Preparation of single-enantiomer biofunctional molecules with (S)-2-methoxy-2-(1-naphthyl)propanoic acid

Article abstract of DOI:10.1271/bbb.80100

(RS)-β-Ionol and (RS)-2-methyl-4-octanol were resolved by using (S)-2-methoxy-2-(1-naphthyl)propanoic acid [(S)-MαNP acid]. The specific stereochemistry of each MαNP ester was elucidated by 2D NMR analyses, and shielding by the 1-naphthyl group was observ

Full text of DOI:10.1271/bbb.80100

Biosci. Biotechnol. Biochem., 72 (9), 2418–2422, 2008
Note
Preparation of Single-Enantiomer Biofunctional Molecules
with (S)-2-Methoxy-2-(1-naphthyl)propanoic Acid
y
1;
2
Akio ICHIKAWA and Hiroshi ONO
1Division of Insect Sciences, National Institute of Agrobiological Sciences,
1-2 Owashi, Tsukuba, Ibaraki 305-8634, Japan
2Analytical Science Division, National Food Research Institute,
2-1-12 Kannondai, Tsukuba, Ibaraki 305-8642, Japan
Received February 14, 2008; Accepted May 16, 2008; Online Publication, September 7, 2008
[doi:10.1271/bbb.80100]
(RS)-ꢀ-Ionol and (RS)-2-methyl-4-octanol were re-
solved by using (S)-2-methoxy-2-(1-naphthyl)propanoic
acid [(S)-MꢁNP acid]. The specific stereochemistry of
each MꢁNP ester was elucidated by 2D NMR analyses,
and shielding by the 1-naphthyl group was observed in
both the 1H- and 13C-NMR spectra. Solvolysis of the
individual (S)-MꢁNP esters gave four single-enantiomer
alcohols. The normal-phase HPLC elution order of each
MꢁNP ester is also discussed.
were as follows: t1 (ester 4) = 9.87 min, t2 (ester 5) =
11.06 min; peak width, W1 ¼ 0:41 min, W2 ¼ 0:40 min;
separation factor, ꢀ ¼ ðt2 ꢁ t0Þ=ðt1 ꢁ t0Þ ¼ 1:32; resolu-
tion, Rs ¼ 2 ꢀ ðt2 ꢁ t1Þ=ðW1 þ W2Þ ¼ 2:94. In a single
operation, esters 4 and 5 were separated by preparative
HPLC in a pre-packed glass column (see the Exper-
imental section).
The proposed conformations of diastereomeric (S)-
MꢀNP esters X and Y are shown in Fig. 1:4,5) (i) the
hydrogen atom at the ꢀ-position of the alcohol moiety
and the carbonyl group were syn; (ii) the carbonyl group
and the methoxy group were syn; (iii) the methyl group
of the MꢀNP moiety and the aromatic hydrogen atom at
the C2-position were syn. The R2 moiety of first-eluted
ester X and the R1 moiety of second-eluted ester Y were
observed at higher fields in the 1H-NMR spectra;
therefore, the R1 and R2 moieties were respectively
assigned to NMR signals that exhibited negative and
positive ꢀꢂ (¼ ꢂY ꢁ ꢂX) values.
