Stereospecific inversion of secondary tosylates to yield chiral methyl-branched building blocks, applied to the asymmetric synthesis of leafminer sex pheromones

Article abstract of DOI:10.1016/j.tetasy.2012.05.023

All four of the possible stereoisomers of 5,9-dimethylheptadecane, the major sex pheromone component secreted by female moths of the mountain-ash bentwing (Leucoptera scitella), were synthesized by the coupling of two chiral blocks with a methyl branch at the 2- or 3-position. The blocks were prepared by applying the stereospecific inversion of secondary tosylates, which were derived from (R)- and (S)-propylene oxide, and their enantiopurities were confirmed by chiral HPLC analysis.

Full text of DOI:10.1016/j.tetasy.2012.05.023

Tetrahedron: Asymmetry 23 (2012) 852–858
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Tetrahedron: Asymmetry
journal homepage: www.elsevier.com/locate/tetasy
Stereospecific inversion of secondary tosylates to yield chiral methyl-branched
building blocks, applied to the asymmetric synthesis of
leafminer sex pheromones
⇑
Tomonori Taguri, Rei Yamakawa, Toru Fujii, Yuta Muraki, Tetsu Ando
Graduate School of Bio-Applications and Systems Engineering, Tokyo University of Agriculture and Technology, Koganei, Tokyo 184-8588, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
All four of the possible stereoisomers of 5,9-dimethylheptadecane, the major sex pheromone component
secreted by female moths of the mountain-ash bentwing (Leucoptera scitella), were synthesized by the
coupling of two chiral blocks with a methyl branch at the 2- or 3-position. The blocks were prepared
by applying the stereospecific inversion of secondary tosylates, which were derived from (R)- and (S)-pro-
pylene oxide, and their enantiopurities were confirmed by chiral HPLC analysis.
Received 17 April 2012
Accepted 15 May 2012
Available online 11 July 2012
Ó 2012 Elsevier Ltd. All rights reserved.
1. Introduction
acid, and 3-methyl-4-butanolide.6 The starting materials are com-
mercially available but rather expensive. For another chiral source,
Species-specific sex pheromones have been identified from
adult females of more than 600 lepidopteran species.1 While pher-
omones are mainly composed of fatty alcohols, polyenyl hydrocar-
bons, and their derivatives with a straight chain, several species
utilize methyl-branched compounds for mating communication.2
In addition to the well-known methyl-branched alkanes, alkenes,
and esters of a primary alcohol or acid, we recently found ketones
and a secondary alcohol with a branched skeleton in the phero-
mone glands of female moths,3 indicating the diverse chemical
structures of lepidopteran sex pheromones. With regard to the
large number of insect species, however, knowledge of the lepidop-
teran species secreting branched compounds remains very limited.
Almost all methyl-branched compounds are chiral because a ter-
tiary carbon is a stereogenic center, except for that at the 2-posi-
tion. In order to understand the communication systems of
moths, it is important to supply not only a sufficient amount of
enantiopure known pheromones but also their analogues, which
could possibly be produced by taxonomically related species. We
investigated the possibilities of making chiral building blocks with
high enantiomeric excess, which could be applied for the system-
atic synthesis of dimethyl hydrocarbons, such as 5,9-dimethylhep-
we selected (R)- and (S)-propylene oxide (R)-2 and (S)-2, which
could be converted into the tosylates of 2-alkanols with a different
chain length, as shown in Scheme 1. If an alkylating reagent attacks
the tosylate via an SN2 reaction, the desired building block is
formed after the inversion of configuration at the reaction site.
By selecting an appropriate carbanion, it might be possible to pro-
duce chiral blocks A and B with a methyl group at the 3- and 2-
positions, respectively. The two building blocks could be useful
for the stereospecific construction of many n,(n+4)-dimethyl com-
pounds, and so we began applying them to the asymmetric synthe-
sis of all of the stereoisomers of 1.
2. Results and discussion
First, chiral blocks (S)-A and (R)-A [R1 = n-C4H9, X = I; (S)-8 and
(R)-8] were synthesized starting from (R)-2 and (S)-2 (>99% ee),
respectively, as shown in Scheme 2. The reaction between (R)-2
and n-C3H7MgBr with Li2CuCl4 gave secondary alcohol (R)-3, which
was converted into tosylate (R)-4. Antipodal tosylate (S)-4 was
prepared from (S)-2. By HPLC equipped with a normal phase chiral
column (Daicel Chiralpak AS-H), (R)-4 and (S)-4 could be detected
separately. The chiral HPLC analysis confirmed their high enantio-
meric excess (>99% ee), as shown in Figure 1A. In order to achieve
an SN2 reaction associated with chain elongation, we attempted to
utilize an enolate of tert-butyl acetate as the nucleophile because
an ester elongated by two carbons would be produced directly.
However, the expected product was not obtained. Therefore, we
examined a reaction with an enolate of dimethyl malonate. While
some studies have reported that the SN2 reaction of 2-bromo or 2-
mesyl compounds with enolates of dialkyl malonate proceed with
tadecane
1 secreted by Leucoptera scitella females as a sex
pheromone component.4
In addition to some unique synthetic routes,5 the asymmetric
synthesis of dimethyl hydrocarbons has reliably been accom-
plished by the coupling of two chiral methyl-branched building
blocks derived from citronellal, 3-hydroxy-2-methylpropanoic
⇑
Corresponding author. Tel./fax: +81 42 388 7278.
E-mail address: antetsu@cc.tuat.ac.jp (T. Ando).
0957-4166/$ - see front matter Ó 2012 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tetasy.2012.05.023

T. Taguri et al. / Tetrahedron: Asymmetry 23 (2012) 852–858
853
R1
OTs
R1
X
O
O
(R)-2
(S)-2
A
(S)-
R1
R2
(5S,9R)-1
R1 = n-C4H9
R2 = n-C8H17
Y
R2
OTs
R2
(R)-B
Scheme 1. Synthetic strategy for n,(n+4)-dimethylalkanes using stereospecific inversion of secondary tosylates.
i
iii
CO2Me
CO2Me
iv
ii
O
n-C4H9
(R)-3
OH
n-C4H9
(S)-5
n-C4H9
(R)-4
OTs
(R)-2
v
(S)-7 X = OH
CO2Me
vi
n-C4H9
n-C4H9
X
8
(S)- X = I
(S)-6
O
n-C4H9
I
(R)-8
(S)-2
Scheme 2. Synthetic routes to (S)-8 (chiral building block A, R1 = n-C4H9, X = I) and the antipode for the synthesis of 5,9-dimethylheptadecane 1. Reagents and conditions: (i)
n-C3H7MgBr, Li2CuCl4 (0.1 mol/L, 3 mol %), THF (84%); (ii) TsCl, Et3N, Me3NꢀHCl (10 mol %), CH2Cl2 (93%); (iii) NaCH(CO2Me)2, 1,2-dimethoxyethane (94%); (iv) LiCl, DMSO,
H2O, 170–180 °C (82%); (v) LiAlH4, THF (89%); (vi) I2, PPh3, imidazole, THF (91%).
