig. 2).14
When the reaction was carried out with dimethyl acetylene-
dicarboxylate (20), the addition took place at 1208C for 1 h
(Scheme 5). These conditions were milder than those used
for dienes 3a (1808C, 1 h), 4a (R2¼Ph) (1308C, 1 h), and 5a/
6a (R2¼Ph) (1508C, 3 h). It is interesting to notice that the
product of the reaction was not the expected bridged-
bicyclic adduct but the 2,3-dihydro-1,3-benzoxazol-2-one
21, which rises from the cleavage of the ethano bridge of
the primary formed adduct by a retro Diels–Alder. The
unusual mild conditions of this process can be ascribed
to the stabilization gained by generation of the aromatic
ring.16
The regioselectivity in the Diels–Alder reactions of diene
8a was investigated with representative dienophiles bearing
electron-withdrawing activating groups, such as methyl
vinyl ketone (22) and methyl propiolate (23). The thermal
addition of the latter readily occurred to yield a mixture of
regioisomers 24/25 (69:31), favoring the para orientation
(with respect to the nitrogen atom of the heterocycle)
(Scheme 6). This ratio is only slightly higher than that
obtained with the unsubstituted exocyclic diene 3a (para/
meta, 60:40)5 and the (4Z,5Z)-dimethyl substituted diene 5a
(para/meta, 62:38),6 but lower than that observed for the
(4E,5Z)-dimethyl diene 6a (para/meta, 92:8). Isomer 24
was isolated by column chromatography as a white solid
in 63% yield, and characterized by NMR spectroscopy. In
contrast to the last three dienes, where the [4þ2] adducts
were isolated, isomers 24/25 were found to be the
corresponding aromatic rings, as previously observed for
dienophile 20. The aromatization of the ring could also be
facilitated by electronic destabilizing interactions inherent
to a bicyclo[2.2.2]octadiene, and angular bicyclic strain
generated by the tetrasubstituted double bond of the
precursor adducts 26.17
Scheme 5.
retains coplanarity with the aryl ring. This conformation
agrees with those shown by crystalline state structures of
non-cyclic captodative olefins.12,15 The crystallographic
data also disclosed intermolecular N–H· · ·OvC and
Cl· · ·H–C-5 interactions in the crystal lattice.
2.2. Diels–Alder cycloadditions
The reactivity in Diels–Alder additions of dienes 8 was
assesed, and compared to that of the non-cyclic dienes 3–6,
by using the N-phenyl derivative 8a. Thus, when the latter
reacted with N-phenylmaleimide (18) under thermal
conditions only the endo adduct 19 was obtained (Scheme
5). The temperature of the reaction was lower (1508C, 2 h)
than that employed for diene 3a (R2¼Ph, Scheme 1) (1808C,
1 h), and the same to that used for addition to diene 6c
(R2¼C2H4Cl), even though the reaction time for the latter
was longer (3 h). Compound 19 was isolated as colorless
Figure 2. X-Ray structure and view of compound 19, showing the C-2/C-6 double bond interplanar angle, and dihedral angles for the bicyclo[2.2.2]octene
moiety (average values of both faces).

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R. Martınez et al. / Tetrahedron 59 (2003) 481–492
485
Scheme 6.
2.3. Tandem Diels–Alder/Michael additions and
p-pyramidalization
provided on 4-oxazolin-2-ones, which have an analogous
structure to that of intermediate 27.18 Thus, 4,5-dimethyl-3-
phenyl-4-oxazolin-2-one reacts with 22 to give the 1,4-
addition product, as suggested for intermediate 28. How-
ever, a formal concerted hetero Diels–Alder addition
cannot be completely ruled out.19
When the Diels–Alder reaction was carried out with
dienophile 22 (2 mol equiv.) an unexpected mixture of
propellanes 29a/29b (90:10) was furnished (Scheme 7).
Although in this case it was not possible to assign
unequivocally the stereochemistry of the minor isomer,
On the other hand, it is noteworthy that the formation of
the dihydropyrane ring was regioselective to give propel-
lanes 29a and 29b. Based on the proposed mechanism, this
means that the 1,4-addition of the C-2/C-6 double bond of
cycloadducts 27 towards the Michael acceptor 22 took place
on carbon C-2. This preference could be explained by the
polarization of the double bond towards carbon C-2, due to
the higher electron-releasing effect of the nitrogen lone pair,
in comparison to the oxygen atom of the heterocycle, as
supported by an FMO study of analogous 4-oxazolin-2-
ones.18
1
the H NMR analysis suggested it to be the propellane
derivative coming from the exo adduct. The structure of the
major isomer, which was isolated as colorless crystals by
silica gel column chromatography (hexane), was established
by X-ray crystallography (Fig. 3).14 Compounds 29a/29b
were likely formed by cascade reactions, starting with the
formation of the expected [4þ2] adducts 27a/27b (Scheme
7). These have an electron-rich and, probably also, strained
tetrasubstituted double bond, as mentioned above for
intermediates 26. This bond behaves as a Michael donor
in a conjugate addition to a second molecule of 22 to give
zwitterions 28a/28b.18 Cyclization of these species com-
pletes the tandem Diels–Alder/Michael additions of diene
8a towards olefin 22. Even when just 1 mol equiv. of 22 was
used, the main product was a mixture of epimers 29. Low
temperatures led to a quite low conversion of starting
materials, with the presence of 29 along with polymeri-
zation of 22, due to the longer reaction times.
As shown by the X-ray structure of 29a, the Michael
addition towards the second molecule of 22 was found to
take place onto the exo face (the opposite face of the ethano
bridge bearing the acetyl group) of the bicyclic framework
of 27. This stereoselection could be attributed to steric
hindrance of the acetyl group in the endo face, or to
geometric constraints.20 However, it could also be associa-
ted to a p-anisotropy of the double bond, increasing the
electron density on the exo face.1j,21 This hypothesis
implicates a deviation from planarity for the double bond,
The non-concerted mechanism proposed above for the last
step in the propellane formation was supported by evidence
Scheme 7.

