Synthetic studies on Diels-Alder adducts: Intramolecular interactions between two functions

Article abstract of DOI:10.3390/70600475

In this paper we describe the synthesis of a ?,?-unsaturated aldehyde from a bicyclic Diels-Alder adduct, to be used in future electrocyclic reaction studies. A number of reactions produced undesired materials resulting from the interaction between functions, forcing the use of partial protection to accomplish a synthesis that would be otherwise straightforward. Suggestions to account for the results are given.

Full text of DOI:10.3390/70600475

Molecules 2002, 7, 475-486
molecules
ISSN 1420-3049
http://www.mdpi.org
Synthetic Studies on Diels-Alder Adducts: Intramolecular
Interactions Between Two Functions
Mauricio Gomes Constantino*, Altamiro Xavier de Souza and Gil Valdo José da Silva
Departamento de Química, Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto, Universidade
de São Paulo, Av. Bandeirantes 3900, 14040-901 – Ribeirão Preto – SP, Brazil. Phone +55/16 602
3747. Fax +55/16 633 8151.
*Author to whom correspondence should be addressed; e-mail: mgconsta@usp.br
Received: 17 August 2001; in revised form: 28 June 2002 / Accepted: 28 June 2002 / Published: 30
June 2002
Abstract: In this paper we describe the synthesis of a γ,δ-unsaturated aldehyde from a
bicyclic Diels-Alder adduct, to be used in future electrocyclic reaction studies. A number
of reactions produced undesired materials resulting from the interaction between
functions, forcing the use of partial protection to accomplish a synthesis that would be
otherwise straightforward. Suggestions to account for the results are given.
Keywords: Diels-Alder adducts, Intramolecular interactions, 1,4-Diols oxidation, Cyclic
phosphite
Introduction
During our studies on the preparation of polycyclic compounds through the Diels-Alder reactions
we have faced a circumstance of unusual recurrence of interference between two functions existing in
the same molecule, resulting in changes of the properties usually associated with each function and
giving rise to unexpected and rather surprising results.
In our view, it is essential to improve the systematization of knowledge about interferences
between functions, thus bringing higher reliability to organic syntheses projects. The results disclosed

Molecules 2002, 7
476
in this paper, for instance, confirm that some 1,4-diols cannot be easily oxidized to 1,4-dialdehydes
due to a strong tendency towards formation of a lactol, which blocks further oxidation with common
reagents. In these cases it is necessary to make use of partial protections, thus preventing one
(protected) function to interfere in the properties of the other (unprotected) one. It is also possible to
make a direct transformation through the use of special reagents [1].
Seeking the development of synthetic methods for the preparation of annulenes [2] and
heliangolides [3] through the Diels-Alder reaction, our aim in this work [4] was the preparation of
compound 2, from 1, for use in electrocyclic reactions studies (Scheme 1).
Scheme 1
R
OH
OH
2a: R = CHO
2b: R = -CH=CH2
1
This is an apparently a very simple transformation, as it would require only the oxidation of the
diol to a dialdehyde and a Wittig reaction, using Ph3P=CH2, with one or both aldehyde groups. The
starting material 1 can be easily prepared by Diels-Alder reaction between cyclopentadiene and maleic
anhydride, followed by reduction (Scheme 2) [5].
Scheme 2
O
LiAlH4
O
+
O
1
O
O
O
3
However, the oxidation of 1,4-diols to 1,4-dialdehydes is not an easily accomplishable
transformation, as these diols usually give lactols or lactones [6] upon treatment with oxidizing
reagents (see, however, reference [1]). The use of o-iodoxybenzoic acid in DMSO to oxidize 1,4-diols
to lactols has recently been proposed [7], the transformation of 1 into 4 (Scheme 3) being one of the
examples used by the authors. In exploratory experiments we have confirmed that only lactol 4 is
obtained when 1 is treated with a number of oxidizing reagents; two examples are mentioned in
Scheme 3.

