Synthesis of all the six components of the female-produced contact sex pheromone of the German cockroach, Blattella germanica (L.)

Article abstract of DOI:10.1016/j.tet.2008.02.040

All of the following six components of the female sex pheromone of the German cockroach, Blattella germanica (L.) were synthesized: (3S,11S)-3,11-dimethyl-2-nonacosanone (1), its 29-hydroxy derivative 2, its 29-oxo derivative 3, (3S,11S)-3,11-dimethyl-2-heptacosanone (4), its 27-hydroxy derivative 5, and its 27-oxo derivative 6. Both the enantiomers of citronellal were employed as the chiral sources and Wacker oxidation was employed for the introduction of the carbonyl group at C-2.

Full text of DOI:10.1016/j.tet.2008.02.040

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Tetrahedron 64 (2008) 4060e4071
www.elsevier.com/locate/tet
Synthesis of all the six components of the female-produced contact sex
pheromone of the German cockroach, Blattella germanica (L.)*
*
Kenji Mori
Photosensitive Materials Research Center, Toyo Gosei Co., Ltd, Wakahagi 4-2-1, Inba-mura, Inba-gun, Chiba 270-1609, Japan
Received 17 December 2007; received in revised form 13 February 2008; accepted 13 February 2008
Available online 16 February 2008
Abstract
All of the following six components of the female sex pheromone of the German cockroach, Blattella germanica (L.) were synthesized:
(3S,11S)-3,11-dimethyl-2-nonacosanone (1), its 29-hydroxy derivative 2, its 29-oxo derivative 3, (3S,11S)-3,11-dimethyl-2-heptacosanone
(4), its 27-hydroxy derivative 5, and its 27-oxo derivative 6. Both the enantiomers of citronellal were employed as the chiral sources and Wacker
oxidation was employed for the introduction of the carbonyl group at C-2.
Ó 2008 Elsevier Ltd. All rights reserved.
1. Introduction
In 1989 Jurenka et al. identified by mass spectrometry 3,11-
dimethyl-2-heptacosanone (4) in the cuticular hydrocarbons of
the female B. germanica.8 The ketone 4 was subsequently re-
ported to be the fourth component of the female sex pheromone
of B. germanica.9 We synthesized (3S,11S)-4 in 1997,10 and its
pheromone activity was confirmed by Eliyahu et al.11 They also
found an interesting fact that the natural pheromone (3S,11S)-1
is the least active one among the four stereoisomers of 1.11 At
a discriminating dose of 1 ng, about 10% of the male B. german-
ica exhibited sexual responses to (3S,11S)-1, while 40e60% of
the males responded to other stereoisomers.11 At a dose of 2 ng,
(3R,11R)-1 was twice as bioactive as (3S,11S)-1.11 The bioassay
works of Eliyahu et al. employed highly pure stereoisomers of 1
synthesized by us in 1990.12
In 1974Nishidaetal. isolatedand identified3,11-dimethyl-2-
nonacosanone (1, Fig. 1) as the major component of the female-
produced contact sex pheromone of the German cockroach,
Blattella germanica (L.).2 Subsequent studies by Nishida et al.
clarified the presence of two additional components, 29-
hydroxy-3,11-dimethyl-2-nonacosanone (2) and 3,11-dimethyl-
29-oxo-2-nonacosanone (3).3e5 The amount of these
components as isolated by them was 239 mg of 1, 1.7 mg of 2,
and 20 mg of 3.5 The biological activities of the pheromone com-
ponents as expressed by the concentration for 50% biological re-
sponse were 3.7ꢀ10ꢁ6 M for 1, 3.9ꢀ10ꢁ7 M for 2, and
1.9ꢀ10ꢁ6 M for 3.5 In other words, 2 was about ten times
more active than 1, while 3 was about twice as active as 1.
Synthesis of all the four stereoisomers of 1 as well as those of
2 by Mori et al. in 1978 established the absolute configuration
of 1 and 2 as 3S,11S after careful comparison of the physical
properties of the natural and synthetic 1 and 2 including IR spec-
trum, mp, and specific rotation.5e7 Both NMR and chromato-
graphic analyses were proved to be useless in comparing the
stereoisomers of these molecules 1 and 2 with two stereogenic
centers separated by seven methylene groups.
In 2007 Schal and his co-workers discovered two additional
pheromone components 5 and 6 in the epicuticle of the
X(CH2)17
(CH2)7
(470 ng)
X(CH2)15
(CH2)7
(97 ng)
O
O
1 X = Me
2 X = CH2OH (25.6 ng)
3 X = CHO (0.5 ng)
4 X = Me
5 X = CH2OH (5.3 ng)
6 X = CHO (0.15 ng)
Figure 1. Structures of the six components 1e6 of the female-produced con-
tact sex pheromone of the German cockroach, B. germanica (L). Figures in
the parentheses indicate the amounts of the components on the cuticular sur-
face of an adult female of B. germanica (L.) as estimated by GC analysis.13
*
Pheromone synthesis, Part 235. For Part 234, see Ref. 1.
* Tel.: þ81 3 3816 6889; fax: þ81 3 3813 1516.
E-mail address: kjk-mori@arion.ocn.ne.jp
0040-4020/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2008.02.040

K. Mori / Tetrahedron 64 (2008) 4060e4071
4061
German cockroach.13 The contact sex pheromone of the fe-
male German cockroach thus consists of six biosynthetically
related components 1e6 as depicted in Figure 1, in which
the amounts of the components on the cuticular surface of
an adult female B. germanica are also shown on the basis of
GC analysis of the cuticular hydrocarbons.13
Schal’s identification of 5 and 6 was made possible by
direct comparison of the natural isolates with the synthetics
as supplied by Mori.13 After having prepared 5 and 6 as re-
quested by Schal, I thought it better to synthesize all the other
pheromone components, too, by a new route employing com-
mon intermediates. Because it is cumbersome and tedious to
synthesize compounds such as 1e6 with two stereogenic cen-
ters separated by seven methylene units, there are only four
publications, one by Katsuki and Yamaguchi14 and three by
ourselves,7,10,12 reporting the synthesis of (3S,11S)-3,11-
dimethyl-2-nonacosanone (1) and related compounds 2 and
4. This paper describes the synthesis of 1e6 by a new syn-
thetic route. Compounds 3, 5, and 6 were synthesized for
the first time.
Our new synthetic plan is based on the idea that the enan-
tiomers of citronellal can be used as the starting materials,
because they are now commercially available in high ee of
97%.15 In our 1978 synthesis, (R)-citronellic acid of 92% ee
was the only available chiral source. In our second synthesis
in 1990, highly pure four stereoisomers of 1 could be synthe-
sized from (R)-citronellal and ethyl (R)-3-hydroxybutanoate.12
However, the synthetic route in this 1990 synthesis was more
complicated than that of our 1978 synthesis.
6 can be derived from alcohol 5 by mild oxidation. Ketone 5
is to be prepared from alkene A by Pd2þ-catalyzed Wacker ox-
idation followed by hydrogenolytic debenzylation. In our 1978
synthesis, this conversion was executed by Hg2þ-catalyzed hy-
dration of A followed by oxidation. Alkene A can be prepared
by coupling B and C via Grignard reaction. Alkylation of ace-
tylene E with iodide D followed by several steps including
carbon-chain shortening gives aldehyde B. Iodide D can be
prepared from commercially available 1,12-dodecanediol F,
while acetylene E is to be synthesized from trimethylsi-
lyl(TMS)acetylene G and (R)-citronellal. Another intermedi-
ate C can be prepared from (S)-citronellal via tosylate I and
potassium cyanide H. All of the six pheromone components
1e6 were synthesized along this line.
2. Results and discussion
2.1. Synthesis of the key building block (S)-19 (¼C)
Scheme 2 summarizes the synthesis of the key building
block (S)-19 (¼C), which constitutes the C-1 to C-7 portion
of the pheromone components 1e6. Tosylate (S)-14 was pre-
viously prepared from (ꢁ)-isopulegol via (R)-citronellic acid
and served as an intermediate for the synthesis of 1 and 2.7
(S)-Citronellal (7, Takasago, 97% ee) was reduced to (S)-
citronellol (8), whose methyl xanthate 9 was pyrolyzed to
give (S)-10.16 The corresponding monoepoxide 1116 was
cleaved with periodic acid to afford aldehyde 12, which was
reduced to alcohol 13. Tosylation of 13 yielded the known to-
sylate 14 (¼I),7 which was treated with potassium cyanide and
sodium iodide in dimethyl sulfoxide (DMSO) to furnish nitrile
Our present retrosynthetic analysis of Schal’s new phero-
mone components 5 and 6 is shown in Scheme 1. Aldehyde
OHC(CH2)15
(CH2)7
HO(CH2)16
(CH2)7
O
O
6
5
BnO(CH2)16
(CH2)7
A
Br
BnO(CH2)16
CHO
C
B
KCN
TsO
BnO(CH2)12
I
H
I
D
E
CHO
OHC
HO(CH2)12OH
HC CTMS
(S)-Citronellal
(R)-Citronellal
F
G
Scheme 1. Retrosynthetic analysis of the new components 5 and 6 of the female-produced contact sex pheromone of the German cockroach, B. germanica (L.).

