Synthesis of chiral methyl-branched linear pheromones starting from (+)-aromadendrene. Part 7

Article abstract of DOI:10.1016/j.tet.2003.09.085

Ethyl (7S)-10-hydroxy-7-methyldecanoate (4), a linear methyl-branched intermediate with its chiral center at C7, and with two different functional groups at the ends of the chain, has been synthesized from (+)-aromadendrene in nine steps. A Baeyer-Villige

Full text of DOI:10.1016/j.tet.2003.09.085

Tetrahedron 59 (2003) 9361–9369
Synthesis of chiral methyl-branched linear pheromones starting
from (1)-aromadendrene. Part 7
Yvonne M. A. W. Lamers,a Ghena Rusu,b Joannes B. P. A. Wijnberga and Aede de Groota
,
*
aLaboratory of Organic Chemistry, Wageningen University, Dreijenplein 8, 6703 HB Wageningen, The Netherlands
bInstitute of Chemistry, Moldovian Academy of Sciences, str. Academia 3, MD-2028 Kishinev, Republic of Moldova
Received 7 July 2003; revised 1 September 2003; accepted 25 September 2003
Abstract—Ethyl (7S)-10-hydroxy-7-methyldecanoate (4), a linear methyl-branched intermediate with its chiral center at C7, and with two
different functional groups at the ends of the chain, has been synthesized from (þ)-aromadendrene in nine steps. A Baeyer–Villiger
oxidation and a Grob fragmentation are the key reactions in this transformation. Intermediate 4 has been applied in the synthesis of three
linear methyl-branched pheromones, (i) (R)-10-methyl-2-tridecanone, the active pheromone of the southern corn rootworm Diabrotica
undecimpunctata howardi Barber, (ii) (S)-9-methylnonadecane, one of the sex pheromones of the cotton leafworm Alabama argillacea, and
(iii) (meso)-13,23-dimethylpentatriacontane, the sex pheromone of the tse tse fly Glossina pallidipes.
q 2003 Elsevier Ltd. All rights reserved.
1. Introduction
of 4 and its application in the synthesis of three linear
methyl-branched pheromones, (i) (R)-10-methyl-2-trideca-
none, the active pheromone of the southern corn rootworm
Diabrotica undecimpunctata howardi Barber, (ii) (S)-9-
methylnonadecane, one of the sex pheromones of the cotton
leafworm Alabama argillacea, and (iii) (meso)-13,23-
dimethylpentatriacontane, the sex pheromone of the tse tse
fly Glossina pallidipes.
(þ)-Aromadendrene (1) is a cheap and abundantly available
chiral starting material1 for organic syntheses. It has been
shown by our laboratory that many other useful inter-
mediates and natural products can be obtained from
aromadendrene.2–8 In most of these products, the basic
structural features of the aromadendrene skeleton have been
retained, although it was also shown that the monocyclic
humulane skeleton could be obtained in an easy way.6
Complex polycyclic sesquiterpenoids like (þ)-aroma-
dendrene have seldom been used for the preparation of
chiral linear compounds. Mostly monoterpenoids like
citronellol and pulegone have served as starting material
for syntheses of, for instance, linear pheromones branched
with one methyl group.9,10 It will be shown here, that the
linear methyl-branched ethyl (7S)-10-hydroxy-7-methyl-
decanoate (4), with its chiral center four carbon atoms from
the end of the chain, can be derived from (þ)-aroma-
dendrene in a limited number of steps. A Baeyer–Villiger
oxidation and a Grob fragmentation are the key reactions in
this transformation. Compound 4 can be a versatile
intermediate for the synthesis of several methyl-branched
linear pheromones because it has two different function-
alities at the ends of the chain. The chain can be elongated or
shortened at will at either side, and pheromones with
varying chain length and different positions of the chiral
center become accessible. Here, we report on the synthesis
2. Results and discussion
Two approaches have been investigated for the transform-
ation of (þ)-aromadendrene (1) to ethyl (7S)-10-hydroxy-7-
methyldecanoate (4) (Scheme 1). In the first approach (þ)-
aromadendrene should be converted to apoaromadendrone
(6), which in turn should undergo a Baeyer–Villiger
oxidation to lactone 2. Opening of the cyclopropane ring
and the introduction of a good leaving group, then should
give lactone 3. This lactone should be subjected to a Grob
fragmentation, and subsequent hydrogenation should finally
lead to 4.
In the second approach, (þ)-aromadendrene (1) is first
converted to the known alcohol 5 in four steps.2 Conversion
of the hydroxyl group in 5 to a good leaving group, followed
by Baeyer–Villiger oxidation or the other way round, again
should lead to lactone 3 and after Grob fragmentation and
hydrogenation, 4 should be obtained.
Keywords: (þ)-aromadendrene; Baeyer–Villiger oxidation; Grob
fragmentation; linear methyl-branched pheromones.
*
In both approaches to lactone 3 the Baeyer–Villiger
oxidation is a key step and for this reaction a carbonyl
Corresponding author. Tel.: þ31-317-482370; fax: þ31-317-484914;
e-mail: aede.degroot@wur.nl
0040–4020/$ - see front matter q 2003 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2003.09.085

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Y. M. A. W. Lamers et al. / Tetrahedron 59 (2003) 9361–9369
Scheme 1.
group is required at C7.11 These ketones can be prepared
from the distillation residue of the oil of Eucalyptus
globulus12 as shown by Gijsen et al.2 The Baeyer–Villiger
reaction of apoaromadendrone (6) went very well and
lactone 2 was obtained in nearly quantitative yield
(Scheme 2). However, attempts to open the cyclopropane
ring with concentrated HCl in EtOH only led to opening of
the lactone ring. When 2 was treated with TMSOTf in
CHCl3, opening of the cyclopropane ring to an unstable
lactone did take place in a moderate yield, but further
conversion of this lactone to a suitable substrate for the Grob
fragmentation appeared to be problematic. This prompted us
to investigate the second route for the synthesis of lactone 3.
which was converted to the more stable ester 10 in a one-pot
reaction with EtOH in the presence of TsOH.
The instability of lactones having a b-oriented mesylate at
C2, might be caused by through-bond orbital interactions
(TBI)14 between the oxygen atom at C8 and the mesylate
group. Because of the antiperiplanar relationship between
the central C1–C8 bond and the b-orientated C2–OMs
bond, TBI can be transmitted efficiently, through which the
lactone function becomes very prone to nucleophilic attack
with all its consequences. A similar TBI-induced instability
has been observed for sulfonated silyl ethers.15 The lactones
2 and 7 are stable because of the absence of a good leaving
group at C2. In lactone 9 there is a bromide available at C2
as a good leaving group, but through its a-orientation there
is no antiperiplanar relationship between the C1–C8 and the
C2–Br bond as a result of which TBI is less efficient.
Although bromo lactone 9 is not very stable, its stability is
sufficient to allow further transformation to the more stable
open ester 10.
The Baeyer–Villiger reaction of 52 with mCPBA in CH2Cl2
also proceeded well when MgSO4 was added to the reaction
mixture, and lactone 7 was isolated in 69% yield13
(Scheme 2). For the Grob fragmentation, a good leaving
group at C2 is necessary, but attempts to synthesize a
lactone with a mesylate group as leaving group were not
successful. The formation of a mesylate from alcohol 5
proceeded in a good yield, but when this b-mesylate was
treated under Baeyer–Villiger conditions, the product
decomposed before isolation. Also the mesylation of lactone
7 only led to a mixture of products. Finally, it was found that
the a-bromide 8, prepared by reaction of 5 with CBr4 and
PPh3, gave a smooth Baeyer–Villiger reaction to lactone 9,
Several bases, like KOtBu and NaOEt were tested for the
Grob fragmentation of hydroxy bromide 10, but the desired
aldehyde 11 could never be isolated in an acceptable yield.