Key words: chiral; resolution; MꢀNP acid; ꢁ-ionol;
2-methyl-4-octanol
There are many examples of enantiomers showing
different biological activities;1) thus, the elucidation of
their absolute configuration and enantiomeric excess (ee)
is an important topic in natural product chemistry.2,3)
2-Methoxy-2-(1-naphthyl)propanoic acid (MꢀNP acid,
1) is a non-racemizable chiral resolving agent, and a
strong tool for the preparation of single-enantiomer
biofunctional molecules (Scheme 1).4,5) The application
of 1 has been exemplified by the enantioresolution
of biofunctional molecules: (A) ꢁ-ionol 2, a volatile
component of starfruit Averrhoa carambola6) and an
attractant for the male tephritid fruit fly Bactrocera
latifrons,7) and (B) 2-methyl-4-octanol 3, an aggrega-
tion pheromone of the West Indian sugarcane borer
Metamasius hemipterus8) and the sugarcane weevil
Sphenophorus levis.9)
ꢁ-Ionol (RS)-2 was condensed with (S)-1 by using
1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydro-
chloride (EDC) and 4-dimethylaminopyridine (DMAP)
in CH2Cl2, yielding a mixture of diastereomeric esters
4 and 5 (Scheme 1A). Esters 4 and 5 were readily
separable via normal-phase HPLC in a silica SG80
column (250 mm ꢀ 4:6 mm I.D.). The amount of mate-
rial injected into the column was 5 mg, and the mobile
phase consisted of hexane/EtOAc (9:1) at a flow rate of
0.5 ml/min. The retention times and peak characteristics
The NMR signals of esters 4 and 5, and the ꢀꢂ
[= ꢂ(ester 5) ꢁ ꢂ(ester 4)] values were assigned based
on two-dimensional (2D) NMR spectral analyses (i.e.,
DQF COSY, HSQC, HMBC, and NOESY). The
observed negative and positive ꢀꢂ values indicated the
*
stereochemistry as (S,R)-4 and (S,S)-5, respectively
(Scheme 1A and Fig. 1A).4,5) Solvolysis of ester 4
yielded (R)-2 {½ꢀꢂD +7.6 (c 0.176, CHCl3); ref.,10)
27
24
½ꢀꢂD +8.5 (c 2.80, CHCl3)}. Solvolysis of ester 5 gave
(S)-2 {½ꢀꢂD ꢁ8:0 (c 0.158, CHCl3); ref.,10) ½ꢀꢂD
24
24
ꢁ8:22 (c 1.01, CHCl3)}. Acid (S)-1 was also recovered
in solvolysis.
The NOESY and NOE difference spectra of esters 4–
7 showed clear NOE between the methyl group of the
MꢀNP moiety and the aromatic proton at the C2-
position (Scheme 1). However, irradiation of the methyl
and methoxy groups in the MꢀNP moieties showed no
*
The stereochemistry of the MꢀNP esters is denoted in the
following order: (chiralityacid, chiralityalcohol).
y
To whom correspondence should be addressed. Fax: +81-29-838-6028; E-mail: ichikawa@affrc.go.jp

Preparation of Single-Enantiomer Biofunctional Molecules
2419
A
NOESY
H3C
H
H
CH3
C3
NaOMe,
MeOH
CH3
CH3
OH
H3C
CH3
H
OH
CH3 CH3
O
CH3H
H3CO
(S)-1
O
H3C
CH3
1) EDC,
DMAP,
CH2Cl2
O
H
O
4
(R)-2
+
2) HPLC
H
CH3
H3C
H
H3C
NaOMe,
MeOH
CH3
O
H3C
H3C
CH3
H
OH
O
C3
H3C
H
O
H3C
CH3
(RS)-2
CH3 CH3
H
H3C
CH3
H
OH
5
(S)-2
B
H3C
CH3
H
NaOMe,
MeOH
CH3
H3C
CH3
CH3
H3C
O
OH
H
OH
O
CH3
CH3
H3CO
1) EDC,
DMAP,
CH2Cl2
O
H
O
(S)-1
(S)-3
6
+
2) HPLC
H
CH3
CH3
NaOMe,
MeOH
CH3
CH3
CH3
H3C
H3C
H3C
H3C
CH3
H
OH
O
H
O
OH
(R)-3
O
H
CH3
(RS)-3
7
CH3
CH3
CH3
ref. 5
CH3
CH3
O
H3C
H3C
O
O
O
CH3
O
CH3
CH3
O
H
H
8
9
Scheme 1. Enantioresolution of (A) (RS)-ꢁ-Ionol and (B) (RS)-2-Methyl-4-octanol Using (S)-MꢀNP Acid.