4062
K. Mori / Tetrahedron 64 (2008) 4060e4071
b
Me(CH2)nI
Me(CH2)nOR
a
c
CHO
OR
20A n = 13 R = H
21A n = 13 R = Ts
22A n = 13
22B n = 11
(S)-7
a
(S)-8 R = H
(S)-9 R = C(S)SMe
b
c
d
d
f
e
h
a
HO(CH2)nOH
MeO2C(CH2)12CO2Me
O
(3S,6RS)-11
(S)-10
23A
24A n = 14
24B n = 12 (=F)
b
BnO(CH2)nOR
BnO(CH2)nI
RO
25A n = 14 R = H
25B n = 12 R = H
27A n = 14
OHC
NC
27B n = 12 (=D)
a
(S)-13 R = H
(S)-12
g
26A n = 14 R = Ts
26B n = 12 R = Ts
(S)-14 R = Ts (= I)
i
HO2C
c
b
OHC
RO
(S)-15
(S)-16
(R)-7
(R)-8 R = H
(R)-28 R = Ts
a
j
e
RO
Br
I
(S)-19 (= C)
(S)-17 R = H
(S)-18 R = Ts
(R)-29
(R)-30 (= E)
g
Scheme 3. Synthesis of 22A, 27A, 27B, and (R)-30. Reagents and conditions:
(a) TsCl, C5H5N (89%-quant.); (b) NaI, DMF (85% for 22A; 96% for 27A;
95% for 27B); (c) LiAlH4 THF [89% for 24A; 90% for (R)-8]; (d) t-BuOK,
BnCl, DMSO (30e35%); (e) (i) TMSC^CH, n-BuLi, THF, HMPA; (ii)
K2CO3, MeOH (71%).
Scheme 2. Synthesis of (S)-19. Reagents and conditions: (a) LiAlH4, Et2O
[90% for 8, quant. for 17 based on (S)-15 (2 steps)]; (b) NaH, CS2, MeI,
THF; (c) heat, 240e270 ꢂC (53e54%, 2 steps); (d) MCPBA, CH2Cl2 (quant.);
(e) HIO4$2H2O, THF, Et2O; (f) LiAlH4, Et2O (65%, 2 steps); (g) TsCl, C5H5N
(quant.); (h) KCN, NaI, DMSO (78%); (i) NaOH, EtOH, H2O, then dil HCl; (j)
LiBr, DMF (82%).
unwanted dibenzyl ether by SiO2 chromatography. Similarly,
commercially available 1,12-dodecanediol 24B (¼F) was con-
verted to iodide 27B (¼D) via 25B and 26B in 22% overall yield
based on 24B (3 steps).
Preparation of the known acetylene (R)-30 (¼E)7 was facil-
itated by using commercially available TMS acetylene as one
of the starting materials. (R)-Citronellal (7, Takasago, 97% ee)
was reduced to (R)-citronellol (8), whose tosylate 28 was
treated with sodium iodide in DMF to give iodide (R)-29. Al-
kylation of the lithiated TMS acetylene (LiC^CTMS) with 29
was followed by removal of the TMS group with potassium
carbonate in methanol to give (R)-30. The overall yield of
(R)-30 was 61% based on (R)-7 (4 steps).
15. Alkaline hydrolysis of 15 gave acid 16 after acidification.
Reduction of 16 with lithium aluminum hydride provided
alcohol 17. The corresponding tosylate 18 was treated with
lithium bromide in N,N-dimethylformamide (DMF) to give
bromide (S)-19 (¼C). The overall yield of (S)-19 was 16.5%
(12 steps) based on citronellal (S)-7.
2.2. Synthesis of the iodides 22A, 27A, 27B (¼D), and
acetylene (R)-30 (¼E)
Scheme 3 shows the synthesis of the iodides 22A, 27A, 27B
(¼D), and acetylene (R)-30 (¼E). The former iodides serve as
the left part (C-16 to C-27 or C-16 to C-29 portion), and the
latter acetylene serves as the middle part (C-8 to C-15 portion)
of the pheromone components 1e6.
2.3. Synthesis of the six components 1e6 of the female sex
pheromone of the German cockroach
1-Iodotetradecane (22A) was prepared in 85% yield (2 steps)
from commercially available 1-tetradecanol (20A)via the corre-
sponding tosylate 21A. 1-Iodododecane (22B) was commer-
cially available. 14-Benzyloxytetradecyl iodide (27A)7 was
prepared from commercially available dimethyl tetradecane-
dioate (23A) by successive reduction to 24A, monobenzylation
to 25A, tosylation to 26A, and iodide formation by Finkelstein
reaction to give 27A in 27% overall yield based on 23A (4 steps).
As to monobenzylation of diol 24Awith benzyl chloride, use of
potassium tert-butoxide in DMSO as the base was found to be
operationally simple, because the desired product 25A could
readily be separated from the recovered diol 24A and the
Scheme 4 summarizes the coupling of the three building
blocks C [¼(S)-19], D [¼22A,B and 27A,B], and E[(R)-30]
to construct the intermediates with the carbon skeletons of
the pheromone molecules and their further conversion to the
six components 1e6 of the German cockroach pheromone.
Synthesis of (3S,11S)-29-hydroxy-3,11-dimethyl-2-nonacosa-
none (2) and the corresponding aldehyde 3 will be described
in detail.
Alkylation of the lithiated acetylene (R)-30 in THF/HMPA
with 14-benzyloxytetradecyl iodide (27A) gave crude 31c,
which was immediately epoxidized with m-chloroperbenzoic

K. Mori / Tetrahedron 64 (2008) 4060e4071
4063
could be purified by SiO2 chromatography. Mesylation of 35c
with methanesulfonyl chloride (mesyl chloride, MsCl) in pyr-
idine provided mesylate 36c, which was reduced with lithium
aluminum hydride to give alkene 37c. Palladium2þ-catalyzed
a
+
RI
(R)-30
22A,B
27A,B
Wacker oxidation of the alkene 37c with PdCl2 and Cu(OAc)2
17e19
in wet N,N-dimethylacetamide (DMA) under O2
yielded
b
methyl ketone 38c in about 45% yield (72% based on the con-
sumed 37c) after 3 days at room temperature. Hydrogenolytic
removal of the benzyl group of 37c with H2 and Pd/C in EtOAc
containing a small amount of AcOH gave (3S,11S)-29-hydroxy-
3,11-dimethyl-2-nonacosanone (2) as needle-like waxy solids,
mp 38e39 ꢂC, [a]2D5 þ3.62 (hexane), in 45% yield based on
37c (2 steps). Finally, oxidation of 2 with DesseMartin period-
inane20 afforded (3S,11S)-3,11-dimethyl-29-oxo-2-nonacosa-
none (3) as a low melting solid, mp 27e29 ꢂC, [a]D23 þ3.47
(hexane), in 69% yield. The overall yield of 3 was 2.1% based
on (S)-citronellal (18 steps) or 5.6% based on (R)-citronellal
(14 steps). Similarly, other four pheromone components were
synthesized: (3S,11S)-3,11-dimethyl-2-nonacosanone (1), mp
38e40 ꢂC, [a]2D5 þ4.35 (hexane), (3S,11S)-3,11-dimethyl-2-
heptacosanone (4), mp 37e39 ꢂC, [a]D27 þ5.44 (hexane),
(3S,11S)-27-hydroxy-3,11-dimethyl-2-heptacosanone (5), mp
30e32 ꢂC, [a]2D3 þ3.27 (hexane), and (3S,11S)-3,11-dimethyl-
27-oxo-2-heptacosanone (6), mp 25 ꢂC, [a]D23 þ3.47 (hexane).
O
R
R
d
31a,b,c,d
32a,b,c,d
c
R(CH2)4
R(CH2)4
34a,b,c,d
CHO
O
33a,b,c,d
e
f
R(CH2)4
OH
35a,b,c,d
g
R(CH2)4
R(CH2)4
(CH2)7
OMs
36a,b,c,d
37a,b,c,d
h
i
R(CH2)4
(CH2)7
1, 4, 38c,d
HO(CH2)n
(CH2)7
3. Conclusion
O
O
O
2 n = 18
5 n = 16
All the six components 1e6 of the female-produced contact
sex pheromone of the German cockroach, B. germanica (L.),
were synthesized from the enantiomers of citronellal. Bioassay
of these components indicates that both the hydroxy ketones 2
and 5 are about 10-fold more active than the respective parent
ketones 1 and 4 of the same chain length.5,11,13 Each of the six
pheromone components can independently elicit the complete
repertoire of sex response with no synergism among others.13
The readily available enantiomers of citronellal will continue
to serve as useful chiral sources in pheromone synthesis.15,21
j
R
OHC(CH2)n
(CH2)7
O
39a,b,c,d
3 n = 17
6 n = 15
1 and a: R = n-C14H29
c: R = BnO(CH2)14
4 and b: R = n-C12H25
d: R = BnO(CH2)12
Scheme 4. Synthesis of the six components 1e6 of the female-produced contact
sex pheromone of the German cockroach, B. germanica (L.). Reagents and
conditions: (a) (R)-30, n-BuLi, THF, HMPA (quant.); (b) MCPBA, CH2Cl2
(43e79%); (c) H2, Pd/C, EtOAc, Et3N (82%-quant.); (d) HIO4$2H2O, THF,
Et2O (88e98%); (e) (S)-19, Mg, THF, then 34 (65e98%); (f) MsCl, C5H5N,
(quant.); (g) LiAlH4, THF (47e64%); (h) PdCl2, Cu(OAc)2$H2O, O2, DMA,
H2O (51e57%); (i) H2, Pd/C, EtOAc, AcOH [45% for 2 (2 steps); 65% for 5
(2 steps)]; (j) DesseMartin periodinane, CH2Cl2 (69% for 3; 56% for 6).
4. Experimental
4.1. General
Boiling and melting points are uncorrected values. Refrac-
tive indices (nD) were measured on an Atago DMT-1 refrac-
tometer. Optical rotations were measured on a Jasco P-1020
polarimeter. IR spectra were measured on a Jasco FT/IR-410
acid (MCPBA) in dichloromethane to give 32c after SiO2 chro-
matography. The triple bond of 32c was then hydrogenated
over Pd/C in ethyl acetate to give epoxide 33c. Hydrogenolysis
of the benzyl protective group as well as the possible hydroge-
nolysis of the epoxy group could be prevented by adding
a small amount of Et3N to the hydrogenation mixture. In
some occasions, however, the presence of Et3N retarded the
complete hydrogenation of the triple bond, having allowed to
leave a double bond intact to give 39c instead of the desired
33c as revealed by 1H NMR analysis. Treatment of the epoxide
33c with periodic acid in THF/ether afforded aldehyde 34c.
Addition of the Grignard reagent prepared from (S)-19 and
Mg in THF to the aldehyde 34c furnished alcohol 35c, which
1
spectrometer. H NMR spectra (400 MHz, TMS at d¼0.00
as internal standard) and 13C NMR spectra (100 MHz,
CDCl3 at d¼77.0 as internal standard) were recorded on
a Jeol JNM-AL 400 spectrometer. HRMS were recorded on
a Jeol JMS-SX 102A. Column chromatography was carried
out on Merck Kieselgel 60 Art 1.07734.
4.2. (S)-3,7-Dimethyl-6-octen-1-ol (citronellol) 8
A solution of (S)-7 (Takasago, 97% ee; 57.6 g, 374 mmol)
in dry Et2O (50 mL) was added dropwise to a stirred and

