Synthesis and reactivity of a new functionalized and highly pyramidalized alkene containing the bisnoradamantane skeleton

Article abstract of DOI:10.1016/S0040-4020(02)01323-6

The generation and trapping of the highly pyramidalized 3,7-isopropylidenedioxytricyclo[3.3.0.0^3,7]oct-1(5)-ene 16 containing ketal functions is reported. Its dimerization followed by a [2+2] retrocycloaddition reaction allows a straightforward access to functionalized polycyclic compounds.

Full text of DOI:10.1016/S0040-4020(02)01323-6

Tetrahedron 58 (2002) 10081–10086
Synthesis and reactivity of a new functionalized and highly
pyramidalized alkene containing the bisnoradamantane skeleton
*
Pelayo Camps, Xavier Pujol and Santiago Vazquez
´
´ ` `
Laboratori de Quımica Farmaceutica (Unitat Associada al CSIC), Facultat de Farmacia, Universitat de Barcelona, Av. Diagonal 643,
Barcelona E-08028, Spain
Received 16 July 2002; accepted 4 October 2002
Abstract—The generation and trapping of the highly pyramidalized 3,7-isopropylidenedioxytricyclo[3.3.0.03,7]oct-1(5)-ene 16 containing
ketal functions is reported. Its dimerization followed by a [2þ2] retrocycloaddition reaction allows a straightforward access to functionalized
polycyclic compounds. q 2002 Elsevier Science Ltd. All rights reserved.
1. Introduction
(DSC). The conversion of cyclobutane 3a to diene 5a was
shown to be faster than the previous one (1H NMR
spectroscopy), a fact that was in accord with theoretical
calculations on the relative stability of these pairs of
compounds. In fact, cyclobutane 3a was obtained at best as a
mixture containing 3a and 5a in the ratio of 4:1. Later on,
we described the first cross coupling reactions between two
highly pyramidalized alkenes (2a/7a and 2b/7a)2 and a
similar cross coupling reaction3 implying for the first time a
functionalized and highly pyramidalized alkene (2b/7b). In
the last case, the corresponding cyclobutane cross product
(8c) was quite thermally stable, although it could be fully
transformed into the corresponding diene 9c which on
irradiation gave back the cyclobutane product (Scheme 2).
Further manipulation of the functional groups in 8c led to
the dienetetrone 11, via the cyclobutane derivative 10.3
Earlier, we described the synthesis of the unfunctionalized
highly pyramidalized alkenes 2a and 2b (Scheme 1), their
trapping with dienes and its dimerization in the absence of
any trapping agent.1 When deiodination was carried out at
room temperature cyclobutane dimers 3 were isolated, while
working under refluxing 1,4-dioxane diene dimers 5 were
obtained. Dienes 5 were transformed photochemically to
cyclobutanes 3 on irradiation in the absence of any
photosensitizer and the cyclobutane compounds 3 were
converted back into dienes 5 on heating.
The thermal conversion of cyclobutane 3b to diene 5b could
be cleanly followed by differential scanning calorimetry
In continuing our interest on the synthesis of functionalized
and highly pyramidalized alkenes as useful intermediates in
organic synthesis, we describe herein the synthesis,
trapping and dimerization of 3,7-isopropylidenedioxy-
tricyclo[3.3.0.03,7]oct-1(5)-ene 16 (Scheme 3).
2. Results and discussion
The preparation of 16 was planned from the diiodo
derivative 15, whose synthesis was 0 envisioned from the
known pinacol 12,4 in which the 2,2 -biphenylene subunit
represents two latent carboxyl functions. Ketalization of
pinacol 12 was carried out in a standard way by reaction
with 2,2-dimethoxypropane under p-TsOH catalysis. For
the conversion of the 2,20-biphenylene subunit into two
carboxyl groups we used ruthenium tetroxide generated
from a catalytic amount of RuCl3·H2O and an excess of an
aqueous solution of NaClO (13%, from Fluka) in a
Scheme 1. Synthesis, chemical trapping and dimerization of highly
pyramidalized alkenes 2a,b.
Keywords: cyclobutane; bisnoradamantane skeleton; pyramidalized
alkenes.