Arrows indicate the clear NOESY cross peaks.
signal enhancement in the alcohol moieties. In esters 4
and 5, NOEs were observed between the gem-dimethyl
group and the olefinic proton at the C3-position of the
alcohol moiety. Weak NOE was also observed between
the olefinic methyl group and the olefinic proton at the
C3-position. These results suggest that the s-cis form11)
was the predominant conformation of esters 4 and 5
(Scheme 1A).
The distribution of the negative and positive ꢀꢂ values
was similar in both the 1H- and 13C-NMR data (Fig. 2A).
This result suggests that shielding by the 1-naphthyl
group was also observed in the 13C-NMR spectra.
We next performed enantioresolution of 2-methy-4-
octanol8,9) (RS)-3. Alcohol (RS)-3 was condensed with
(S)-1, yielding a mixture of diastereomeric esters 6 and
7 (Scheme 1B). Esters 6 and 7 (10 mg in total) were
separated by HPLC in a silica SG80 column (250 mm ꢀ
10 mm I.D.). The mobile phase consisted of hexane/
EtOAc (96:4) at a flow rate of 3 ml/min. The reten-
tion times and peak characteristics were as follows: t1
(ester 6) = 13.79 min, t2 (ester 7) = 14.77 min; W1 ¼
0:52 min, W2 ¼ 0:57 min; ꢀ ¼ 1:11; Rs ¼ 1:80. This
separation profile was better than that obtained for
esters 8 and 9,5) which had been prepared from (S)-1
and (RS)-2-methyl-4-heptanol, under identical HPLC
conditions: t1 (ester 8) = 15.11 min, t2 (ester 9) =
16.03 min; W1 ¼ 0:61 min, W2 ¼ 0:64 min; ꢀ ¼ 1:09;
Rs ¼ 1:47.
The NMR signals were assigned from analyses of the
DQF COSY, HSQC, HMBC, and NOESY spectra. The
ꢀꢂ [= ꢂ(ester 7) ꢁ ꢂ(ester 6)] values observed in the
1H-NMR spectra indicated the stereochemistry of the

2420
A. ICHIKAWA and H. ONO
H
syn
O
Negative ∆δ Positive ∆δ
R1
R2
2
CH3
CH3
H3C
H3C
R1
R2
O
R2
R1
O
O
H
O
H
O
H
(S)-MαNP
syn
High-field shift
High-field shift
syn
∆δ = δY – δX
X: first fraction in HPLC
Y: second fraction in HPLC
A
B
1
0.5
0
1
0.5
0
3
2
5 4
3
3
2 1
4' 3' 7'
–0.07
1
(C-position)
1" (C-position)
1' 2' 3'
-0.5
-1
-0.5
-1
H
–0.07
–0.06 H
–0.20
CH3
H
3'
+0.27 +0.87
7'
–0.18
1"
H
2
4'
–0.4
4
–0.3+0.20
1
+0.41
3'
CH3
–0.06
–0.07
H
H
H
+0.25
5
1'
CH3
3
1
2
1'
H
H3C
–0.33
2'
CH3
–0.07 H
H3C CH
–0.17* –0.16* O
–0.7
–0.8
O
+0.02
H
–0.28
3 H
+0.06
O
+0.43
O
H3C
H3C
H3CO
H3CO
*(or –0.15 and –0.18)
∆δ = δ(ester 5) – δ(ester 4)
∆δ = δ(ester 7) – δ(ester 6)
Fig. 1. ꢀꢂ Values for (S)-MꢀNP Esters in the 1H-NMR Spectra (500 MHz, CDCl3).
Black bars indicate ꢀꢂ values for the alcohol moieties.