Under the strongly basic conditions of the Grob fragmenta-
tion, this aldehyde appeared to be unstable and decomposed
easily to a mixture of products (Scheme 3).
Scheme 2. (a) mCPBA, MgSO4, CH2Cl2 (70–90%); (b) CBr4, PPh3, CH2Cl2 (78%); (c) TsOH, EtOH (69%).

Y. M. A. W. Lamers et al. / Tetrahedron 59 (2003) 9361–9369
9363
Scheme 3. (a) NaOEt, NaBH4, EtOH (77%); (b) H2, Pd (C), EtOAc (83%).
This problem could be solved by adding a reducing agent to
the reaction mixture, and when the Grob fragmentation was
carried out with NaOEt in EtOH in the presence of 5 equiv.
of NaBH4, alcohol 12 could be obtained in 80% yield.
removed and at the right side, the chain has to be elongated
with a three-carbon fragment. For that reason the hydroxy
group was converted to a tosylate group by reaction of 4
with TsCl in pyridine, followed by reduction of both the
tosylate and the ester group to give the alcohol 13 in an
overall yield of 75%. Replacement of the hydroxy group in
13 by iodide resulted in the formation of 14 in 91% yield.26
Coupling of an allyl group to 14 and oxidation of the double
bond23 finally gave pheromone 16 in 83% yield.
The reduction of the double bond in 12 with H2 in the
presence of Pd(C) went well and gave 4 in 85% yield.
Sometimes partial racemization of allylic chiral centers may
take place in catalytic reductions of double bonds. However,
Larcheveque et al.16 have shown that this is not a serious
problem in reductions with Pd(C) as catalyst. Diimide
reduction of 12 did not give satisfactory results. Attempts
were made to establish the optical purity of 4, but the
preparation of diastereomeric esters of 4 with a chiral acid
did not lead to a crystalline product, and no crystal structure
could be determined.17
(S)-9-Methylnonadecane 20 has been identified as one of the
sex pheromones of the cotton leafworm, A. argillacea.27
The synthesis described below is the first synthesis of this
pheromone (Scheme 5). For the synthesis of this pheromone
from 4, a seven-and a two-carbon fragment have to be added
at the left and right side, respectively. For that reason the
alcohol in 4 was oxidized first to afford aldehyde 17, which
in turn was elongated with a seven-carbon fragment via a
Wittig reaction with heptyltriphenylphosphonium iodide.
This reaction gave a mixture of the Z and E isomers of 18 in
a ratio of 3:1 (according to GC-analysis) in 76% yield over
two steps. Reduction of the ester group in compounds 18
with DIBAL-H28 resulted in the formation of Z and E
aldehydes in 86% yield, and a second Wittig reaction led to
19 as a mixture of four stereoisomers in 92% yield. The
Ethyl (7S)-10-hydroxy-7-methyldecanoate (4) has been
used for the synthesis of three linear methyl-branched
pheromones. (R)-10-Methyl-2-tridecanone (16) is the
active pheromone of the southern corn rootworm,
D. undecimpunctata howardi Barber.18 This pheromone
has been synthesized before19–25 and in our hands it was
obtained from 4 in five steps with an overall yield of 57%
(Scheme 4). At the left side of 4 the hydroxy group has to be
Scheme 4. (a) TsCl, pyridine (79%); (b) LiAlH4, THF (95%); (c) I2, PPh3, imidazole, CH2Cl2 (91%); (d) allylMgCl, THF (83%); (e) PdCl2, CuCl, O2, DMF
(wet) (100%).
Scheme 5. (a) PCC, CH2Cl2 (78%); (b) [C7H15PPh3]þI2, nBuLi, THF, 2788C (98%); (c) DIBAL-H, toluene, 2788C (86%); (d) [C2H5PPh3]þI2, nBuLi, THF,
2788C (92%); H2, Pd(C), EtOAc (95%).

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Y. M. A. W. Lamers et al. / Tetrahedron 59 (2003) 9361–9369
Scheme 6. (a) [C9H19PPh3]þBr2, nBuLi, THF, 2788C (89%); (b) DIBAL-H, toluene, 2788C (80%); (c) TBDPSCl, imidazole, DMAP, DMF (81%);
(d) [C6H13PPh3]þI2, nBuLi, THF, 2788C (61%); (e) TBAF, THF (94%); (f) I2, PPh3, imidazole, CH3CN, Et2O, 08C to room temperature (87%); (g) PPh3,
toluene, reflux (80%); (h) nBuLi, THF, 2788C; (i) H2, Pd(C) (99%).
formation of these stereoisomers was no problem, because
hydrogenation of all double bonds led to a single product,
pheromone 20, in 95% yield. The synthesis of 20 from 4
took five steps and proceeded in an overall yield of 58%.
via a Wittig reaction (80% yield). In the final step, all the
double bonds of the resulting triene were hydrogenated and
pheromone 28 was obtained in 95% yield.
(meso)-13,23-Dimethylpentatriacontane (28) has been
identified as the sex pheromone of the tse tse fly, G.
pallidipes.27 In this pheromone, the two chiral centers are
separated from each other by nine carbon atoms, which
makes it possible to use two units of 4, coupled head to tail,
to synthesize the central part of the chain. In our synthetic
route, the left and right segments of the molecule are
synthesized first. Both segments are then coupled to form
the chain of 35 carbon atoms. The left segment consists of
one molecule of 4 elongated at the left side with nine
carbons whereas the right segment is built up from a second
molecule of 4 elongated with a six-carbon segment
(Scheme 6).
3. Conclusions
Ethyl (7S)-10-hydroxy-7-methyldecanoate (4), a linear
methyl-branched intermediate with its chiral center at C7,
and with two different functional groups at the ends of the
chain, has been synthesized from (þ)-aromadendrene in
nine steps. A Baeyer–Villiger oxidation of keto-bromide 8
and a Grob fragmentation of hydroxy-bromide 10 are the
key reactions in this transformation. Intermediate 4 has
been applied in the synthesis of three linear methyl-
branched pheromones, (i) (R)-10-methyl-2-tridecanone,
the active pheromone of the southern corn rootworm
D. undecimpunctata howardi Barber, (ii) (S)-9-methyl-
nonadecane, one of the sex pheromones of the cotton
leafworm A. argillacea, and (iii) (meso)-13,23-dimethyl-
pentatriacontane, the sex pheromone of the tse tse fly
G. pallidipes.
The left side of the molecule was synthesized via a Wittig
reaction of aldehyde 17 (see Scheme 5) to give compound
21 in 89% yield. After reduction of 21 with DIBAL-H,28
aldehyde 22 was obtained in 85% yield.