*
Corresponding author. Tel.: þ34-93-402-4536; fax: þ34-93-403-5941;
e-mail: camps@farmacia.far.ub.es
0040–4020/02/$ - see front matter q 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020(02)01323-6

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P. Camps et al. / Tetrahedron 58 (2002) 10081–10086
into account the Sharpless related procedure.6 In this way,
diacid 14 could be obtained in 68% yield of crystallized
product. Worthy of note, in a run in which oxidation was not
complete for unknown reasons, we isolated acid 20 in 25%
yield instead of diacid 14 (Scheme 4). Compound 20 was
converted into 14 in 68% yield, on further oxidation under
similar conditions.
Compound 20, might be an intermediate in the conversion
of 13 to 14, formed by oxidation of only one of the phenyl
rings. It is interesting the fact that the phenyl ring of 20 is
oxidized by this procedure in spite of having an electron-
withdrawing substituent.7 To the best of our knowledge, this
is the first time a biphenylene group has been used as two
latent carboxyl groups.
Iododecarboxylation of 14 was carried out as usual by
reaction with iodosobenzene diacetate and iodine in
8
´
CH2Cl2, following the Moriarty modification of the Suarez
procedure.9 In this way, diiodo compound 15 was obtained
as a white solid in 49% yield. Reaction of 15 with t-BuLi in
the presence of 1,3-diphenylisobenzofuran (1,3-DPIBF)
gave in good yield compound 17, the Diels–Alder adduct
derived from the expected highly pyramidalized alkene 16
and the 1,3-DPIBF, as the diene. When compound 15 was
reacted with melted sodium in boiling 1,4-dioxane, diene
dimer 19 was obtained in 63% yield. No cyclobutane dimer
Scheme 2. Cross-coupling of highly pyramidalized alkenes leading to
tetrasecododecahedradienes.
˚
Scheme 3. (i) 2,2-Dimethoxypropane, p-TsOH, 4 A molecular sieves, CHCl3, reflux, 3 h, 69%; (ii) RuCl3·H2O, NaOCl, CH3CN/CH2Cl2/H2O, room
temperature, 60 h, 68%; (iii) I2, iodosobenzene diacetate, CH2Cl2, hn, 4 h, 49%; (iv) t-BuLi, 1,3-diphenylisobenzofuran, 2788C, 30 min, 61%; (v) Na, 1,4-
dioxane, reflux, 4 h, 63%; (vi) hn, cyclohexane, 6 h.
two-phase system, using a mixture of acetonitrile/CH2Cl2 as
the organic phase. This procedure is an improved modifi-
cation of the Wolfe method,5 in which the solvent (CCl4) is
replaced by CH2Cl2 and acetonitrile is also added taking
was observed in this reaction. Moreover, when compound
19 was irradiated with a 300 W tungsten lamp in
cyclohexane, contrary to all of the previously studied dienes
(5a, 5b, 9a–9c), no cyclobutane derivative 18 was ever
observed.
This different behavior can be understood taking into
account the relative enthalpies of reaction and strain
energies calculated (MM210) for the conversion of the
cyclobutane derivatives into the corresponding dienes
(Table 1). Since, we had previously carried out different
ab initio calculations (including MP2/6-31Gp and B3LYP/
6-31Gp) on cyclobutanes 3b and 10 and dienes 5b and 11
which gave comparable results to the MM2 method and to
the experimental values,1c,3b we did not perform ab initio
calculations in the cases of 18 and 19. As can be seen
Scheme 4. (i) RuCl3·H2O, aqueous 5.4% NaOCl, CH3CN/CH2Cl2/H2O,
room temperature, 60 h, 25%; (ii) RuCl3·H2O, aqueous 4.25% NaOCl,
CH3CN/CH2Cl2/H2O, room temperature, 60 h, 68%.