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Scheme 3
OH
O
oxidizing
reagent
1
4
Reagent / solvent
Yield
o-iodoxybenzoic acid in DMSO
PDC in CH2Cl2
82 % (ref. 7)
60 %
Dess-Martin Periodinane in CH2Cl2
66 %
These results show that, as soon as one of the CH2OH groups is oxidized (or even during the
oxidation), the other –OH attacks the carbonyl group, forming the stable lactol 4 and preventing the
oxidation of the second alcohol group. The obvious solution to this kind of problem is to protect one of
the -OH groups and make the desired transformations on the other. However, before following this
distended route (described ahead), we decided to try a smaller modification in the same method, just
interchanging carbonyl group and phosphorane in the Wittig reaction: diol 1 could be transformed into
the corresponding dibromo compound, and this into the di-Wittig reagent, which would be treated with
formaldehyde.
Treatment of 1 with PBr3, however, led to a surprising result: after hydrolysis and extraction, a
phosphite of the diol was obtained as a mixture of stereoisomers that were separated by column
chromatography (compounds 7a and 7b). The transformation of an alcohol into the corresponding
bromide with PBr3 normally involves the initial formation of phosphites [8] such as 5, 6 (Scheme 4) or
trialkyl phosphites, that undergo a C-O bond breaking and simultaneous or successive C-Br bond
formation.
Scheme 4
CH2OH
OPBr2
O
O
PBr3
1
P
Br
5
6
O
O
O
H2O
P
H
(1:1)
7a + 7b
90 %

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478
The final result of this reaction suggests that intermediate 5 has been fully transformed into
intermediate 6 and no further reaction occurred; hydrolysis during extraction resulted in the formation
of cyclic phosphites 7. The unusual structures of compounds 7a and 7b was first suggested by the
1
occurrence, in their H-NMR spectra, of doublets corresponding to one hydrogen each in 6.71 δ (7a)
and 6.73 δ (7b) with very large coupling constants (725 Hz for 7a and 660 Hz for 7b), values observed
only when a P-H bond is present [9]. The 13C-NMR spectra of these compounds also show doublets for
the methylene carbons (CH2O) corresponding to coupling between these methylene carbons and the
phosphorus atom with normal J values [10] for this type of structure (6.9 Hz for 7a and 5.1 Hz for 7b).
31
Further confirmation of these structures is given by the P-NMR spectra. As shown in Figures 1 and
2, each of these spectra contains a double triple triplet with the same J values found in the
1
corresponding H-NMR spectra. Obviously, the coupling between phosphorus and carbon cannot be
seen in these spectra due to the low abundance of the 13C isotope.
Figure 1. 31P NMR spectrum of 7a
10.77
δ
7a
J1 = 725 Hz
J2 = 20.6 Hz
J3 = 20.6 Hz
J4 = 9.3 Hz
J5 = 9.3 Hz
14
13
12
11
10
9
8
7
ppm,
δ
It is clear, from the data we have collected until now, that compounds 7a and 7b are stereoisomers
differing by the relative stereochemistry at the phosphorus atom; however, we could not yet assign the
corresponding stereochemistry to each isomer. Further studies with this purpose are presently in
course.

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479
Figure 2. 31P NMR spectrum of 7b
7b
12.85 δ
J1 = 661 Hz
J2 = 28.4 Hz
J3 = 28.4 Hz
J4 = 10.5 Hz
J5 = 10.5 Hz
16.0
15.5
15.0
14.5
14.0
13.5
13.0
12.5
12.0
11.5
11.0
10.5
10.0
9.5
ppm, δ
The two cases of interactions just discussed, resulting in formation of 4 and of 7,respectively,
however similar, are not quite the same. To some extent, the formation of lactol 4 could be considered
as a foreseeable result, because a 5-membered ring is formed, a transformation usually favored both
kinetically and thermodynamically (entropy playing a very important role here); on the other hand, this
doesn’t seem to be the case of compound 7, as 7-membered rings are not as easily formed. We should
remark, however, that this is a special type of 7-membered ring: it contains two oxygen atoms (which,
contrary to the usual carbon atom case, have no substituents, thus reducing transannular interactions)
and two strong P-O bonds. Similar compounds, also containing 7-membered rings, have been
previously reported [11].
Through the use of partial protection it was possible to realize the desired transformations.
Compound 1 was converted to the monoprotected compound 8. By using the technique of
transforming the alcohol into an alcoxide before adding the electrophile, the formation of the
diprotected compound 9 was reduced to a minimum, due to the low tendency towards dianion
formation (Scheme 5).
Scheme 5
1) NaH, THF
OMOM
OH
OMOM
OMOM
1
+
2) ClMOM
8
9
67 %
< 1 %