The first steps in the synthesis of the right side of the
pheromone involved protection of the hydroxy group with a
silyl group and reduction of the ester group to aldehyde 24
in 77% yield over two steps. Addition of a six-carbon
fragment via a Wittig reaction (60% yield), followed by
removal of the silyl group (94% yield), led to the formation
of alcohol 26. Replacement of the hydroxy group in 26 by
iodide,26 and subsequent reaction with PPh3 gave phos-
phonium salt 27 in 86% yield over two steps. Then, the left
and right parts of the pheromone (22 and 27) were coupled
4. Experimental
4.1. General
1H NMR spectra (200 MHz) and 13C NMR spectra
(50 MHz) were recorded on a Bruker AC-E 200. CDCl3
was used as solvent, unless stated otherwise, and chemical
shifts are reported in parts per million (d) relative to
tetramethylsilane (d 0.0). MS and HRMS data were
obtained with a Finnigan Mat 95 spectrometer. MSD

Y. M. A. W. Lamers et al. / Tetrahedron 59 (2003) 9361–9369
9365
spectra were recorded on a HP5973 spectrometer. Analyti-
cal data were obtained using a Carlo Erba Analyzer 1106.
GC analyses were performed using a Fisons GC 8000 gas
chromatograph with a flame ionization detector and a
DB-17 fused silica capillary column (30 m£0.25 mm i.d.,
film thickness 0.25 mm). GC peak areas were integrated
electronically with a Fisons integrator DP700 or the Lab
Systems X-Chrom integrating system. For dry reactions,
flasks were dried at 1258C, flushed with nitrogen just before
use and kept under nitrogen atmosphere during the reaction.
Column and flash chromatography were performed with
ICN silica gel 60 (230–400 mesh), using mixtures of
petroleum ether bp 40–608C (PE) and ethyl acetate (EA) as
eluents, unless reported otherwise.
(42), 71 (55), 67 (64), 55 (61), 43 (36), 41 (40); HRMS calcd
for C11H16O2 (Mþ2H2O) 180.1150, found 180.1150.
4.1.3. (1R,3aR,8S,8aR)-8-Bromo-1-methyloctahydro-
4(1H)-azulenone (8). To a stirred solution of 1.5 g
(8.2 mmol) of 5 and 3.0 g (9.0 mmol) of CBr4 in 75 mL of
CH2Cl2 was added 4.3 g (16.4 mmol) of PPh3, in small
portions over a period of 1 h. After stirring for 15 min. at
room temperature, the reaction mixture was concentrated to
a volume of approximately 10 mL and then column
chromatographed (PE/EA 1:1) to yield 1.57 g (78%) of 8
1
as a light yellow oil. H NMR d 1.18 (d, J¼6.7 Hz, 3H,
CHMe), 1.37–2.57 (m, 12H), 3.62 (q, J¼8.6 Hz, 1H,
CHCvO), 4.79 (t, J¼3.2 Hz, 1H, CHBr); 13C NMR d 13.9
(q), 18.9 (t), 25.8 (t), 33.6 (t), 37.6 (d), 40.7 (t), 42.5 (t), 47.8
(d), 53.7 (d), 59.7 (d), 213.1 (s); MS m/z (r.i.) 246 (Mþ, 81Br,
36), 244 (Mþ, 79Br, 36), 165 (100), 164 (32), 162 (31), 147
(24), 137 (22), 109 (51), 95 (41), 81 (64); HRMS calcd for
C11H17O79Br/C11H17O81Br 244.0463/246.0443, found
244.0470/246.0440.
Compounds 5 and 6 were prepared from the distillation tail
of E. globulus as described by Gijsen et al.2
4.1.1. (1R,3aR,7aR,8aR,8bS)-1,8,8-Trimethyldecahydro-
5H-cyclopenta[b]cyclopropa-[d]-oxocin-5-one (2). To a
stirred solution of 13.4 g (65 mmol) of 6 in 300 mL of
CH2Cl2, cooled to 08C, was added 30.7 g (125–133 mmol)
of 70–75% mCPBA and 21 g of NaHCO3. After stirring for
1 h at room temperature, 100 mL of CH2Cl2 was added to
the suspension, because stirring became increasingly
difficult. After stirring for another 1.5 h, the reaction
mixture was diluted with 300 mL of water and 100 mL of
saturated aqueous NaHCO3. After separation of the layers,
the organic layer was washed successively with 300 mL of
10% aqueous Na2S2O3, 400 mL of saturated aqueous
NaHCO3, and brine, and then dried over MgSO4. After
evaporation of the solvent under reduced pressure, 14.9 g
(99%) of 2 was obtained as a white solid.
4.1.4. Ethyl (5S)-5-bromo-5-[(1R,2R,5R)-2-hydroxy-5-
methylcyclopentyl]pentanoate (10). To a stirred solution
of 1.7 g (6.9 mmol) of 8 in 100 mL of CH2Cl2 was added
8.3 g (ca. 35 mmol) of 70–71% mCPBA. After stirring for 2
days at room temperature, 40 mL of EtOH and a catalytic
amount of TsOH·H2O were added. After stirring for another
day, the reaction mixture was diluted with 200 mL of
saturated aqueous NaHCO3. The two-phase system was
separated and the water layer extracted with two 100-mL
portions of CH2Cl2. The combined organic layers were
washed with 10% aqueous Na2S2O3 and brine, dried over
MgSO4 and evaporated under reduced pressure. The residue
was chromatographed (PE/EA 1:1) to give 0.16 g (10%) of
starting material and 1.25 g (59%) of 10 as a colorless oil.
IR (CCl4) 2956, 2872, 1743, 1456, 1430, 1377, 1322, 1225,
1089, 1036 cm21
;
1H NMR d 0.35–0.54 (m, 2H, 2£
cyclopropane–H), 0.82 (d, J¼7.2 Hz, 3H, CHMe), 0.90 (s,
3H, Me), 0.99 (s, 3H, Me), 1.0–1.7 (m, 4H), 1.86–2.07 (m,
4H), 2.27 (dt, J¼4.7, 10.5 Hz, 1H), 2.56 (m, 1H), 4.89 (dt,
J¼1.9, 9.2 Hz, 1H, CHOCvO); 13C NMR d 15.0 (q), 18.0
(q), 19.2 (s), 21.5 (t), 25.4 (d), 27.0 (d), 28.6 (t), 28.8 (q),
30.7 (t), 31.9 (d), 35.9 (t), 47.8 (d), 84.8 (d), 179.2 (s);
HRMS calcd for C14H22O2 (Mþ) 222.1620, found
222.1616.
IR (CCl4) 3577, 2962, 2874, 1736, 1459, 1376, 1245, 1187,
1041 cm21; 1H NMR d 0.75 (d, J¼7.1 Hz, 3H, CHMe), 1.19
(t, J¼7.1 Hz, 3H, OCH2Me), 1.3–2.4 (m, 13H), 4.11 (q,
J¼7.1 Hz, 2H, OCH2Me), 4.04–4.42 (m, 2H, CHOH and
CHBr); 13C NMR d 14.3 (q), 14.5 (q), 22.5 (t), 31.8 (t), 31.8
(t), 33.4 (t), 37.0 (t), 37.1 (d), 59.0 (d), 60.5 (t), 60.6 (d), 77.3
(d), 173.2 (s); MS m/z (r.i.) 227 (Mþ2Br, 28), 209 (88), 181
(100), 163 (98), 135 (81), 121 (61), 95 (70), 93 (60), 81 (92),
55 (87), 41 (56); HRMS calcd for C13H23O3 (Mþ2Br)
227.1647, found 227.1650.
4.1.2. (6R,6aS,7R,9aR)-6-Hydroxy-7-methyloctahydro-
cyclopenta[b]oxocin-2(3H)-one (7). To a stirred solution
of 182 mg (1.0 mmol) of 5 in 10 mL of CH2Cl2, cooled to
08C, were added 1.2 g (4.9–5.2 mmol) of 70–75% mCPBA
and 1.2 g of MgSO4. After stirring for 72 h at room
temperature, the reaction mixture was washed with 10%
aqueous Na2S2O3, saturated aqueous NaHCO3 and brine.