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R. Martınez et al. / Tetrahedron 59 (2003) 481–492
486
Figure 3. X-Ray structure of propellane 29a, and a view of the dihedral angles for the bicyclo[2.2.2]octane moiety (average values of both faces).
giving rise to an endo pyramidalization.22 In adduct 19,
which has an analogous structure to that of the nonisolated
adduct 27, the tetrasubstituted central C-2/C-6 double bond
exhibits a p-distortion by ca. 88 from planarity with tilting
occurring toward the endo face (Fig. 2). This deviation is
appreciable for a bicyclo[2.2.2]octene, since an angle
deviation from planarity in the range 3–238 has been
determined from crystallography data for norbornene and
bicyclo[2.2.2]octene frameworks, and in syn-sesquinorbor-
nenes and related molecules.1i,j,21b,23
In contrast with the bicyclo[2.2.1]hept-2-ene derivatives,24c
the ethano bridges in 19 are not tilted away from the
endocyclic C-2/C-6 double bond (Fig. 2). Furthermore,
the ethano bridges in 29a are not tilted either (Fig. 3), in
spite of the presence of the vicinal propellane moiety, and
the possibly different perturbation of the heterocycles on the
puckered cyclohexane ring.
The endo selectivity shown by diene 8a with dienophiles
such as 18 and 22 under thermal conditions is probably due
to secondary orbital interactions (SOI),26 which stabilize
this transition state preferentially, in spite of the presence of
the N-phenyl ring. The latter appears to adopt an orthogonal
conformation with respect to the heterocyclic ring in the
diene,5 and, in principle, it could increase the steric
repulsion when the dienophile approach is endo (Fig. 4).
On the other hand, the ethano bridge could generate
destabilizing steric interactions in the exo approach,27
favoring the endo adduct, as well as the SOI.6 This
stereoselection is in agreement with the thermal addition
of 1,3-cyclohexadiene to similar dienophiles.28
The observed olefinic pyramidalization of 19 occurred
contrasterically, since the oxazolidin-2-one ring is tilted
toward the N-phenylmaleimide ring. Electronic factors are
hence predominant with respect to the steric ones, and they
might be associated to hyperconjugative interactions
between the p bond and the rest of the bicyclo[2.2.2]octane
sigma skeleton, which can also be viewed as a puckered
cyclohexane ring.21 The stereochemistry of the N-phenyl-
maleimide moiety should be on the origin of the electron
density polarization of this cyclohexane ring, promoting in
consequence the p-anisotropy of the double bond toward
the exo face.22a,24 Therefore, the stereoselective Michael
addition on the exo face of the likely intermediate 27,
leading to propellane 29a, parallels the pyramidalization of
the double bond.22d,25
From the FMO theory viewpoint, the relative higher
reactivity of diene 8a with respect to the non-cyclic dienes
3a, 4a, and 5a/6a would be accounted for on the basis of
relative energies of the corresponding HOMOs, when the
Figure 4. endo and exo Diels–Alder transition states for the addition of diene 8a to dienophile 18.

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R. Martınez et al. / Tetrahedron 59 (2003) 481–492
487
Table 2. Ab initio HF/6-31Gp calculations of energies (eV) and coefficientes (Ci) of the frontier molecular orbitals for dienes 3a, 4a, 5a, 6a, and 8a–8c, and
olefin 22
Compda
E
HOMO
dCib
E
LUMO
dCib
C1
C2
C3
C4
C1
C2
C3
C4
8a
8b
8c
28.2351 20.2481 20.1778
28.3869 20.2449 20.1772
28.5276 20.2617 20.1933
0.2136
0.2105
0.2170
0.3169 20.0688 3.1847
0.3129 20.0680 2.9335
0.3222 20.0605 3.0258
0.2494 20.2081 20.2232
0.1994 20.1609 20.1874
0.2793 20.2331 20.2442
0.2494 0.0000
0.2049 20.0055
0.2738
0.2470 20.2625
0.2535 20.2592
0.0055
0.0065
0.0269
3ac
4ac
5ad
6ad
22e
28.8342
0.2591
0.1758 20.2173 20.3339 20.0748 2.9470 20.2690
0.2501
0.2345
28.5804 20.2679 20.2084
28.2675 20.2573 20.1883
28.4601 20.2154 20.1571
210.4895 20.3464 20.3669
0.2042
0.2210
0.1947
0.0327
0.3278 20.0599 3.1448 20.2861
0.3164 20.0591 3.2832
0.2782 20.0628 3.1983
0.2213 20.0205 2.9222
0.2630 20.2250 20.2342
0.2532 20.1890 20.2005
0.3109 20.2069 20.2809
0.2763 20.0133
0.2438
0.2549
0.0094
0.1040
These are the values of the 2pz coefficients, the relative 2pz contributions and their dCi are analogous.
For the most stable planar s-cis conformation for olefin 22.
a
b
Carbon 1–carbon 4 for the dienes; carbon 1–carbon 2 for the olefin.
Refs. 5,6.
Ref. 6.
Ref. 15a.
c
d
e
interaction is under normal electron demand,29 which is
indeed our case.5,6 Frontier molecular orbitals of diene 8a
were calculated using ab initio HF theory, and employing
the 6-31Gp basis set.30 The energy levels derived from
these and previous calculations for the above mentioned
dienes are summarized in Table 2. Thus, the more energetic
HOMO of diene 8a with respect to the other dienes would
explain its higher reactivity.
methyl groups in the substituted dienes 4 and 5/6.5,6 In fact,
the geometry of 8a was optimized (HF/6-31Gp), and a
dihedral angle of 9.58 for the diene moiety was calculated
(HF/6-31Gp) (Fig. 5). In this nonplanar geometry, two of
the vicinal protons of the methylene groups adopt a pseudo-
axial conformation, possibly due to the strain generated by
the eclipsed methylenes when the cyclohexadiene becomes
planar.32 Therefore, it is likely that hyperconjugation
between the pseudoaxial methylene protons and the diene
moiety will be more efficient in the nonplanar conformation.
The increase in energy of the HOMO of diene 8a may be
due to the hyperconjugative effect of the two methylenes
forming the six-membered ring,31 as suggested for the
The relative magnitude of the coefficient of the diene
Figure 5. Minimum potential-energy conformation of diene 8a, showing (in parentheses) the torsion angles of the diene moiety.

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R. Martınez et al. / Tetrahedron 59 (2003) 481–492
488
´
(Phoenix, AZ), and Centro de Investigaciones Quımicas,
´
terminus C4 is bigger than that of carbon C1 in the HOMO of
diene 8a, and for the other dienes as well (Table 2), then the
para orientation is expected for dienophiles 22 and 23,5,6
in agreement with the experiments. The comparable coef-
ficient differences (dCi) with dienes 3a and 8a could explain
the also similar regioisomeric ratio obtained when the
reaction was carried out with olefin 23. Nevertheless, the
regioselectivity for diene 8a was strongly improved for
olefin 22, in comparison with diene 3a. This discrepancy
may be rationalized by a larger perturbation found between
8a and 22, since the dE HOMOdiene–LUMOdienophile
(11.1573 eV) is smaller than that found for 3a (11.7564 eV).