4064
K. Mori / Tetrahedron 64 (2008) 4060e4071
ice-cooled suspension of LiAlH4 (8.0 g, 210 mmol) in dry
Et2O (300 mL) at 5e15 ꢂC. The mixture was stirred for 2 h
at 10e15 ꢂC and carefully poured onto iceedil HCl portion-
wise. Subsequent work-up and distillation gave 8 (52.5 g,
90%) as a colorless oil, bp 96e97 ꢂC/6 Torr; nmax (film):
3330 (s, OH), 1672 (w, C]C), 1059 (s, CeO).
(1H, m, CH]CH2). HRMS calcd for C8H13N: 123. 1048,
found: 123. 1063.
4.9. (S)-5-Methyl-6-hexenoic acid 16
A solution of (S)-15 (12.5 g, 102 mmol) and NaOH (16 g,
400 mmol) in 95% EtOH (60 mL) and water (40 mL) was
stirred and heated under reflux for 8 h. After dilution with wa-
ter, the mixture was extracted with hexane to remove neutral
impurities. The aqueous layer was acidified with dil HCl and
extracted with ether. The extract was washed with water and
brine, dried (MgSO4), and concentrated in vacuo to give
14.4 g of crude (S)-16. A portion of it was distilled to give
an analytical sample, bp 108e109 ꢂC/6 Torr, nD18¼1.4420;
[a]2D3 þ14.8 (c 3.48, hexane); nmax (film): ca. 3200e2700
(m, CO2H), 1711 (s, C]O), 1641 (w, C]C), 1292 (m), 995
(m), 912 (s); dH (CDCl3): 0.99 (3H, d, J 6.8, CHCH3), 1.33
(2H, m), 1.63 (2H, m), 2.13 (1H, m), 2.34 (2H, t, J 7.2,
CH2CO), 4.72e4.99 (2H, m, CH]CH2), 5.67 (1H, m,
CH]CH2). HRMS calcd for C8H14O2: 142.0994, found:
142.0993.
4.3. (S)-3,7-Dimethyl-1,6-octadiene (citronellene) 10
Conversion of (S)-8 to (S)-10 was carried out via (S)-9
according to Cernigliaro and Kocienski16 to give (S)-10 in
53e54% yield, bp 70e75 ꢂC/35e40 Torr; nmax (film): 3078
(w, C]CH2), 1641 (m, C]C), 995 (m), 910 (s).
4.4. (3S,6RS)-6,7-Epoxy-3,7-dimethyl-1-octene 11
Oxidation of (S)-10 with 1.1 equiv of MCPBA in dichloro-
methane yielded (3S,6RS)-11 (quant.) as an oil, which was
used immediately in the next step. nmax (film): 3078 (w,
C]CH2), 1641 (m, C]C), 1122 (m, CeO), 995 (m), 910 (s).
4.5. (S)-4-Methyl-5-hexenal 12
4.10. (S)-5-Methyl-6-hexen-1-ol 17
Cleavage of the epoxide 11 with HIO4$2H2O in THF gave
(S)-12 as an odoriferous oil, which was used in the next step
without distillation. nmax (film): 3078 (w, C]CH2), 2719 (w,
O]CeH), 1726 (s, C]O), 1641 (w, C]C), 997 (m), 914 (s).
A solution of (S)-16 (14.4 g, 80.3 mmol) in dry Et2O
(10 mL) was added dropwise to a stirred and ice-cooled sus-
pension of LiAlH4 (4.8 g, 126 mmol) in dry Et2O (200 mL)
at 5e15 ꢂC. The mixture was stirred overnight at room tem-
perature, and the excess LiAlH4 was destroyed by dropwise
addition of water to the stirred and ice-cooled mixture. It
was then acidified with dil HCl, and extracted with Et2O.
The extract was washed with water, NaHCO3 solution and
brine, dried (MgSO4), and concentrated in vacuo. The residue
was distilled to give (S)-17 (10.7 g, 82% based on 15; 2 steps)
as a colorless oil, bp 100e103 ꢂC/37 Torr, nD21¼1.4408; [a]2D3
þ16.0 (c 4.68, hexane); nmax (film): 3334 (s, OH), 3078 (m,
C]CH2), 1639 (m, C]C), 1051 (s, CeO), 993 (m), 910
(s); dH (CDCl3): 0.99 (3H, d, J 6.8, CHCH3), 1.32 (4H, m),
1.41 (1H, s), 1.54 (2H, m), 2.12 (1H, m), 3.63 (2H, t, J 6.8,
CH2OH), 4.90e4.97 (2H, m, CH]CH2), 5.64e5.73 (1H, m,
CH]CH2). HRMS calcd for C8H16O: 128.1201, found:
128.1200.
4.6. (S)-4-Methyl-5-hexen-1-ol 13
Reduction of (S)-12 with excess LiAlH4 in ether gave the
known (S)-13 (62e65% based on 10).7 nmax (film): 3327 (s,
OH), 3078 (w, C]CH2), 1641 (w, C]C), 1059 (s, CeO),
910 (s).
4.7. (S)-4-Methyl-5-hexenyl tosylate 14
Tosylation of (S)-13 in the standard manner afforded (S)-14
(quant.) as an oil.7 nmax (film): 3074 (w, C]CH2), 1641 (w,
C]C), 1599 (m, arom. C]C), 1188 (s), 1178 (s), 1097 (m),
966 (s), 918 (s), 816 (s), 663 (s), 555 (s).
4.8. (S)-5-Methyl-6-hexenenitrile 15
4.11. (S)-5-Methyl-6-hexenyl tosylate 18
Crude (S)-14 [29.4 g (110 mmol); prepared from 14.8 g of
(S)-13] was dissolved in DMSO (80 mL). To the stirred solu-
tion was added KCN (9.6 g, 148 mmol) and NaI (0.5 g), and
the mixture was stirred and heated at 100 ꢂC for 2 h. After
cooling, the mixture was diluted with water and extracted
with ether. The ether extract was washed with water and brine,
dried (MgSO4), and concentrated in vacuo. The residue was
distilled to give (S)-15 (12.5 g, 78%) as an oil, bp 112e
114 ꢂC/54 Torr, nD21¼1.4366; [a]2D3 þ14.6 (c 5.12, hexane);
nmax (film): 3078 (m, C]CH2), 2247 (m, C^N), 1641 (m,
C]C), 997 (m), 914 (s); dH (CDCl3): 1.02 (3H, d, J 6.8,
CHCH3), 1.21 (2H, m), 1.65 (2H, m), 2.15 (1H, m), 2.33
(2H, t, J 6.8, CH2CN), 4.95e5.00 (2H, m, CH]CH2), 5.63
Powdered tosyl chloride (6.0 g, 31 mmol) was added por-
tionwise to a stirred and ice-cooled solution of (S)-17 (3.3 g,
26 mmol) in dry pyridine (15 mL) at 5e10 ꢂC. The mixture
was left to stand overnight in a refrigerator (0e5 ꢂC). It was
then diluted with water and extracted with ether. The extract
was washed with dil HCl, water, NaHCO3 solution, and brine,
dried (MgSO4), and concentrated in vacuo to give (S)-18
(7.3 g, quant.) as an oil. nmax (film): 3072 (w, C]CH2),
1639 (w, C]C), 1599 (m, arom. C]C), 1176 (s), 935 (s),
816 (s), 663 (s); dH (CDCl3): 0.94 (3H, d, J 6.8, CHCH3),
1.20e1.29 (4H, m), 1.59e1.64 (2H, m), 2.04 (1H, m), 2.45
(3H, s, C6H4CH3), 4.01 (2H, t, J 6.8, CH2OTs), 4.87e4.93