P. Camps et al. / Tetrahedron 58 (2002) 10081–10086
10083
Table 1. Molecular mechanics (MM2) data [enthalpies of reaction (DHr,
kcal/mol), strain energy differences (DEstr, kcal/mol)] calculated for the
conversion of cyclobutane derivatives 3a,b, 8c, 10 and 18 to dienes 5a,b,
9c, 11 and 19, respectively
Table 2. Molecular mechanics (MM2) data [distances between the olefinic
˚
carbon atoms (d, A), angle of pyramidalization (F, degrees), strain energy
(Estr, kcal/mol) and strain energy differences (OSE)] calculated for
compound 19 and its mono-(19þH2) and di-hydrogenated (19þ2H2)
products
Transformation
DHr (diene–cyclobutane)
DEstr (diene–cyclobutane)
Parameter
19
19þH2
19þ2H2
3a!5a
3b!5b
8c!9c
10!11
18!19
246.1
243.2a,b
221.0
284.2
281.2
259.1
274.3
295.2
dC1–C8
F
Estr
2.91
11.1
46.8
12.2
3.28
10.7
59.0
3.73
–
68.3
236.2b,c
257.1
OSE [192(19þH2)]
OSE [(19þH2)2(19þ2H2)]
9.3
a
The experimental value obtained by DSC in dynamic experiments was
245.6^1.1 kcal/mol.1b
Different ab initio methods, including MP2/6-31Gp and B3LYP/6-31Gp,
gave comparable results.1c,3b
b
c
Worthy of note, the calculated shortening of the C4–C5
(C10–C11) bonds in passing from 18 to 19 was only
˚
0.006 A. This fact must be related to the presence of the
The experimental value obtained by DSC in dynamic experiments was
230.7^1.4 kcal/mol.3b
ketal rings in these compounds, altogether explaining the
lower strain energy increase in the conversion of 18 to 19
and the relative instability of 18, which could not be
detected.
from Table 1, the conversion of 18 to 19 (DHr¼257.1 kcal/
mol) is by far the most exothermic of these processes. The
closest more exothermic process corresponds to the
conversion of 3a to 5a (DHr¼246.1 kcal/mol) and as we
previously stated,1c pure cyclobutane derivative 3a could
not be obtained because of its easy opening to 5a. The rest of
the cyclobutane derivatives collected in Table 1 (3b, 8c and
10) showed to be stable compounds that were converted into
the corresponding dienes (5b, 9c and 11) on heating. As a
rule, the more exothermic is the reaction the faster it is, what
suggests product-like transition states.
The calculated pyramidalization angle (F) of 16 (62.68,
B3LYP/6-31Gp)11 is similar to those previously calculated
for the related alkenes 2a, 2b, 7a and 7b.2 Also, diene 19 is a
slightly pyramidalized (F¼11.18, MM210) and hyperstable
alkene12 (see Table 2) as it was the case for dienes 5a, 5b,
9a–9c.3b,13
All of the new compounds herein described have been fully
characterized on the basis of their spectral data (IR, 1H- and
As can be seen from Table 1, the strain energy associated
with these transformations (DEstr) is the main responsible
for the enthalpy differences (DHr). The main contribution to
DEstr in these reactions is due to the opening of the
cyclobutane ring while other contributions can account for
the observed DEstr differences. For instance, we explained
the relative high stability of cyclobutane 8c taking into
account the strain energy involved in its conversion to the
more spherical diene 9c. The strain energy due to the
approach of the 4H/18Hb, 5H/20Hb, 10H/19Hb and 11H/
15Hb pairs of protons in the opened compound may
partially compensate the strain release associated with the
opening of the cyclobutane. The absence in 11 of the
4(5,10,11)-H protons due to the sp2 hybridized C4(5,10,11)
carbon atoms, reduces the strain energy associated with the
conversion of 10 to 11, making this a faster reaction.3a The
absence in 3a, 3b and 18 of the substituted ethylene bridges,
present in the above compounds, further reduces the strain
energies associated with their conversion to the correspond-
ing dienes, all these transformations being faster than the
previous ones. We also explained the greater stability of 3b
as compared with 3a on the basis of the increased crowding
around the C4–C5 (C10–C11) bonds in passing from 3b to
5b due to the shortening of these bonds. The experimental
1
1
13C NMR, COSY H/1H, COSY H/13C and MS spectra)
and elemental analyses.
In conclusion, the functionalized and highly pyramidalized
alkene 16 has been generated, trapped as the Diels–Alder
adduct 17 and dimerized to diene 19.0 A key-step of this
synthesis consists of the use of the 2,2 -biphenylene group
as two latent carboxyl groups, this transformation being
carried out by RuO4 oxidation using a catalytic amount of
RuCl3·H2O and excess of NaClO in an improved two-phase
system (acetonitrile–CH2Cl2/H2O).