Universidad Autonoma de Hidalgo (Pachuca, Hgo.,
Mexico). Analytical thin-layer chromatography was carried
out using E. Merck silica gel 60 F254 coated 0.25 plates,
visualizing by long and short-wavelength UV lamp. Flash
column chromatography was performed on a Flash40i of
Biotage, Dyax Corp. All air moisture sensitive reactions
were carried out under nitrogen using oven-dried glassware.
Dioxane, ethyl ether, THF, toluene, and xylene were freshly
distilled over sodium, and methylene chloride, ethyl acetate,
acetonitrile, and DMSO over calcium hydride, prior to use.
Li2CO3 and molecular sieves were dried overnight at 1208C
prior to use. Triethylamine was distilled over sodium
hydroxide. All other reagents were used without further
purification.
3. Conclusions
4.2. General procedure for the preparation of dienes
N-substituted 2,3,5,6-tetrahydrobenzoxazol-2-ones (8a–8c)
The condensation reaction between the six-membered ring
a-diketone 7a and the corresponding isocyanates 2a–2c
gave rise to dienes 8a–8c. The electron demand of the
substituent in the isocyanate seems to have an effect on
the outcome of diene formation, since isocyanates 2d and
2e yielded only the enones 10d and 10e, inhibiting the
cyclization step that leads to the dienes. The five-membered
ring a-diketone 7b was unable to produce the expected
diene 9, stopping in the enone intermediate 13, which could
be associated to a ring strain effect during the cyclization
process.
A solution of 1,2-cyclohexanedione (7a) (0.4 g, 3.6 mmol)
in dry dioxane (3 mL) was added dropwise to a magnetically
stirred solution of triethylamine (0.71 g, 7.0 mmol) in dry
˚
dioxane (2 mL) containing molecular sieves (4 A) (0.3 g), at
rt under N2 atmosphere, and the mixture was stirred for
30 min. Then, a solution of the corresponding isocyanate
(10.4 mmol) in dry dioxane (2 mL) was added dropwise and
stirring was continued for 12 h at rt. The mixture was
filtered and the solvent removed under vacuo. The residue
was purified by column chromatography over silica gel
impregnated with triethylamine (10%) in hexane (hexane/
EtOAc, 9:1), (30 g/g of crude), to give dienes 8a–8c.
Both high reactivity and stereoselectivity in thermal Diels–
Alder additions were found with symmetric dienophiles.
The reaction with acetylenic dienophiles 20 and 23 yielded
the 1,3-benzoxazol-2-ones, through a [4þ2] addition and a
subsequent ethano bridge cleavage. Methyl vinyl ketone
(22) reacted with 8a in a highly regio- and stereoselective
cycloaddition to furnish not the expected adduct, but
propellanes 29a/29b, through a tandem reaction as well:
[4þ2] addition and conjugate Michael addition with two
molecules of the olefin. The exo stereoselection in this
process was rationalized in terms of p-anisotropy of the
tetrasubstituted double bond C-2/C-6 of adduct 19, which
can be considered as an analogous precursor of 29. The
FMO model was useful to account for the reactivity and
regioselectivity observed in these cycloadditions, as a
consequence of a high interaction energy between dienes
8 and dienophiles.
4.2.1. 3-Phenyl-2,3,5,6-tetrahydrobenzoxazol-2-one (8a).
2-(N-Phenylcarbamoyloxy)-2-cyclohexen-1-one (10a).
1-(N-Phenylcarbamoyl)-1,3-diphenyl urea (11a). Using
the general procedure with 1.24 g of phenyl isocyanate (2a)
gave 0.30 g (40%) of 8a as colorless crystals (CH2Cl2/
hexane, 1:1), 0.25 g (31%) of 10a as colorless crystals
(CH2Cl2/hexane, 1:1), and 0.22 g (19%) of 11a as colorless
crystals (CH2Cl2/hexane, 1:1). Data of 8a: Rf 0.55 (hexane/
EtOAc, 7:3). Mp 81–828C [lit.7 81–828C]; IR (KBr): 1779,
1
1655, 1493, 1408, 1193, 1123, 993, 915, 746 cm21; H
NMR (300 MHz, CDCl3) d 2.33–2.51 (m, 4H, 2CH2),
4.94–4.98 (m, 1H, H-4), 5.25–5.29 (m, 1H, H-7), 7.32–
7.50 (m, 5H, PhH); 13C NMR (75.4 MHz, CDCl3) d 21.2
(C-5 or C-6), 21.3 (C-6 or C-5), 95.3 (C-4), 96.8 (C-7),
125.2 (C-9), 127.8 (C-11), 129.4 (C-10), 131.9 (C-3a),
133.6 (C-8), 142.7 (C-7a), 155.8 (C-2); MS (70 eV) 213
(Mþ, 9), 157 (3), 130 (4), 119 (78), 93 (100), 78 (11), 66
(35), 64 (32), 51 (13). Anal. calcd for C13H11NO2: C, 73.22;
H, 5.20; N, 6.57. Found: C, 73.09; H, 5.16; N, 6.65. Data of
10a: Rf 0.47 (hexane/EtOAc, 7:3). Mp 173–1748C; IR
(KBr): 3290, 3050, 1732, 1698, 1594, 1539, 1501, 1440,
1316, 1231, 1139, 1116 cm21; 1H NMR (300 MHz, CDCl3)
d 2.05 (qi, J¼6.3 Hz, 2H, H-5), 2.40–2.50 (m, 2H, H-4),
2.55 (t, J¼6.3 Hz, 2H, H-6), 6.58 (t, J¼4.3 Hz, 1H, H-3),
7.00–7.60 (m, 5H, PhH), 10.57 (br s, 1H, NH); 13C NMR
(75.4 MHz, CDCl3) d 22.4 (C-5), 24.7 (C-4), 37.8 (C-6),
120.0 (C-9), 124.1 (C-11), 128.8 (C-10), 128.9 (C-8), 136.3
(C-3), 144.8 (C-2), 154.1 (NCO2), 191.2 (C-1); MS (70 eV)
231 (Mþ, 16), 151 (11), 140 (15), 91 (100), 65 (9). Anal.
calcd for C13H13NO3: C, 67.52; H, 5.67; N, 6.06. Found: C,
67.93; H, 5.44; N, 5.85. Data of 11a: Rf 0.43 (hexane/
4. Experimental
4.1. General
Melting points (uncorrected) were determined with an
Electrothermal capillary melting point apparatus. IR spectra
were recorded on a Perkin-Elmer 1600 spectrophotometer.