K. Mori / Tetrahedron 64 (2008) 4060e4071
4065
(2H, m, CH]CH2), 5.57e5.66 (1H, m, CH]CH2), 7.34 (2H,
d, J 8.8, arom. H), 7.79 (2H, d, J 8.8, arom. H). This was em-
ployed for the next step without further purification.
Elution with hexane/EtOAc (2:1) gave 2.4 g of 24A. Total
amount of the recovered 24A was 10.2 g. Accordingly, the
yield of 25A based on the consumed 24A was 70%. The mono-
benzyl ether 25A showed the following spectral properties:
nmax (film): 3370 (s, OH), 1117 (m), 1061 (m), 735 (m), 696
(m); dH (CDCl3): 1.26 (20H, br s), 1.58 (4H, m), 3.46 (2H,
t, J 6.8, CH2OBn), 3.63 (2H, t, J 6.8, CH2OH), 4.50 (2H, s,
C6H5CH2), 7.26e7.37 (5H, m, C6H5).
4.12. (S)-5-Methyl-6-hexenyl bromide 19
Powdered LiBr (7.0 g, 80 mmol) was added to a stirred so-
lution of (S)-18 (7.3 g, 26 mmol) in DMF (50 mL). After the
exothermic reaction, the mixture was stirred at room tempera-
ture for 1 h, poured into ice-water, and extracted with hexane.
The extract was washed with water and brine, dried (MgSO4),
and concentrated in vacuo. The residue was distilled to give
(S)-19 (4.1 g, 82%) as an oil, bp 86e90 ꢂC/28 Torr,
n1D8¼1.4651; [a]D24 þ10.9 (c 4.49, hexane); nmax (film): 3078
(m, C]CH2), 1641 (m, C]C), 995 (s), 912 (s); dH
(CDCl3): 0.99 (3H, d, J 6.8, CHCH3), 1.27e1.33 (2H, m),
1.42 (2H, m), 1.85 (2H, m), 2.12 (1H, m), 3.40 (2H, t, J 6.8,
CH2Br), 4.91e4.98 (2H, m, CH]CH2), 5.63e5.72 (1H, m,
CH]CH2). HRMS calcd for C8H15Br: 190.0357, found:
190.0359.
4.16. 12-Benzyloxy-1-dodecanol 25B
In the same manner as described above for the preparation
of 25A, 24B (20.2 g, 100 mmol), t-BuOK (11.2 g, 100 mmol),
BnCl (15 g, 120 mmol) in dry DMSO (100 mL) yielded 7.8 g
(26%) of 25B; n2D1¼1.4912; nmax (film): 3375 (s, OH), 1103 (s,
CeO), 735 (s), 698 (s); dH (CDCl3): 1.27 (16H, br s), 1.54e
1.63 (4H, m), 3.46 (2H, t, J 6.8, CH2OBn), 3.63 (2H, t, J
6.8, CH2OH), 4.50 (2H, s, C6H5CH2), 7.26e7.35 (5H, m,
C6H5). HRMS calcd for C19H32O2: 292.2402, found:
292.2401.
4.13. 1-Iodotetradecane 22A
4.17. 14-Benzyloxytetradecyl tosylate 26A
1-Tetradecanol (20A, 25 g, 117 mmol) was treated with to-
syl chloride (24.5 g, 129 mmol) in dry pyridine (100 mL) to
give 21A (43 g, quant.), which was stirred and heated at
80 ꢂC for 1 h with NaI (45 g, 300 mmol) in DMF (250 mL).
After standard work-up and distillation 32.2 g (85%) of 22A
was obtained, bp 160e165 ꢂC/7 Torr; nmax (film): 2922 (s),
2854 (s), 1466 (m), 1178 (w), 721 (w), 602 (w); dH
(CDCl3): 0.88 (3H, t, J 6.8, CH3), 1.26 (20H, br s), 1.38
(2H, m), 1.82 (2H, m), 3.19 (2H, t, J 7.1).
In the same manner as described for the preparation of 18,
tosylation of 25A (7.9 g, 25 mmol) with tosyl chloride (5.5 g,
29 mmol) in dry pyridine (50 mL) afforded 10.4 g (89%) of
26A. nmax (film): 3030 (w, arom. CeH), 1599 (w, arom.
C]C), 1186 (s), 1171 (s), 949 (s), 733 (s); dH (CDCl3):
1.15e1.40 (20H, m), 1.52e1.68 (4H, m), 2.45 (3H, s,
C6H4CH3), 3.46 (2H, t, J 6.8, BnOCH2), 4.01 (2H, t, J 6.8,
TsOCH2), 4.50 (2H, s, C6H5CH2), 7.25e7.28 (2H, C6H4),
7.33e7.34 (5H, C6H5), 7.78 (2H, d, J 8.0, C6H4).
4.14. 1,14-Tetradecanediol 24A
4.18. 12-Benzyloxydodecyl tosylate 26B
Reduction of 23A (25 g, 87.4 mmol) with LiAlH4 (7.0 g,
184 mmol) in dry THF (400 mL) at reflux (1 h) gave 24A
(17.8 g, 89%), mp 87e89 ꢂC; nmax (Nujol): 3351 (s, OH),
1051 (m, CeO), 1016 (m, CeO), 997 (w), 972 (w), 729
(w), 615 (w); dH (CDCl3): 1.26 (24H, br s), 1.56 (2H, m),
3.64 (4H, t, J 6.8, CH2OH).
In the same manner under the standard tosylation condi-
tions, 25B (7.8 g, 26 mmol) was treated with tosyl chloride
(6.0 g, 32 mmol) in dry pyridine (50 mL) to give 10.5 g
(90%) of 26B. nmax (film): 3030 (m, arom. CeH), 1599 (m,
arom. C]C), 1171 (s), 1107 (s), 945 (s), 733 (s); dH
(CDCl3): 1.15e1.40 (16H, m), 1.55e1.70 (4H, m), 2.44
(3H, s, C6H4CH3), 3.46 (2H, t, J 6.4, CH2OBn), 4.01 (2H, t,
J 6.4, CH2OTs), 7.25e7.27 (2H, m, C6H4), 7.33e7.34 (5H,
m, C6H5), 7.78 (2H, d, J 8.0, C6H4).
4.15. 14-Benzyloxy-1-tetradecanol 25A
Potassium tert-butoxide (11.2 g, 100 mmol) and 24A
(20.5 g, 89 mmol) were mixed in dry DMSO (100 mL) to
give voluminous precipitates of the potassium salt of 24A.
Benzyl chloride (16.5 g, 130 mmol) was added to the mixture,
which was heated on a water bath at 80 ꢂC with swirling (later
stirring) to dissolve the solid. After stirring for 1.5 h at 80 ꢂC,
the mixture was left to stand for 3 days. It was poured into ice-
water and extracted with ether. The ether extract was washed
with water and brine, dried (MgSO4), and concentrated in va-
cuo. The residue was triturated with hexane to recover 7.8 g of
24A. The residue was chromatographed on SiO2 (150 g). Elu-
tion with hexane gave 12.5 g of dibenzyl ether. Further elution
with hexane/EtOAc (3:1) gave the known 25A (10.0 g, 35%).7
4.19. 14-Benzyloxytetradecyl iodide 27A
Powdered NaI (7.5 g, 50 mmol) was added to a solution of
26A (10.4 g, 22 mmol) in DMF (50 mL). The mixture was
stirred and heated at 50 ꢂC for 4 h, then diluted with water
and extracted with hexane. The hexane solution was washed
with water and brine, dried (MgSO4), and concentrated in va-
cuo to give 9.0 g (96%) of 27A as an oil, n2D5¼1.5116; nmax
(film): 1103 (s, CeO), 735 (s), 696 (s); dH (CDCl3) 1.26
(20H, m), 1.59 (2H, m), 1.80 (2H, m), 3.18 (2H, t, J 6.8,
CH2I), 3.46 (2H, t, J 6.8, BnOCH2), 4.50 (2H, s, C6H5CH2),

4066
K. Mori / Tetrahedron 64 (2008) 4060e4071
7.26e7.34 (5H, m, C6H5). HRMS calcd for C21H35IO:
430.1733, found: 430.1729.
was washed with water and brine, dried (MgSO4), and concen-
trated in vacuo to give 10.0 g (quant.) of crude 31d. nmax
(film): 1103 (m), 735 (m), 696 (m); dH (CDCl3): 1.59 (3H,
s, C]CCH3), 1.63 (3H, s, C]CCH3), 5.10 (1H, br,
C]CH). This was employed for the next step without further
purification.
4.20. 12-Benzyloxydodecyl iodide 27B
In the same manner as described above for 27A, 26B
(10.5 g, 24 mmol) was treated with NaI (10 g, 67 mmol) in
DMF (80 mL) to give 9.5 g (95%) of 27B as an oil. nmax
(film): 1103 (s, CeO), 735 (s), 696 (s); dH (CDCl3): 1.26
(16H, m), 1.61 (2H, m), 1.81 (2H, m), 3.18 (2H, t, J 6.8,
CH2I), 3.46 (2H, t, J 6.8, BnOCH2), 4.50 (2H, s, C6H5CH2),
7.25e7.34 (5H, m, C6H5). HRMS calcd for C19H31IO:
402.1420, found: 402.1415.
4.23. (R)-2,6-Dimethyl-2-tetracosen-9-yne 31a
In the same manner as described above for 31d, (R)-30
(2.5 g, 15 mmol) was alkylated with 22A (5.2 g, 16 mmol)
and n-BuLi in hexane (1.6 M, 10 ml, 16 mmol) in THF
(19 mL) and HMPA (1.5 mL) to give 6.54 g (quant.) of crude
31a, whose 1H NMR spectrum showed the presence of
CH]CMe2.
4.21. (R)-5,9-Dimethyl-8-decen-1-yne 30
(R)-3,7-Dimethyl-6-octenyl iodide (29) was prepared from
(R)-citronellal (7, Takasago, 97% ee) via (R)-8 and 28 as re-
ported previously.7 A solution of n-BuLi (1.6 M in hexane,
100 mL, 160 mmol) was slowly added to a stirred and cooled
solution of TMSC^CH (15.7 g, 160 mmol) in dry THF
(150 mL) and HMPA (10 mL) at ꢁ70 to ꢁ30 ꢂC under Ar.
The mixture was warmed to ꢁ10 ꢂC and then cooled again
to ꢁ70 ꢂC. A solution of (R)-29 (36.3 g, 136 mmol) in THF
(10 mL) was added dropwise to the stirred and cooled solution
at ꢁ70 to ꢁ30 ꢂC. After having left to stand for 2 days at room
temperature, the mixture was diluted with water and extracted
with hexane. The extract was washed with water and brine,
dried (MgSO4), and concentrated to give ca. 36 g of crude
1-trimethylsilylated 30. nmax (film): 2175 (m, C^C), 1249
(s), 845 (s), 760 (s). This was dissolved in MeOH (300 mL),
and K2CO3 (15 g) and water (20 mL) were added to the solu-
tion. The mixture was stirred at 50 ꢂC for 1 h, diluted with wa-
ter, and extracted with hexane. The extract was washed with
water and brine, dried (MgSO4), and concentrated in vacuo.
The residue was distilled to give 16.0 g (71%) of the known
(R)-30 as a colorless oil, bp 110e120 ꢂC/38 Torr, [a]D21
þ2.64 (c 4.22, hexane); [Ref.7: [a]2D1 þ3.8 (neat, l¼1 dm)];
nmax (film): 3311 (m, C^CeH), 2119 (w, C^C), 629 (s);
dH (CDCl3): 0.89 (3H, d, J 6, CHCH3), 1.10e1.21 (1H, m),
1.30e1.40 (2H, m), 1.52e1.62 (2H, m), 1.60 (3H, s,
C]CCH3), 1.68 (3H, s, C]CCH3), 1.92 (1H, t, J 1.2,
C^CH), 1.94e2.06 (2H, m), 2.10e2.28 (2H, m), 5.09 (1H,
br t, C]CH).
4.24. (R)-2,6-Dimethyl-2-docosen-9-yne 31b
In the same manner as described above for 31d, (R)-30 (2.5 g,
15 mmol) was alkylated with 22B (4.6 g, 15.5 mmol) and
n-BuLi in hexane (1.6 M, 10 mL, 16 mmol) in THF (19 mL)
and HMPA (1.5 mL) to give 6.3 g (quant.) of crude 31b, whose
1H NMR spectrum showed the presence of CH]CMe2.
4.25. (R)-1-Benzyloxy-19,23-dimethyl-22-tetracosen-15-yne
31c
In the same manner as described above for 31d, (R)-30 (1.6 g,
10 mmol) was alkylated with 27A (4.2 g, 9.8 mmol) and n-BuLi
in hexane (1.6 M, 7 mL, 11 mmol) in THF (13 mL) and HMPA
(1 mL) to give 5.1 g (quant.) of crude 31c, whose 1H NMR spec-
trum showed the presence of CH]CMe2.
4.26. (17S,20RS)-1-Benzyloxy-20,21-epoxy-17,21-dimethyl-
13-docosyne 32d
MCPBA (77% purity, 4.9 g, 22 mmol) was added portion-
wise to a stirred and ice-cooled solution of crude 31d
(10.0 g) in dry CH2Cl2 (100 mL) at 0e5 ꢂC. After 1.5 h, the
mixture was diluted with hexane and filtered to remove solid
MCBA. The filtrate was washed with dil K2CO3 solution
and brine, dried (MgSO4), and concentrated in vacuo. The res-
idue (10.6 g) was chromatographed over SiO2 (70 g). After
elution of less polar materials (3.16 g) with hexane/
EtOAc¼50:1, elution with hexane/EtOAc¼50:1e20:1 gave
4.06 g [43% based on (R)-30, 2 steps] of 32d as an oil,
n2D5¼1.4892; nmax (film): 1250 (w), 1205 (w), 1103 (s), 735
(m), 698 (m); dH (CDCl3): 0.89 (3H, d, J 6.8, CHCH3), 1.27
(3H, s, CH3), 1.31 (3H, s, CH3), 1.20e1.60 (27H, m), 2.13
(4H, m), 2.67 (1H, m, epoxide H), 3.46 (2H, t, J 6.8,
CH2O), 4.50 (2H, s, C6H5CH2), 7.25e7.35 (5H, m, C6H5).
HRMS calcd for C31H50O2: 454.3811, found: 454.3810.
4.22. (R)-1-Benzyloxy-17,21-dimethyl-20-docosen-13-yne
31d
A solution of n-BuLi in hexane (1.6 M, 14 mL, 22 mmol)
was added dropwise to a stirred and cooled solution of (R)-
30 (3.3 g, 20 mmol) in dry THF (20 mL) and HMPA (2 mL)
at ꢁ70 ꢂC under Ar. The mixture was warmed to ꢁ10 ꢂC
and then cooled again at ꢁ70 ꢂC. A solution of 27B (9.0 g,
22 mmol) in dry THF (10 mL) was added to the stirred and
cooled mixture at ꢁ70 to ꢁ30 ꢂC, and it was left to stand at
room temperature for 3 days. Subsequently the mixture was
diluted with water and extracted with hexane. The extract
4.27. (3RS,6S)-2,3-Epoxy-2,6-dimethyl-9-tetracosyne 32a
In the same manner as described above for 32d, (R)-31a
(6.6 g, 15 mmol) in CH2Cl2 (70 mL) was epoxidized with