considerable racemization,7 it has also been reported that the reac-
tion of a secondary tosylate with an enolate forms a new C–C-bond
along with the complete inversion of stereochemistry.8 Based on
(A)
(R)-4
this result, (R)-4 was treated with the enolate of dimethyl malon-
(S)-4
ate to yield geminal ester (S)-5, which was decarboxylated to ester
(S)-6 by the Krapcho’s method.9 The reduction of (S)-6 with LiAlH4
produced primary alcohol (S)-7, which had been synthesized from
(S)-b-citronellol in related research.3b The antipode (R)-7 was pre-
pared in the same manner. The two chiral alcohols could be sepa-
rated by another normal phase chiral HPLC column (Daicel
Chiralpak AY-H), as shown in Figure 1B, and their high enantio-
meric purity (>99% ee) indicated that the nucleophile attacked
the tosylates 4 via an SN2 reaction. By treatment with a mixture
of I2, triphenylphosphine (PPh3), and imidazole, (S)-7 and (R)-7
were converted into iodides (S)-8 and (R)-8, respectively. The over-
all yield of (S)-8 was 49% from (R)-2, and that of (R)-8 was 53% from
(S)-2.
0
10
20
30
tR (min)
(S)-7
(B)
(R)-7
Next, the chiral building block B was synthesized starting from
(S)-2 and (R)-2, respectively, as shown in Scheme 3. The reaction
between (S)-2 and n-C7H15MgBr with Li2CuCl4 gave secondary
alcohol (S)-9, which was converted into tosylate (S)-10. The antip-
odal tosylate (R)-10 was prepared from (R)-2. Chiral HPLC analysis
confirmed their high enantiomeric purity (>99% ee). It has been re-
ported that the cyanide ion and the base-generated carbanion of
methylthiomethyl p-tolyl sulfone can be utilized as a nucleophile
in an SN2 reaction,10 but information on other reactions for one
chain elongation associated with the complete inversion of config-
uration is to the best of our knowledge very limited. Therefore, we
examined other reactions to make an optically active 2-methylun-
decanyl derivative. One idea was a coupling reaction between the
secondary tosylate 10 and a sulfonyl acetate with an active meth-
ylene to yield a methyl-branched sulfonyl compound 11, which
might be converted into building block B (R2 = n-C8H17, X = Ts,
20
25
30
tR (min)
(R)-12
(C)
(S)-12
10
0
20
30
40
50
60
tR (min)
Figure 1. Chiral HPLC analyses of stereoisomers of 2-hexanyl tosylate 4 (A), 3-
methylheptan-1-ol 7 (B), and 2-methyl-1-(tolylsulfonyl)decane 12 (C). The HPLC was
conducted with a Chiralpack AS-H column (4.6 mm ID ꢁ 25 cm) and a UV detector
(254 nm) using 10% 2-propanol in hexane as an eluent (flow rate, 0.5 mL/min) for 4
and 12 and with a Chiralpack AY-H column (4.6 mm ID ꢁ 25 cm) and an RI detector
using 0.4% 2-propanol in hexane as an eluent (flow rate, 0.5 mL/min) for 7.

854
T. Taguri et al. / Tetrahedron: Asymmetry 23 (2012) 852–858
i
iii
X
X iv
ii
Ts
n-C8H17
OTs
(R)-12
O
n-C8H17
n-C8H17
(S)-9
OH
(S)-10
(S)-2
11
CO2Me
v
S
n-C8H17
13
p-Tol
CO2Me
(S)-8
vii
Ts
n-C8H17
(R)-12
n-C4H9
(5S,9R)-16
n-C8H17
(5S,9R)-1
/ vi
Ts
8
+
12
(S)-
(S)-
1
(5S,9S)-
Ts
O
n-C8H17
(S)-12
(R)-8 + (R)-12
(R)-8 + (S)-12
1
(5R,9R)-
(R)-2
(5R,9S)-1
Scheme 3. Synthetic routes to (R)-12 (chiral building block B, R2 = n-C8H17, X = Ts) and the antipode, which were coupled with block A to make all stereoisomers of
5,9-dimethylheptadecane 1. Reagents and conditions: (i) n-C7H15MgBr, Li2CuCl4 (0.1 mol/L, 3 mol %), THF (92%); (ii) TsCl, Et3N, Me3NꢀHCl (10 mol %), CH2Cl2 (93%); (iii)
p-Me(C6H4)SO2CH2CO2Me/base; (iv) p-Me(C6H4)SCH2CO2Me/base; (v) p-Me(C6H4)SO2Me/BuLi, THF (72%); (vi) BuLi, THF, HMPA (86%); (vii) Mg, MeOH (79%).
12) after decarboxylation. Methyl (toluene-4-sulfonyl)acetate,
which was prepared with sodium p-toluenesulfinate and methyl
2-chloroacetate, was treated with NaH, but the base-generated
carbanion did not couple to 10 even when heating at 85 °C for
24 h. Another reaction of 10 with the dianion of sulfonylacetate,
which was prepared by treatment with NaH and butyllithium
(BuLi), produced a complicated mixture. Next, we attempted the
reaction with a carbanion of methyl p-tolylsulfanylacetate, which
was synthesized by the reaction with 4-methylbenzenethiol and
methyl 2-chloroacetate. When lithium diisopropylamide (LDA), so-
dium hexamethyldisilazide (NaHMDS), or potassium hexamethyl-
disilazide (KHMDS) were used as a base, the desired sulfanyl
product 13 was not obtained.
However, the carbanion of 1-methanesulfonyl-4-methylben-
zene (methyl p-tolyl sulfone), which was generated by treatment
with BuLi, successfully attacked (S)-10, and (R)-12 was produced.
We examined the best reaction conditions by changing the type
of base, solvent, temperature, and substrate concentration, as
shown in Table 1. The highest yield (72%) was achieved with BuLi
in THF at 55 °C and a low concentration of methyl p-tolyl sulfone.