1H (300 MHz) and 13C (75.4 MHz) NMR spectra were
recorded on a Varian Gemini-300 instrument, in CDCl3,
DMSO-d6, or acetone-d6 as solvents and TMS as internal
standard. Mass spectra (MS) and high-resolution mass
spectra (HRMS) were obtained, in electron impact (EI)
(70 eV) mode, on a Hewlett–Packard 5971A and on a Jeol
JMS-AX 505 HA spectrometers, respectively. X-Ray
analyses were collected on a Siemens P4 diffractometer.
Microanalyses were performed by M-H-W Laboratories

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R. Martınez et al. / Tetrahedron 59 (2003) 481–492
489
EtOAc, 7:3). Mp 148–1498C; IR (KBr): 3400–3000, 1709,
1671, 1593, 1516, 1439, 1316, 1262, 1231, 1170, 746,
CDCl3) d 2.30–2.46 (m, 4H, 2CH2), 3.66–3.74 (m, 2H,
CH2N), 3.76–3.84 (m, 2H, CH2Cl), 4.83–4.88 (m, 1H,
H-4), 5.17–5.23 (m, 1H, H-7); 13C NMR (75.4 MHz,
CDCl3) d 21.0 (C-5 or C-6), 21.3 (C-6 or C-5), 39.8 (NCH2),
43.1 (ClCH2), 93.9 (C-4), 97.0 (C-7), 131.3 (C-3a), 142.6
(C-7a), 154.2 (C-2); MS (70 eV) 201 (Mþþ2, 3), 199 (Mþ,
10), 164 (4), 150 (9), 136 (47), 122 (26), 103 (20), 94 (96),
80 (49), 65 (100), 63 (91). HRMS (70 eV) calculated for
C9H10ClNO2 [M]þz: 199.0400. Found: 199.0410. Data of
10c: Rf 0.43 (hexane/EtOAc, 7:3). Mp 95–978C; IR (KBr):
1
692 cm21; H NMR (300 MHz, CDCl3) d 7.04–7.14 (m,
2H, PhH), 7.22–7.45 (m, 10H, PhH), 7.50–7.62 (m, 3H,
PhH), 8.92 (br s, 2H, NH); 13C NMR (75.4 MHz, CDCl3) d
120.6, 124.4, 128.9, 129.8, 130.1, 136.5, 137.2, 153.1; MS
(70 eV) 119 (Mþ2212, 100), 93 (50), 91 (55), 64 (42).
Anal. Calcd for C20H17N3O2: C, 72.49; H, 5.17; N, 12.68.
Found: C, 72.26; H, 4.94; N, 12.80.
4.2.2. 3-(4-Chlorophenyl)-2,3,5,6-tetrahydrobenzoxazol-
2-one (8b). 2-[N-(4-Chlorophenyl)carbamoyloxy]-2-
cyclohexen-1-one (10b). 1-[N-(4-Chlorophenyl)carba-
moyl]-1,3-bis(4-chlorophenyl) urea (11b). Using the
general procedure with 1.60 g of 4-chlorophenyl isocyanate
(2b) gave 0.35 g (40%) of 8b as colorless crystals
(CH2Cl2/hexane, 1:1), 0.28 g (30%) of 10b as a white
powder (CH2Cl2/hexane, 1:1), and 0.36 g (24%) of 11b as
colorless crystals (CH2Cl2/hexane, 1:1). Data of 8b: Rf 0.58
(hexane/EtOAc, 7:3). Mp 123–1248C; IR (KBr): 1780,
3335, 1730, 1690, 1523, 1235, 1175 cm21 1H NMR
;
(300 MHz, CDCl3) d 2.00–2.12 (m, 2H, H-5), 2.45–2.60
(m, 4H, H-4, H-6), 3.50–3.71 (m, 4H, 2CH2), 5.57 (br s, 1H,
NH), 6.65 (t, J¼4.3 Hz, 1H, H-3); 13C NMR (75.4 MHz,
CDCl3) d 22.6 (C-5), 24.8 (C-4), 38.1 (C-6), 43.1 (CH2N),
43.5 (CH2Cl), 136.0 (C-3), 144.9 (C-2), 153.9 (NCO2),
192.7 (C-1); MS (70 eV) 215 (Mþ22, 6), 179 (10), 166 (8),
125 (18), 112 (23), 83 (21), 70 (23), 56 (100). Anal. calcd
for C9H12ClNO3: C, 49.67; H, 5.56; N, 6.44. Found: C,
49.79; H, 5.72; N, 6.43. Data of 11c: Rf 0.32 (hexane/
EtOAc, 7:3); IR (film): 3600–3000, 1731, 1678, 1531,
1
1665, 1496, 1359, 1207, 815 cm21; H NMR (300 MHz,
1
CDCl3) d 2.30–2.52 (m, 4H, 2CH2), 4.94–4.97 (m, 1H,
H-4), 5.27–5.30 (m, 1H, H-7), 7.34–7.38 (m, 2H, ArH),
7.40–7.46 (m, 2H, ArH); 13C NMR (75.4 MHz, CDCl3) d
21.2 (C-5 or C-6), 21.3 (C-6 or C-5), 95.5 (C-4), 97.0 (C-7),
126.4 (C-9), 129.6 (C-10), 131.6 (C-11), 132.2 (C-3a),
133.3 (C-8), 142.5 (C-7a), 152.8 (C-2); MS (70 eV) 249
(Mþþ2, 30), 247 (Mþ, 100), 219 (10), 191 (17), 164 (24),
151 (36), 111 (22), 75 (18). Anal. Calcd for C13H10ClNO2:
C, 63.04; H, 4.07; N, 5.66. Found: C, 62.89; H, 4.23; N,
5.50. Data of 10b: Rf 0.41 (hexane/EtOAc, 7:3). Mp 133–
1348C; IR (KBr): 3295, 1742, 1670, 1595, 1531, 1490,
1514, 1173, 1137, 1108, 1002 cm21; H NMR (300 MHz,
DMSO-d6) d 3.38–4.10 (m, 12H, 6CH2), 6.67 (br s, 2H,
NH); 13C NMR (75.4 MHz, DMSO-d6) d 40.7, 41.2, 42.0,
42.7, 43.3, 43.4, 155.5; MS (70 eV) 292 (Mþþ2, 1), 290
(Mþ, 3), 199 (6), 136 (63), 122 (50), 94 (92), 80 (59), 65
(100).