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480
The subsequent transformations gave the expected results (Scheme 6): oxidation of the free alcohol
of 8 with PDC to produce the aldehyde in 60 % yield, a Wittig reaction giving olefin 11 (77 %) and
deprotection of the alcohol (59 %). Compound 12 is rather unstable, and had to be kept in benzene
solution with a small amount of hydroquinone to prevent decomposition during storage.
Scheme 6
Ph3P=CH2
PDC
OMOM
CHO
OMOM
8
CH2Cl2
60 %
77 %
10
11
O
OH
HCl
PDC
CH2Cl2
+
2a
H2O/MeOH
59 %
57 %
O
12
13
5 %
The last step, oxidation of 12 with PDC, gave the desired product 2a (57 % yield) together with a
small amount of the by-product 13 (5 % yield), again an evidence of interference between two
functions. The formation of compound 13 could be rationalized by at least two different ways, as
depicted in Scheme 7.
Scheme 7
O
O
Cr
XO
XO Cr O
OY
O
H
a)
O
O
H
14
12
H2O
PDC
H2O
HO
H
PDC
b)
13
O
O
Cr
O
O
16
OX
15

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481
According to hypothesis (a), the chromate reagent attacks the double bond (and not the alcohol),
whose reactivity could be enhanced by influence of the –OH group, resulting in the intermediate 14;
this would be either hydrolyzed to 16 and then oxidized to 13, or would be directly oxidized to 13,
more likely via reaction with Cr (VI). In hypothesis (b), the normal intermediate for this kind of
oxidation (15) [8] would be formed first but, instead of the normal abstraction of the hydrogen α to the
−OH group, a nucleophillic attack of the double bond (possibly assisted by water) would take place,
resulting in the same intermediate 16. In any case it is obvious that the formation of compound 13 is a
result of the proximity and the resulting interactions between the double bond and the –OH group in
compound 12.
Conclusions
The relatively simple synthesis of compound 2a here described shows the importance of taking
into account the intramolecular interactions between two functions, even in simple molecules, and how
valuable the use of protective groups can be to overcome this sort of problems. The ease of formation
and the stability of 5-membered ring lactols is remarkable, as well as the surprising formation of the
cyclic phosphite 7. As compound 13 is formed in only 5 % yield, this reaction is obviously less
important. However, it is a further evidence of how close to each other are the functions in these Diels-
Alder adducts, and how important this aspect can be when designing organic syntheses.
Acknowledgments
The authors thank the Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP), the
Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) and the Coordenadoria de
Aperfeiçoamento de Pessoal do Ensino Superior (CAPES) for financial support.
Experimental section
General
1
NMR spectra were measured using a Bruker DPX-300 (300 MHz H-NMR and 75 MHz
13C-NMR) or DRX-400 (400 MHz 1H-NMR and 100 MHz 13C-NMR) instruments; deuterochloroform
31
was used as solvent and tetramethylsilane as the internal standard; P-NMR spectra were measured
with Bruker DPX-300 (121.5 MHz) using H3PO4/D2O as external standard. IR spectra were measured
with a Perkin-Elmer 1600-FT or Nicolet 5ZDX spectrometers. TLC was performed on precoated silica
gel 60 F254 plates (0.25 mm thick, Merck), and for column chromatography silica gel 60 70-230 mesh
(Merck) was used. Reported yields refer to samples with the same purity as the samples used in the
following step.