K. Mori / Tetrahedron 64 (2008) 4060e4071
4067
MCPBA (3.8 g, 17 mmol) at 0e5 ꢂC for 1.5 h. Subsequent
4.31. (3RS,6S)-2,3-Epoxy-2,6-dimethyltetracosane 33a
work-up was followed by chromatography of crude 32a
(7.0 g) over SiO2 (70 g). Elution with hexane gave 1.63 g of
less polar materials. Then elution with hexane/EtOAc¼50:1
gave 3.0 g [53% based on (R)-30, 2 steps] of 32a as an oil.
nmax (film): 1290 (w), 1255 (m), 1122 (w), 750 (w); dH
(CDCl3): 0.86e0.92 (6H, m, CHCH3 and CH2CH3), 1.20e
1.60 (34H, m), 1.31 (3H, s, CH3), 2.10e2.24 (4H, m), 2.69
(1H, t, J 6.8, epoxide H).
In the same manner as described above for 33d, 32a (2.9 g,
7.7 mmol) was hydrogenated over 10% Pd/C (500 mg) in
EtOAc (30 mL) and Et3N (0.1 mL) to give 2.7 g (93%) of
33a after SiO2 chromatography (20 g SiO2 and elution with
hexane/EtOAc¼50:3). nmax (film): 1254 (m), 1122 (m), 899
(w), 750 (w); dH (CDCl3): 0.87 (6H, m, CH2CH3 and
CHCH3), 1.20e1.60 (34H, m), 1.31 (3H, s, CH3), 2.70 (1H,
t-like, epoxide H).
4.28. (3RS,6S)-2,3-Epoxy-2,6-dimethyl-9-docosyne 32b
4.32. (3RS,6S)-2,3-Epoxy-2,6-dimethyldocosane 33b
In the same manner as described above for 32d, (R)-31b
(6.3 g, 15 mmol) in CH2Cl2 (70 mL) was epoxidized with
MCPBA (3.8 g, 17 mmol) at 0e5 ꢂC for 1 h. Subsequent
work-up was followed by chromatography of crude 32b
(6.2 g) over SiO2 (50 g). Elution with hexane gave 1.3 g of
less polar materials. Then elution with hexane/EtOAc¼50:3
gave 4.1 g [77% based on (R)-30, 2 steps] of 32b as an oil.
nmax (film): 1290 (w), 1255 (m), 1122 (w), 750 (w); dH
(CDCl3): 0.86e0.92 (6H, m, CHCH3 and CH2CH3), 1.20e
1.62 (30H, m), 1.31 (3H, s, CH3), 2.10e2.22 (4H, m), 2.70
(1H, m, epoxide H); dC (CDCl3): 79.95 and 80.30 (C^C).
In the same manner as described above for 33d, 32b (2.2 g,
6.3 mmol) was hydrogenated over 10% Pd/C (500 mg) in
EtOAc (25 mL) and Et3N (1 mL) to give 1.8 g (82%) of 33b
after SiO2 chromatography (20 g SiO2 and elution with hex-
ane/EtOAc¼100:3). nmax (film): 1254 (m), 1122 (m), 871
(w), 750 (w); dH (CDCl3): 0.86e0.90 (6H, m, CH2CH3 and
CHCH3), 1.20e1.60 (30H, m), 1.31 (3H, s, CH3), 2.70 (1H,
t-like, epoxide H).
4.33. (19S,22RS)-1-Benzyloxy-22,23-epoxy-19,23-
dimethyltetracosane 33c
In the same manner as described above for 33d, 32c (3.8 g,
7.6 mmol) was hydrogenated over 10% Pd/C (700 mg) in
EtOAc (35 mL) and Et3N (0.5 mL) to give 3.5 g (92%) of
33c after SiO2 chromatography (20 g SiO2 and elution with
hexane/EtOAc¼50:3). nmax (film): 1254 (m), 1103 (s), 735
(m), 696 (m); dH (CDCl3): 0.87 (3H, d, J 7.2, CHCH3),
1.22e1.65 (38H, m), 1.31 (3H, s, CH3), 2.09 (1H, t-like, epox-
ide H), 3.46 (2H, t, J 6.8, CH2O), 4.50 (2H, s, C6H5CH2),
7.25e7.40 (5H, m, C6H5). In these hydrogenation experi-
ments, the triple bond could not be reduced to the single
bond, giving 39aed as evidenced by the presence of a signal
at d¼5.38 due to olefinic protons, if too much Et3N was added
or too short time was allowed for hydrogenation. Contamina-
tion of olefins at this stage necessitated another hydrogenation
at the final step (37a/1).
4.29. (19S,22RS)-1-Benzyloxy-22,23-epoxy-19,23-dimethyl-
15-tetracosyne 32c
In the same manner as described above for 32d, (R)-31c
(5.1 g, 11 mmol) in CH2Cl2 (50 mL) was epoxidized with
MCPBA (2.7 g, 12 mmol) at 0e10 ꢂC for 1 h. Subsequent
work-up was followed by chromatography over SiO2 (50 g).
Elution with hexane/EtOAc¼50:3 gave 3.8 g [79% based on
(R)-30, 2 steps] of 32c as an oil. nmax (film): 1255 (m), 1103
(s), 735 (m), 696 (m); dH (CDCl3): 0.89 (3H, d, J 6.8,
CHCH3), 1.26 (3H, s, CH3), 1.31 (3H, s, CH3), 1.20e1.65
(31H, m), 2.10e2.22 (4H, m), 2.67 (1H, t-like, epoxide H),
3.46 (2H, t, J 6.8, CH2O), 4.50 (2H, s, C6H5CH2), 7.25e
7.35 (5H, m, C6H5).
4.34. (S)-20-Benzyloxy-4-methylicosanal 34d
4.30. (17S,20RS)-1-Benzyloxy-20,21-epoxy-17,21-
dimethyldocosane 33d
A solution of 33d (3.8 g, 8.3 mmol) in ether (20 mL) was
added to a stirred and ice-cooled solution of HIO4$2H2O
(2.3 g, 10 mmol) in THF (40 mL) at 0e5 ꢂC. The mixture
soon became turbid and white solid (HIO3) precipitated. The
stirring was continued for 1 h at 0e5 ꢂC. Subsequently, the
mixture was diluted with water, and extracted with ether.
The extract was washed with water, NaHCO3 solution and
brine, dried (MgSO4), and concentrated in vacuo to give
3.38 g (98%) of 34d as an oil, n2D5¼1.4852; [a]D25 ꢁ0.70 (c
3.60, hexane); nmax (film): 2713 (w, O]CeH), 1726 (s,
C]O), 1103 (m), 735 (m), 698 (m); dH (CDCl3): 0.87 (3H,
d, J 6.8, CHCH3), 1.20e1.50 (27H, m), 1.58e1.80 (4H, m),
1.97 (2H, m), 2.40 (2H, m), 3.46 (2H, t, J 6.8, OCH2), 4.50
(2H, s, C6H5CH2), 7.25e7.40 (5H, m, C6H5), 9.76 (1H,
Palladiumecharcoal (10%, 700 mg) was added to a solution
of 32d (4.0 g, 8.6 mmol) in EtOAc (40 mL) and Et3N
(0.4 mL). The mixture was stirred under H2 (balloon) for
22 h at room temperature. The catalyst was filtered off through
Celite and washed with EtOAc. The filtrate was concentrated
in vacuo and the residue was chromatographed over SiO2
(20 g). Elution with hexane/EtOAc¼50:3 gave 4.0 g (quant.)
of 33d as an oil. nmax (film): 1254 (m), 1103 (s), 735 (s),
696 (s); dH (CDCl3): 0.87 (3H, d, J 6.4, CHCH3), 1.22e1.65
(34H, m), 1.30 (3H, s, CH3), 2.69 (1H, t, J 6.4, epoxide H),
3.46 (2H, t, J 6.8, CH2O), 4.50 (2H, s, C6H5CH2), 7.25e
7.40 (5H, m, C6H5).