4.2.4. 2-[N-(4-Tolyl)carbamoyloxy]-2-cyclohexen-1-one
(10d). Using the general procedure with 1.38 g of 4-tolyl
isocyanate (2d) gave 0.67 g (77%) of 10d as a colorless oil.
Rf 0.58 (hexane/EtOAc, 7:3); IR (film): 3300, 1773, 1712,
1673, 1612, 1519, 1304 cm21; 1H NMR (300 MHz, CDCl3)
d 1.96–2.06 (m, 2H, H-5), 2.29 (s, 3H, MeAr), 2.42
(dt, J¼5.8, 5.3 Hz, 2H, H-4), 2.55 (dd, J¼6.9, 6.5 Hz, 2H,
H-6), 6.25 (br s, 1H, NH), 6.32 (t, J¼4.2 Hz, 1H, H-3),
6.92–6.96 (m, 2H, ArH), 7.03–7.08 (m, 2H, ArH); 13C
NMR (75.4 MHz, CDCl3) d 20.7 (CH3Ar), 23.0 (C-5), 24.5
(C-4), 37.7 (C-6), 115.3, 119.4, 129.7, 130.7, 136.7 (C-3),
139.2 (C-2), 154.9 (NCO2), 195.6 (C-1); MS (70 eV) 245
(Mþ, 96), 230 (5), 127 (70), 90 (100), 63 (12). Anal. calcd
for C14H15NO3: C, 68.56; H, 6.16; N, 5.71. Found: C, 68.13;
H, 6.22; N, 5.69.
1
1396, 1208, 1108, 1002, 820 cm21; H NMR (300 MHz,
CDCl3) d 2.03–2.15 (m, 2H, H-5), 2.48–2.56 (m, 2H, H-4),
2.56–2.66 (m, 2H, H-6), 6.71 (t, J¼4.3 Hz, 1H, H-3), 7.15–
7.19 (m, 2H, ArH), 7.27–7.31 (m, 2H, ArH), 8.00 (br s, 1H,
NH); 13C NMR (75.4 MHz, CDCl3) d 22.5 (C-5), 24.8
(C-4), 38.0 (C-6), 119.8 (C-9), 128.7 (C-10, C-11), 136.1
(C-3), 137.6 (C-8), 144.5 (C-2), 151.0 (NCO2), 193.6 (C-1);
MS (70 eV) 265 (Mþ, 1), 189 (3), 118 (18), 104 (19), 91
(16), 77 (100), 51 (90). Anal. calcd for C13H12ClNO3: C,
58.77; H, 4.55; N, 5.27. Found: C, 58.59; H, 4.77; N, 5.30.
Data of 11b: Rf 0.46 (hexane/EtOAc, 7:3). Mp 168–1698C;
IR (KBr): 3500–2900, 1743, 1719, 1678, 1601, 1537, 1496,
1402, 1214, 1108, 750 cm21; 1H NMR (300 MHz, CDCl3) d
7.30–7.40 (m, 5H, ArH), 7.40–7.46 (m, 2H, ArH), 7.47–
7.56 (m, 5H, ArH), 8.84 (br s, 2H, NH); 13C NMR
(75.4 MHz, DMSO-d6) d 121.6, 127.4, 127.7, 128.1, 129.1,
129.7, 130.6, 131.0, 152.7; MS (70 eV) 155 [(Mþþ2)2281,
45], 153 (Mþ2281, 100), 127 (15), 125 (49), 90 (41), 63
(22). Anal. calcd for C20H14Cl3N3O2: C, 54.26; H, 3.25; N,
9.66. Found: C, 54.38; H, 3.51; N, 9.86.
4.2.5. 2-[N-(4-Anisyl)carbamoyloxy]-2-cyclohexen-1-one
(10e). Using the general procedure with 1.55 g of 4-anisyl
isocyanate (2e) gave 0.76 g (82%) of 10e as a colorless oil.
Rf 0.56 (hexane/EtOAc, 7:3); IR (film): 3286, 1775, 1728,
1680, 1510, 1280, 1200, 1150, 1000, 840, 760, 690 cm21
;
1H NMR (300 MHz, CDCl3) d 2.00–2.08 (m, 2H, H-5),
2.47 (dt, J¼5.7, 4.7 Hz, 2H, H-4), 2.55 (dd, J¼6.9, 6.3 Hz,
2H, H-6), 3.73 (s, 3H, MeO), 6.67 (t, J¼4.1 Hz, 1H, H-3),
6.73–6.85 (m, 2H, ArH), 7.23–7.40 (m, 2H, ArH), 7.88 (br
s, 1H, NH); 13C NMR (75.4 MHz, CDCl3) d 22.4 (C-5), 24.7
(C-4), 38.0 (C-6), 55.3 (CH3O), 114.0 (C-10), 120.5 (C-9),
130.5 (C-8), 136.9 (C-3), 144.5 (C-2), 151.4 (NCO2), 155.8
(C-11), 193.2 (C-1); MS (70 eV) 261 (Mþ, 1), 241 (100),
182 (47), 154 (52), 128 (20), 63 (20). Anal. calcd for
C14H15NO4: C, 64.34; H, 5.79; N, 5.36. Found: C, 64.30; H,
5.86; N, 5.56.