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4-Oxatricyclo[5.2.1.02,6]dec-8-en-3-ol (4)
a) Oxidation with PDC. To a solution of pyridinium dichromate (3.0 g, 8.0 mmol) in anhydrous
CH2Cl2 (30 mL), maintained under N2 atmosphere, was added a solution of compound 1 (640 mg, 4.1
mmol) in CH2Cl2 (10 mL). After stirring for 24 h at room temperature, the solution was filtered
through a small column of MgSO4. The solvent was removed under vacuum and the residue was
chromatographed in a column of silica gel using a 4:6 mixture of hexane / ethyl acetate. Yield 374 mg
(60 %).
b) Oxidation with Dess-Martin periodinane. To a solution of diol 1 (61 mg, 0.37 mmol) in anhydrous
CH2Cl2 (1.2 mL), maintained under N2 atmosphere, was added a solution of Dess-Martin periodinane
[12] (351 mg, 0.80 mmol) in CH2Cl2 (3 mL). After stirring at room temperature for 20 min, the
reaction mixture was diluted with ethyl ether (10 mL) and quenched with a 1.3 M aqueous solution of
NaOH. After 10 min of vigorous stirring the organic phase was separated, washed with aqueous NaOH
solution, water, and dried with MgSO4. The solvent was removed under vacuum and the residue was
purified by chromatography as described in (a). Yield 37 mg (66 %).
Spectroscopic data: 1H-NMR (CDCl3, 400 MHz) δ 6.20 (dd, 1 H, J1 = 5.6 Hz, J2 = 3.0 Hz), 6.09 (dd, 1
H, J1 = 5.8 Hz, J2 = 3.0 Hz), 4.98 (s, 1 H), 3.98 (dd, 1 H, J1 = 7.6 Hz, J2 = 8.8 Hz), 3.46 (dd, 1 H, J1 =
8.8 Hz, J2 = 2.0 Hz), 3.03 (m, 1 H), 2.95 (m, 1 H), 2.87 (m, 2 H), 2.63 (br. s, 1 H), 1.45 (dt, 1 H, J1 =
13
8.3 Hz, J2 = J3 = 1.6 Hz), 1.36 (d, 1 H, J = 8.3 Hz); C-NMR (CDCl3, 100 MHz), 134.7 (CH), 134.6
(CH), 100.4 (CH), 69.3 (CH2), 55.6 (CH), 51.9 (CH), 46.0 (CH), 45.9 (CH), 44.9 (CH).
4,6-Dioxa-5-phosphatricyclo[7.2.1.02,8]dodec-10-en-5-one (7a and 7b).
A solution of diol 1 (50 mg, 0.32 mmol) and PBr3 (26 mg, 0.96 mmol) in anhydrous ethyl ether (10
mL) was kept under N2 atmosphere at 5°C for 45 h. After quenching with chopped ice and extraction
with ethyl ether, the organic phase was washed with water and saturated brine, and dried with MgSO4.
The solvent was removed under vacuum to give 58 mg (90 %) of a mixture of isomers that were
separated by chromatography in a silica gel column using a 3:7 mixture of hexane / ethyl acetate as
1
eluent. Both isomers are white crystalline solids. Compound 7a: yield 29 mg (45 %); H-NMR
(CDCl3, 300 MHz) δ 6.71 (d, 1 H, J [H-P] = 725 Hz), 6.13 (br. t, 2 H, J = 1.6 Hz), 4.16 (dt, 2 H, J1 = J2
= 11.7 Hz, J3 [H-P] = 9.3 Hz), 4.05 (ddd, 2H, J1 = 11.7 Hz, J2 [H-P] = 20.4 Hz, J3 = 3.6 Hz), 2.84 (m, 2
H), 2.81 (m, 2 H), 1.59 (dt, 1 H, J1 = 8.5 Hz, J2 = J3 = 1.7 Hz), 1.53 (br. d, 1 H, J = 8.5 Hz); 13C-NMR
(CDCl3, 75 MHz) δ 134.9 (CH), 66.0 (CH2, d, JC-P = 6.9 Hz), 51.2 (CH2), 45.7 (CH), 44.7 (CH); 31P-
NMR (CDCl3, 121.5 MHz) δ 10.77 (dtt, J1 = J2 = 9.3 Hz, J3 = J4 = 20.6 Hz, J5 = 725 Hz). Compound
7b: yield 29 mg (45 %) 1H-NMR (CDCl3, 300 MHz) δ 6.73 (d, 1H, J [H-P] = 660 Hz), 6.13 (t, 2H, J =
1.9 Hz), 4.14 (ddd, 2H, J1 [H-P] = 28.4 Hz, J2 = 12.0 Hz, J3 = 3.0 Hz), 3.68 (dt, 2H, J1 = J2 = 12.0 Hz,
J3 [H-P] = 10.7 Hz), 2.88 (m, 2H), 2.83 (m, 2H), 1.59 (dt, 1H, J1 = 8.5 Hz, J2 = J3 = 1.7 Hz), 1.50 (br.