4068
K. Mori / Tetrahedron 64 (2008) 4060e4071
CHO). HRMS calcd for C28H48O2: 416.3654, found:
416.3655.
(74%) of 35d as an oil, nD24¼1.4841; [a]2D5 þ2.97 (c 3.65, hex-
ane); nmax (film): 3394 (m, OH), 3066 (w), 3030 (w), 1639 (w,
C]C), 1101 (s), 908 (m), 733 (m), 696 (m); dH (CDCl3): 0.87
(3H, d, J 6.0, 11-CH3), 0.98 (3H, d, J 60, 3-CH3), 1.20e1.50
(38H, m), 1.57e1.70 (4H, m), 1.92e2.05 (2H, m), 2.11 (1H,
m), 3.46 (2H, t, J 6.8, CH2O), 3.55 (1H, m, CHOH), 4.50
(2H, s, C6H5CH2), 4.85e5.00 (2H, m, CH]CH2), 5.64e
5.70 (1H, m, CH]CH2), 7.25e7.34 (5H, m, C6H5). HRMS
calcd for C36H62O (MþꢁH2O): 510.4801, found: 510.4801.
4.35. (S)-4-Methyldocosanal 34a
In the same manner as described above for 34d, 33a (2.7 g,
7.2 mmol) was treated with HIO4$2H2O (2.1 g, 9 mmol) in
THF (30 mL) and ether (10 mL) at 0e5 ꢂC for 1 h. Subsequent
work-up and chromatographic purification over SiO2 (20 g;
elution with hexne/EtOAc¼10:1) gave 2.2 g (91%) of 34a as
an oil, n2D5¼1.4598; [a]D25 ꢁ0.23 (c 2.68, hexane); nmax
(film): 2711 (w, O]CeH), 1728 (s, C]O), 1255 (m), 750
(m); dH (CDCl3): 0.86e0.90 (6H, m, CHCH3, CH2CH3),
1.20e1.43 (33H, m), 1.92e2.03 (2H, m), 2.40e2.45 (2H,
m), 9.77 (1H, CHO). HRMS calcd for C23H46O: 338.3545,
found: 338.3538.
4.39. (3S,8RS,11S)-3,11-Dimethyl-1-nonacosen-8-ol 35a
In the same manner as described above for 35d, 34a (1.9 g,
5.6 mmol) in THF (3 mL) was added to the Grignard reagent
prepared from (S)-19 (1.6 g, 8.3 mmol) and Mg (240 mg,
10 mmol) in THF (5 mL). Subsequent work-up and chromato-
graphic purification over SiO2 (25 g; elution with hexane/
EtOAc¼4:1) gave 2.5 g (98%) of 35a as an oil, n2D5¼1.4632;
[a]2D5 þ3.35 (c 4.80, hexane); nmax (film): 3361 (m), 3076 (w
C]CeH), 1639 (w, C]C), 1255 (s), 910 (s); dH (CDCl3):
0.86e0.90 (6H, m, CHCH3, CH2CH3), 0.98 (3H, d, J 6.8, 3-
CH3), 1.20e1.60 (49H, m), 3.55 (1H, m CHOH), 4.85e5.00
(2H, m, CH]CH2), 5.64e5.73 (1H, m, CH]CH2). HRMS
calcd for C31H60 (MþꢁH2O): 432.4695, found: 432.4698.
4.36. (S)-4-Methylicosanal 34b
In the same manner as described above for 34d, 33b (1.8 g,
5.1 mmol) was treated with HIO4$2H2O (1.4 g, 6 mmol) in
THF (25 mL) and ether (5 mL) at 0e5 ꢂC for 1 h. Subsequent
work-up and chromatographic purification gave 1.4 g (88%) of
34b as an oil, nD25¼1.4582; [a]D25 ꢁ0.32 (c 2.78, hexane); nmax
(film): 2711 (w, O]CeH), 1728 (s, C]O), 1257 (m), 968
(m); dH (CDCl3): 0.85e0.90 (6H, m, CHCH3, CH2CH3),
1.20e1.45 (31H, m), 1.90e2.10 (2H, m), 2.40e2.44 (2H,
m), 9.77 (1H, CHO). HRMS calcd for C21H42O: 310.3236,
found: 310.3233.
4.40. (3S,8RS,11S)-3,11-Dimethyl-1-heptacosen-8-ol 35b
In the same manner as described above for 35d, 34b (1.4 g,
4.5 mmol) in THF (3 mL) was added to the Grignard reagent
prepared from (S)-19 (1.4 g, 7.3 mmol) and Mg (240 mg,
10 mmol) in THF (5 mL). Subsequent work-up and chromato-
graphic purification over SiO2 (20 g; elution with hexane/
EtOAc¼10:1) gave 1.8 g (95%) of 35b as an oil, n2D6¼
1.4652; [a]2D5 þ4.16 (c 3.07, hexane); nmax (film): 3356 (s,
OH), 3076 (w, C]CeH), 1639 (w, C]C), 910 (m); dH
(CDCl3): 0.86e0.90 (6H, m, CHCH3, CH2CH3), 0.98 (3H,
d, J 6.8, 3-CH3), 1.20e1.60 (45H, m), 3.55 (1H, m, CHOH),
4.85e5.00 (2H, m, CH]CH2), 5.64e5.73 (1H, m, CH]
CH2). HRMS calcd for C29H56 (MþꢁH2O): 404.4436, found:
404.4442.
4.37. (S)-22-Benzyloxy-4-methyldocosanal 34c
In the same manner as described above for 34d, 33c (3.5 g,
7 mmol) was treated with HIO4$2H2O (1.8 g, 8 mmol) in THF
(30 mL) and ether (10 mL) at 0e5 ꢂC for 1 h. Subsequent
work-up gave 3.1 g (97%) of 34c as an oil, n2D5¼1.4860; [a]D25
ꢁ0.26 (c 2.88, hexane); nmax (film): 2713 (w, O]CeH), 1726
(s, C]O), 1103 (s), 1072 (s), 735 (m), 698 (m); dH (CDCl3):
0.88 (3H, d-like, CHCH3), 1.20e1.42 (31H, m), 1.58e1.70
(4H, m), 1.90e2.05 (2H, m), 2.38e2.42 (2H, m), 3.46 (2H, t,
J 6.8, OCH2), 4.50 (2H, s, C6H5CH2), 9.77 (1H, CHO).
HRMS calcd for C30H52O2: 444.3967, found: 444.3968.
4.41. (3S,8RS,11S)-29-Benzyloxy-3,11-dimethyl-1-
nonacosen-8-ol 35c
4.38. (3S,8RS,11S)-27-Benzyloxy-3,11-dimethyl-1-
heptacosen-8-ol 35d
In the same manner as described above for 35d, 34c (2.8 g,
6.2 mmol) in THF (3 mL) was added to the Grignard reagent
prepared from (S)-19 (1.5 g, 8 mmol) and Mg (240 mg,
10 mmol) in THF (5 mL). Subsequent work-up and chromato-
graphic purification over SiO2 (30 g; elution with hexane/
EtOAc¼10:1) gave 2.2 g (65%) of 35c as an oil, n2D5¼
1.4836; [a]2D5 þ3.00 (c 2.68, hexane); nmax (film): 3384 (s,
OH), 3066 (w), 3030 (w), 1639 (w, C]C), 1101 (s), 910
(s), 733 (m), 696 (m); dH (CDCl3): 0.87 (3H, d, J 6, 11-
CH3), 0.98 (3H, d, J 6, 3-CH3), 1.20e1.50 (42H, m), 1.57e
1.70 (4H, m), 1.92e2.05 (2H, m), 2.11 (1H, m), 3.46 (2H, t,
J 6.8, CH2O), 3.55 (1H, m, CHOH), 4.50 (2H, s, C6H5CH2),
4.85e5.00 (2H, m, CH]CH2), 5.64e5.71 (1H, m,
Grignard reagent was prepared from bromide (S)-19 (1.9 g,
10 mmol) and Mg (300 mg, 12.5 mmol) in dry THF (6 mL) by
initiating the reaction with a trace amount of I2, with stirring
and heating under reflux under Ar. A solution of 34d (3.1 g,
7.5 mmol) in dry THF (3 mL) was added dropwise to the
stirred and ice-cooled Grignard reagent. After 2 h at room
temperature, the mixture was quenched with NH4Cl solution
and ice. Then the mixture was extracted with ether. The extract
was washed with water and brine, dried (MgSO4), and concen-
trated in vacuo. The residue (4.8 g) was chromatographed over
SiO2 (30 g). Elution with hexane/EtOAc¼4:1 gave 2.9 g

