A convenient preparation of 1,2,3,4,5,6,7,8-octahydro-naphthalene skeleton. Synthesis of (±)-isocaridiene

Article abstract of DOI:10.1081/SCC-120003636

Synthesis of isocaridiene, an isomeric compound of natural sesquiterpene caridiene, is described starting from myrcene. Dehydration of tertiary alcohol leading exclusively to isocaridiene was in agreement with the semiempirical and ab initio quantum mechanical calculations.

Full text of DOI:10.1081/SCC-120003636

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A CONVENIENT PREPARATION OF 1,2,3,4,5,6,7,8-
OCTAHYDRO-NAPHTHALENE SKELETON. SYNTHESIS OF
(±)-ISOCARIDIENE
Paulo M. Imamura a , Marta Costa b & Rogério Custódio a
a Instituto de Química , UNICAMP , C.P. 6154, Campinas, SP, 13083-970, Brazil
b Departamento de Química , UFPE , PE, Brazil
Published online: 17 Aug 2006.
To cite this article: Paulo M. Imamura , Marta Costa & Rogério Custódio (2002) A CONVENIENT PREPARATION OF
1,2,3,4,5,6,7,8-OCTAHYDRO-NAPHTHALENE SKELETON. SYNTHESIS OF (±)-ISOCARIDIENE, Synthetic Communications: An
International Journal for Rapid Communication of Synthetic Organic Chemistry, 32:9, 1393-1399, DOI: 10.1081/SCC-120003636
To link to this article: http://dx.doi.org/10.1081/SCC-120003636
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SYNTHETIC COMMUNICATIONS, 32(9), 1393–1399 (2002)
A CONVENIENT PREPARATION OF
1,2,3,4,5,6,7,8-OCTAHYDRO-
NAPHTHALENE SKELETON.
SYNTHESIS OF (6)-ISOCARIDIENE
Paulo M. Imamura,1, Marta Costa,2
*
and Rogerio Custodio1
1Instituto de Quımica, UNICAMP, C.P. 6154,
Campinas, SP, Brazil 13083-970
2Departamento de Quımica, UFPE, PE, Brazil
ABSTRACT
Synthesis of isocaridiene, an isomeric compound of natural
sesquiterpene caridiene, is described starting from myrcene.
Dehydration of tertiary alcohol leading exclusively to isocar-
idiene was in agreement with the semiempirical and ab initio
quantum mechanical calculations.
Caridiene (1)1 is a new sesquiterpene isolated from Pseudoterogorgonia
americana, a gorgonian collected in Havana, Cuba, whose structure was
determined through careful analysis of its spectroscopic data. The occur-
rence of natural products having 1,2,3,4,5,6,7,8-octahydronaphthalene
moiety as part of the molecule is becoming frequent nowadays, such as in
*Corresponding author.
1393
Copyright & 2002 by Marcel Dekker, Inc.
www.dekker.com

1394
IMAMURA, COSTA, AND CUSTODIO
nanaimoal (2)2,3 ent-halima-5(10), 13E-dien-15-oic acid (3),4 salmantic acid
(4),5 and many others.
Continuing our interest in the synthesis of marine sesquiterpenoid,6 we
would like to describe here a straightforward synthesis of isocaridiene (5), an
isomeric compound of 1. The Diels-Alder reaction of myrcene (6) with
methyl vinyl ketone (7) using Me2AlCl supported on silica gel as catalyst,7
gave exclusively a known para-adduct 88 in 72% yield (Scheme 1).
Scheme 1.
Refluxing 8 in formic acid at 60ꢀC for8 h afforded a bicyclic methyl
ketone 9 in 85%. The chemical shift of dimethyl group at C-4 appeared as a
singlet at d 0.98 and 0.99, and the methyl ketone as a singlet at d 2.18. The
13C NMR spectra showed 14 signals, two of them corresponding to tetra-
substituted sp2 carbon at d 133.6 and 127.2, and a carbonyl carbon at
d 212.7. Treatment of 9 with methyl magnesium iodide furnished, as