When a THF solution of the carbanion was stirred without (S)-10
for several minutes, the yield of (R)-12 decreased. The coupling
reaction between an anion of the sulfone and an alkyl halide usu-
ally required the addition of a very polar solvent, such as hexam-
ethylphosphoric triamide (HMPA),11 but the co-solvent had a
negative effect on the synthesis of (R)-12. The SN2 reaction of a pri-
mary alkyl halide by the anion of methyl sulfone has been more of-
ten reported than that of an alkyl tosylate.6a,d To the best of our
knowledge, the SN2 reaction of 10 is the first successful example
of an intermolecular coupling between an optically active second-
ary tosylate and an anion of a sulfonyl compound, although an
intramolecular SN2 reaction compound with a secondary tosyl
and methanesulfonyl groups has been reported.11 The desired
intermolecular SN2 reaction produced successfully the methyl-
branched sulfone 12 without racemization and E2 elimination of
the secondary tosylate. The absolute configuration was confirmed
by comparison with (R)-12, which was synthesized starting from
methyl (S)-3-bromoisobutylate 14 by the route shown in Scheme 4.
By using N-methylpyrrolidinone (NMP) as the co-solvent,12 bro-
mide 14 was treated with n-C7H15MgBr and Li2CuCl4 to yield
methyl 2-methyloctadecanoate 15. Reduction of 15 with LiAlH4,
iodination of the produced alcohol, and the substitution of the io-
dine with a sulfonyl group yielded (R)-12. The sulfones synthesized
by two different routes showed almost the same specific rotation
values. Compound (S)-12 was prepared from (R)-10, and the high
enantiomeric purity of (R)-12 and (S)-12 (>99% ee) was confirmed
by chiral HPLC analyses using an AS-H column (Fig. 1C). The total
yield of (R)-12 was 62% from (S)-2, while that of (S)-12 was 63%
from (R)-2.
Sulfone (R)-12 was alkylated with (S)-8 to give (5S,9R)-16 with
a 5,9-dimethyl skeleton by using a known procedure.6a,d Reductive
removal of the sulfonyl moiety of (5S,9R)-16 was achieved
smoothly by using magnesium turnings in methanol,13 and the de-
sired final product (5S,9R)-1 was obtained in 68% yield from (R)-12.
Before the reaction, magnesium was activated with a catalytic
amount of methylmagnesium bromide (MeMgBr) in THF. No ole-
finic by-products were formed, as reported by Kuwahara et al.
using a method involving lithium in liquid ethylamine.6d In the
same manner, three other stereoisomers were synthesized by the
following combination of two synthetic building blocks; (5S,9S)-1
from (S)-8 and (S)-12, (5R,9R)-1 from (R)-8 and (R)-12, and
(5R,9S)-1 from (R)-8 and (S)-12. The chemical data for each isomer
were almost identical to those published with regard to previous
syntheses,6 indicating that racemization did not occur after the
alkylation. While the 13C NMR spectra of the enantiomers were
identical, the diastereomers showed small but discernible differ-
Table 1
Synthesis of methyl (R)-2-methyl-1-(4-methylphenylsulfonyl)decane (12) by
coupling of
a
tosylate [(S)-10] and
a
carbanion of methyl p-tolyl sulfone
(S)-10
.
p-Me(C6H4)SO2Me + base
(R)-12
Entry Base
Solvent
Temp (°C) Concentration (M) Yield (ee)
1
2
3
4
5
6
7
8
9
BuLi
BuLi
BuLi
BuLi
BuLi
BuLi
LDA
THF
THF
THF
THF–HMPA
THF–HMPA
THF–NMP
THF
55
55
20
55
20
20
55
55
55
0.5
41% (>99%)
72% (>99%)
None
None
23% (>99%)
None
18%
30%
None
0.07
0.07
0.07
0.07
0.07
0.07
0.07
0.07
NaHMDS THF
KHMDS THF

T. Taguri et al. / Tetrahedron: Asymmetry 23 (2012) 852–858
855
i
ii, iii, iv
n-C7H15
(R)-12
Br
CO2Me
CO2Me
14
15
Scheme 4. Synthetic route to (R)-12 starting from methyl (S)-3-bromoisobutyrate 14. Reagents and conditions: (i) n-C7H15MgBr, Li2CuCl4, NMP–THF (91%); (ii) LiAlH4, THF;
(iii) I2, PPh3, imidazole, THF; (iv) p-Me(C6H4)SO2Na, PEG400, MeOH (44% from 15).
ences of chemical shifts for some 13C signals as indicated for 5,9-
dimethylpentadecane.6d We tentatively assigned each 13C signal,
and the assignments indicated the differences for carbons of the
two branched-methyl groups and carbons around the branches,
reflecting the conformational differences of the diastereomers
(see Section 4).
was achieved with the AS-H column using 10% 2-propanol in hex-
ane as an eluent, and each enantiomer was detected by UV 254 nm.
The resolution of alcohol 7 was achieved with the AY-H column
using 0.4% 2-propanol in hexane, and each enantiomer was de-
tected by RI. The flow rate of the eluents was 0.5 mL/min.