4.2.3. 3-(2-Chloroethyl)-2,3,5,6-tetrahydrobenzoxazol-2-
one (8c). 2-[N-(2-Chloroethyl)carbamoyloxy]-2-cyclo-
hexen-1-one (10c). 1-[N-(2-Chloroethyl)carbamoyl]-1,3-
bis(2-chloroethyl) urea (11c). Using the general procedure
with 1.10 g of 2-chloroethyl isocyanate (2c) gave 0.25 g
(35%) of 8c as a white powder (CH2Cl2/hexane, 1:1), 0.27 g
(35%) of 10c as colorless crystals (CH2Cl2/hexane, 1:1), and
0.20 g (20%) of 11c as a colorless oil. Data of 8c: Rf 0.60
(hexane/EtOAc, 7:3). Mp 65–678C; IR (KBr): 1766, 1701,
4.2.6. 2-[N-(4-Chlorophenyl)carbamoyloxy]-3-methyl-2-
cyclopenten-1-one (13). Using the general procedure for
1
1437, 1331, 1255, 1090, 750 cm21; H NMR (300 MHz,

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490
the preparation of dienes 8a–8c, with 0.4 g (3.6 mmol) of
3-methyl-1,2-cyclopentanedione (7b) and 1.60 g of
4-chlorophenyl isocyanate (2b), gave 0.52 g (55%) of 13
as colorless crystals (CH2Cl2/hexane, 1:1). Rf 0.50
(hexane/EtOAc, 7:3). Mp 170–1718C; IR (KBr): 3273,
3120, 3058, 1762, 1655, 1604, 1541, 1401, 1301, 1208,
(C-7a), 152.7 (C-2), 166.5 (CO2CH3), 167.5 (CO2CH3);
MS (70 eV) 327 (Mþ, 25), 297 (16), 296 (100), 237 (16),
209 (15), 164 (11), 148 (18), 77 (60). Anal. calcd for
C17H13NO6: C, 62.39; H, 4.00; N, 4.28. Found: C, 62.18; H,
3.77; N, 3.96.
1
1093, 985, 823, 731 cm21; H NMR (300 MHz, CDCl3) d
4.3.3. 6-Methoxycarbonyl-3-phenyl-2,3-dihydrobenzoxa-
zol-2-one (24). 5-Methoxycarbonyl-3-phenyl-2,3-dihydro-
benzoxazol-2-one (25). Using the general procedure with
0.42 g of 23, and heating at 1508C for 3 h, gave a mixture of
24/25 (69:31), which was purified by column chroma-
tography on silica gel (hexane) to yield 0.47 g (63%) of 24
as a white powder (CH2Cl2/hexane, 7:3). Mp 128–1298C
[lit.33 128–1298C]. Rf 0.40 (hexane/EtOAc, 7:3). IR (KBr)
2.04 (s, 3H, CH3), 2.50–2.55 (m, 2H, H-5), 2.57–2.64 (m,
2H, H-4), 7.13–7.16 (m, 2H, ArH), 7.24–7.28 (m, 2H,
ArH), 8.53 (br s, 1H, NH); 13C NMR (75.4 MHz, CDCl3) d
15.3 (CH3), 28.0 (C-4), 32.5 (C-5), 119.9 (C-9), 128.6 (C-8),
128.7 (C-10), 136.1 (C-11), 145.6 (C-2), 149.9 (C-3), 162.7
(NCO2), 202.0 (C-1); MS (70 eV) 153 (Mþ2112, 100), 125
(37), 112 (44), 90 (26), 69 (15), 63 (14), 55 (15). Anal. calcd
for C13H12ClNO3: C, 58.77; H, 4.55; N, 5.27. Found: C,
58.67; H, 4.65; N, 5.28.
1
1803, 1722, 1607, 1482, 1242 cm21; H NMR (300 MHz,
CDCl3) d 3.95 (s, 3H, CO2CH3), 7.11 (d, J¼8.1 Hz, 1H,
H-4), 7.47–7.62 (m, 5H, PhH), 7.94–7.97 (m, 2H, H-5,
H-7); signals attributed to minor isomer 25: 3.91 (s,
CO2CH3), 7.34 (d, J¼8.4 Hz, H-7), 7.74 (d, J¼1.8 Hz,
H-4); 13C NMR (75.4 MHz, CDCl3) d 52.32 (CO2CH3),
108.7 (C-4), 111.5 (C-7), 125.2 (2C-Ph), 125.6 (C-6), 126.3
(C-5), 128.5 (C-Ph), 130.0 (2C-Ph), 133.1 (C-3a or NC-Ph),
135.1 (NC-Ph or C-3a), 142.4 (C-7a), 153.2 (C-2), 166.0
(CO2CH3); signals attributed to minor isomer 25: 52.33
(CO2CH3), 110.0 (C-7), 110.7 (C-4), 125.4 (C-3a), 130.2
(C-Ph); MS (70 eV) 269 (Mþ, 8), 238 (20), 194 (10), 182
(7), 154 (23), 139 (10), 127 (8), 77 (100). Anal. calcd for
C15H11NO4: C, 66.91; H, 4.12; N, 5.20. Found: C, 67.17; H,
4.36; N, 5.11.
4.3. General procedure for the Diels–Alder reaction of
dienophiles N-phenylmaleimide (18), dimethyl acetyl-
enedicarboxylate (20), methyl vinyl ketone (22), and
methyl propiolate (23) with diene 8a
A mixture of diene 8a (0.53 g, 2.5 mmol), dienophile
(5.0 mmol), and hydroquinone (0.003 g) in dry xylene
(3 mL) was placed in a threaded ACE glass pressure tube
with a sealed Teflon screw cap, under N2 atmosphere, and in
the dark. The mixture was stirred and heated until complete
reaction. The solvent was removed under vacuum and
the residue purified by column chromatography (hexane/
EtOAc, 4:1) on silica gel (30 g/g of crude) to give the
corresponding adducts.
4.3.4. (1R p,6R p,7S p,8R p,10R p)-8-Acetyl-3-methyl-2,13-di-
oxa-11-phenyl-11-azatetracyclo[4.4.3.27,10.01,6]tridec-3-
en-12-one (29a). (1R p,6R p,7S p,8S p,10R p)-8-Acetyl-3-
methyl-2,13-dioxa-11-azatetracyclo[4.4.3.27,10.01,6]tri-
dec-3-en-12-one (29b). Using the general procedure with
0.35 g of 22, and heating at 1308C for 1 h, gave a mixture of
29a/29b (90:10), which was purified by column chroma-
tography (hexane) to yield 0.57 g (57%) of 29a as colorless
crystals (CH2Cl2/hexane, 7:3). Mp 206–2088C. Rf 0.29
(hexane/EtOAc, 7:3). IR (KBr) 1754, 1705, 1602, 1492,
4.3.1. (1R p,7R p,8S p,12R p)-5,10-Diphenyl-3-oxa-5,10-di-
azatricyclo[5.5.2.02,6.08,12]tetradec-2(6)-ene-4,9,11-tri-
one (19). Using the general procedure with 0.86 g of 18, and
heating at 1508C for 2 h, gave 0.47 g (70%) of 19 as
colorless crystals (CH2Cl2/hexane, 7:3). Mp 184–1858C. Rf
0.33 (hexane/EtOAc, 7:3). IR (KBr) 1757, 1712, 1595,
1
1419, 1383, 1190 cm21; H NMR (300 MHz, CDCl3) d
1.50–1.97 (m, 4H, H-13, H-14), 3.20–3.30 (m, 2H, H-8,
H-12), 3.86–3.92 (m, 2H, H-1, H-7), 7.07–7.15 (m, 2H,
PhH), 7.26–7.53 (m, 8H, PhH); 13C NMR (75.4 MHz,
CDCl3) d 25.1 (C-13 or C-14), 25.8 (C-14 or C-13), 31.4
(C-1 or C-7), 32.2 (C-7 or C-1), 44.7 (C-8 or C-12), 45.1
(C-12 or C-8), 123.1, 123.3 (C-6a), 126.2, 127.2, 128.9,
129.3, 129.5, 131.2, 134.0, 137.2 (C-2), 154.2 (C-4), 175.7
(CONPh), 176.3 (CONPh); MS (70 eV) 386 (Mþ, 90), 358
(14), 330 (24), 213 (100), 167 (18), 119 (20), 77 (72). Anal.