The organic layer was dried over MgSO4 and evaporated
under reduced pressure. The residue was flash chromato-
graphed (PE/EA 3:2) to yield 137 mg (69%) of 7 as white
crystals: mp 99–1008C; [a]D¼2100.78 (c¼1.425, CHCl3);
IR (CCl4) 3623, 3483, 2958, 2906, 2876, 1742, 1237,
4.1.5. Ethyl (5Z,7R)-10-hydroxy-7-methyl-5-decenoate
(12). To a stirred solution of 0.60 g (1.95 mmol) of 10 in
70 mL of 0.5 M ethanolic NaOEt was added 0.38 g
(10 mmol) of NaBH4. After stirring for 2 h at room
temperature, the reaction mixture was diluted with
100 mL of 1 M aqueous HCl and extracted with three
50-mL portions of CH2Cl2. The combined organic layers
were washed with saturated aqueous NaHCO3 and brine,
dried over MgSO4 and evaporated under reduced pressure.
The residue was column chromatographed (PE/EA 1:1) to
yield 0.26 g (77%) of 19 as a colorless oil. IR (film) 3410,
2936, 2870, 1736, 1457, 1374, 1096, 1058 cm21; 1H NMR d
0.87 (d, J¼5.1 Hz, 3H, CHMe), 1.19 (t, J¼7.1 Hz, 3H,
OCH2Me), 1.30–1.69 (m, 8H), 1.95–2.02 (m, 2H), 2.2–2.4
(m, 2H), 3.55 (t, J¼6.5 Hz, 2H, CH2OH), 4.06 (q, J¼7.1 Hz,
2H, OCH2Me), 5.04–5.29 (m, 2H, CHvCH); 13C NMR d
1
1045 cm21; H NMR d 0.86 (d, J¼7.2 Hz, 3H, CHMe),
1.32–2.66 (m, 13H), 4.07 (dt, J¼4.6, 8.1 Hz, 1H, CHOH),
4.35 (dt, J¼3.1, 9.7 Hz, 1H, CHOCvO); 13C NMR d 15.8
(q), 18.7 (t), 27.1 (t), 29.7 (t), 30.9 (t), 33.9 (t), 34.1 (d), 56.4
(d), 73.6 (d), 80.8 (d), 172.1 (s); MS m/z (r.i.) 180
(Mþ2H2O, 25), 154 (100), 99 (84), 95 (46), 82 (57), 81

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Y. M. A. W. Lamers et al. / Tetrahedron 59 (2003) 9361–9369
14.3 (q), 21.4 (q), 25.0 (t), 26.8 (t), 30.8 (t), 31.5 (d), 33.4 (t),
33.8 (t), 60.3 (t), 63.1 (t), 127.4 (d), 137.0 (d), 174 (s); MS
m/z (r.i.) 210 (Mþ2H2O, 16), 185 (33), 152 (86), 123 (35),
99 (47), 95 (73), 81 (100), 69 (34), 67 (42), 55 (51), 41 (34);
HRMS calcd for C13H22O2 (Mþ2H2O) 210.1620, found
210.1616.
4.1.8. (7R)-1-Iodo-7-methyldecane (14). To a stirred
solution of 106 mg (0.62 mmol) of 13 in 20 mL of
CH2Cl2 were added 0.32 g (1.2 mmol) of PPh3, 90 mg
(1.3 mmol) of imidazole and 0.32 g (1.3 mmol) of I2. After
stirring for 40 min at room temperature, the reaction
mixture was diluted with saturated aqueous NaHCO3 and
extracted three times with CH2Cl2. The combined organic
layers were washed with brine, dried over MgSO4 and
evaporated under reduced pressure. The residue was column
chromatographed twice (PE/EA 5:1) to yield 158 mg (91%)
of 14 as a colorless oil.
4.1.6. Ethyl (7S)-10-hydroxy-7-methyldecanoate (4). To a
solution of 100 mg (0.44 mmol) of 12 in 5 mL of EtOAc
was added 50 mg of 10% Pd(C). The solution was
hydrogenated for 1 h in a Parr apparatus under 4 atm of
H2 and then filtered over hyflo. The hyflo was washed with
CH2Cl2 and the filtrate was evaporated under reduced
pressure. The residue was column chromatographed (PE/EA
2:1) to yield 84 mg (83%) of 4 as a colorless oil.
IR (film) 2956, 2927, 2855, 1464, 1378, 1200, 1169 cm21
;
1H NMR d 0.83 (d, J¼6.3 Hz, 3H, CHMe), 0.87 (t,
J¼6.9 Hz, 3H, CH2Me), 1.04–1.37 (m, 13H), 1.75–1.89
(m, 2H), 3.18 (t, J¼7.0 Hz, 2H, CH2I); 13C NMR d 7.4 (t),
14.4 (q), 19.7 (q), 20.1 (t), 26.9 (t), 28.9 (t), 30.6 (t), 32.4 (d),
33.6 (t), 36.9 (t), 39.4 (t); MS m/z (r.i.) 282 (Mþ, 8), 155
(35), 99 (12), 85 (47), 71 (69), 69 (17), 57 (100), 55 (35), 43
(92), 41 (41), 39 (9); HRMS calcd for C11H23I (Mþ)
282.0845, found 282.0838.
IR (film) 3373, 2932, 2859, 1737, 1464, 1375, 1181,
1057 cm21; 1H NMR d 0.86 (d, J¼6.3 Hz, 3H, CHMe), 1.25
(t, J¼7.1 Hz, 3H, OCH2Me), 1.00–1.70 (m, 14H), 2.28 (t,
J¼7.5 Hz, 2H), 3.61 (t, J¼6.6 Hz, 2H, CH2OH), 4.12 (q,
J¼7.1 Hz, 2H, OCH2Me); 13C NMR d 14.3 (q), 19.6 (q),
25.0 (t), 26.6 (t), 29.4 (t), 30.3 (t), 32.5 (d), 32.9 (t), 34.4 (t),
36.7 (t), 60.2 (t), 63.3 (t), 174.0 (s); HRMS calcd for
C12H24O2 (Mþ2CH2O) 200.1776, found 200.1778.
4.1.9. (10R)-10-Methyl-1-tridecene (15). To a stirred
solution of 32 mg (0.11 mmol) of 14 in 2 mL of dry THF,
cooled to 08C, was added 0.22 mL of 1 M allylMgCl in
THF. After stirring for 1 h at 08C, the reaction mixture was
diluted with 1 M aqueous HCl and extracted three times
with Et2O. The combined organic layers were washed with
saturated aqueous NaHCO3 and brine, dried over MgSO4
and evaporated under reduced pressure. The residue was
column chromatographed (PE/EA 5:1) to yield 19 mg
(83%) of 15 as a colorless oil.
4.1.7. (7R)-7-Methyl-1-decanol (13). To a stirred solution
of 0.22 g (0.96 mmol) of 4 in 20 mL of pyridine was added
0.91 g (4.8 mmol) of TsCl. After stirring for 4 h at room
temperature, the reaction mixture was diluted with 100 mL
of 1 M aqueous HCl and extracted with three 50-mL
portions of EtOAc. The combined organic layers were
washed with 1 M aqueous HCl and brine, dried over MgSO4
and evaporated under reduced pressure. The residue was
column chromatographed (PE/EA 2:1) to yield 0.29 g (79%)
of the corresponding tosylate as a colorless oil.