4.2. 2-Hexanols (R)- and (S)-3
3. Conclusion
To an ice-cooled and stirred mixture of n-C3H7Br (7.38 g,
60 mmol) and magnesium turnings (2.92 g, 120 mmol) in dry
THF (60 mL), a catalytic amount of MeMgBr (3.0 M, two drops)
was added as an initiator for making a Grignard reagent under
an argon atmosphere. After stirring for 1 h at 0 °C, Li2CuCl4 in
THF (0.1 M, 18 mL, 1.8 mmol) was added to a solution with a clou-
dy gray color at ꢂ78 °C. Then, (R)-(+)-propylene oxide (R)-2 (2.90 g,
50 mmol) dissolved in dry THF (5 mL) was added dropwise
through a syringe, and stirring of the mixture was continued for
30 min at ꢂ78 °C and an additional 1 h at room temperature. The
reaction mixture was then poured into an ice-cooled aqueous solu-
tion of NH4Cl (300 mL), and the crude products were extracted
with Et2O. The extract was washed with brine, dried over Na2SO4,
and concentrated in vacuo. The residue was chromatographed over
SiO2 (50 g). Elution with hexane/EtOAc (4:1) afforded 4.28 g
In many syntheses of chiral methyl-branched insect phero-
mones, the original configuration at a stereogenic center in the
starting material was retained in the final product.14 Stereospecific
conversion has been rarely used in pheromone syntheses because
of the risk of racemization. Our synthetic strategy, however, uti-
lized the SN2 reaction of a tosylate of a 2-alkanol. The reason was
that we expected the possibility of enantiomeric separation of
methyl-branched synthetic intermediates by a chiral HPLC col-
umn.3 In fact, we could confirm, by chiral HPLC analyses, the ste-
reospecific conversion of a chiral secondary tosylate after an SN2
reaction with an alkylating reagent, such as the enolate of dimethyl
malonate and the anion of methyl sulfone. In the reaction, elonga-
tion by two or one carbon(s) was accomplished, in association with
complete inversion of the original stereochemistry, which success-
fully produced two chiral methyl-branched building blocks, A and
B, with high enantiomeric purity (>99% ee). In addition to 5,9-dim-
ethylheptadecane 1, these building blocks can be utilized for the
synthesis of other 5,9-dimethylalkanes with a different carbon
chain identified from Lyonetiidae species as well as 7,11-dim-
ethylalkanes identified from Geometridae species. The synthetic
pheromones will be utilized as a monitoring tool for pest control
and an authentic standard for the identification of new
pheromones.2
(42 mmol, 84%) of (R)-3 as an oil, ½a D23
¼ ꢂ8:1 (c 1.5, CHCl3); mmax
ꢃ
(cmꢂ1): 3354 (s, O-H), 2925 (s), 2854 (s), 1458 (m), 1377 (m),
1115 (m); dH: 0.91 (3H, t, CH3CH2, J = 7.0 Hz), 1.19 (3H, d, CH3CHOH
J = 6.2 Hz), ꢄ1.3 (4H, m), ꢄ1.4 (2H, m), 3.80 (1H, m, CH3CHOH); dC:
14.0, 22.7, 23.4, 28.0, 39.0, 68.1. In the same manner, (S)-(ꢂ)-pro-
pylene oxide (S)-2 (2.90 g, 50 mmol) was reacted with n-C3H7MgBr
to yield 4.59 g (45 mmol, 90%) of (S)-3 as an oil, ½a D23
¼ þ7:9 (c 1.2,
ꢃ
CHCl3).
4.3. 2-Hexanyl tosylates (R)- and (S)-4
Triethylamine (8.10 g, 80 mmol) was added dropwise to a stir-
red solution of tosyl chloride (TsCl, 11.4 g, 60 mmol) and Me3NꢀHCl
(0.38 g, 4 mmol) in CH2Cl2 (70 mL) at 0 °C under an argon atmo-
sphere. Then (R)-3 (4.08 g, 40 mmol) dissolved in CH2Cl2 (8 mL)
was added to the solution through a syringe. After stirring at 0 °C
for 1.5 h, 1,3-diaminopropane (1.48 g, 20 mmol) dissolved in
CH2Cl2 (2 mL) was added to decompose the excess TsCl. The mix-
ture was stirred for 10 min and poured into water, after which
the crude product was extracted with CH2Cl2. The extract was
washed with dil HCl, saturated NaHCO3 solution, and brine, dried
over Na2SO4, and concentrated in vacuo. The residue was chro-
matographed over SiO2 (50 g). Elution with hexane/EtOAc (9:1)
4. Experimental
4.1. General
The specific rotation of each CHCl3 solution was measured on a
JASCO DIP-4 polarimeter. IR spectra were recorded as a thin film
(neat liquid) with a Jasco FT/IR-350 (JASCO, Tokyo, Japan). 1H and
13C NMR spectra were recorded by a JNM-ECA 500 FT-NMR spec-
trometer (JEOL, Tokyo, Japan) at 500.16 and 125.77 MHz, respec-
tively, for CDCl3 solutions containing TMS as the internal
standard. GC–MS was conducted in EI mode (70 eV) with an
HP5973 mass spectrometer system (Hewlett–Packard) equipped
with a split/splitless injector and a DB-23 column (0.25 mm
afforded 9.49 g (37 mmol, 93%) of (R)-4 as an oil, ½a D23
¼ ꢂ3:7 (c
ꢃ
2.0, CHCl3); m
max (cmꢂ1): 2931 (s), 2856 (s), 1599 (m, benzene ring),
ID ꢁ 30 m, 0.25
lm film, J & W Scientific, Folsom, CA, USA). The col-
1363 (s, S@O), 1176 (s, S@O); dH: 0.81 (3H, t, CH3CH2, J = 6.9 Hz),
ꢄ1.2 (4H, m), 1.25 (3H, d, CH3CHOTs, J = 6.3 Hz), 1.50 and 1.59
(2H, m), 2.45 (3H, s, CH3Ph), 4.60 (1H, tq, J = 6.3, 6.3 Hz, CH3CHOTs),
7.33 (2H, d, CH@CH, J = 8.2 Hz), 7.80 (2H, d, CH@CH, J = 8.2 Hz); dC:
13.8, 20.8, 21.6, 22.2, 27.0, 36.2, 80.7, 127.7 (ꢁ2), 129.7 (ꢁ2), 134.6,
144.4; GC-MS: tR 20.32 min, m/z 256 (M+, 1%), 199 (18%), 155
(100%). In the same manner, (S)-3 (4.08 g, 40 mmol) was treated
with tosyl chloride to yield 10.0 g (39 mmol, 98%) of (S)-4 as an
umn temperature program was 50 °C for 2 min, 4 °C/min to 150 °C,
10 °C/min to 220 °C, and 220 °C for 10 min. The carrier gas was He.
High-resolution MS (HR-MS) analysis was performed with a JMS-
MS700V mass spectrometer (JEOL). Enantiomeric excess (ee) was
determined by a Chiral HPLC analysis, which employed a system
composed of a pump (PU-980, JASCO), an RI detector (RI-98SCOPE,
Labo System, Tokyo, Japan) or a UV detector (UV-970, JASCO), an
integrator (807-IT, JASCO), and a normal phase chiral column, Chir-
alpak AS-H or AY-H (4.6 mm ID ꢁ 25 cm, Daicel Chemical Industry,
Osaka, Japan). The resolution of tosylates 4 and 10 and sulfone 12
oil, ½a 2D3
¼ þ3:8 (c 2.1, CHCl3). The two enantiomers were analyzed
ꢃ
by chiral HPLC equipped with a Chiralpak AS-H column and a UV

856
T. Taguri et al. / Tetrahedron: Asymmetry 23 (2012) 852–858
detector (254 nm). Peaks of the two enantiomers were detected at
different tR values [(R)-4, 18.8 min and (S)-4, 16.0 min] by elution
with hexane/2-propanol (9:1) at a flow rate (0.5 mL/min), and
chromatograms showed their enantiomeric purity (>99% ee).
produced 3.26 g (25 mmol, 89%) of (R)-7 as an oil, ½a D23
¼ þ2:7 (c
ꢃ
1.2, CHCl3). The two enantiomers were analyzed by chiral HPLC
equipped with a Chiralpak AY-H column and a RI detector. The
peaks of the two enantiomers were detected at different tR values
[(S)-7, 29.6 min and (R)-7, 28.4 min] by elution with hexane/2-pro-
panol (99.6:0.4) at a flow rate (0.5 mL/min), and chromatograms
showed their enantiomeric purity (>99% ee).