A
B
1
0.5
0
1
0.5
3
2 1
5
3 2 1
4
4' 3' 2'
–0.09
0
-0.5
-1
-0.5
-1
(C-position)
+0.25
(C-position)
+0.16
CH3
+0.82
+0.76
1"
1"
1' 2'
3'
3'
-1.5
–0.15
CH3
2'
–0.04
3'
4'
–0.31
–0.33 –0.51 +0.09
–0.10 –0.19
5
3
1
2'
–0.06
CH3
3
1
4
2
1'
H3C
–0.32
2
–0.16
H3C
–1.05 –0.16
–0.20
–0.45
CH3
CH3
O
O
O
O
–0.12*–0.12*
H3C
H3C
H3CO
H3CO
*(or –0.14 and –0.10)
∆δ = δ(ester 5) – δ(ester 4)
∆δ = δ(ester 7) – δ(ester 6)
Fig. 2. ꢀꢂ Values for (S)-MꢀNP Esters in the 13C-NMR Spectra (126 MHz, CDCl3).
Black bars indicate ꢀꢂ values for the alcohol moieties.
first- and second-eluted esters as (S,S)-6 and (S,R)-7,
respectively (Scheme 1B and Fig. 1B). This stereo-
chemistry was further supported by the ꢀꢂ values
observed in the 13C-NMR spectra (Fig. 2B). The 13C-
NMR data for esters 8 and 9 also indicate the use of ꢀꢂ
values for stereochemical assignment.5) Solvolysis of
24
esters 6 and 7 yielded (S)-3 f½ꢀꢂD +11 (c 0.205,
MeOH); ref.,12) ½ꢀꢂD +11.6 (c 1.04, MeOH)} and
22

Preparation of Single-Enantiomer Biofunctional Molecules
2421
26
23
27
(R)-3 {½ꢀꢂD ꢁ11 (c 0.157, MeOH); ref.,12) ½ꢀꢂD ꢁ10:5
½ꢀꢂD ꢁ4:5 (c 0.614, CHCl3); NMR ꢂH (500 MHz,
CDCl3): 0.88 (3H, s), 0.90 (3H, s), 1.02 (3H, d,
J ¼ 6 Hz), 1.40 (2H, m), 1.55 (3H, br d, J ¼ 1 Hz),
1.57 (2H, m), 1.93 (2H, br t, J ¼ 6 Hz), 1.97 (3H, s),
3.11 (3H, s), 5.27 (1H, dd, J ¼ 16, 7 Hz), 5.41 (1H, dqd,
J ¼ 7, 6, 1 Hz), 6.02 (1H, br d, J ¼ 16 Hz), 7.44 (1H,
dd, J ¼ 8, 7 Hz), 7.46 (1H, m), 7.46 (1H, m), 7.59 (1H,
dd, J ¼ 7, 1 Hz), 7.81 (1H, br d, J ¼ 8 Hz), 7.84 (1H,
m), 8.42 (1H, m); NMR ꢂC (126 MHz, CDCl3): 19.19,
20.17, 21.22. 21.85, 28.56, 28.58, 32.60, 33.80, 39.28,
51.02, 72.83, 81.67, 124.62, 125.30, 125.59, 125.59,
126.32, 128.62, 129.03, 129.32, 130.65, 131.34, 132.17,
134.07, 135.32, 136.46, 173.30; IR (KBr, CHCl3)
cmꢁ1: 2934, 1732, 1261, 1138, 1038; LC-MS (ESI,
MeCN:H2O = 17:3) m/z: 429 (½M þ Naꢂþ, 22%), 253
(18), 221 (7), 177 (100).
(c 1.17, MeOH)}, respectively.
We had already resolved the four semiochemicals
by using (S)-1: 3-octanol, sulcatol (6-methyl-5-hepten-
2-ol), 1-octen-3-ol, and 2-methyl-4-heptanol.5) In the
previous study the normal-phase HPLC elution order of
the diastereomeric MꢀNP esters was dependent on the
size of aliphatic substituents R1 and R2 (Fig. 1). The
compound X with larger R1 was the first to elute.5) The
elution order of esters 4 and 5 was in good agreement
with these previous results. However, for esters 6 and 7,
the R1 substituent (butyl group) was longer than the R2
substituent (isobutyl group).