1,2,3,4,5,6,7,8-OCTAHYDRONAPHTHALENE
1395
expected, alcohol 10 in 77% yield. The IR spectra of 10 showed absorption
1
at 3384 cmꢁ1 (n O-H), and H NMR spectra showed two singlets at d 0.97
and 0.99 corresponding to two methyl groups at C-4, and one singlet at d
1.20 (6H) corresponding to two methyl groups at C-9. The 13C NMR analy-
sis showed two chemical shifts at d 127.2 and 134.5 corresponding to the
tetrasubstituted sp2 carbons, at d 73.1 corresponding to carbinolic carbon,
and chemical shifts of fourmethyl groups at d 26.8, 27.1, 27.4 and 28.5. In
order to obtain caridiene (1), compound 10 was submitted to the dehydra-
tion reaction in both acidic and basic conditions. In either case the reaction
took place, affording isocaridiene (5) as the sole product, instead of the
1
desirable 1. The H NMR spectra of this compound showed three singlets
at d 0.97, 0.99 and 1.02 corresponding to the methyl groups, and two olefinic
hydrogens at d 4.71 as broad singlet. The structure of 5 was confirmed by
analysis of 13C NMR spectra where the chemical shifts of sp2 carbons of
isopropenyl moiety appeared at d 108.4 (¼CH2) and 151.1 (C). Compound 5
was also prepared through Wittig reaction of ketone 9 with methylenetri-
phenylphosphorane in 70% yield. Any attempts for isomerization of disub-
stituted olefin to the tetrasubstituted olefin, always lead to the known
aromatized product 11.9 Thus isocaridiene (5), an isomeric compound of
caridiene (1), was prepared in three steps from myrcene (6) in 43% overall
yield. The sesquiterpenes 10 and 11 were also obtained in good yields.
The difficulty in the dehydration of 10 to give 1 was investigated by
quantum mechanical calculations. The molecular geometries and total ener-
gies of compounds 1 and 5 were calculated in three different levels of theory:
the semiempirical methods, the Hartree-Fock ab initio method and the
density functional theory. The semiempirical calculations were carried out
using the AMI10 and PM311 methods. Stevens, Basch and Krauss12 compact
effective pseudopotential (CEP) was used at the Hartree-Fock ab initio level
of theory with CEP-31G basis set in order to minimize computational
efforts. The electronic correlation effects were included through the use of
the density functional theory using the B3LYP functional13 also with pseu-
dopotential and the CEP-31G basis set. The Hartree-Fock calculations with
the CEP-31G basis set were compared with those including polarization
functions in all atoms, CEP-31G**, while the correlated calculations were
also reproduced with the CEP-31G* basis set. The structures of all com-
pounds were fully optimized at the three different levels of theory. All cal-
culations were done using the Gaussian 94 program.14
Table 1 shows the difference between the total equilibrium energies of
compounds 1 and 5 (ÁE ¼ E1 ꢁ E5). The semiempirical data indicate that
compound 5 is more stable than 1 by approximately 5–7 kcal molꢁ1
,
in agreement with the experimental observation. The ab initio results
show an opposite tendency. The Hartree-Fock calculation suggests that

1396
IMAMURA, COSTA, AND CUSTODIO
Table 1. Difference Between the Total Equilibrium Energies of
Compounds 1 and 5
Structure 1
(a.u.)
Structure 5
(a.u.)
ÁE ¼ E1 ꢁ E5
Method
(kcal molꢁ1
)
Aml
Pm3
ꢁ 0.0377535
ꢁ 0.0361915
ꢁ 96.0135370
ꢁ 96.2923434
ꢁ 99.0117797
ꢁ 99.1477940
ꢁ 99.1825865
ꢁ 0.0455074
ꢁ 0.0471473
ꢁ 96.0088415
ꢁ 96.2881163
ꢁ 99.0117166
ꢁ 99.1474149
ꢁ 99.1821601
4.86
6.87
Hf/cep-31g
Hf/cep-31g**
B3lyp/cep-31g
B3lyp/cep-31g*
B3lyp/cep-31g**
ꢁ 2.95
ꢁ 2.65
ꢁ 0.04
ꢁ 0.24
ꢁ 0.30
compound 1 is more stable than 5 by almost 3 kcal molꢁ1. The inclusion of
polarization functions diminishes the difference favoring structure 5. The
improvement of the Hartree-Fock calculation by the inclusion of electronic
correlation effects reduces significantly the difference between the total
energy of compounds 1 and 5. The B3LYP calculations show almost no
energetic difference between both compounds. The tendency from Hartree-
Fock to the B3LYP energies suggests that higher level calculations should
support the semiempirical results, confirming the greater stability of com-
pound 5 with respect to 1, in agreement with the experimental data. It must
be emphasized that the ab initio results reflect only the differences between
the total energy of molecules 5 and 1, while the semiempirical results con-
sider the differences between enthalpy of formation of both molecules.
EXPERIMENTAL
IR spectra were recorded on a Perkin-Elmer 1600 FT IR instrument.
MS spectra were obtained at 70 eV on an HP-5990/5970 system equipped
with a J and W Scientific DB-5 fused silica capillary column (30 m Â
1
0.25 mm  0.25 mm). H NMR and 13C NMR spectra were obtained with a
Bruker AC 300. Elemental analyses were performed with a Perkin-Elmer
2400 CHN analyzer.
1-[4-(40-Methyl-30-pentenyl)-3-cyclohexenyl] ethanone (8): To a suspen-
sion of 125 mg of catalyst (Me2AlCl/silica gel) in dry toluene (10 ml) was
added methyl vinyl ketone (56.62 mg, 0.94 mmol) at 0ꢀC, and mixture stirred
for20 min. Myrcene ( 6) (382.6 mg, 2.81 mmol) was then added to the mixture
and after stirring for 2.5 h the solution was filtered, and residue washed
several times with toluene. The solvent was removed under reduced pressure,