Molecules 2002, 7
483
d, 1H, J = 8.5 Hz); 13C-NMR (CDCl3, 75 MHz) δ 135.0 (CH), 65.5 (CH2, d, JC-P = 5.1 Hz), 50.6 (CH2),
45.7 (CH), 42.8 (CH); 31P-NMR (CDCl3, 121.5 MHz) δ 12.85 (dtt, J1 = J2 = 10.5 Hz, J3 = J4 = 28.4 Hz,
J5 = 660 Hz); IR (KBr) νmax 2966, 2389, 1267, 1047, 797 cm-1.
{3-[(Methoxymethoxy)methyl]bicyclo[2.2.1]hept-5-en-2-yl}methan-1-ol (8) and (methoxy-
methoxy)-{3-[(methoxymethoxy)methyl]bicyclo[2.2.1]hept-5-en-2-yl}methane (9).
To a suspension of NaH (29 mg of a 60 % suspension in mineral oil, corresponding to 1.2 mmol),
previously washed with anhydrous hexane, in anhydrous THF (10 mL), maintained at 0°C under N2
atmosphere, was added a solution of diol 1 (103 mg, 0.66 mmol) in THF (1 mL). After 5 min the ice
bath was removed and the reaction mixture was stirred for 1 h. Chloromethyl methyl ether (80 mg, 1.0
mmol) was then added and the mixture was stirred for a further 1 h period. After quenching with
chopped ice, the product was extracted with ethyl ether, the organic phase was dried with MgSO4 and
the solvent was removed under vacuum. The crude product was purified by column chromatography in
silica gel, using a 7:3 mixture of hexane and ethyl acetate as eluent. Compound 8: yield 88 mg (67 %);
1H-NMR (CDCl3, 300 MHz) δ 6.10 (dd, 1H, J1 = 5.5 Hz, J2 = 2.6 Hz), 6.06 (dd, 1H, J1 = 5.5 Hz, J2 =
2.6 Hz), 4.60 (s, 2H), 3.42 (m, 4H), 3.37 (s, 3H), 2.85 (m, 2H), 2.55 (m, 2H), 1.45 (dt, 1H, J1 = 8.3 Hz,
13
J2 = J3 = 1.9 Hz), 1.37 (dt, 1H, J1 = 8.3 Hz, J2 = J3 = 1.5 Hz); C-NMR (CDCl3, 75 MHz) δ 135.1
(CH), 134.8 (CH), 96.6 (CH2), 68.9 (CH2), 63.0 (CH2), 55.6 (CH3), 49.7 (CH2), 46.43 (CH), 46.38
(CH), 45.4 (CH), 41.9 (CH); IR (KBr) νmax 3421, 2934, 1383, 1157, 1111, 1045 cm-1. Compound 9:
yield 1 mg (< 1 %); this sample was identical (by 1H-NMR) to other samples obtained in higher yields
1
by other methods, from which come some of the spectral data that follow: H-NMR (CDCl3, 300
MHz) δ 6.14 (t, 2H, J = 1.9 Hz), 4.58 (d, 2H, J = 8.4 Hz), 4.56 (d, 2H, J = 8.4 Hz), 3.38 (m, 2H), 3.35
(s, 6H), 3.13 (t, 2H, J = 9.1 Hz), 2.95 (m, 2H), 2.48 (m, 2H), 1.50 (dt, 1H, J1 = 8.3 Hz, J2 = J3 = 1.9
Hz), 1.35 (dt, 1H, J1 = 8.3 Hz, J2 = J3 = 1.5 Hz); 13C-NMR (CDCl3, 75 MHz) δ 135.4 (CH), 96.5
(CH2), 67.9 (CH2), 55.2 (CH3), 49.0 (CH2), 45.6 (CH), 41.5 (CH); IR (KBr) νmax 2991, 1158, 1111,
1055 cm-1.
3-[(Methoxymethoxy)methyl]bicyclo[2.2.1]hept-5-ene-2-carbaldehyde (10).
To a solution of pyridinium dichromate (113 mg, 0.30 mmol) in anhydrous CH2Cl2 (3 mL),
maintained under N2 atmosphere, was added a solution of compound 8 (39 mg, 0.19 mmol) in CH2Cl2
(3 mL). After stirring for 24 h at room temperature, the product was extracted and purified as
1
described in experiment 1a. Yield 22 mg (60 %). H-NMR δ (CDCl3, 300 MHz) 9.41 (d, 1H, J = 3.9
Hz), 6.33 (dd, 1H, J1 = 5.7 Hz, J2 = 2.7 Hz), 6.20 (dd, 1H, J1 = 5.7 Hz, J2 = 3.0 Hz), 4.54 (s, 3H), 3.38
(d, 2H, J = 7.8 Hz), 3.32 (s, 3H), 3.10 (m, 1H), 3.01 (m, 1H), 2.97 (m, 1H), 2.83 (m, 1H), 1.55 (dt, 1H,
13
J1 = 8.7 Hz, J2 = J3 = 2.0 Hz), 1.40 (dt, 1H, J1 = 8.7 Hz, J2 = J3 = 1.5 Hz); C-NMR δ (CDCl3, 75
MHz) 204.6 (C=O), 135.03 (CH), 134.95 (CH), 96.1 (CH2), 67.9 (CH2), 54.9 (CH or CH3), 54.3 (CH3
or CH), 49.1 (CH2), 45.7 (CH2), 44.9 (CH), 44.8 (CH); IR (KBr) νmax 2935, 2740, 1713, 1391 cm-1.