Enantioresolution of (RS)-ꢁ-ionol and (RS)-2-methyl-
4-octanol was achieved by using (S)-MꢀNP acid. 2D
NMR analyses elucidated the stereochemistry of the
(S)-MꢀNP esters. Solvolysis of the individual (S)-MꢀNP
esters gave four single-enantiomer alcohols, the specific
rotation values of which were consistent with those
previously reported. The ꢀꢂ values observed in the 13C-
NMR spectra were useful for stereochemical assignment
of the secondary alcohols. Diastereomeric MꢀNP esters
containing a methyl group coupled to a bulkier and more
hydrophobic substituent were first to elute from the
normal-phase HPLC column. The MꢀNP acid has been
shown to be useful for the facile preparation and
stereochemical determination of single-enantiomer bio-
functional molecules.
(1S,2E)-1-Methyl-3-(2,6,6-trimethyl-1-cyclohexen-1-yl)-
2-propenyl (S)-2-methoxy-2-(1-naphthyl)propanoate (5).
½ꢀꢂD ꢁ35 (c 0.608, CHCl3); mp 80–81 ꢃC; NMR ꢂH
27
(500 MHz, CDCl3): 0.72 (3H, s), 0.73 (3H, s), 1.27 (3H,
d, J ¼ 7 Hz), 1.33 (2H, m), 1.35 (3H, br d, J ¼ 1 Hz),
1.51 (2H, m), 1.86 (2H, br t, J ¼ 6 Hz), 1.99 (3H, s), 3.10
(3H, s), 5.09 (1H, dd, J ¼ 16, 7 Hz), 5.43 (1H, quint d,
J ¼ 7, 1 Hz), 5.74 (1H, br d, J ¼ 16 Hz), 7.43 (1H, m),
7.44 (1H, m), 7.44 (1H, m), 7.59 (1H, dd, J ¼ 7, 1 Hz),
7.80 (1H, br d, J ¼ 8 Hz), 7.81 (1H, m), 8.41 (1H, m);
NMR ꢂC (126 MHz, CDCl3): 19.15, 20.42, 21.07, 21.97,
28.44, 28.46, 32.51, 33.64, 39.22, 51.01, 72.63, 81.69,
124.57, 125.28, 125.60, 125.65, 126.38, 128.64, 128.72,
129.38, 130.20, 131.33, 131.98, 134.10, 135.26, 136.36,
173.31; IR (KBr, CHCl3) cmꢁ1: 2934, 1734, 1259, 1138,
1036; LC-MS (ESI, MeCN:H2O = 17:3) m/z: 429
(½M þ Naꢂþ, 18%), 253 (15), 221 (7), 177 (100).
Experimental
General. NMR spectra were obtained with a Bruker
Avance 500 spectrometer. The mixing time for NOESY
was 300 msec. IR spectra were recorded with a Shimad-
zu FTIR-8200 spectrophotometer. MS data were ob-
tained with an Agilent HP1100 LC/MSD instrument.
Specific rotation values were determined with a Jasco
DIP1000 spectropolarimeter. HPLC was performed with
the LC10AT VP system (Shimadzu). Pre-packed silica
gel (100 mm ꢀ 15 or 22 mm I.D.; Kusano, Tokyo,
Japan) and silica SG80 (250 mm ꢀ 10 or 4.6 mm I.D.;
Shiseido, Tokyo, Japan) columns were used for HPLC.
Each analyte was injected as an ethanol solution. 1,3,5-
tri-tert-Butylbenzene was used to determine t0.
Preparation of esters 4 and 5. A mixture of (S)-1
(52.4 mg, 228 mmol, >99% ee), (RS)-2 (28.2 mg, 145
mmol; Fluka, Buchs, Switzerland), EDC (97.6 mg,
509 mmol), and DMAP (106.9 mg, 875 mmol) in CH2Cl2
(0.5 ml) was allowed to stand at room temperature for
18 h. The mixture was chromatographed over silica gel
with CH2Cl2. The diastereomeric esters obtained were
purified by HPLC in a pre-packed silica gel column
(100 mm ꢀ 22 mm I.D.; hexane:EtOAc = 9:1) in a sin-
gle operation, giving esters 4 (20.8 mg, 51 mmol, 35%
yield, >99% de) and 5 (21.2 mg, 52 mmol, 36% yield,
>99% de) as a colorless oil and colorless crystal,
respectively.