4.4. 2-(1-Methylpentyl)malonic acid dimethyl esters (S)- and
(R)-5
Dimethyl malonate (7.13 g, 54 mmol) was added dropwise to a
suspension of sodium hydride (60%, 2.16 g, 54 mmol) in 1,2-dime-
thoxyethane at 0 °C and stirred for 15 min. Then (R)-4 (9.23 g,
36 mmol) was added to the mixture, which produced sodium p-
toluenesulfonate as a white solid after stirring at 80–85 °C for
12 h. The suspension was concentrated in vacuo and a saturated
NH4Cl solution was poured into the residue. The product was ex-
tracted with EtOAc, and the extract was washed with brine, dried
over Na2SO4, concentrated in vacuo, and chromatographed over
SiO2 (50 g). Elution with hexane/EtOAc (9:1) afforded 7.35 g
4.7. 1-Iodo-3-methylheptanes (S)- and (R)-8
Iodine (7.11 g, 28 mmol) was added to a solution of triphenyl-
phosphine (6.56 g, 25 mmol) and imidazole (3.74 g, 55 mmol) in
dry THF (150 mL) at 0 °C under an argon atmosphere. After stirring
for 15 min, (S)-7 (3.00 g, 23 mmol) dissolved in THF (5 mL) was
added through a syringe. The mixture was stirred at 0 °C for 1 h,
and then poured into saturated Na2S2O3 solution and the product
was extracted with EtOAc. The extract was washed with water
and brine, dried over Na2SO4, and concentrated in vacuo. The res-
idue was chromatographed over SiO2 (50 g), and elution with hex-
ane/EtOAc (9:1) to afford 5.04 g (21 mmol, 91%) of (S)-8 as an oil,
(34 mmol, 94%) of (S)-5 as an oil, ½a D23
¼ ꢂ2:9 (c 1.2, CHCl3); mmax
ꢃ
(cmꢂ1): 2956 (s), 1737 (s, C@O), 1435 (s), 1151 (s), 1022 (m); dH:
0.89 (3H, t, CH3CH2, J = 6.8 Hz), 0.97 (3H, d, CH3CH, J = 6.8 Hz),
ꢄ1.3 (6H, m), 2.25 (1H, m, CH3CH), 3.27 (1H, d, CHCO2CH3,
J = 8.2 Hz), 3.73 (6H, s, CO2CH3); dC: 14.0, 17.0, 22.7, 29.0, 33.5,
34.0, 52.2, 52.3, 57.6, 169.3, 169.5; GC-MS: tR 12.04 min, m/z 185
([Mꢂ32]+, 10%), 132 (100%). In the same manner, (S)-4 (9.74 g,
38 mmol) was treated with sodium malonic ester to yield 7.35 g
½
a 2D3
ꢃ
¼ ꢂ12:6 (c 1.4, CHCl3); mmax (cmꢂ1): 2956 (s), 2925 (s), 2856
(s), 1464 (s), 1379 (m), 1178 (s), 602 (w); dH: 0.87 (3H, d, CH3CH,
J = 6.5 Hz), 0.89 (3H, t, CH3CH2, J = 6.5 Hz), 1.14 (1H, m) ꢄ1.3 (5H,
m), 1.54 (1H, m, CHCH2), 1.64 (1H, ddd, CHHCH2I, J = 21.3, 8.1,
5.8 Hz), 1.87 (1H, ddd, CHHCH2I, J = 21.3, 8.1, 5.8 Hz), 3.17 (1H,
ddd, CHHI, J = 9.0, 8.0, 8.0 Hz), 3.25 (1H, ddd, CHHI, J = 9.0, 9.0,
5.8 Hz); dC: 5.3, 14.1, 18.8, 22.9, 29.0, 33.9, 35.9, 41.0; GC-MS: tR
9.72 min, m/z 240 (M+, 3%), 113 (23%), 57 (100%). In the same man-
ner, iodization of (R)-7 (3.26 g, 25 mmol) produced 5.52 g
(34 mmol, 89%) of (R)-5 as an oil, ½a D23
¼ þ3:0 (c 0.74, CHCl3).
ꢃ
4.5. Methyl 3-methylheptanoates (S)- and (R)-6
(23 mmol, 92%) of (R)-8 as an oil, ½a D23
¼ þ12:5 (c 0.60, CHCl3).
ꢃ
Water (2.34 g, 130 mmol) was added to a solution of (S)-5
(7.14 g, 33 mmol) and lithium chloride (2.80 g, 66 mmol) in DMSO
(170 mL), and the mixture was stirred at 170–180 °C for 3.5 h. After
cooling, the mixture was poured into NaCl solution (12%, 500 mL)
and the product was extracted with EtOAc. The extract was washed
with water and brine, dried over Na2SO4, concentrated in vacuo,
and chromatographed over SiO2 (50 g). Elution with hexane/EtOAc
4.8. 2-Decanols (S)- and (R)-9
In the same manner as that described for the preparation of (S)-
3, (S)-2 (3.48 g, 60 mmol) was reacted with n-C7H15MgBr, which
was prepared from n-C7H15Br (16.1 g, 90 mmol), to produce
8.71 g (55 mmol, 92%) of (S)-9 as an oil, ½a D23
¼ þ8:1 (c 1.1, CHCl3);
ꢃ
(9:1) afforded 4.27 g (27 mmol, 82%) of (S)-6 as an oil, ½a D23
ꢃ
¼ ꢂ3:1
m
max (cmꢂ1): 3354 (s, O-H), 2925 (s), 2854 (s), 1458 (m), 1377 (m),
(c 0.82, CHCl3);
m
max (cmꢂ1): 2956 (s), 2858 (s), 1741 (s, C@O), 1437
1115 (m); dH: 0.88 (3H, t, CH3CH2, J = 6.7 Hz), 1.19 (3H, d, CH3CHOH
J = 6.2 Hz), ꢄ1.3 (12H, m), ꢄ1.4 (2H, m), 3.79 (1H, m, CH3CHOH);
dC: 14.1, 22.7, 23.5, 25.8, 29.3, 29.6, 29.7, 31.9, 39.4, 68.2; GC-MS:
tR 9.90 min, m/z 140 (M-18, 3%), 112 (7%), 45 (100%). In the same
manner, (R)-2 (4.07 g, 70 mmol) was reacted with n-C7H15MgBr
(s), 1173 (s), 1009 (m); dH: 0.89 (3H, t, CH3CH2, J = 6.8 Hz), 0.93 (3H,
d, CH3CH, J = 6.6 Hz), ꢄ1.3 (6H, m), 1.95 (1H, m, CH3CH), 2.11 (1H,
dd, CHHCO2CH3, J = 14.5, 8.1 Hz), 2.31 (1H, dd, CHHCO2CH3,
J = 14.5, 6.1 Hz), 3.67 (3H, s, CO2CH3); dC: 14.1, 19.8, 22.8, 29.1,
30.3, 36.4, 41.7, 51.4, 173.9; GC-MS: tR 6.53 min, m/z 158 (M+,
1%), 127 (11%), 74 (100%). In the same manner, decarboxylation
of (R)-5 (7.57 g, 35 mmol) produced 4.59 g (29 mmol, 83%) of (R)-
to yield 10.9 g (69 mmol, 99%) of (R)-9 as an oil, ½a D23
¼ ꢂ8:0 (c
ꢃ
0.61, CHCl3).