1H NMR d 0.93–0.99 (m, 6H), 1.08–1.42 (m, 17H), 2.00–
2.18 (m, 2H), 5.01–5.15 (m, 2H, CHvCH2), 5.75–5.95 (m,
1H, CHvCH2); 13C NMR d 14.4 (q), 19.6 (q), 20.3 (t), 27.3
(t), 29.1 (t), 29.3 (t), 29.7 (t), 30.2 (t), 32.7 (d), 34.0 (t), 37.3
1H NMR d 0.79 (d, J¼6.2 Hz, 3H, CHMe), 1.24 (t,
J¼7.1 Hz, 3H, OCH2Me), 1.0–1.4 (m, 8H), 1.53–1.70
(m, 5H), 2.27 (t, J¼7.5 Hz, 2H), 2.68 (s, 3H, ArMe), 3.99 (t,
J¼6.5 Hz, 2H, CH2OSO2), 4.11 (q, J¼7.1 Hz, 2H,
OCH2Me), 7.33 (d, J¼8.2 Hz, 2H, 2£Ar–H), 7.78 (d,
J¼8.3 Hz, 2H, 2£Ar–H); 13C NMR d 14.3 (q), 19.4 (q),
21.7 (q), 25.0 (t), 26.5 (t), 26.6 (t), 29.4 (t), 32.2 (d), 32.5 (t),
34.4 (t), 36.5 (t), 60.2 (t), 71.1 (t), 127.9 (d, 2C), 129.8 (d,
2C), 133.2 (s), 144.7 (s), 173.9 (s).
1
(t), 39.5 (t), 114.3 (t), 139.0 (d). The H NMR spectrum of
15 corresponds to that of the racemic compound reported in
literature.19
4.1.10. (10R)-10-Methyl-2-tridecanone (16). A suspension
of 7.8 mg (0.079 mmol) of CuCl and 1.4 mg (0.008 mmol)
of PdCl2 in 0.5 mL of DMF, containing one drop of water,
was stirred for 2 h under oxygen atmosphere. Then, a
solution of 15 mg (0.077 mmol) of 15 in 1 mL of DMF was
added and the reaction mixture was stirred for 1 day. The
mixture was diluted with 1 M aqueous HCl and extracted
three times with Et2O. The combined organic layers were
washed with saturated aqueous NaHCO3 and brine, dried
over MgSO4 and evaporated under reduced pressure. The
residue was column chromatographed (PE/EA 5:1) to yield
16 mg (100%) of 16 as a colorless oil. The 1H and 13C NMR
spectra of 16 correspond to those reported in literature.24
To a stirred solution of 0.29 g (0.76 mmol) of this tosylate in
25 mL of dry THF was added 0.15 g (4.0 mmol) of LiAlH4.
After stirring for 1.5 h at room temperature, the reaction
mixture was diluted with 100 mL of 1 M aqueous HCl and
extracted with three 40-mL portions of CH2Cl2. The
combined organic layers were washed with brine, dried
over MgSO4 and evaporated under reduced pressure. The
residue was column chromatographed (PE/EA 2:1) to yield
124 mg (95%) of 13 as a colorless oil.
4.1.11. Ethyl (7S)-7-methyl-10-oxodecanoate (17). To a
stirred solution of 0.35 g (1.52 mmol) of 4 in 7 mL of
CH2Cl2 were added 41 mg (0.5 mmol) of NaOAc and 0.49 g
(2.25 mmol) of PCC. After stirring for 2.5 h at room
temperature, the reaction mixture was loaded to a silica gel
column. Elution with PE/EA 19:1 yielded 0.27 g (78%) of
17 as a colorless oil. [a]D¼20.368 (c¼1.4, CHCl3); IR
1H NMR d 0.85 (d, J¼6.3 Hz, 3H, CHMe), 0.88
(t, J¼6.9 Hz, 3H, CH2Me), 1.04–1.65 (m, 15H), 3.65
(t, J¼6.5 Hz, 2H, CH2OH); 13C NMR d 14.4 (q), 19.7 (q),
20.1 (t), 25.8 (t), 27.0 (t), 29.8 (t), 32.5 (d), 32.8 (t), 37.0 (t),
39.4 (t), 63.1 (t). The 1H NMR spectrum of 13
corresponds to that of the racemic compound reported in
literature.29
(film) 1735, 1720, 1179 cm21
;
1H NMR d 0.83 (d,

Y. M. A. W. Lamers et al. / Tetrahedron 59 (2003) 9361–9369
9367
J¼6.7 Hz, 3H, CHMe), 1.23 (t, J¼7.1 Hz, 3H, OCH2Me),
1.10–1.66 (m, 11H), 2.27 (t, J¼7.6 Hz, 2H), 2.39 (dt,
J¼1.8, 6.9 Hz, 2H), 4.10 (q, J¼7.1 Hz, 2H, OCH2Me), 9.75
(t, J¼1.8 Hz, 1H, CHvO); 13C NMR d 14.3 (q), 19.3 (q),
24.9 (t), 26.6 (t), 28.8 (t), 29.3 (t), 32.3 (d), 34.3 (t), 36.5 (t),
41.7 (t), 60.2 (t), 173.9 (s), 203.1 (d); MS m/z (r.i.) 200
(Mþ2CO, 21), 185 (92), 183 (40), 172 (37), 139 (75), 101
(78), 97 (45), 88 (100), 83 (34), 69 (42), 55 (62); HRMS
calcd for C12H24O2 (Mþ2CO) 200.1776, found 200.1774.
1H NMR d 0.85 (d, J¼6.5 Hz, 3H, CHMe), 0.85 (t,
J¼6.0 Hz, 3H, CH2Me), 1.07–1.64 (m, 19H), 1.59 (d,
J¼5.4 Hz, 3H, vCHMe), 1.97–2.03 (m, 6H), 5.25–5.48
(m, 4H, CH2CHvCHCH2 and CH2CHvCHMe); 13C NMR
d 14.2 (q, 2C atoms), 19.6 (q), 22.7 (q), 24.8 (t), 26.9 (t),
27.2 (t), 29.0 (t), 29.6 (t, 2C atoms), 29.8 (t), 31.8 (t), 32.4
(d), 32.6 (t), 36.9 (t), 37.1 (t), 123.6, 124.5, 129.7, 130.1,
130.9, 131.7 (all d, 4C, Z/E); MS m/z (r.i.) 278 (Mþ, 30),
109 (39), 97 (53), 96 (67), 95 (37), 83 (58), 81 (43), 69 (73),
68 (46), 55 (100), 41 (38); HRMS calcd for C20H38 (Mþ)
278.2974, found 278.2971.