Preparation of (R)-2. A mixture of ester 4 (57.4 mg,
141 mmol) and 28% NaOMe/MeOH (1.5 ml) was
refluxed at 70 ꢃC for 6 h under argon. The solution was
diluted with ice-cooled water and extracted four times
with CH2Cl2. The organic layer was washed with brine,
and dried over anhydrous Na2SO4. The CH2Cl2 solution
was filtered through silica gel, and concentrated in vacuo
27
to give (R)-2 (17.6 mg, 91 mmol, 64% yield, ½ꢀꢂD +7.6
(c 0.176, CHCl3)). The aqueous layer was acidified with
2 mol/l hydrochloric acid and extracted three times with
CH2Cl2. The organic layer was washed with brine, and
dried over anhydrous Na2SO4. The CH2Cl2 solution was
concentrated in vacuo to give crude (S)-1 (35 mg).
Preparation of (S)-2. See the procedure for the
preparation of (R)-2 for details. The materials used
were ester 5 (61.0 mg, 150 mmol) and 28% NaOMe/
MeOH (1.5 ml). The reaction time was 6 h, and the
temperature was 60 ꢃC. This procedure yielded (S)-2
24
(15.8 mg, 81 mmol, 54% yield, ½ꢀꢂD ꢁ8:0 (c 0.158,
CHCl3)) and (S)-1 (29.3 mg, 127 mmol, 85% yield).
Preparation of esters 6 and 7. See the procedure for
enantioresolution of (RS)-2 for details. The materials
used were (S)-1 (50.5 mg, 219 mmol), (RS)-3 (27.4 mg,
190 mmol; Pfaltz & Bauer, Waterbury, CT, USA), EDC
(110.4 mg, 576 mmol), DMAP (102.0 mg, 835 mmol),
(1R,2E)-1-Methyl-3-(2,6,6-trimethyl-1-cyclohexen-1-yl)-
2-propenyl (S)-2-methoxy-2-(1-naphthyl)propanoate (4).

2422
A. ICHIKAWA and H. ONO
and CH2Cl2 (0.5 ml). This procedure yielded a 1:1
mixture of diastereomeric esters 6 and 7 (total 63.3 mg,
total 178 mmol, total 93% yield). This esterification
procedure was repeated, and the resulting mixture of
esters was purified by HPLC in a silica SG80 column
Acknowledgments
We thank Ms. Ikuko Maeda for obtaining the NMR
spectra. We also thank an anonymous referee for a
helpful suggestion on the chemical shift differences in
the 13C-NMR spectra.
(250 mm ꢀ 10 mm I.D.), yielding esters
6 (50 mg,
>99% de) and 7 (46 mg, >99% de) as colorless oils.
The mobile phase consisted of hexane/EtOAc (193:7) at
a flow rate of 3 ml/min. The injected amount for each
operation was ca. 1 mg.
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(S)-1-Isobutylpentyl (S)-2-methoxy-2-(1-naphthyl)-
26
propanoate (6). ½ꢀꢂD +9.3 (c 0.451, EtOH); NMR ꢂH
(500 MHz, CDCl3): 0.40 (3H, d, J ¼ 6 Hz), 0.42 (3H, d,
J ¼ 6 Hz), 0.59 (1H, m), 0.82 (3H, t, J ¼ 7 Hz), 0.92
(1H, ddd, J ¼ 14, 9, 4 Hz), 1.10–1.29 (4H, m), 1.13 (1H,
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42.76, 50.84, 73.77, 81.54, 124.58, 125.52, 125.64,
125.71, 126.35, 128.52, 129.27, 131.53, 134.04, 135.17,
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ˆ
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8) Ramirez-Lucas, P., Malosse, C., Ducrot, P. H., Lettere,
M., and Zagatti, P., Chemical identification, electro-
physiological and behavioral activities of the pheromone
of Metamasius hemipterus (Coleoptera: Curculionidae).