1,2,3,4,5,6,7,8-OCTAHYDRONAPHTHALENE
1397
and residue purified by silica gel chromatography (n-hexane/diethyl ether,
8 : 2) to give 140.0 mg (72%) of 8. IR (neat) n ¼ 2967, 1711, 1438, 1372,
1
1353, 1165 cmꢁ1; H NMR (300 MHz, CDCl3) d 1.60 (s, 3H), 1.68 (s, 3H),
1.70–2.08 (m, 9H), 2.17 (s, 3H), 2.30–2.70 (m, 2H), 5.09 (t, J ¼ 1.32, 1H), 5.41
(bs, 1H); 13C NMR (75 MHz, CDCl3) d 212.15 (C), 137.80 (C), 131.78 (C),
124.41 (CH), 119.17 (CH), 47.56 (CH), 37.59 (CH2), 28.04 (CH3), 27.97
(CH2), 27.13 (CH2), 26.45 (CH2), 25.74 (CH3), 25.04 (CH2), 17.70 (CH3);
MS (m/z, relative intensity): 206 (Mþ, 20), 163 (30), 93 (40), 43 (100);
C14H22O (206.3): Calcd C 81.50, H 10.75; found C 81.22, H 10.43.
1,1-Dimethyl-7-acetyl-1,2,3,4,5,6,7,8-octahydronaphthalene (9): A solu-
tion of 8 (52.8 mg, 0.26 mmol) in formic acid 99% (5 ml) was heated at 60ꢀC
for 8 h. After cooling at room temperature, H2O was added (20 ml), and solu-
tion extracted with diethyl ether (3 Â 15 ml). The organic layer was washed
with 1 N NaHCO3 solution (10 ml), brine (2 Â 10 ml), dried with anhydrous
sodium sulfate, filtered, and solvent removed under reduced pressure. The
residue was purified by silica gel chromatography (n-hexane) to give 44.8 mg
(85%) of 9. IR (neat) n ¼ 2927, 1709, 1438, 1359, 1169 cmꢁ1
;
1H NMR
(300 MHz, CDCl3) d 0.98 (s, 3H), 0.99 (s, 3H), 1.05–1.70 (m, 6H), 1.80–2.17
(m, 6H), 2.18 (s, 3H), 2.40–2.60 (m, 1H); 13C NMR (75 MHz, CDCl3) d 212.66
(C), 133.59 (C), 127.18 (C), 48.66 (CH), 39.70 (CH2), 33.86 (C), 31.14 (CH2),
30.53 (CH2), 28.25 (CH3), 28.09 (CH3), 27.19 (CH3), 26.33(CH2), 25.20
(CH2), 19.28 (CH2); MS (m/z, relative intensity): 206 (Mþ, 70), 163 (80),
105 (50), 91 (100), 43 (90); C14H22O (206.3): Calcd C 81.50, H 10.75; found
C 81.31, H 10.53.
1,1-Dimethyl-7-(propan-20-ol-20-yl)-1,2,3,4,5,6,7,8-octahydronaphtha-
lene (10): To a solution of methyl magnesium iodide (141.9 mg, 5.8 mmol of
Mg and 82.9 mg, 5.8 mmol of methyl iodide) in dry diethyl ether (25 ml) at
0ꢀC was added ketone 9 (120.3 mg, 0.58 mmol). Afterthe mixture had been
stirred for 4 h at 0ꢀC, a saturated solution of NH4Cl (10 ml) was added and
solution extracted with diethyl ether (3 Â 20 ml). The combined organic layer
was washed with brine (2 Â 20 ml), dried with anhydrous sodium sulfate,
filtered, and solvent removed under reduced pressure. The residue was pur-
ified by silica gel chromatography (n-hexane) to give 99.4 mg (77%) of 10. IR
(neat) n ¼ 3384, 2967, 1459, 1380, 1138 cmꢁ1; 1H NMR (300 MHz, CDCl3) d
0.97 (s, 3H), 0.99 (s, 3H), 1.20 (s, 6H), 1.30–2.20 (m, 14H); 13C NMR
(75 MHz, CDCl3) d 134.52 (C), 127.25 (C), 73.07 (C), 46.15 (CH), 39.81
(CH2), 33.90 (C), 31.94 (CH2), 33.11 (CH2), 28.51 (CH3), 27.15 (CH3),
27.12 (CH3), 26.78 (CH3), 25.76 (CH2), 24.18 (CH2), 19.36 (CH2); MS
(m/z, relative intensity): 222 (Mþ, 10), 170 (10), 133 (10), 121 (30), 109 (40),
69 (50); C15H26O (222.4): Calcd C 81.02, H 11.79; found C 80.89, H 11.47.
1,1-Dimethyl-7-isopropenyl-1,2,3,4,5,6,7,8-octahydronaphthalene (iso-
caridiene-5). Procedure A: To a solution of 10 (41.5 mg, 0.19 mmol) in