Molecules 2002, 7
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Methoxy[(3-vinylbicyclo[2.2.1]hept-5-en-2-yl)methoxy]methane (11)
To a mixture of the phosphonium salt Ph3PCH3Br (207 mg, 0.58 mmol) and THF (5 mL), cooled
to 0°C under a N2 atmosphere, was added a solution of n-BuLi (0.35 mL of a 1.17 M solution in
hexane, 0.67 mmol). After stirring for 15 min at 0°C, a solution of compound 10 (56 mg, 0.29 mmol)
in THF (1 mL) was added. The ice bath was removed and the reaction mixture was stirred at room
temperature for 22 h. After quenching with chopped ice and extracting with ethyl ether, the resulting
organic solution was washed with water and saturated brine, and dried with MgSO4. The solvent was
removed under vacuum and the residue was purified by column chromatography (silica gel), eluting
with a 7:3 mixture of hexane / ethyl acetate. Yield 43 mg (77 %). 1H-NMR δ (CDCl3, 300 MHz) 6.18
(t, 2H, J = 1.1 Hz), 5.30 (dt, 1H, J1 = 16.9 Hz, J2 = J3 = 9.9 Hz), 5.07 (ddd, 1H, J1 = 16.9 Hz, J2 = 2.5
Hz, J3 = 0.6 Hz), 4.90 (ddd, 1H, J1 = 9.9 Hz, J2 = 2.6 Hz, J3 = 0.4 Hz), 4.58 (d, 1H, J = 6.4 Hz), 4.55 (d,
1H, J = 6.4 Hz), 3.34 (s, 3H), 3.29 (dd, 1H, J1 = 9.6 Hz, J2 = 5.6 Hz), 3.04 (dd, 1H, J1 = 9.6 Hz, J2 =
10.5 Hz), 2.98 (m, 1H), 2.86 (dt, 1H, J1 = J2 = 9.9 Hz, J3 = 3.4 Hz), 2.79 (m, 1H), 2.46 (dddd, 1H, J1 =
10.5 Hz, J2 = 9.9 Hz, J3 = 5.6 Hz, J4 = 3.4 Hz), 1.49 (dt, 1H, J1 = 8.1 Hz, J2 = J3 = 1.5 Hz), 1.35 (dt, 1H,
13
J1 = 8.1 Hz, J2 = J3 = 1.5 Hz); C-NMR δ (CDCl3, 75 MHz) 139.6 (CH), 135.8 (CH), 135.3 (CH),
115.9 (CH2), 96.5 (CH2), 69.0 (CH2), 55.1 (CH3), 49.0 (CH2), 48.2 (CH), 46.9 (CH), 45.2 (CH), 43.6
(CH); IR (KBr) νmax 2924, 1634, 1453, 1151, 1041, 912, 732 cm-1.
(3-Vinylbicyclo[2.2.1]hept-5-en-2-yl)methan-1-ol (12).
To a solution of compound 11 (2.41 g, 12.4 mmol) in MeOH (70 mL) were added a few drops of
concentrated HCl. The reaction mixture was heated to 60°C for 3 h (following the disappearance of the
starting material by TLC) and then most of the MeOH was removed under vacuum. The product was
extracted with ethyl ether, the organic solution was washed with NaHCO3 solution and dried with
MgSO4. The solvent was removed under vacuum and the residue was purified by chromatography on a
1
silica gel column, using a 7:3 mixture of hexane / ethyl acetate as eluent. Yield 1.10 g (59 %). H-
NMR δ (CDCl3, 300 MHz) 6.17 (m, 2H), 5.34 (dt, 1H, J1 = 17.0 Hz, J2 = J3 = 10 Hz), 5.11 (dd, 1H, J1
= 17.0 Hz, J2 = 2.4 Hz), 4.94 (dd, 1H, J1 = 10 Hz, J2 = 2.4 Hz), 3.37 (dd, 1H, J1 = 10 Hz, J2 = 6.6 Hz),
3.15 (dt, 1H, J1 = J2 = 10 Hz, J3 = 3.5 Hz), 3.02 (br. s, 1H), 2.94 (m, 1H), 2.85 (dt, 1H, J1 = J2 = 10 Hz,
J3 = 3.4 Hz), 2.78 (m, 1H), 2.40 (ddt, 1H, J1 = J2 = 10 Hz, J3 = 6.6 Hz, J4 = 3.4 Hz), 1.49 (dt, 1H, J1 =
13
8.4 Hz, J2 = J3 = 1.8 Hz), 1.35 (d, 1H, J = 8.4 Hz); C-NMR δ (CDCl3, 75 MHz) 139.9 (CH), 135.6
(CH), 135.3 (CH), 116.1 (CH2), 63.4 (CH2), 49.4 (CH2), 48.9 (CH), 46.8 (CH), 46.6 (CH), 44.9 (CH);
IR (KBr) νmax 3329, 2966, 1636, 1451, 1342, 910, 732 cm-1.