Bioorg. Med. Chem., 4, 323–330 (1996).
9) Zarbin, P. H. G., Arrigoni, E. D. B., Reckziegel, A.,
Moreira, J. A., Baraldi, P. T., and Vieira, P. C.,
Identification of male-specific chiral compound from
the sugarcane weevil Sphenophorus levis. J. Chem.
Ecol., 29, 377–386 (2003).
10) Noyori, R., Tomino, I., Yamada, M., and Nishizawa, M.,
Synthetic applications of the enantioselective reduction
by binaphthol-modified lithium alminum hydride re-
agents. J. Am. Chem. Soc., 106, 6717–6725 (1984).
11) Wada, A., Sakai, M., Kinumi, T., Tsujimoto, K.,
Yamauchi, M., and Ito, M., Conformational study of
retinochrome chromophore: synthesis of 8,18-ethanor-
etinal and a new retinochrome analog. J. Org. Chem., 59,
6922–6927 (1994).
(R)-1-Isobutylpentyl (S)-2-methoxy-2-(1-naphthyl)-
27
propanoate (7). ½ꢀꢂD ꢁ9:0 (c 0.431, EtOH); NMR ꢂH
(500 MHz, CDCl3): 0.40 (1H, m), 0.49 (3H, t, J ¼ 7 Hz),
0.52 (1H, m), 0.72–0.81 (2H, m), 0.83 (3H, d, J ¼ 7 Hz),
0.83 (3H, d, J ¼ 7 Hz), 1.10–1.17 (2H, m), 1.12 (1H, m),
1.40 (1H, ddd, J ¼ 14, 9, 5 Hz), 1.46 (1H, m), 1.99 (3H, s),
3.09 (3H, s), 4.94 (1H, m), 7.45 (1H, m), 7.46 (1H, m),
7.46 (1H, m), 7.60 (1H, dd, J ¼ 7, 1 Hz), 7.82 (1H, br d,
J ¼ 8 Hz), 7.83 (1H, m), 8.48 (1H, m); NMR ꢂC (126
MHz, CDCl3): 13.64, 21.57, 22.12, 22.22, 23.13, 24.55,
26.16, 33.70, 42.85, 50.78, 73.61, 81.46, 124.59, 125.50,
125.70, 125.75, 126.38, 128.53, 129.33, 131.52, 134.03,
135.15, 173.75; IR (KBr, CHCl3) cmꢁ1: 2959, 2936,
1732, 1261, 1138, 1123; LC-MS (ESI, MeCN:H2O =
9:1) m/z: 379 (½M þ Naꢂþ, 100%), 199 (9).
Preparation of (S)-3. See the procedure for the
preparation of (R)-2 for details. The materials used
were ester 6 (50 mg, ca. 140 mmol) and 28% NaOMe/
MeOH (1.5 ml). The reaction time was 7 h, and the
temperature was 70 ꢃC. This procedure yielded (S)-3
24
(20.5 mg, 142 mmol, quantitative yield, ½ꢀꢂD +11 (c
0.205, MeOH)) and (S)-1 (21.1 mg, 92 mmol, 65% yield).
Preparation of (R)-3. See the procedure for the
preparation of (R)-2 for details. The materials used were
ester 7 (45.5 mg, 128 mmol) and 28% NaOMe/MeOH
(1.5 ml). The reaction time was 6 h, and the temperature
was 70 ꢃC. This procedure yielded (R)-3 (15.7 mg,
12) Takenaka, M., Takikawa, H., and Mori, K., Synthesis of
the enantiomers of 2-methyl-4-heptanol and 2-methyl-4-
octanol, the pheromone components of the West Indian
sugarcane borer. Liebigs Ann. Chem., 1963–1964 (1996).
26
109 mmol, 85% yield, ½ꢀꢂD ꢁ11 (c 0.157, MeOH))
and (S)-1 (18.5 mg, 80 mmol, 63% yield).