calcd for C23H18N2O4: C, 71.49; H, 4.70; N, 7.25. Found: C,
71.33; H, 4.84; N, 7.18.
1367, 1177, 768 cm21 1H NMR (300 MHz, CDCl3) d
;
0.19–1.32 (m, 2H, H-9), 1.56–1.72 (m, 1H, H-15), 1.77–
1.88 (m, 4H, CH3Cv, H-15), 1.94–2.12 (m, 1H, H-14),
2.20–2.32 (m, 2H, H-10, H-5), 2.27 (s, 3H, CH3CO), 2.44–
2.56 (m, 2H, H-8, H-5), 2.68–2.72 (m, 1H, H-7), 5.11–5.20
(m, 1H, H-4), 7.18–7.25 (m, 1H, PhH), 7.36–7.43 (m, 2H,
PhH), 7.80–7.86 (m, 2H, PhH); 13C NMR (75.4 MHz,
CDCl3) d 19.25 (CH3Cv), 19.26 (C-5), 20.4 (C-9), 23.9
(C-15), 27.8 (C-14), 27.9 (COCH3), 31.3 (C-10), 38.1 (C-7),
48.9 (C-8), 86.1 (C-6), 96.0 (C-1), 103.6 (C-4), 124.1
(C-Ph), 126.0 (C-Ph), 128.7 (C-Ph), 136.9 (NC-Ph), 152.4
(C-12), 163.1 (C-3), 206.4 (COCH3); MS (70 eV) 283
(Mþ270, 16), 239 (12), 213 (100), 185 (14), 168 (12), 157
(20), 130 (22), 117 (37), 77 (53). Anal. calcd for
C21H23NO4: C, 71.37; H, 6.56; N, 3.96. Found: C, 71.47;
H, 6.35; N, 3.94.
4.3.2. 5,6-Dimethoxycarbonyl-3-phenyl-2,3-dihydrobenz-
oxazol-2-one (21). Using the general procedure with 0.71 g
of 20, and heating at 1508C for 1 h, yielded 0.61 g (75%) of
21 as a white powder (CH2Cl2/hexane, 7:3). Mp 143–
1458C. Rf 0.29 (hexane/EtOAc, 7:3). IR (KBr): 1790, 1724,
1
1505, 1436, 1292, 1260, 985 cm21; H NMR (300 MHz,
CDCl3) d 3.92 (s, 3H, CO2CH3), 3.97 (s, 3H, CO2CH3),
7.33 (s, 1H, H-4), 7.46–7.63 (m, 5H, PhH), 7.70 (s, 1H,
H-7); 13C NMR (75.4 MHz, CDCl3) d 52.8 (CO2CH3), 52.9
(CO2CH3), 109.5 (C-4 or C-7), 111.2 (C-7 or C-4), 125.2
(C-13), 127.0 (C-5 or C-6), 129.1 (C-15), 130.0 (C-6 or
C-5), 130.1 (C-14), 132.7 (C-3a), 133.6 (C-12), 143.6
4.4. Single-crystal X-ray crystallography
Single-crystal of cyclopentenone 13 was obtained by
recrystallization from CH2Cl2/hexane, 1:1, and adducts 19
and 29a from CH2Cl2/hexane, 7:3, as colorless crystals.
These were mounted in glass fibers. Crystallographic

´
R. Martınez et al. / Tetrahedron 59 (2003) 481–492
491
Diels–Alder Reaction; Wiley: New York, 1990. (d) Fringuelli,
F.; Taticchi, A. The Diels–Alder Reaction: Selected Practical
Methods; Wiley: Chichester, 2002. (e) Hartmann, H.; Abdel
Hady, A. F.; Sartor, K.; Weetman, J.; Helmchen, G. Angew.
Chem., Int. Ed. Engl. 1987, 26, 1143–1145. (f) Furuta, K.;
Shimizu, S.; Miwa, Y.; Yamamoto, H. J. Org. Chem. 1989, 54,
1481–1483. (g) Martin, J. G.; Hill, R. K. Chem. Rev. 1961, 61,
¨
537–562. (h) Paquette, L. A.; Carr, R. V. C.; Bohm, M. C.;
Gleiter, R. J. Am. Chem. Soc. 1980, 102, 1186–1188.
¨
(i) Paquette, L. A.; Hayes, P. C.; Charumilind, P.; Bohm,
measurements were performed on a Siemens P4 diffracto-
meter using Mo Ka radiation (graphite crystal mono-
chromator, l¼71073 A), and at room temperature. Three
˚
standard reflections were monitored periodically; they
showed no change during data collection. Unit cell
parameters were obtained from least-squares refinement of
26 reflections in the range 2,2Q,208. Intensities were
corrected for Lorentz and polarization effects. No absorp-
tion correction was applied. Anisotropic temperature factors
were introduced for all non-hydrogen atoms. Hydrogen
atoms were placed in idealized positions and their atomic
coordinates refined. Unit weights were used in the
refinement. Structures were solved using the SHELXTL34
program on a personal computer. Data for 13: Formula:
C13H12ClNO3; molecular weight: 265.69; cryst. size:
0.42£0.54£0.94 mm3; cryst. syst.: orthorhombic; space
group: P212121; unit cell parameters: a¼6.709(2), b¼
M. C.; Gleiter, R.; Blount, J. F. J. Am. Chem. Soc. 1983, 105,
3148–3161. (j) Hagenbuch, J.-P.; Vogel, P.; Pinkerton, A. A.;
Schwarzenbach, D. Helv. Chim. Acta 1981, 64, 1818–1832.