Work is in progress to use the developed methodology for
the generation and trapping of reactive intermediates having
two highly pyramidalized double bonds.
3. Experimental
3.1. General
Melting points were determined with a MFB 595010 M
Gallenkamp melting point apparatus. Unless otherwise
stated, NMR spectra were recorded in CDCl3 in the
following spectrometers: 1H NMR (500 MHz, Varian
˚
C4–C5 (C10–C11) bond length in 3b is 1.649(4) A and the
1b
˚
corresponding length in 5b is 1.622(4) A (X-ray). The
1
˚
shortening of these bonds (0.027 A) in going from 3b to 5b
˚
is close to the value calculated by MM2 (0.020 A). A similar
VXR 500), 13C NMR (75.4 MHz, Varian Gemini 300). H
and 13C NMR chemical shifts (d) are reported in ppm with
respect to internal tetramethylsilane (TMS). The multi-
plicity of the signals is: s, singulet; d, doublet; t, triplet; m,
multiplet. Assignments given for the NMR spectra are based
on DEPT, COSY 1H/1H, HETCOR 1H/13C (HMQC
sequence) experiments. IR spectra were recorded on a
FT/IR Perkin–Elmer spectrometer, model 1600. Routine
shortening of these bonds were also calculated for the
˚
conversion of 3a to 5a (0.025 A). Obviously, the strain
increase associated with the shortening of these bonds,
should be higher in the conversion of 3b to 5b, due to the
presence of the methyl groups on these carbon atoms,
making this process less exothermic and 3b more stable.

10084
P. Camps et al. / Tetrahedron 58 (2002) 10081–10086
1
MS spectra were taken on a Hewlett-Packard 5988A
spectrometer, the sample was introduced directly or through
a gas chromatograph, Hewlett-Packard model 5890 Series
II, equipped with a 30-meter HP-5 (5% diphenyl–95%
dimethyl-polysiloxane) column [10 psi, initial temperature:
1008C (2 min), then heating at a rate of 10 8C/min till 2508C,
then isothermic] and the electron impact technique (70 eV).
Only significant ions are given: those with higher relative
abundance, except for the ions with higher m/z values.
Neutral aluminum oxide MN and silica gel SDS 60 (60–
200 mm) were usually used for the standard column
chromatography. NMR and routine MS spectra were
709 cm21. H NMR (CD3OD) 1.50 [s, 6H, C(CH3)2], 2.03
[d, J¼7.0 Hz, 4H, 2(4,6,8)-Hb], 2.32 [d, J¼7.0 Hz, 4H,
2(4,6,8)-Ha], 4.87 (broad s, 2H, mobile H). 13C NMR
(CD3OD) 28.6 [CH3, (CH3)2C], 52.8 [CH2, C2(4,6,8)], 55.6
[C, C1(5)], 90.2 [C, C3(7)], 122.2 [C, (CH3)2C], 174.7 (C,
COOH). MS (EI), m/z (%): 268 (Mzþ, 1), 253 [(M2CH3)þ,
8], 210 [(M2C3H6O)zþ, 50], 192 [(M2C3H6O–H2O)zþ,
53], 165 [(M2C3H6O–COOH)zþ, 25], 164 (35), 146 (38),
119 (31), 91 (100), 59 (89). Anal. calcd for
C13H16O6·1/2H2O: C 56.31, H 6.18. Found C 56.37, H
6.08. The same yield was obtained by using 4.25% aqueous
NaOCl.