6 as an oil, ½a 2D3
ꢃ
¼ þ2:9 (c 0.63, CHCl3).
4.9. 2-Decanyl tosylates (S)- and (R)-10
4.6. 3-Methylheptan-1-ols (S)- and (R)-7
In the same manner as that described for the preparation of (S)-
4, (S)-9 (7.28 g, 46 mmol) was treated with tosyl chloride (13.2 g,
69 mmol) to produce 13.4 g (43 mmol, 93%) of (S)-10 as an oil,
A solution of (S)-6 (4.27 g, 27 mmol) in dry THF (10 mL) was
added dropwise through a syringe to an ice-cooled and stirred sus-
pension of LiAlH4 (1.02 g, 27 mmol) in dry THF (50 mL) under an
argon atmosphere. The mixture was stirred for 30 min at 0 °C, after
which water (50 mL) was added slowly to the mixture. After acid-
ification with dilute HCl solution, the product was extracted with
Et2O. The extract was washed with saturated NaHCO3 solution
and brine, dried over Na2SO4, and concentrated in vacuo. The res-
idue was chromatographed over SiO2 (50 g), and elution with hex-
ane/EtOAc (4:1) to afford 3.13 g (24 mmol, 89%) of (S)-7 as an oil,
½
a 2D3
ꢃ
¼ þ3:5 (c 2.0, CHCl3); mmax (cmꢂ1): 2927 (s), 2856 (s), 1599
(m, benzene ring), 1363 (s, S@O), 1176 (s, S@O); dH: 0.87 (3H, t,
CH3CH2, J = 6.9 Hz), ꢄ1.2 (12H, m), 1.26 (3H, d, CH3CHOTs,
J = 6.2 Hz), 1.50 and 1.59 (2H, m), 2.44 (3H, s, CH3Ph), 4.59 (1H,
tq, J = 6.3, 6.3 Hz, CH3CHOTs), 7.33 (2H, d, CH@CH, J = 8.2 Hz),
7.80 (2H, d, CH@CH, J = 8.2 Hz); dC: 14.1, 20.9, 21.6, 22.6, 24.9,
29.07, 29.09 (ꢁ2), 31.7, 36.5, 80.7, 127.7 (ꢁ2), 129.7 (ꢁ2), 134.6,
144.4. In the same manner, (R)-9 (8.86 g, 56 mmol) was treated
with tosyl chloride to yield 15.9 g (51 mmol, 91%) of (R)-10 as an
½
a 2D3
ꢃ
¼ ꢂ2:6 (c 1.4, CHCl3); mmax (cmꢂ1): 3336 (s, O-H), 2925 (s),
oil, ½a 2D3
¼ ꢂ3:5 (c 2.0, CHCl3). The two enantiomers were analyzed
ꢃ
1460 (s), 1379 (m), 1057 (s); dH: 0.89 (3H, t, CH3CH2, J = 6.8 Hz),
0.89 (3H, d, CH3CH, J = 6.6 Hz), ꢄ1.3 (7H, m), ꢄ1.6 (2H, m), 3.68
(2H, m, CH2OH); dC: 14.2, 19.7, 23.0, 29.2, 29.5, 36.8, 40.0, 61.3;
GC-MS: tR 8.00 min, m/z 112 ([Mꢂ18]+, 2%), 84 (72%), 55 (100%).
In the same manner, LiAlH4 reduction of (R)-6 (4.43 g, 28 mmol)
by chiral HPLC equipped with a Chiralpak AS-H column and a UV
detector (254 nm). The peaks of the two enantiomers were de-
tected at different tR values [(S)-10, 11.5 min and (R)-10,
14.5 min] and the chromatograms showed their enantiomeric pur-
ity (>99% ee).

T. Taguri et al. / Tetrahedron: Asymmetry 23 (2012) 852–858
857
4.10. 2-Methyl-1-(4-methylphenylsulfonyl)decanes (R)- and (S)-
12 from 10
was extracted with EtOAc and the extract was washed with water
and brine, dried over Na2SO4, and concentrated in vacuo. The res-
idue was chromatographed over SiO2 (50 g). Elution with hexane/
EtOAc (14:1) afforded 1.37 g (4.4 mmol, 60%) of (R)-12 as an oil,
which was analyzed by chiral HPLC.
In a two necked flask, methyl p-tolyl sulfone (2.04 g, 12 mmol)
was dissolved in dry THF (180 mL). A hexane solution of BuLi
(2.69 M, 4.7 mL, 12 mmol) and (S)-10 (2.50 g, 8.0 mmol) dissolved
in THF (4 mL) were added successively into the flask through a syr-
inge at 0 °C under an argon atmosphere. The reaction mixture was
stirred at 55 °C for 4 h and then poured into an aqueous solution of
NH4Cl (100 mL). The crude product was extracted with EtOAc and
the extract was washed with brine, dried over Na2SO4, and concen-
trated in vacuo. The residue was chromatographed over SiO2
(40 g). Elution with hexane/EtOAc (14:1) afforded 1.79 g
4.13. 5,9-Dimethyl-8-(4-methylphenylsulfonyl)heptadecanes
(5S,8SR,9R)-, (5S,8SR,9S)-, (5R,8SR,9S)-, and (5R,8SR,9R)-16
A hexane solution of BuLi (1.63 M, 3.7 mL, 6.0 mmol) was added
through a syringe to a stirred solution of (R)-12 (1.55 g, 5.0 mmol)
in THF (10 mL) at ꢂ78 °C under an argon atmosphere. The mixture
was stirred at ꢂ78 °C for 10 min and then at ꢂ35 °C for 30 min.