(k) Feast, W. J.; Hughes, R. R.; Musgrave, W. K. R. J. Chem.
Soc., Perkin Trans. 1 1977, 152–158.
2. (a) Paquette, L. A.; Carr, R. V. C. J. Am. Chem. Soc. 1980,
102, 853–855. (b) Corey, E. J.; Kozikowski, A. P.
Tetrahedron Lett. 1975, 2389–2392. (c) Jurczak, J.; Kozluk,
T.; Filipek, S.; Eugster, C. H. Helv. Chim. Acta 1982, 65,
1021–1024. (d) Kelly, T. R.; Whiting, A.; Chandrakumar,
N. S. J. Am. Chem. Soc. 1986, 108, 3510–3512. (e) Evans,
D. A.; Scott, W. L.; Truedale, L. K. Tetrahedron Lett. 1972,
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1313–1314. (h) Murai, A.; Sato, S.; Masamune, T. Chem. Lett.
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˚
9.6397(12), c¼19.958(2) (A); a¼90, b¼90, g¼90 (deg);
3
˚
V¼1290.7(4) (A ); temp. (8K)¼293(2); Z¼4; Dx¼
1.367 mg/m3; absorption coefficient: 0.295 mm21; u scan
range: 2.04–23.99 (deg); No. of reflections collected: 1681;
No. of independent reflections: 1522; No. of observed
reflections: 1520; R¼0.0422; wR¼0.0538; s¼1.065. Data
for 19: Formula: C23H18N2O4; molecular weight: 386.39;
cryst. size: 0.16£0.28£0.60 mm3; cryst. syst.: monoclinic;
space group: P21/c; unit cell parameters: a¼15.840(3), b¼
˚
11.857(3), c¼9.970(6) (A); a¼90, b¼105.03(3), u¼90
3
˚
(deg); V¼1808.3(12) (A ); temp. (8K)¼293(2); Z¼4; Dx¼
´
Int. Ed. Engl. 1985, 24, 412–414. (j) Belanger, J.; Landry,
´
N. L.; Pare, J. R. J.; Jankowski, K. J. Org. Chem. 1982, 47,
1.419 mg/m3; absorption coefficient: 0.098 mm21; u scan
range: 1.33–28.02 (deg); No. of reflections collected: 5577;
No. of independent reflections: 4374; No. of observed
reflections: 4315; R¼0.0524; wR¼0.1127; s¼1.021. Data
for 29a: Formula: C21H23NO4; molecular weight: 353.40;
cryst. size: 0.2£0.2£0.3 mm3; cryst. syst.: monoclinic;
space group: P21/c; unit cell parameters: a¼7.897(2), b¼
3649–3652. (k) White, K. B.; Reusch, W. Tetrahedron 1978,
34, 2439–2443. (l) Pyne, S. G.; Safaei-G, J.; Hockless, D. C.
R.; Skelton, B. W.; Sobolev, A. N.; White, A. H. Tetrahedron
1994, 50, 941–956. (m) Souchet, M.; Guilhem, J.; Le Goffic,
F. Tetrahedron Lett. 1987, 28, 2371–2374.
3. (a) Jung, M. E.; McCombs, C. A.; Takeda, Y.; Pan, Y.-G.
J. Am. Chem. Soc. 1981, 103, 6677–6685. (b) Smith, III.,
A. B.; Liverton, N. J.; Hrib, J.; Siraramakrishnan, H.;
Winzenberg, K. J. Am. Chem. Soc. 1986, 108, 3040–3048.
(c) May, C.; Moody, C. J. J. Chem. Soc., Chem. Commun.
1984, 926–927. (d) Holmes, A. B.; Thompson, J.; Baxter, A. J.
G.; Dixon, J. J. Chem. Soc., Chem. Commun. 1985, 37–39.
(e) Birkinshaw, T. N.; Holmes, A. B. Tetrahedron Lett. 1987,
28, 813–816. (f) Monti, S. A.; Yang, Y.-L. J. Org. Chem.
1979, 44, 897–898. (g) Nicolaou, K. C.; Snyder, S. A.;
Montagnon, T.; Vassilikogiannakis, G. Angew. Chem., Int. Ed.
Engl. 2002, 41, 1668–1698.
˚
15.7498(8), c¼14.3996(9) (A); a¼90, b¼95.250(9), u¼90
3
˚
(deg); V¼1783.5(4) (A ); temp. (8K)¼293(2); Z¼4;
Dx¼1.316 mg/m3; absorption coefficient: 0.091 mm21; u
scan range: 1.92–26.00 (deg); No. of reflections collected:
4624; No. of independent reflections: 3512; No. of observed
reflections: 3446; R¼0.0617; wR¼0.1437; s¼1.021.
Acknowledgements
We thank Fernando Labarrios for his help in spectrometric
measurements. J. T. is grateful to CGPI/IPN (Grants
916510, 200410, 32.14, and 200140) and CONACYT
(Grants 1203-E9203 and 32273-E) for financial support.
R. M. thanks CGPI/IPN and PIFI/IPN for scholarships, and
Ludwig K. Hellweg Foundation for a scholarship comple-
ment. H. A. J. acknowledges support from CONACYT
´
´
´
4. Hernandez, R.; Sanchez, J. M.; Gomez, A.; Trujillo, G.;
Aboytes, R.; Zepeda, G.; Bates, R. W.; Tamariz, J. Hetero-
cycles 1993, 36, 1951–1956.
´ ´
5. Mandal, A. B.; Gomez, A.; Trujillo, G.; Mendez, F.; Jimenez,
´
´
H. A.; Rosales, M. J.; Martınez, R.; Delgado, F.; Tamariz, J.
J. Org. Chem. 1997, 62, 4105–4115.
´ ´ ´
6. Martınez, R.; Jimenez-Vazquez, H. A.; Reyes, A.; Tamariz, J.
Helv. Chim. Acta 2002, 85, 464–482.
7. Diene 8a has been previously prepared in low yield (18%):
´
(Grant 3251P), and thanks IPN’s Programa de Contratacion
de Personal de Excelencia.
´
´
´
Benavides, A.; Martınez, R.; Jimenez-Vazquez, H. A.;
Delgado, F.; Tamariz, J. Heterocycles 2001, 55, 469–485.
8. Compounds 10a and 10b have been previously prepared:
Neidlein, R.; Friederich, W. Arch. Pharm. 1977, 310,
622–635.
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