´
`
performed at the Serveis Cientıfico-Tecnics of the Univer-
sity of Barcelona, while elemental analyses were carried out
at the Microanalysis Service of the IIQAB (CID, CSIC),
Barcelona, Spain. Systematic names for 17 and 19 were
obtained with the POLCYC program.14
3.1.3. 5-(2-Hydroxycarbonylphenyl)-3,7-(isopropyl-
idenedioxy)tricyclo[3.3.0.03,7]octane-1-carboxylic acid
(20). To a solution of 13 (660 mg, 2.0 mmol) in CH2Cl2
(14 mL), acetonitrile (14 mL) and H2O (24 mL), RuCl3·H2O
(24 mg, 0.11 mmol) was added, and then, aqueous NaOCl
(195 mL, 5.4% aqueous solution, approx. 142 mmol) was
added dropwise. The flask was stopped and the mixture was
vigorously stirred at room temperature for 60 h. After a
working-up similar to that described in Section 3.1.2, an oily
residue was obtained which was dissolved in CHCl3 (5 mL)
and treated with cyclohexylamine (2 mL). The obtained
solid was filtered, taken in water (5 mL) and the solution
was made acidic with 1N HCl. The aqueous solution was
extracted with ethyl acetate (3£5 mL) and the combined
organic extracts were dried (Na2SO4), filtered and concen-
trated in vacuo to give 20 as a white solid (170 mg, 25%
yield). An analytical sample of 20 was obtained by
crystallization, mp 204–2058C (dec.) (hexane/ethyl acetate,
1:1). IR (KBr) 3500-2400 (max. at 3147, 3065, 3002, 2951,
2901, 2623, 2590, OH st and CH st), 1735 and 1703 (CO st),
1488, 1434, 1379, 1335, 1288, 1249, 1211, 1164, 1125,
3.1.1. 1,5-(2,20-Biphenylene)-3,7-(isopropylidenedioxy)-
tricyclo[3.3.0.03,7]octane (13). To a solution of 3,7-(2,20-
biphenylene)tricyclo[3.3.0.03,7]octane-1,5-diol
(12)4
˚
(3.49 g, 12.0 mmol) in CHCl3 (230 mL), 4 A molecular
sieves (20 g), 2,2-dimethoxypropane (6.5 mL) and
p-toluenesulfonic acid monohydrate (120 mg) were added
and the mixture was heated under reflux for 3 h. The mixture
was allowed to cool to room temperature and filtered and the
filtrate was concentrated in vacuo to give crude 13 (3.51 g).
Crystallization of the above solid (isopropanol) gave pure
13 as a white solid (2.73 g, 69% yield), mp 195.5–196.58C
(isopropanol). IR (KBr) 3065, 2989, 2940, 2891, 1496,
1442, 1373, 1277, 1258, 1227, 1202, 1164, 1120, 991, 971,
1
848, 763, 728 cm21. H NMR 1.63 (s, 6H, C(CH3)2), 2.32
(d, J¼6.8 Hz, 4H) and 2.38 (d, J¼6.8 Hz, 4H) [2(4,6,8)-Ha
and 2(4,6,8)-Hb], 7.21–7.25 [m, 6H, 30(300)-H, 40(400)-H and
50(500)-H], 7.87–7.91 [m, 2H, 60(600)-H]. 13C NMR 28.6
[CH3, (CH3)2C], 46.9 [C, C1(5)], 56.9 [CH2, C2(4,6,8)],
88.6 [C, C3(7)], 120.0 [C, (CH3)2C], 123.0 (CH), 126.9
(CH), 127.3 (CH) and 128.1 (CH) (Ar-CH), 130.6 (C) and
136.2 (C) (Ar-C). MS (EI), m/z (%): 330 (Mzþ, 11), 272
[(M2C3H6O)zþ, 10], 232 (40), 229 (32), 215 (24), 204 (25),
203 (38), 202 (35), 98 (30), 59 (100). Anal. calcd for
C23H22O2: C 83.60, H 6.72. Found C 83.85, H 6.77.