4.1.12. Ethyl (7S)-7-methyl-10-heptadecenoate (18). To a
stirred solution of 0.73 g (1.5 mmol) of [H15C7PPh3]þI2 in
5 mL of dry THF, cooled to 08C and under argon
atmosphere, was added 0.94 mL (1.5 mmol) of 1.6 M
nBuLi in hexane. After stirring for 2 h at 08C, the solution
was cooled to 2788C and a solution of 0.27 g (1.18 mmol)
of 17 in 3 mL of THF was added dropwise. After stirring for
1 h at 2788C and 1 h at room temperature, the reaction
mixture was diluted with 20 mL of water and extracted with
four 20-mL portions of Et2O. The combined organic layers
were washed with brine, dried over MgSO4 and evaporated
under reduced pressure. The residue was column chromato-
graphed (PE/EA 19:1) to yield 0.36 g (98%) of 18 as a
mixture of Z/E isomers in a ratio of 3:1 (according to GC-
4.1.14. (9S)-9-Methylnonadecane (20). To a solution of
0.24 g (0.86 mmol) of 19 in 35 mL of EtOAc was added
80 mg of 10% Pd(C). The solution was hydrogenated for
1.5 h in a Parr apparatus under 4 atm of H2 and then filtered
over silica gel. The filtrate was evaporated under reduced
pressure and the residue was flash chromatographed (PE) to
yield 0.23 g (95%) of 20 as a colorless oil.
1H NMR d 0.86 (d, J¼6.4 Hz, 3H, CHMe), 0.85 (t,
J¼8.2 Hz, 6H, 2£CH2Me), 1.00–1.55 (m, 33H); 13C
NMR d 14.1 (q, 2C), 19.7 (q), 22.7 (t, 2C), 27.1 (t, 2C),
29.4 (t, 3C), 29.7 (t, 3C), 30.0 (t, 2C), 31.9 (t, 2C), 32.7 (d),
37.1 (t, 2C); MS m/z (r.i.) 282 (Mþ, 4), 168 (17), 141 (17),
140 (28), 85 (63), 71 (72), 57 (100), 56 (17), 55 (23), 43
(68), 41 (27); HRMS calcd for C20H42 (Mþ) 282.3287,
found 282.3287.
1
analysis): H NMR d 0.85 (d, J¼6.3 Hz, 3H, CHMe), 0.87
(t, J¼5.9 Hz, 3H, CH2Me), 1.24 (t, J¼7.1 Hz, 3H,
OCH2Me), 1.03–1.65 (m, 19H), 2.00 (m, 4H), 2.28 (t,
J¼7.7 Hz, 2H), 4.11 (q, J¼7.1 Hz, 2H, OCH2Me), 5.25–
5.39 (m, 2H, CHvCH); 13C NMR d 14.1 (q), 14.2 (q), 19.5
(q), 22.6 (t), 24.7 (t), 25.0 (t), 26.6 (t), 27.2 (t), 29.0 (t), 29.5
(t), 29.7 (t), 31.8 (t), 32.1 (d), 34.4 (t), 36.7 (t), 37.0 (t), 60.1
(t), 129.8 (d, Z), 130.0 (d, Z), 130.2 (d, E), 130.4 (d, E),
173.9 (s).
4.1.15. Ethyl (7S)-7-methyl-10-nonadecenoate (21). To a
stirred solution of 0.70 g (1.5 mmol) of [H19C9PPh3]þBr2
in 5 mL of dry THF, cooled to 08C and under argon
atmosphere, was added 0.60 mL (1.5 mmol) of 2.5 M nBuLi
in hexane. After stirring for 2 h at 08C, the solution was
cooled to 2788C and a solution of 0.27 g (1.18 mmol) of 17
in 3 mL of THF was added dropwise. After stirring for 1 h at
2788C and 1 h at room temperature, the reaction mixture
was diluted with 20 mL of water and extracted with four
20-mL portions of Et2O. The combined organic layers were
washed with brine, dried over MgSO4 and evaporated under
reduced pressure. The residue was column chromato-
graphed (PE/EA 19:1) to yield 0.36 g (89%) of 21 as a 4:1
mixture of Z/E isomers.
4.1.13. (9S)-9-Methyl-2,12-nonadecadiene (19). To a
stirred solution of 0.34 g (1.1 mmol) of 18 in 30 mL of
toluene, cooled to 2788C, was added slowly 0.77 mL
(1.2 mmol) of 1.5 M DIBAL-H in toluene. After stirring for
1 h, 3 mL of 1 M aqueous AcOH was carefully added, while
keeping the temperature below 2658C, and the reaction
mixture was stirred for another 30 min. Then the reaction
mixture was poured slowly into ice-cold 1 M aqueous HCl
and extracted with three 30-mL portions of Et2O. The
combined organic layers were washed with saturated
aqueous NaHCO3 and brine, dried over MgSO4 and
evaporated under reduced pressure. The residue was flash
chromatographed (PE/EA 97:3) to yield 0.25 (86%) of the
corresponding aldehyde as a colorless oil, which was used
immediately in the next reaction.
IR (CCl4) 2930, 2858, 1737, 1712, 1464, 1418, 1375,
1179 cm21; 1H NMR d 0.88 (d, J¼6.4 Hz, 3H, CHMe), 0.87
(t, J¼7.2 Hz, 3H, CH2Me), 1.25 (t, J¼7.1 Hz, 3H,
OCH2Me), 1.07–2.18 (m, 23H), 1.99–2.02 (m, 4H) 2.28
(t, J¼7.3 Hz, 2H), 4.12 (q, J¼7.1 Hz, 2H, OCH2Me), 5.25–
5.39 (m, 2H, CHvCH); 13C NMR d 14.1 (q), 14.2 (q), 19.5
(q), 22.7 (t), 24.7 (t), 25.0 (t), 26.7 (t), 27.2 (t), 29.3 (t, 2C),
29.5 (t, 2C), 29.7 (t), 31.9 (t), 32.3 (d), 34.4 (t), 36.7 (t), 37.0
(t), 60.1 (t), 129.8 (d, Z), 123.0 (d, Z), 130.2 (d, E), 130.4 (d,
E), 173.9 (s); MS m/z (r.i.) 338 (Mþ, 24), 209 (54), 138
(100), 97 (65), 91 (40), 83 (66), 69 (72), 57 (49), 55 (96), 43
(52), 41 (46); HRMS calcd for C22H42O2 (Mþ) 338.3185,
found 338.3185.
To a stirred solution of 0.46 g (1.2 mmol) of [H5C2PPh3]þI2
in 4 mL of dry THF, cooled to 08C and under argon
atmosphere, was added 0.70 mL (1.1 mmol) of 1.6 M nBuLi
in hexane. After stirring for 2 h at 08C, the solution was
cooled to 2788C and a solution of 0.25 g (0.94 mmol) of the
aldehyde in 2 mL of THF was added dropwise. After stirring
for 1 h at 2788C and 1 h at room temperature, the reaction
mixture was diluted with 20 mL of water and extracted with
four 20-mL portions of Et2O. The combined organic layers
were washed with brine, dried over MgSO4 and evaporated
under reduced pressure. The residue was flash chromato-
graphed (PE) to yield 0.24 g (92%) of 19 as a mixture of four
stereoisomers.
4.1.16. (7S)-7-Methyl-10-nonadecenal (22). To a stirred
solution of 0.29 g (0.85 mmol) of 21 in 25 mL of toluene,
cooled to 2788C, was added slowly 0.60 mL (0.90 mmol)
of 1.5 M DIBAL-H in toluene. After stirring for 1 h, 3 mL
of 1 M aqueous AcOH was added carefully maintaining the

9368
Y. M. A. W. Lamers et al. / Tetrahedron 59 (2003) 9361–9369
temperature below 2658C, and then stirring was continued
for another 30 min. The reaction mixture was poured slowly
into ice-cold 1 M aqueous HCl and extracted with three
30-mL portions of Et2O. The combined organic layers were
washed with saturated aqueous NaHCO3 and brine, dried
over MgSO4 and evaporated under reduced pressure. The
residue was flash chromatographed (PE/EA 97:3) to yield
0.75 mL (1.2 mmol) of 1.6 M nBuLi in hexane. After
stirring for 2 h at 08C, the solution was cooled to 2788C and
a solution of 0.47 g (0.94 mmol) of 24 in 3 mL of THF was
added dropwise. After stirring for 1 h at 2788C and 1 h at
room temperature, the reaction mixture was diluted with
20 mL of water and extracted with four 20-mL portions of
Et2O. The combined organic layers were washed with brine,
dried over MgSO4 and evaporated under reduced pressure.