Molecules 2002, 7
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3-Vinylbicyclo[2.2.1]hept-5-ene-2-carbaldehyde (2a) and 4-Oxa-9-vinyltricyclo[4.2.1.03,7]-nonan-
2-one (13)
To a solution of pyridinium dichromate (230 mg, 0.59 mmol) in anhydrous CH2Cl2 (4 mL)
maintained under N2 atmosphere, was added a solution of compound 12 (62 mg, 0.41 mmol) in
CH2Cl2 (2 mL). After stirring for 24 h at room temperature, the product was extracted and purified as
described in experiment 1a, using a 7:3 mixture of hexane / ethyl acetate as eluent. Compound 2a:
yield 35 mg (57 %). 1H-NMR δ (CDCl3, 300 MHz) 9.35 (d, 1H, J = 3.4 Hz), 6.36 (dd, 1H, J1 = 5.9 Hz,
J2 = 2.8 Hz), 6.24 (dd, 1H, J1 = 5.9 Hz, J2 = 2.8 Hz), 5.41 (dt, 1H, J1 = 17.0 Hz, J2 = J3 = 10.0 Hz), 5.21
(ddd, 1H, J1 = 17.0 Hz, J2 = 2.0 Hz, J3 = 0.6 Hz), 5.02 (ddd, 1H, J1 = 10.0 Hz, J2 = 2.0 Hz, J3 = 0.6 Hz),
3.24 (dt, 1H, J1 = J2 = 10.0 Hz, J3 = 3.4 Hz), 3.12 (m, 1H), 3.02 (dt, 1H, J1 = 10.0 Hz, J2 = J3 = 3.4 Hz),
2.92 (m, 1H), 1.54 (dt, 1H, J1 = 8.6 Hz, J2 = J3 = 1.9 Hz), 1.41 (m, 1H); 13C-NMR δ (CDCl3, 75 MHz)
205.5 (C=O), 138.6 (CH), 135.9 (CH), 135.5 (CH), 117.0 (CH2), 57.4 (CH), 49.4 (CH2), 49.0 (CH),
48.5 (CH), 45.4 (CH); IR (KBr) νmax 2972, 2729, 1716, 1636, 1453, 1392, 912, 737 cm-1. Compound
1
13: yield 3 mg (5 %). H-NMR δ (CDCl3, 300 MHz) 5.59 (ddd, 1H, J1 = 17.4, J2 = 10.0 Hz, J3 = 8.3
Hz), 5.19 (ddd, 1H, J1 = 17.4 Hz, J2 = 1.5 Hz, J3 = 1.0 Hz), 5.15 (dd, 1H, J1 = 10.0, J2 = 1.5 Hz), 3.85
(m, 3H), 3.09 (m, 1H), 2.78 (m, 2H), 2.47 (m, 1H), 1.91 (d, 1H, J = 11.5 Hz), 1.78 (d, 1H, J = 11.5
13
Hz); C-NMR (CDCl3, 75 MHz) δ 211.9 (C=O), 134.9 (CH), 118.3 (CH2), 80.8 (CH), 70.4 (CH2),
50.7 (CH), 44.6 (CH), 44.1 (CH), 41.2 (CH), 29.1 (CH2); IR (KBr) νmax 2974, 1753, 1639, 1178, 1129,
1040 cm-1.
References and Notes
1. Wu, H. J.; C. Y. J. Org. Chem. 1999, 64, 1576-1584; in this paper the oxidation of a diol similar to
1 to a dihemiacetal with the Swern reagent is described. The dihemiacetal obtained has the same
oxidation state of the dialdehyde, but is not an appropriate substrate for the Wittig reaction we
intended to perform subsequently.
2. (a) Garrat, P. J. in Aromaticity, Wiley-Interscience, New York, 1986; Vogel, E.; Roth, H. D.
Angew. Chem. Int. Ed. Engl. 1964, 3, 228; (b) Masamune, S.; Brooks, D. W. Tetrahedron Lett.
1977, 42, 3239-3240; (c) Scott, L. T.; Brunsvold, W. R. J. Amer. Chem. Soc., 1978, 100, 4320-
4321.
3. (a) Fischer, N. H. Recent Advances in Phytochemistry 1991, 24, 161-201; (b) Minnaard, A. J.;
Wijnberg, B. P. A.; de Groot, A. Tetrahedron 1999, 55, 2115-2146; (c) Vichnewski, W.;
Takahashi, A. M.; Nasi, A. M. T. T.; Gonçalves, D. C. R. G.; Dias, D. A.; Lopes, J. N. C.;
Goedken, V. L.; Gutiérrez, A. B.; Herz, W. Phytochemistry 1989, 28, 1441-1451.
4. Related previous works: (a) Constantino, M. G.; Beatriz, A.; da Silva, G. V. J. Tetrahedron Lett.
2000, 41, 7001-7004; (b) Constantino, M. G.; Beatriz, A.; da Silva, G. V. J.; Zukerman-Schpector,
J. Synth. Commun., in press.