1
1080, 1050, 994, 972, 845, 797, 756, 725, 641 cm21. H
NMR (CD3OD) 1.52 (s, 3H) and 1.54 (s, 3H)[C(CH3)2],
2.00 [dd, J¼7.8 Hz, J0¼3.8 Hz, 2H, 4(6)-Hb], 2.12 [dd,
J¼8.0 Hz, J0¼3.5 Hz, 2H, 2(8)-Hb], 2.57 [d, J¼8.0 Hz, 2H,
2(8)-Ha], 2.77 [d, J¼7.5 Hz, 2H, 4(6)-Ha], 4.87 (s, 2H,
mobile H), 7.27 (dt, J¼1.3 Hz, J0¼7.5 Hz, 1H, Ar-4-H),
7.42 (dt, J¼0 1.5 Hz, J0¼7.5 Hz, 1H, Ar-5-H), 7.47 (dd,
J0¼1.0 Hz, J ¼8.0 Hz, 1H, Ar-6-H), 7.58 (dd, J¼1.3 Hz,
J ¼7.8 Hz, 1H, Ar-3-H). 13C NMR (CD3OD) 28.8 [CH3,
(CH3)2C], 52.9 [CH2, C2(8)], 54.1 [CH2, C4(6)], 56.5 (C,
C1), 58.3 (C, C5), 90.0 [C, C3(7)], 121.6 [C, (CH3)2C],
127.6 (CH, Ar-C4), 130.3 (CH, Ar-C3), 130.8 (CH, Ar-C6),
131.6 (CH, Ar-C5), 134.2 (C, Ar-C2), 140.4 (C, Ar-C1),
173.2 (C, Ar-COOH), 175.9 (C, 1-COOH). MS (EI), m/z
(%): 329 [(M2CH3)þ, 58], 326 [(M2H2O)þ, 16], 269
[(M2C3H8O–OH)þ, 69], 268 [(M2C3H8O–H2O)zþ, 31],
251 (47), 223 (42), 165 (54), 115 (51), 69 (60), 59 (57), 57
(79), 55 (100). Anal. calcd for C19H20O6·1/2H2O: C 64.58,
H 5.99. Found C 64.67, H 5.91.
3.1.2. 3,7-(Isopropylidenedioxy)tricyclo[3.3.0.03,7]-
octane-1,5-dicarboxylic acid (14). To a solution of 13
(0.29 g, 0.88 mmol) in CH2Cl2 (6 mL), acetonitrile (6 mL)
and H2O (12 mL), RuCl3·H2O (12 mg, 0.053 mmol) was
added and then aqueous NaOCl (31 mL, 13% aqueous
solution, approx. 54 mmol, approximately double than the
maximum theoretical amount) was added dropwise. The
flask was stopped and the mixture was vigorously stirred at
room temperature for 60 h. The organic layer was separated
and the aqueous phase was washed with CH2Cl2 (4£10 mL),
cooled (ice-bath), made acidic (pH 2–3) with 2N HCl
(5 mL) and extracted with ethyl acetate (4£15 mL). The
combined ethyl acetate extracts were dried (Na2SO4),
filtered and concentrated in vacuo to give pure 14 as a
white solid (0.16 g, 68% yield). An analytical sample of 14
was obtained by crystallization, mp 2308C (hexane/ethyl
acetate). IR (KBr) 3400–2500 (max. at 3195, 2982, 2937,
2902, 2686, 2581, OH st, CH st), 1739, 1713 and 1679 (CO
st), 1487, 1409, 1373, 1290, 1266, 1238, 1205, 1180, 1165,
1150, 1133, 1119, 1089, 1023, 965, 890, 857, 827, 767,
3.1.4. Oxidation of 20 to 14. To a solution of 20·1/2H2O
(120 mg, 0.35 mmol) in CH2Cl2 (3 mL), acetonitrile (3 mL)
and H2O (5 mL), RuCl3·H2O (5 mg, 0.022 mmol) was
added, and then aqueous NaOCl (40 mL, 4.25% aqueous
solution, approx. 23 mmol) was added dropwise. The flask
was stopped and the mixture was vigorously stirred at room
temperature for 60 h. The organic layer was separated and
the aqueous phase was washed with CH2Cl2 (4£10 mL),
cooled (ice-bath), made acidic (pH 2–3) with 2N HCl

P. Camps et al. / Tetrahedron 58 (2002) 10081–10086
10085
(2 mL) and extracted with ethyl acetate (4£15 mL). The
combined ethyl acetate extracts were dried (Na2SO4),
filtered and concentrated in vacuo to give 14 (64 mg, 68%
yield).