K. Mori / Tetrahedron 64 (2008) 4060e4071
4069
CH]CH2), 7.25e7.34 (5H, m, C6H5). HRMS calcd for
C38H66O (MþꢁH2O): 538.5113, found: 538.5115.
36b. Reduction of 36b with LiAlH4 (0.6 g, 15.8 mmol) in
THF (20 mL) furnished 0.89 g (54% based on 35b, 2 steps)
of 37b after chromatographic purification [SiO2 (20 g); elution
with hexane] as an oil, nD26¼1.4562; [a]2D5 þ4.51 (c 2.95, hex-
ane); nmax (film): 3078 (w, C]CeH), 1639 (w, C]C), 993
(w), 966 (w), 910 (m); dH (CDCl3): 0.83 (3H, d, J 6.4,
11-CH3), 0.88 (3H, t, J 6.8, CH2CH3), 0.97 (3H, d, J 6.8,
3-CH3), 1.00e1.18 (2H), 1.20e1.45 (41H, m), 1.90e2.05
(2H), 2.05e2.15 (1H), 4.88e4.96 (2H, m, CH]CH2),
5.64e5.74 (1H, m, CH]CH2). HRMS calcd for C29H58:
406.4539, found: 406.4546.
4.42. (3S,11S)-27-Benzyloxy-3,11-dimethyl-1-heptacosene
37d
Methanesulfonyl chloride (1.0 mL, ca. 1.5 g, 13 mmol) was
added to a stirred and ice-cooled solution of 35d (2.9 g,
5.5 mmol) in CH2Cl2 (5 mL) and C5H5N (5 mL) at 0e5 ꢂC.
The mixture was left to stand overnight in a refrigerator
(5 ꢂC), poured into ice-water, and extracted with ether. The
ether extract was washed with dil HCl, NaHCO3 solution,
and brine, dried (MgSO4), and concentrated in vacuo to give
2.1 g of crude 36d. nmax (film): 3066 (w), 3030 (w), 1639
(w, C]C), 1358 (s), 1176 (s), 906 (s); dH (CDCl3): 3.00
(3H, s, SO2CH3). A solution of crude 36d (2.1 g) in dry
THF (10 mL) was added dropwise to a stirred and ice-cooled
suspension of LiALH4 (0.6 g, 15.8 mmol) in dry THF
(15 mL). The mixture was then stirred and heated under reflux
for 1 h. After cooling, the mixture was carefully acidified with
ice and dil HCl, and extracted with ether. The extract was
washed with water, NaHCO3 solution and brine, dried
(MgSO4), and concentrated in vacuo. The residue (1.7 g)
was chromatographed over SiO2 (20 g). Elution with hexane
gave 0.28 g of less polar impurities. Further elution with hex-
ane/EtOAc¼20:1 afforded 1.37 g (49% based on 35d; 2 steps)
of 37d, n2D4¼1.4822; [a]D25 þ2.47 (c 3.11, hexane); nmax (film):
3066 (w), 3030 (w), 1639 (w, C]C), 1103 (s), 908 (m), 733
(m), 696 (m); dH (CDCl3): 0.83 (3H, d, J 6.8, CHCH3), 0.97
(3H, d, J 6.8, CHCH3), 1.10e1.40 (41H, br s), 1.55e1.65
(3H, m), 1.90e2.10 (2H, m), 3.46 (2H, t, J 6.4, OCH2), 4.50
(2H, s, C6H5CH2), 4.88e5.00 (2H, m, CH]CH2), 5.64e
5.74 (1H, m, CH]CH2), 7.25e7.34 (5H, m, C6H5). HRMS
calcd for C36H64O: 512.4957, found: 512.4939.
4.45. (3S,11S)-29-Benzyloxy-3,11-dimethyl-1-nonacosene
37c
In the same manner as described above for 37d, 35c (2.2 g,
4.0 mmol) was mesylated with MsCl (1.0 mL, 13 mmol) in
CH2Cl2 (10 mL) and C5H5N (10 mL) to give 2.1 g of crude
36c. Reduction of 36c with LiAlH4 (0.6 g, 15.8 mmol) in
THF (25 mL) furnished 1.37 g (64% based on 35c; 2 steps)
of 37c as an oil, n2D5¼1.4840; [a]2D5 þ2.02 (c 3.38, hexane);
nmax (film): 3064 (w), 3030 (w), 1639 (w, C]C), 1103 (s),
908 (m), 733 (s), 696 (s); dH (CDCl3): 0.83 (3H, d, J 6.4,
11-CH3), 0.88 (3H, t, J 6.8, CH2CH3), 0.97 (3H, d, J 6.8, 3-
CH3), 1.05e1.15 (2H), 1.15e1.45 (45H, m), 1.55e1.65 (3H,
m), 1.90e2.10 (2H, m), 3.46 (2H, t, J 6.4, OCH2), 4.50 (2H,
s, C6H5CH2), 4.88e4.96 (2H, m, CH]CH2), 5.64e5.74
(1H, m, CH]CH2), 7.25e7.34 (5H, m, C6H5). HRMS calcd
for C38H68O: 540.5270, found: 540.5264.
4.46. (3S,11S)-3,11-Dimethyl-2-nonacosanone 1
A
suspension of PdCl2 (492 mg, 2.8 mmol) and
Cu(OAc)2$H2O (1.047 g, 5.2 mmol) in N,N-dimethylacetamide
(DMA, 7 mL) and water (2 mL) was stirred vigorously under O2
(balloon) for 0.5 h. Then a solution of 37a (1.01 g, 2.3 mmol) in
DMA (5 mL) was added to the mixture. The stirring was contin-
ued for 3 days at room temperature under O2. Subsequently, the
mixture was diluted with dil HCl and extracted with ether. The
extract was washed with water and brine, dried (MgSO4), and
concentrated in vacuo. The residue (1.1 g) was chromato-
graphed over SiO2 (10 g). Elution with hexane gave recovered
37a (0.4 g, 39.6%). Further elution with hexane/EtOAc¼20:1
gave 0.65 g of crude 1. This was dissolved in EtOAc (20 mL)
containing 1 drop of AcOH, and hydrogenated over 10% Pd/C
(0.4 g) for 1.5 h under H2. The catalyst was filtered off through
Celite and the filtrate was concentrated in vacuo to give 600 mg
(57%) of 1 as a solid. This was recrystallized from 99% EtOH
to give 220 mg of 1 as needles, mp 38e40 ꢂC (Ref.7:
44.0e44.5 ꢂC); [a]D25 þ4.35 (c¼1.17, hexane) {Ref.7: [a]2D1
þ5.98ꢃ0.30 (c 0.90, hexane)}; nmax (Nujol): 1709 (s, C]O),
1186 (w), 1149 (w), 955 (w), 719 (m); dH (CDCl3): 0.83 (3H,
d, J 6.4, 11-CH3), 0.88 (3H, t, J 6.8, CH2CH3), 1.07 (3H, d, J
6.8, 3-CH3), 1.05e1.40 (48H, m), 1.58e1.70 (1H, m), 2.13
(3H, s, COCH3), 2.45e2.60 (1H, m, COCH); dC (CDCl3):
14.1, 16.2, 19.7, 22.7, 27.02, 27.07, 27.09, 27.2, 27.9, 29.3,
29.48, 29.50, 29.63, 29.67, 29.71, 29.9, 30.0, 31.9, 32.7, 32.9,
4.43. (3S,11S)-3,11-Dimethyl-1-nonacosene 37a
In the same manner as described above for 37d, 35a (2.2 g,
4.9 mmol) was mesylated with MsCl (1.0 mL, 13 mmol) in
CH2Cl2 (5 mL) and C5H5N (5 mL) to give 2.3 g of crude
36a. Reduction of 36a with LiAlH4 (0.6 g, 15.8 mmol) in
THF (25 mL) furnished 1.01 g (47% based on 35a; 2 steps)
of 37a after chromatographic purification [SiO2 (20 g); elution
with hexane] as an oil, nD24¼1.4523; [a]2D4 þ4.19 (c 3.48, hex-
ane); nmax (film): 3078 (w, C]CeH), 1639 (w, C]C), 993
(m), 966 (w), 910 (m); dH (CDCl3): 0.83 (3H, d, J 6.4, 11-
CH3), 0.88 (3H, t, J 6.8, CH2CH3), 0.97 (3H, d, J 6.4, 3-
CH3), 1.00e1.15 (2H), 1.20e1.50 (45H, m), 1.90e2.04
(2H), 2.05e2.15 (1H), 4.88e4.96 (2H, m, CH]CH2),
5.64e5.74 (1H, m, CH]CH2). HRMS calcd for C31H62:
434.4852, found: 434.4851.
4.44. (3S,11S)-3,11-Dimethyl-1-heptacosene 37b
In the same manner as described above for 37d, 35b (1.7 g,
4.0 mmol) was mesylated with MsCl (1.2 mL, 16 mmol) in
CH2Cl2 (5 mL) and C5H5N (5 mL) to give 1.53 g of crude