Molecules 2002, 7
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5. (a) Culberson, C. F.; Seward, J. H.; Wilder Jr., P. J. Amer. Chem. Soc. 1960, 82, 2541-2547; (b)
Lok, K. P.; Jakovac, I. J.; Jones, J. B. J. Amer. Chem. Soc. 1985, 107, 2521-2526.
6. Aït-Mohand, S.; Muzart, J. J. Mol. Catal. 1998, 129, 135-139.
7. Corey, E. J.; Palani, A. Tetrahedron Lett. 1995, 36, 3485-3488.
8. For instance: House, H. O. Modern Synthetic Reactions, 2nd Edition, W. A. Benjamin, Inc.: Menlo
Park, California, 1972.
9. (a) Silverstein, R. M.; Bassler, G. C.; Morril, T. C. Spectrometric Identification of Organic
Compounds, 5th Edition, John Wiley & Sons, Inc.: New York, 1991; (b) Williams, D. H.; Fleming,
I. Spectroscopic Methods in Organic Chemistry, McGraw-Hill: London, 1987.
10. (a) Breitmeier, E.; Voelter, W. Carbon-13 NMR Spectroscopy, 3rd Edition, VCH: Weinheim, 1990;
(b) Wehrli, F. W.; Wirthlin, T. Interpretation of Carbon-13 NMR Spectra, Heyden & Son Ltd.:
London, 1976.
11. (a) Setzer, W. N.; Brown, M. L.; Yang, X. J.; Thompsom, M. A.; Whitaker, K. W. J. Org. Chem.
1992, 57, 2812-2818; (b) Laurenti, D.; Feuerstein, M.; Pèpe, H. D.; Santelli, M. J. Org. Chem.
2001, 66, 1633-1637; (c) Harada, T.; Wada, I.; Oku, A. J. Org. Chem. 1989, 54, 2599-2605.
12. (a) Dess, D. B.; Martin, J. C. J. Amer. Chem. Soc. 1991, 113, 7277-7287; (b) Ireland, R. E.; Liu, L.
J. Org. Chem. 1993, 58, 2899.
Sample availability: Samples of compounds 1 and 12 are available from MDPI.
© 2002 by MDPI (http://www.mdpi.org). Reproduction is permitted for noncommercial purposes.