C3(17)], 59.6 [C, C2(7)], 87.9 [C, C1(8)], 88.8 (C) and 89.4
(C) (C4 and C5), 119.4 [C, C(CH3)2], 120.0 [CH, C11(12)],
125.6 [CH, Ar-Cortho], 126.9 [CH, C10(13)], 127.6 (CH, Ar-
Cpara), 128.4 (CH, Ar-Cmeta), 137.4 (C, Ar-Cipso), 146.4 [C,
C9(14)]. GC/MS (EI), tr¼36.9 min, m/z (%): 448 (Mzþ, 2),
390 [(M2C3H6O)zþ, 14], 362 [(M2C3H6O–CO)zþ, 23],
334 (26), 306 (22), 285 (27), 271 (27), 270 [(C20H14O)zþ,
100], 105 (C6H5COþ, 94), 77 (61). Anal. calcd for
C31H28O3: C 83.01, H 6.29. Found C 82.99, H 6.37.
3.1.5. 1,5-Diiodo-3,7-(isopropylidenedioxy)tricyclo
[3.3.0.03,7]octane (15). A suspension of diacid 14 (2.0 g,
7.46 mmol), iodosobenzene diacetate (5.3 g, 16.4 mmol)
and iodine (4.17 g, 16.4 mmol) in anhydrous CH2Cl2
(100 mL) was irradiated under reflux with a 60 W tungsten
lamp for 4 h. The mixture was allowed to cool to room
temperature, more iodosobenzene diacetate (5.3 g,
16.4 mmol) and iodine (4.17 g, 16.4 mmol) were added
and irradiation under reflux was continued for 18 h more.
The cold (room temperature) solution was washed with 10%
aqueous solution of sodium thiosulfate (3£30 mL), satu-
rated NaHCO3 aqueous solution (3£30 mL) and brine
(2£30 mL), dried (Na2SO4), filtered and concentrated in
vacuo to give a residue (3.7 g) which was submitted to
column chromatography (silica gel, hexane/ethyl acetate
mixtures). On elution with hexane/ethyl acetate mixture in
the ratio of 96:4, pure 15 (1.57 g, 49% yield) was obtained
as a white solid. An analytical sample of 15 was obtained by
crystallization, mp 157–1588C (hexane). IR (KBr) 2985,
2940, 2896, 1474, 1374, 1273, 1238, 1202, 1158, 1109,
3.1.7. 4,5:10,11-Bis(isopropylidenedioxy)pentacyclo
[8.2.1.12,5.14,7.18,11]hexadeca-1,7-diene (19). A mixture
of freshly cut sodium (460 mg, 20 mmol) in anhydrous
1,4-dioxane (20 mL) was heated under reflux until sodium
melted. Then, diiodide 15 (864 mg, 2.0 mmol) was added
and the mixture was heated under reflux for 4 h. The
resulting suspension was allowed to warm to room
temperature and filtered through Celitew. The solid material
was washed with CHCl3 (3£10 mL) and the combined
organic phases were concentrated in vacuo to give a residue
(359 mg). Column chromatography (neutral aluminum
oxide, hexane/CHCl3 mixtures) of the above residue
furnished, on elution with a mixture hexane/CHCl3 in the
ratio of 65:35, pure 19 as a white solid, (225 mg, 63% yield).
The analytical sample of 19 was obtained by crystallization,
mp .3308C (CHCl3). IR (KBr) 2977, 2931, 2916, 2885,
2855, 1456, 1371, 1311, 1274, 1228, 1208, 1150, 1098, 994,
1
1059, 980, 899, 851, 821, 797, 752, 679 cm21. H NMR
1.49 [s, 6H, C(CH3)2], 2.26 [d, J¼7.5 Hz, 4H, 2(4,6,8)-Hb],
2.66 [d, J¼7.5 Hz, 4H, 2(4,6,8)-Ha]. 13C NMR 28.4 [CH3,
C(CH3)2], 38.7 [C, C1(5)], 61.3 [CH2, C2(4,6,8)], 88.5 [C,
C3(7)], 121.4 [C, C(CH3)2]. GC/MS (IE), tr¼22.9 min, m/z
(%): 417 [(M2CH3)þ, 1], 305 [(M2I)þ, 97], 247 [(M2I–
C3H6O)þ, 13], 178 [(M22I)zþ, 11], 120 [(M22I–
C3H6O)zþ, 72], 92 (70), 91 (100). Anal. calcd for
C11H14I2O2: C 30.58, H 3.27, I 58.75. Found C 30.86, H
3.27, I 58.61. In different runs, the yields were in the range
49–53%.