After cooling to ꢂ78 °C, (S)-8 (1.44 g, 6.0 mmol) dissolved in HMPA
(3.5 mL) was added dropwise. The mixture was then allowed to
warm gradually to room temperature and stirred for 8 h. The
resulting mixture was poured into 1 M HCl (50 mL) and the crude
products were extracted with EtOAc, washed with a saturated
NaHCO3 solution and brine, dried over Na2SO4, and concentrated
in vacuo. The residue was chromatographed over SiO2 (50 g). Elu-
tion with hexane/EtOAc (19:1) afforded 1.82 g (4.3 mmol, 86%) of
(5S,8SR,9R)-16 as an oil, mmax (cmꢂ1): 2925 (s), 2854 (s), 1597 (m,
benzene ring), 1464 (s), 1300 (s, S@O), 1146 (s, S@O), 1086 (s);
dH: 0.77 and 0.78 (3H, d, CH3CH, J = 6.1 Hz), 0.87 (3H, t, CH3CH2,
J = 6.3 Hz), 0.88 (3H, t, CH3CH2, J = 6.3 Hz), 1.00 and 1.03 (3H, d,
CH3CH, J = 7.1 Hz), ꢄ1.2 (22H, m), 1.67 (2H, m), 1.82 (1H, m),
2.19 (1H, m), 2.44 (3H, s, CH3Ph), 2.85 (1H, m, CHTs), 7.33 (2H, d,
CH@CH, J = 8.0 Hz), 7.76 (2H, d, CH@CH, J = 8.0 Hz). In the same
manner, the syntheses of (5S,8SR,9S)-16 from (S)-8 and (S)-12,
(5R,8SR,9S)-16 from (R)-8 and (S)-12, and (5R,8SR,9R)-16 from
(R)-8 and (R)-12 were accomplished in similar yields (80–85%).
(5.8 mmol, 72%) of (R)-12 as an oil, ½a D23
¼ ꢂ1:1 (c 2.5, CHCl3); mmax
ꢃ
(cmꢂ1): 2925 (s), 2854 (s), 1599 (m, benzene ring), 1313 (s, S@O),
1147 (s, S@O), 1088 (s); dH: 0.88 (3H, t, CH3CH2, J = 6.9 Hz), 1.05
(3H, d, CH3CH, J = 6.2 Hz), ꢄ1.2 (12H, m), 2.04 (3H, m, CH3CH),
2.45 (3H, s, CH3Ph), 2.90 (1H, dd, J = 14.2, 7.9 Hz, CHHTs), 3.06
(1H, dd, J = 14.2, 4.6 Hz, CHHTs), 7.35 (2H, d, CH@CH, J = 8.2 Hz),
7.79 (2H, d, CH@CH, J = 8.2 Hz); dC: 14.1, 19.9, 21.6, 22.7, 26.3,
28.6, 29.2, 29.5 (ꢁ2), 31.8, 36.7, 62.7, 127.9 (ꢁ2), 129.9 (ꢁ2),
137.3, 144.4. In the same manner, (R)-10 (2.50 g, 8.0 mmol) was
treated with the carbanion of methyl p-tolyl sulfone to yield
1.74 g (5.6 mmol, 70%) of (S)-12 as an oil, ½a D23
¼ þ1:1 (c 2.5,
ꢃ
CHCl3). The two enantiomers were analyzed by chiral HPLC
(AS-H column) and detected at different tR values [(R)-12,
53.4 min and (S)-12, 28.2 min] by elution with hexane/2-propanol
(9:1). The chromatograms showed their enantiomeric purity
(>99% ee).
4.11. Methyl (R)-2-methylundecanoate (R)-15
In the same manner as that described for the preparation of
(S)-3, methyl (S)-3-bromoisobutylate (S)-14 (1.99 g, 11 mmol)
was reacted with n-C7H15MgBr, which was prepared from
n-C7H15Br (4.48 g, 25 mmol), to produce 2.00 g (10 mmol, 91%) of
4.14. 5,9-Dimethylheptadecanes (5S,9R)-, (5S,9S)-, (5R,9S)-, and
(5R,9R)-1
To magnesium turnings (1.46 g, 60 mmol) stirred in dry THF
(2.5 mL), a catalytic amount of MeMgBr (3.0 M, two drops) was
added to activate the metal under an argon atmosphere. After stir-
ring for 15 min at room temperature, a solution of (5S,8SR,9R)-16
(1.65 g, 3.9 mmol) in dry MeOH (60 mL) was added through a syr-
inge, and the mixture was stirred at 50 °C for 4 h. Next, the mixture
was evaporated to remove MeOH and an ice-cooled 1 M HCl solu-
tion (20 mL) was added to dissolve the white residues. The crude
products were extracted with Et2O, washed with saturated NaH-
CO3 solution and brine, dried over Na2SO4, and concentrated in va-
cuo. The residue was chromatographed over SiO2 (20 g). Elution
with hexane afforded 0.84 g (3.1 mmol, 79%) of (5S,9R)-1 as an
(R)-15 as an oil, ½a D23
ꢃ
¼ ꢂ16:0 (c 1.0, CHCl3); mmax (cmꢂ1): 2925
(s), 2856 (s), 1739 (s, C@O), 1464 (s), 1196 (s), 1167 (s); dH: 0.88
(3H, t, CH3CH2, J = 6.7 Hz), 1.14 (3H, d, CH3CH, J = 6.9 Hz), ꢄ1.3
(12H, m), 1.64 (1H, m, CHHCH), 2.43 (1H, tq, J = 6.9, 6.9 Hz, CH3CH),
3.67 (3H, s, OCH3); dC: 14.1, 17.1, 22.7, 27.3, 29.3, 29.46, 29.54,
31.9, 33.8, 39.5, 51.5, 177.5.