4070
K. Mori / Tetrahedron 64 (2008) 4060e4071
37.1, 47.2, 212.8 (C]O). HRMS calcd for C31H62O: 450.4801,
found: 450.4803.
(70%) of crude 38d. This was dissolved in EtOAc (15 mL) con-
taining 3 drops of AcOH and hydrogenated over 10% Pd/C
(0.4 g) for 2 days at room temperature to give 500 mg (65%)
of 5 as a waxy solid. Recrystallization from pentane gave
380 mg of 5 as waxy needles, mp 30e32 ꢂC, [a]D23 þ3.27 (c
1.92, hexane); nmax (Nujol): 3437 (s, OH), 1712 (s, C]O),
1059 (m), 723 (m); dH (CDCl3): 0.83 (3H, d, J 6.4, 11-CH3),
1.07 (3H, d, J 6.8, 3-CH3), 1.15e1.40 (43H, m), 1.50e1.70
(3H, m), 2.13 (3H, s, COCH3), 2.45e2.60 (1H, m, COCH),
3.64 (2H, t, J 6.8, CH2OH); dC (CDCl3): 16.2, 19.7, 25.7,
27.01, 27.06, 27.21, 27.93, many signals around 29.2e30.0,
32.7, 32.8, 32.9, 37.03, 37.06, 42.8, 47.2, 63.0, 212.8 (C]O).
HRMS calcd for C29H58O2: 438.4437, found: 438.4433.
4.47. (3S,11S)-3,11-Dimethyl-2-heptacosanone 4
In the same manner as described above for 1, 37b (600 mg,
1.5 mmol) was oxidized with O2, PdCl2 (267 mg, 1.5 mmol)
and Cu(OAc)2$H2O (600 mg, 3 mmol) in DMA (7 mL) and
water (1 mL) for 2 days at room temperature. The resulting
oil (570 mg) was chromatographed over SiO2 (10 g). Elution
with hexane gave recovered 37b (260 mg, 43%). Further elu-
tion with hexane/EtOAc¼20:1 gave 320 mg (51%) of 4 as
a solid. Recrystallization from 99% EtOH gave needles, mp
37e39 ꢂC (Ref.10: mp 41.0e41.5 ꢂC); [a]2D7 þ5.44 (c 0.268,
hexane) {Ref.10: [a]D22 þ5.84 (c 1.09, hexane)}; nmax (Nujol):
1708 (s, C]O), 1180 (w), 1149 (w), 958 (w), 721 (m); dH
(CDCl3): 0.83 (3H, d, J 6.4, 11-CH3), 0.88 (3H, t, J 6.8,
CH2CH3), 1.07 (3H, d, J 6.8, 3-CH3), 1.05e1.40 (44H, m),
1.58e1.70 (1H, m), 2.13 (3H, s, COCH3), 2.45e2.55 (1H,
m, COCH); dC (CDCl3): 14.1, 16.1, 19.7, 22.7, 27.06, 27.2,
27.9, 29.3, 29.46, 29.5, 29.62, 29.67, 29.7, 29.9, 30.0, 31.9,
32.7, 32.9, 37.0, 47.2, 212.8 (C]O). HRMS calcd for
C29H58O: 422.4488, found: 422.4487.
4.50. (3S,11S)-3,11-Dimethyl-29-oxo-2-nonacosanone 3
DesseMartin periodinane (600 mg, 1.4 mmol) was added
to a stirred and ice-cooled solution of 2 (160 mg, 0.4 mmol)
in dry CH2Cl2 (10 mL). After the addition, the mixture was
stirred for 45 min at room temperature. Then hexane
(10 mL) and ca. 10 mL of dil NaHCO3 and Na2S2O3 solution
were added to the mixture. After having stirred for 5 min, the
mixture was extracted with hexane. The extract was washed
with NaHCO3 solution and brine, dried (MgSO4), and concen-
trated in vacuo. The residue was chromatographed over SiO2
(5 g). Elution with hexane/EtOAc (20:1) gave 110 mg (69%)
of 3 as a waxy solid, mp 27e29 ꢂC, [a]D23 þ3.47 (c 0.70, hex-
ane); nmax (Nujol): 2713 (w, O]CeH), 1718 (s, C]O), 1169
(w), 721 (m); dH (CDCl3): 0.83 (3H, d, J 6.8, 11-CH3), 1.07
(3H, d, J 6.8, 3-CH3), 1.15e1.40 (45H, m), 1.50e1.70 (2H,
m), 2.13 (3H, s, COCH3), 2.32e2.43 (2H, m), 2.44e2.52
(1H, m, COCH), 9.76 (1H, CHO); dC (CDCl3): 11.4, 14.1,
16.1, 19.2, 19.7, 22.1, 27.1, 27.2, 27.9, many signals around
29.1e30.0, 32.7, 32.9, 34.4, 36.6, 37.1, 42.8, 43.9, 47.2,
202.7 (C]O), 212.8 (C]O). HRMS calcd for C31H60O2:
464.4593, found: 464.4589.
4.48. (3S,11S)-29-Hydroxy-3,11-dimethyl-2-nonacosanone 2
A
suspension of PdCl2 (302 mg, 1.7 mmol) and
Cu(OAc)2$H2O (605 mg, 3.0 mmol) in DMA (7 mL) and wa-
ter (2 mL) was stirred vigorously under O2 for 0.5 h. Then a so-
lution of 37c (990 mg, 1.9 mmol) in DMA (5 mL) was added
to the mixture. The stirring was continued for 3 days at room
temperature under O2. Subsequent work-up and chromatogra-
phy over SiO2 (20 g) gave 390 mg (39%) of the recovered 37c
and 430 mg (45%) of 38c. This was dissolved in EtOAc
(15 mL) containing 3 drops of AcOH and hydrogenated over
10% Pd/C (0.4 g) for 2.5 h under H2. The catalyst was filtered
off through Celite and the filtrate was concentrated in vacuo to
give 400 mg (45%) of 2 as a waxy solid. Recrystallization
from pentane gave needle-like waxy solids, mp 38e39 ꢂC
(Ref.7: mp 41e42 ꢂC); [a]D25 þ3.62 (c 1.06, hexane) {Ref.7:
[a]2D0þ6.1ꢃ0.7 (c 0.65, hexane)}; nmax (Nujol): 3435 (s,
OH), 1712 (s, C]O), 1240 (m), 1057 (m), 723 (m); dH
(CDCl3): 0.83 (3H, d, J 6.4, 11-CH3), 1.07 (3H, d, J 6.8, 3-
CH3), 1.15e1.40 (47H, m), 1.52e1.68 (3H, m), 2.13 (3H, s,
COCH3), 2.45e2.60 (1H, m, COCH), 3.64 (2H, t, J 6.8,
CH2OH); dC (CDCl3): 16.2, 19.7, 25.7, 27.02, 27.07, 27.09,
27.93, many signals around 29.2e30.0, 32.7, 32.8, 32.9,
37.03, 37.05, 42.8, 47.2, 63.0, 212.8 (C]O). HRMS calcd
for C31H62O2: 466.4750, found: 466.4749.
4.51. (3S,11S)-3,11-Dimethyl-27-oxo-2-heptacosanone 6
In the same manner as described above for 3, oxidation of 5
(214 mg, 0.49 mmol) with DesseMartin perodinane (750 mg,
1.8 mmol) in CH2Cl2 (12 mL) gave 120.1 mg (56%) of 6 as
a waxy solid melting around 25 ꢂC, [a]D22 þ3.70 (c 0.49, hex-
ane); nmax (film): 2713 (w, O]CeH), 1722 (s, C]O), 1167
(m), 721 (m); dH (CDCl3): 0.83 (3H, d, J 6.8, 11-CH3), 1.07
(3H, d, J 6.8, 3-CH3), 1.15e1.40 (41H, m), 1.50e1.70 (2H,
m), 2.13 (3H, s, COCH3), 2.32e2.43 (2H, m), 2.44e2.52
(1H, m, COCH), 9.76 (1H, CHO); dC (CDCl3): 11.4, 16.2,
19.2, 19.7, 22.1, 27.1, 27.2, 27.9, many signals around
29.1e30.0, 32.6, 32.7, 34.4, 36.6, 37.1, 42.8, 43.9, 47.2,
202.7 (C]O), 212.8 (C]O). HRMS calcd for C29H56O2:
436.4280, found: 436.4279.
4.49. (3S,11S)-27-Hydroxy-3,11-dimethyl-2-heptacosanone 5
In the same manner as described above for 2, 37d (900 mg,
1.8 mmol) was oxidized with O2, PdCl2 (662 mg, 3.7 mmol)
and Cu(OAc)2$H2O (1.196 g, 6.0 mmol) in DMA (11 mL) and
water (2 mL) for 3 days at room temperature. Subsequent
work-up gave 240 mg (27%) of the recovered 37d and 660 mg
Acknowledgements
My thanks are due to Mr. M. Kimura (President, Toyo Go-
sei Co., Ltd) for his support. I am indebted to Prof. C. Schal

K. Mori / Tetrahedron 64 (2008) 4060e4071
4071
8. Jurenka, R. A.; Schal, C.; Burns, E.; Chase, J.; Blomquist, G. J. J. Chem.
Ecol. 1989, 15, 939e949.
(North Carolina State University) for his initiative in the pres-
ent work. I thank Dr. T. Tashiro (RIKEN) for preparing
Figure and Schemes, Mr. Y. Shikichi (Toyo Gosei Co., Ltd)
for NMR measurements, and Mr. H. Tawaragi (RIKEN) for
MS measurements. The enantiomers of citronellal were sup-
plied by Takasago International Corporation.
9. Schal, C.; Burns, E.; Jurenka, R. A.; Blomquist, G. J. J. Chem. Ecol. 1990,
16, 1997e2008.
10. Takikawa, H.; Fujita, K.; Mori, K. Liebigs Ann./Recueil 1997, 815e820.
11. Eliyahu, D.; Mori, K.; Takikawa, H.; Leal, W. S.; Schal, C. J. Chem. Ecol.
2004, 30, 1839e1848.
12. Mori, K.; Takikawa, H. Tetrahedron 1990, 46, 4473e4486.
13. Eliyahu, D.; Nojima, S.; Mori, K.; Schal, C. J. Chem. Ecol., in press.
14. Katsuki, T.; Yamaguchi, M. Tetrahedron Lett. 1987, 28, 651e654.
References and notes
~
15. Lenardao, E. J.; Botteselle, G. V.; de Azambuja, F.; Perin, G.; Jacob, R. G.
Tetrahedron 2007, 63, 6671e6712.
1. Mori, K. Tetrahedron Lett. 2007, 48, 5609e5611.
16. Cernigliaro, G. J.; Kocienski, P. J. J. Org. Chem. 1977, 42, 3622e3624.
17. Keith, J. A.; Nielsen, R. J.; Oxgaard, J.; Goddard, W. A., III. J. Am. Chem.
Soc. 2007, 129, 12342e12343.
2. Nishida, R.; Fukami, H.; Ishii, S. Experientia 1974, 30, 978e979.
3. Nishida, R.; Fukami, H.; Ishii, S. Appl. Entomol. Zool. 1975, 10, 10e18.
4. Nishida, R.; Sato, T.; Kuwahara, Y.; Fukami, H.; Ishii, S. J. Chem. Ecol.
1976, 2, 449e455.
18. Das, S.; Abraham, S.; Sinha, S. C. Org. Lett. 2007, 9, 2273e2276.
19. Tsuji, J.; Shimizu, I.; Yamamoto, K. Tetrahedron Lett. 1976, 2975e
2976.
5. Review: Nishida, R.; Fukami, H. Mem. Coll. Agric., Kyoto Univ. 1983,
122, 1e24.
20. Dess, D. B.; Martin, J. C. J. Org. Chem. 1983, 48, 4155e4156.
21. Mori, K. Top. Curr. Chem. 2004, 239, 1e50.
6. Mori, K.; Suguro, T.; Masuda, S. Tetrahedron Lett. 1978, 3447e3450.
7. Mori, K.; Masuda, S.; Suguro, T. Tetrahedron 1981, 37, 1329e1340.