1
912, 895, 845, 749, 702, 654 cm21. H NMR (300 MHz)
1.52 [s, 12H, C(CH3)2], 2.47 (d, J¼12.5 Hz, 8H) and 3.05
(d, J¼12.5 Hz, 8H) [3(6,9,12,13,14,15,16)-Ha and
3(6,9,12,13,14,15,16)-Hb]. 13C NMR 29.6 [CH3,
C(CH3)2], 46.1 [CH2, C3(6,9,12,13,14,15,16)], 89.6 [C,
C4(5,10,11)], 117.9 [C, C(CH3)2], 135.9 [C, C1(2,7,8)].
GC/MS (EI), tr¼29.9 min, m/z (%): 357 [(MþH)þ, 18], 356
(Mzþ, 70), 341 [(M2CH3)þ, 40], 298 [(M2C3H8O)zþ, 10],
240 [(M22C3H8O)zþ, 47], 212 (49), 184 (76), 170 (48), 169
(100), 155 (43), 141 (47), 129 (43), 128 (45), 91 (64), 77
(44). Anal. calcd for C22H28O4: C 74.13, H 7.92. Found C
74.00, H 7.96.
3.1.6. 4,5-Isopropylidenedioxy-1,8-diphenyl-15-oxahexa-
cyclo[6.6.1.12,5.14,7.02,7.09,14]heptadeca-9,11,13-triene
(17). A mixture of 15 (203 mg, 0.47 mmol) and 1,3-
diphenylisobenzofuran (152 mg, 0.56 mmol) in anhydrous
THF (7.5 mL) was cooled to 2788C and a solution of
t-butyllithium (1.5 M in pentane, 535 mL, 0.8 mmol) was
added dropwise. After stirring for 30 min at this tempera-
ture, methanol (2 mL) and water (10 mL) were added and
the mixture was extracted with diethyl ether (3£10 mL).
The combined organic phases were dried (Na2SO4) and
concentrated in vacuo to give a residue (266 mg), which was
submitted to column chromatography (silica gel, mixture of
hexane/ethyl acetate in the ratio of 96:4) to give pure 17
(128 mg, 61% yield). The analytical sample was obtained
by crystallization, mp 186–1878C (hexane). IR (KBr) 3060,
3032, 2990, 2938, 2889, 1601, 1498, 1474, 1453, 1371,
1348, 1305, 1265, 1246, 1210, 1194, 1155, 979, 886, 859,
764, 743, 717, 697, 678 cm21. 1H NMR 1.36 [dd, J¼3.5 Hz,
J0¼7.5 Hz, 2H, 3(17)-Hsyn], 1.46 [s, 6H, C(CH3)2], 1.85 [d,
J¼8.0 Hz, 2H, 6(16)-Hanti], 1.98 [dd, J¼3.5 Hz, J0¼7.8 Hz,
2H, 6(16)-Hsyn], 2.03 [d, J¼8.0 Hz, 2H, 3(17)-Hanti], 6.95
[dd, J¼3.0 0Hz, J0¼5.5 Hz, 2H, 11(12)-H], 7.12 [dd,
J0¼3.0 Hz, J ¼5.5 Hz, 2H, 10(13)-H], 7.37 [tt, J¼7.5 Hz,
J ¼1.5 Hz, 2H, Ar-Hpara], 7.46 [pseudo t, J¼7.5 Hz, 4H,
Ar-Hmeta], 7.61 [dd, J¼8.5, J0¼1.5 Hz, 4H, Ar-Hortho]. 13C
NMR 28.2 [CH3, (CH3)2C], 50.2 [CH2, C6(16)], 50.9 [CH2,
Acknowledgements
Financial support from Comissionat per a Universitats i
Recerca of the Generalitat de Catalunya (project 2001-SGR-
00085) is gratefully acknowledged. S. V. thanks to the
´
Ministerio de Ciencia y Tecnologıa for a fellowship
(Programa Ramon y Cajal). We thank the Serveis
´
´
`
Cientıfico-Tecnics of the University of Barcelona and
particularly Dr M. Feliz and Dr A. Linares for recording
´
the NMR spectra, the Centre de Supercomputacio de
Catalunya (CESCA) for computational facilities and Ms
`
P. Domenech from the IIQAB (CSIC, Barcelona, Spain) for
carrying out the elemental analyses.
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