4.12. (R)-2-Methyl-1-(4-methylphenylsulfonyl)decane (R)-12
from (R)-15
In the same manner as that described for the preparation of (S)-
7, (R)-15 (2.00 g, 10 mmol) was treated with LiAlH4 (0.38 g,
10 mmol) to produce 1.38 g (8.0 mmol, 80%) of (R)-2-methyl-1-
decanol as an oil; dH: 0.88 (3H, t, CH3CH2, J = 6.9 Hz), 0.91 (3H, d,
CH3CH, J = 6.7 Hz), ꢄ1.3 (14H, m), 1.61 (1H, m, CH3CH), 3.41 (1H,
dd, CHHOH, J = 10.5, 6.6 Hz), 3.51 (1H, dd, CHHOH, J = 10.5,
5.7 Hz); dC: 14.1, 16.6, 22.7, 27.0, 29.4, 29.6, 30.0, 31.9, 33.2, 35.8.
Next, in the same manner as that described for the preparation
of (S)-8, the alcohol was treated with a mixture of iodine (2.28 g,
9.0 mmol), triphenylphosphine (2.62 g, 10 mmol), and imidazole
(1.36 g, 20 mmol) to produce 2.05 g (7.3 mmol, 91%) of (R)-1-
iodo-2-methyldecane as an oil; dH: 0.88 (3H, t, CH3CH2,
J = 6.6 Hz), 0.97 (3H, d, CH3CH, J = 6.4 Hz), ꢄ1.3 (14H, m), 1.45
(1H, m, CH3CH), 3.15 (1H, dd, CHHI, J = 9.5, 5.9 Hz), 3.23 (1H, dd,
CHHI, J = 9.5, 4.6 Hz); dC: 14.1, 18.1, 20.6, 22.7, 26.9, 29.3, 29.6,
29.7, 31.9, 34.7, 36.5. The iodo compound was added into a stirred
mixture of sodium p-toluenesulfinate (1.78 g, 10 mmol), PEG-400
(10 mL), and DMSO (5 mL) at 80 °C. The reaction mixture was stir-
red for 2 h at 80 °C and then poured into a 10% NaCl solution
(75 mL) after cooling to room temperature. The crude product
oil, ½a 2D3
ꢃ
¼ þ1:1 (c 0.63, CHCl3); mmax (cmꢂ1): 2924 (s), 2854 (s),
1464 (m), 1377 (m), 723 (w); dH: 0.841 and 0.843 (6H, d, CH3CH,
J = 6.7 Hz), 0.88 (3H, t, CH3CH2, J = 7.2 Hz), 0.89 (3H, t, CH3CH2,
J = 7.2 Hz), 1.0-1.4 (28H, m); dC: 14.14 and 14.19 (C-1, 17), 19.78
(ꢁ2, CHCH3), 22.73 (C-16), 23.09 (C-2), 24.50 (C-7), 27.12 (C-11),
29.38 and 29.41 (C-13, 14), 29.73 (C-12), 30.08 (C-3), 31.98 (C-
15), 32.80 (ꢁ2, C-5, 9), 36.79 (C-10), 37.10 (C-4), 37.47 (ꢁ2, C-6,
8); GC-MS: tR 18.95 min, m/z 268 (M+, 1%), 211 (9%), 155 (15%),
140 (13%), 85 (83%), 57 (100%); HR-MS calcd for
C19H40
268.3130; found 268.3126. In the same manner, the syntheses of
(5S,9S)-1 from (5S,8SR,9S)-16, (5R,9S)-1 from (5R,8SR,9S)-16, and
(5R,9R)-1 from (5R,8SR,9R)-16 were accomplished in similar yields
(75–80%). (5S,9S)-1, ½a D23
ꢃ
¼ þ2:2 (c 1.3, CHCl3); mmax (cmꢂ1): 2924
(s), 2854 (s), 1464 (m), 1377 (m), 723 (w); dH: 0.839 and 0.841
(6H, d, CH3CH, J = 6.3 Hz), 0.88 (3H, t, CH3CH2, J = 7.0 Hz), 0.89
(3H, t, CH3CH2, J = 7.0 Hz), 1.0–1.4 (28H, m); dC: 14.14 and 14.19
(C-1, 17), 19.72 (ꢁ2, CHCH3), 22.73 (C-16), 23.09 (C-2), 24.50 (C-
7), 27.13 (C-11), 29.39 and 29.41 (C-13, 14), 29.73 (C-12), 30.08
(C-3), 31.98 (C-15), 32.77 (ꢁ2, C-5, 9), 36.89 (C-10), 37.19 (C-4),

858
T. Taguri et al. / Tetrahedron: Asymmetry 23 (2012) 852–858
37.41 (ꢁ2, C-6, 8) GC-MS: tR 18.93 min, m/z 268 (M+, 1%), 211 (8%),
4. Francke, W.; Franke, S.; Toth, M.; Szöcs, G.; Guerin, P.; Arn, H.
Naturwissenschaften 1987, 74, 143–144.
155 (13%), 140 (13%), 85 (83%), 57 (100%); HR-MS calcd for C19H40
5. (a) Díaz, D. D.; Martín, V. S. J. Org. Chem. 2000, 65. 7896-7801; (b) Moreira, J. A.;
Corrêa, A. G. Tetrahedron: Asymmetry 2003, 14, 3787–3795; (c) Chow, S.;
Koenig, W. A.; Kitching, W. Eur. J. Org. Chem. 2004, 1198–1201; (d) Zarbin, P. H.
G.; Princival, J. L.; de Lima, E. R.; dos Santos, A. A.; Ambrogio, B. G.; de Oliveira,
A. R. M. Tetrahedron Lett. 2004, 45, 239–241; (e) van Summeren, R. P.; Reijmer,
S. J. W.; Feringa, B. L.; Minnaard, A. J. Chem. Commun. 2005, 1387–1389.
6. (a) Mori, K.; Wu, J. Liebigs Ann. Chem. 1991, 439–443; (b) Mori, K.; Horikiri, H.
Liebigs Ann. 1996, 501–505; (c) Tamagawa, H.; Takikawa, H.; Mori, K. Eur. J. Org.
Chem. 1999, 973–978; (d) Kuwahara, S.; Liang, T.; Leal, W. S.; Ishikawa, J.;
Kodama, O. Biosci., Biotechnol., Biochem. 2000, 64, 2723–2726; (e) Mori, K.
Tetrahedron: Asymmetry 2008, 19, 857–861.
7. (a) Cason, J.; Coad, R. A. J. Am. Chem. Soc. 1950, 72, 4695–4697; (b) Sato, T.;
Otera, J. J. Org. Chem. 1995, 60, 2627–2629.
8. Sorger, K.; Stohrer, J. US 2007/0225519 A1.
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268.3130; found 268.3125. (5R,9S)-1, ½a D23
¼ ꢂ1:1 (c 1.2, CHCl3);
ꢃ
HR-MS calcd for C19H40 268.3130; found 268.3125. (5R,9R)-1,
½
a 2D3
268.3126.
ꢃ
¼ ꢂ2:1 (c 1.3, CHCl3); HR-MS calcd for C19H40 268.3130; found
Acknowledgments
This work was supported in part by grant-aid for scientific re-
search from the Ministry of Education, Culture, Sports, Science,
and Technology (MEXT) of Japan [Grant-in-Aid for Scientific Re-
search (C) No. 24580158].
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