The residue was column chromatographed (PE/EA 99:1) to
yield 0.33 g (61%) of 25 as a colorless oil, which was used
immediately in the next reaction.
1
0.20 g (80%) of 22 as a 4:1 mixture of Z/E isomers: H
NMR d 0.85 (d, J¼6.5 Hz, 3H, CHMe), 0.85 (t, J¼6.1 Hz,
3H, CH2Me), 1.08–1.30 (m, 21H), 1.5–1.66 (m, 2H), 1.90–
2.05 (m, 4H), 2.42 (dt, J¼1.9, 7.3 Hz, 2H), 5.25–5.39 (m,
2H, CHvCH), 9.76 (t, J¼1.9 Hz, 1H, CHvO); 13C NMR d
14.2 (q), 19.5 (q), 22.1 (t), 22.7 (t), 24.8 (t), 26.8 (t), 27.2 (t),
29.2 (t), 29.3 (t), 29.5 (t), 29.7 (t), 29.8 (t), 31.9 (t), 32.3 (d),
36.7 (t), 36.9 (t), 43.9 (t), 129.8, 130.0, 130.4 (all d, 2C,
Z/E), 203.0 (d); MS m/z (r.i.) 294 (Mþ, 25), 135 (65), 126
(79), 109 (61), 97 (85), 83 (70), 81 (56), 69 (75), 57 (57), 55
(100), 43 (51); HRMS calcd for C20H38O (Mþ) 294.2923,
found 294.2924.
4.1.20. (4S)-4-Methyl-10-hexadecen-1-ol (26). To a stirred
solution of 0.33 g (0.67 mmol) of 25 in 5.5 mL of THF was
added dropwise 0.8 mL of 1.1 M TBAF in THF. After
stirring for 3 h at room temperature, the reaction mixture
was diluted with water and extracted with four 20-mL
portions of Et2O. The combined organic layers were washed
with saturated aqueous NaHCO3 and brine, dried over
MgSO4 and evaporated under reduced pressure. The residue
was flash chromatographed (PE/EA 17:3) to yield 0.16 g
(94%) of 26 as a mixture of Z/E isomers: 1H NMR d 0.85 (d,
J¼6.3 Hz, 3H, CHMe), 0.85 (t, J¼6.1 Hz, 3H, CH2Me),
1.03–1.68 (m, 20H), 1.96–2.04 (m, 4H), 3.62 (t, J¼6.6 Hz,
2H, CH2OH), 5.26–5.42 (m, 2H, CHvCH); 13C NMR d
14.1 (q), 19.6 (q), 22.6 (t), 26.9 (t), 27.2 (t), 29.4 (t), 29.6 (t),
29.7 (t), 30.3 (t), 31.5 (t), 32.6 (d), 32.6 (t), 32.9 (t), 36.9 (t),
63.4 (t), 129.8 (d, Z), 129.90 (d, Z), 130.3 (d, E), 130.4 (d,
E).
4.1.17. Ethyl (7S)-10-{[tert-butyl(diphenyl)silyl]oxy}-7-
methyldecanoate (23). To a stirred solution of 0.35 g
(1.5 mmol) of 4, 0.23 g (3.0 mmol) of imidazole and 30 mg
of DMAP in 4 mL of DMF was added a solution of 0.42 g
(1.55 mmol) of TBDPSCl in 1.5 mL of DMF. After stirring
for 4 h at room temperature, the reaction mixture was
diluted with 30 mL of water and extracted with four 20-mL
portions of Et2O. The combined organic layers were washed
with brine, dried over MgSO4 and evaporated under reduced
pressure. The residue was flash chromatographed (PE/EA
97:3) to yield 0.61 g (81%) of 23 as a colorless oil: 1H NMR
d 0.82 (d, J¼6.2 Hz, 3H, CHMe), 1.03 (s, 9H, CMe3), 1.25
(t, J¼7.2 Hz, 3H, OCH2Me), 1.01–1.61 (m, 13H), 2.29 (t,
J¼7.3 Hz, 2H), 3. 64 (t, J¼6.5 Hz, 2H), 4.12 (q, J¼7.2 Hz,
2H), 7.33–7.43 (m, 6H, 6£Ar–H), 7.65–7.71 (m, 4H,
4£Ar–H).
4.1.21. (4S)-4-Methyl-10-hexadecenyltriphenylphos-
phonium iodide (27). To a stirred solution of 0.19 g
(0.73 mmol) of PPh3 and 57 mg (0.73 mmol) of imidazole
in 3.5 mL of Et2O/CH3CN 5:2, cooled to 08C, was added
0.18 g (0.72 mmol) of I2. The resulting slurry was stirred for
30 min at room temperature and then cooled again to 08C. A
solution of 0.16 g (0.63 mmol) of 26 in 0.5 mL of Et2O was
added slowly and the reaction mixture was stirred for 2 h at
room temperature. The mixture was flash chromatographed
directly (PE/EA 99:1) to yield 0.20 g (87%) of the iodide as
a mixture of Z/E isomers.
4.1.18. (7S)-10-{[tert-Butyl(diphenyl)silyl]oxy}-7-methyl-
decanal (24). To a stirred solution of 0.61 g (1.3 mmol) of
23 in 35 mL of toluene, cooled to 2788C, was added slowly
0.92 mL (1.4 mmol) of 1.5 M DIBALH in toluene. After
stirring for 1 h, 3 mL of 1 M aqueous AcOH was carefully
added, while keeping the temperature below 2658C, and the
reaction mixture was stirred for another 30 min. Then the
reaction mixture was poured slowly into ice-cold 1 M
aqueous HCl and extracted with three 30-mL portions of
Et2O. The combined organic layers were washed with
saturated aqueous NaHCO3 and brine, dried over MgSO4
and evaporated under reduced pressure. The residue was
flash chromatographed (PE/EA 97:3) to yield 0.49 g (89%)
1H NMR d 0.85 (d, J¼6.3 Hz, 3H), 0.88 (t, J¼6.2 Hz, 3H),
1.06–1.87 (m, 19H), 1.97–2.20 (m, 4H), 3.16 (t, J¼7.1 Hz,
2H), 5.27–5.40 (m, 2H, Z/E); 13C NMR d 14.1 (q), 19.6 (q),
22.6 (t), 26.9 (t), 27.2 (t, 2C), 29.5 (t), 29.6 (t), 29.8 (t), 31.3
(t), 31.6 (t), 32.1 (t), 32.6 (d), 36.8 (t), 37.9 (t), 129.8 (d, Z),
129.9 (d, Z), 130.3 (d, E), 130.5 (d, E).