1398
IMAMURA, COSTA, AND CUSTODIO
pyridine (1 ml) at 0ꢀC was added phosphorous oxychloride (0.1 ml). After the
mixture of the solution had been stirred for 4 h at room temperature, a sol-
ution of HCl 0.1N (10 ml) was added, and mixture extracted with diethyl
ether(3 Â 20 ml), washed with brine (20 ml), dried with anhydrous sodium
sulfate, filtered, and solvent removed under reduced pressure. The residue was
purified by silica gel chromatography (n-hexane) to give 28.9 mg (78%) of 5.
Procedure B: To a solution of triphenylphosphonium bromide
ꢀ
(190.4 mg, 0.53 mmol) in diethyl ether(25 ml), at 0 C was added n-BuLi
(0.21 ml, 0.53 mmol). After stirring for 30 min, a solution of ketone 9
(54.9 mg, 0.17 mmol) in diethyl ether (1 ml) was added. After stirring for 2 h
at room temperature, the mixture was filtered, and residue washed several
times with diethyl ether. After removal of the solvent under reduced pressure,
the residue was purified by column chromatography (n-hexane) to give
38.1 mg (70%) of 5. IR (neat) n ¼ 2926, 1642, 1458, 1358, 886 cmꢁ1
;
1H NMR (300 MHz, CDCl3) d 0.97 (s, 3H), 0.99 (s, 3H), 1.67 (s, 3H),
1.30–2.10 (m, 11H), 2.24 (t, J ¼ 6.23 Hz, 1H), 2.70 (bs, 1H), 4.71 (bs, 2H);
13C NMR (75 MHz, CDCl3) d 151.09 (C), 134.62 (C), 126.95 (C), 108.42
(CH2), 42.27 (CH), 39.76 (CH2), 33.81 (C), 31.46 (CH2), 31.16 (CH2), 30.09
(CH2), 28.03 (CH2), 27.11 (CH3), 26.17 (CH3), 20.98 (CH3), 19.40 (CH2); MS
(m/z, relative intensity): 204 (Mþ, 62), 161 (100), 133 (60), 105 (90), 91 (78), 79
(80), 41 (70); C15H24 (204.4): Calcd C 88.16, H 11.84; found C 88.02, H 11.49.
1,1-Dimethyl-7-isopropyl-1,2,3,4-tetrahydronaphthalene (11): To a sol-
ution of 5 (28.7 mg, 0.14 mmol) in benzene was added p-toluenesulphonic acid
(3.5 mg, 0.02 mmol). After stirring for 3 h at room temperature, the mixture
was diluted with diethyl ether(15 ml) and washed with 1N solution of
NaHCO3 (2 Â 10 ml), brine (15 ml), dried with anhydrous sodium sulfate,
filtered, and solvent removed under reduced pressure. The residue was pur-
ified by silica gel column chromatography (n-hexane : diethyl ether99 : 1) to
give 15.9 mg (55%) of 11. IR (neat) n ¼ 3386, 3008, 2958, 1609, 1459, 1264,
1
739 cmꢁ1; H NMR (300 MHz, CDCl3) d 1.24 (d, J ¼ 6.0 Hz, 6H), 1.26 (s,
3H), 1.29 (s, 3H), 1.65 (m, 2H), 1.80 (m, 2H), 2.73 (t, J ¼ 6.59, 2H), 2.86
(septet, J ¼ 6.0 Hz, 1H), 6.97 (m, 2H), 7.18 (s, 1H); MS (m/z, relative inten-
sity): 202 (Mþ, 10), 187 (100), 145 (85), 128 (36), 117 (43), 91 (25), 77 (18), 43
(36); C15H22 (202.3): Calcd C 89.04, H 10.96; found C 88.76, H 10.63.
ACKNOWLEDGMENTS
This work was performed with financial support of FAPESP and MC
thanks CAPES-PICD forfellowship. We also thank Dr. L.H.B. Baptistella
forhelpful discussions.

1,2,3,4,5,6,7,8-OCTAHYDRONAPHTHALENE
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Received in the USA May 14, 2001