Upon a 24 h-treatment with 1 equiv. of PPh3 in toluene at
reflux temperature, the iodide was converted quantitatively
to its phosphonium salt 27.30
1
of 24 as a colorless oil: H NMR d 0.83 (d, J¼6.2 Hz, 3H,
CHMe), 1.05 (s, 9H, CMe3), 1.03–1.66 (m, 13H), 2.41 (dt,
J¼1.8, 7.3 Hz, 2H), 3.64 (t, J¼6.5 Hz, 2H, CH2OSi), 7.33–
7.46 (m, 6H, 6£Ar–H), 7.65–7.69 (m, 4H, 4£Ar–H), 9.76
(t, J¼1.8 Hz, 1H, CHvO); 13C NMR d 19.2 (s), 19.7 (q),
22.1 (t), 26.8 (t), 26.9 (q, 3C), 29.5 (t), 30.1 (t), 32.5 (d), 32.9
(t), 36.7 (t), 44.0 (t), 64.3 (t), 127.6 (d, 4C), 129.5 (d, 2C),
134.2 (s, 2C), 135.6 (d, 4C), 203.0 (d).
4.1.22. (13R,23S)-13,23-Dimethylhexatriacontane (28).
To a stirred solution of 255 mg (0.41 mmol) of 27 in
4 mL of dry THF, cooled to 08C and under argon
atmosphere, was added 0.25 mL (0.4 mmol) of 1.6 M
nBuLi in hexane. After stirring for 2 h at 08C, the solution
was cooled to 2788C and a solution of 100 mg (0.34 mmol)
of 22 in 2 mL of THF was added dropwise. After stirring for
1 h at 2788C and 1 h at room temperature, the reaction
mixture was diluted with 20 mL of water and extracted with
four 20 mL portions of Et2O. The combined organic layers
4.1.19. tert-Butyl(diphenyl)silyl (4S)-4-methyl-10-hexa-
decenyl ether (25). To a stirred solution of 0.58 g
(1.22 mmol) of [H13C6PPh3]þI2 in 5 mL of dry THF,
cooled to 08C and under argon atmosphere, was added

Y. M. A. W. Lamers et al. / Tetrahedron 59 (2003) 9361–9369
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6. Gijsen, H. J. M.; Wijnberg, J. B. P. A.; de Groot, Ae.
Tetrahedron 1994, 50, 4745–4754.
were washed with brine, dried over MgSO4 and evaporated
under reduced pressure. The residue was column chromato-
graphed (PE) to yield 140 mg (80%) of the triene as a
mixture of stereoisomers.
7. Gijsen, H. J. M.; Wijnberg, J. B. P. A.; de Groot, Ae. Structure,
Occurrence, Biosynthesis, Biological Activity, Synthesis and
Chemistry of Aromadendrane Sesquiterpenoids. Progress in
the Chemistry of Natural Products; 1995; Vol. 64,
pp 149–193.
1H NMR d 0.85 (d, J¼6.6 Hz, 6H, 2£CHMe), 0.86 (t,
J¼6.1 Hz, 6H, 2£CH2Me), 1.08–1.45 (m, 40H), 1.90–2.10
(m, 12H), 5.23–5.40 (m, 6H, 3£CHvCH); 13C NMR d 14.1
(q, 2C), 19.6 (q, 2C), 22.6 (t), 22.7 (t), 24.8 (t, 2C), 26.9 (t,
2C), 27.2 (t, 2C), 29.3, 29.5, 29.6, 29.7, 29.8 (all t, 7C), 30.2
(t), 31.4 (t), 31.6 (t), 31.9 (t), 32.3 (t), 32.4 (d, 2C), 32.6 (t),
36.9 (t, 2C), 37.1 (t, 2C), 129.8, 129.9, 129.9, 130.1, 130.4
(all d, 6C).
8. Moreno-Dorado, F. J.; Lamers, Y. M. A. W.; Mironov, G.;
Wijnberg, J. P. B. A.; de Groot, A. Tetrahedron 2003, 59,
7743–7750.
9. Mori, K. The Synthesis of Insect Pheromones; Wiley: New
York, 1992; Vol. 9.
10. Koutek, B.; Streinz, L.; Romanuk, M. Coll. Czech. Chem.
Commun. 1998, 63, 899–954.
To a solution of 140 mg (0.27 mmol) of the triene from the
previous reaction in 50 mL of EA was added 60 mg of 10%
Pd(C). The solution was hydrogenated for 1.5 h in a Parr
apparatus under 4 atm of H2 and then filtered over silica gel.
The filtrate was evaporated under reduced pressure and the
residue was column chromatographed (PE) to yield 141 mg
(99%) of 28 as a colorless oil, which solidified upon
standing at room temperature: mp 33–348C (lit. 29–
11. The numbering of aromadendrene and aromadendrene derived
skeltons as indicated in structure 1 (Scheme 1) is used
throughout the discussion.
12. This fraction mainly consists of sesquiterpenes and contains
ca. 70% of aromadendrene and ca. 10% of its C8 epimer
alloaromadendrene.
13. The stereochemistry of the lactones depicted in Scheme 2 was
not established, but it was assumed that the configuration at the
bridgehead carbon is as shown, because the Baeyer–Villiger
reaction usually proceeds with retention of configuration.
14. Wijnberg, J. B. P. A.; de Groot, A. Curr. Org. Chem. 2003, 7,
257–274.
1
308C29); H NMR d 0.85 (d, J¼6.4 Hz, 6H, 2£CHMe),
0.84 (t, J¼6.1 Hz, 6H, 2£CH2Me), 1.25 (m, 64H); 13C NMR
d 14.1 (q, 2C), 19.7 (q, 2C), 22.7 (t, 2C), 27.1 (t, 4C), 29.4,
29.7, 30.0 (all t, 19C), 31.9 (t, 2C), 32.7 (d, 2C), 37.1 (t, 4C);
MS m/z (r.i.) 520 (Mþ, 4), 351 (71), 350 (41), 197 (46), 196
(100), 85 (53), 71 (69), 69 (25), 57 (90), 55 (22), 43 (43);
HRMS calcd for C37H76 520.5947, found 520.5941. The 1H
NMR spectrum of 28 corresponds to that reported in
literature.31
15. Bastiaansen, P. M. F. M.; Orru, R. V. A.; Wijnberg, J. B. P. A.;
de Groot, A. J. Org. Chem. 1995, 60, 6154–6158.
16. Larcheveque, M.; Sanner, C. Tetrahedron 1988, 44,
6407–6418.
17. Compound 4 and all compounds derived from 4 showed very
small and therefore unreliable values for the optical rotation.
18. Guss, P. L.; Tumlinson, J. H.; Sonnet, P. E.; Mc Laughlin, J. R.
J. Chem. Ecol. 1983, 9, 1363–1375.
Acknowledgements
19. Sonnet, P. E. J. Org. Chem. 1982, 47, 3793–3796.
20. Senda, S.; Mori, K. Agric. Biol. Chem. 1983, 47, 795–798.
21. Oppolzer, W.; Dudfield, P.; Stevenson, T.; Godel, T. Helv.
Chim. Acta 1985, 68, 212–215.
The authors gratefully acknowledge financial support from
the European Union (Fair CT96-1781). The authors thank
A. van Veldhuizen for NMR data, B van Lagen for IR
spectroscopic data, and M. A. Posthumus for mass spectro-
scopic measurements.
22. Hao, N. C.; Mavrov, M. V.; Serebryakov, E. P. Izv. Akad. Nauk
SSSR, Ser. Khim. 1987, 2083.
23. Rossi, R.; Carpita, A.; Chini, M. Tetrahedron 1985, 41,
627–633.
24. Enders, D.; Jandeleit, B. Liebigs Ann. 1995, 1173–1176.
25. Chow, S.; Kitching, W. Tetrahedron: Asymmetry 2002, 13,
779–793.
References
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