Preparation of single-enantiomer semiochemicals using 2-methoxy-2-(1- naphthyl)propionic acid and 2-methoxy-2-(9-phenanthryl)propionic acid

Article abstract of DOI:10.1016/j.tetasy.2005.05.036

Enantioresolution of 3-octanol, 6-methyl-5-hepten-2-ol (sulcatol), and 1-octen-3-ol was conducted using (S)-(+)-2-methoxy-2-(1-naphthyl)propionic acid (MαNP acid) and (S)-(+)-2-methoxy-2-(9-phenanthryl)propionic acid (M9PP acid). In each case, the diastereomeric esters obtained were readily separated by HPLC. The stereochemistry of the esters could be assigned from their respective ¹H NMR analyses. Solvolyses of the esters gave enantiopure alcohols and acids. MαNP and M9PP acids displayed almost equivalent properties in ¹H NMR anisotropy. The chiral resolving ability of M9PP acid was slightly superior to that of MαNP acid in HPLC.

Full text of DOI:10.1016/j.tetasy.2005.05.036

Tetrahedron:
Asymmetry
Tetrahedron: Asymmetry 16 (2005) 2559–2568
Preparation of single-enantiomer semiochemicals using
-methoxy-2-(1-naphthyl)propionic acid and
-methoxy-2-(9-phenanthryl)propionic acid
2
2
a,
Akio Ichikawa and Hiroshi Ono
b
*
a
National Institute of Agrobiological Sciences, 1-2 Owashi, Tsukuba, Ibaraki 305-8634, Japan
b
National Food Research Institute, 2-1-12 Kannondai, Tsukuba, Ibaraki 305-8642, Japan
Received 5 April 2005; accepted 19 May 2005
Available online 26 July 2005
Abstract—Enantioresolution of 3-octanol, 6-methyl-5-hepten-2-ol (sulcatol), and 1-octen-3-ol was conducted using (S)-(+)-2-meth-
oxy-2-(1-naphthyl)propionic acid (MaNP acid) and (S)-(+)-2-methoxy-2-(9-phenanthryl)propionic acid (M9PP acid). In each case,
the diastereomeric esters obtained were readily separated by HPLC. The stereochemistry of the esters could be assigned from their
1
respective H NMR analyses. Solvolyses of the esters gave enantiopure alcohols and acids. MaNP and M9PP acids displayed almost
1
equivalent properties in H NMR anisotropy. The chiral resolving ability of M9PP acid was slightly superior to that of MaNP acid
in HPLC.
ꢀ
2005 Elsevier Ltd. All rights reserved.
1
. Introduction
OCH3
OH
H
O
H
O
OH
OH
Semiochemicals are compounds involved in the chemical
interactions between organisms. A semiochemical that
conveys information between the same species is known
as a pheromone. Various relationships have been re-
ported between the chirality of insect pheromones and
H CO
3
F C
3
H CO
3
O
(
R)-(+)-1: MTPA
(S)-(+)-2: MPA
(S)-(+)-3: 2NMA
1
,2
their biological activity. Therefore, enantiopure com-
pounds are necessary for evaluating the biological activ-
ity of each enantiomer. Enantiopurity is particularly
important in pharmaceuticals, because the presence of
a minor enantiomer impurity could cause undesirable
effects.
CH3
OH
CH3
OH
H3CO
O
H3CO
O
(S)-(+)-4: MαNP acid
(S)-(+)-5: M9PP acid
1
Dale and Mosher reported various H NMR shift
O
O
O
NH
O
NH
3
reagents. Of these, MTPA 1 and MPA 2 have been used
most widely to determine the absolute configurations of
N
N
4
–6
H
H C
3
O
secondary alcohols and primary amines (Fig. 1). In
the case of MPA 2, Trost et al. reported a slight loss
of enantiopurity during the base hydrolysis of its ester
O
O
O
6
: Thalidomide
7: Methylthalidomide
4
1
derivative. To increase the H NMR anisotropy of
Figure 1. The structures of chiral resolving agents 1–5, thalidomide 6,
and methylthalidomide 7.
10,11
MPA 2, Kusumi and Riguera added large aryl groups;
that is, 2-methoxy-2-(2-naphthyl)acetic acid
3
7
–9
(
2NMA).
Hashimoto et al. determined the rate of racemization of
single-enantiomer thalidomide 6 under physiological
1
0,11
*
Corresponding author. Tel.: +81 298 38 6267; fax: +81 298 38
028; e-mail: ichikawa@affrc.go.jp
conditions. They also prepared both enantiomers
of methylthalidomide 7, a nonracemizable thalidomide
6
0
957-4166/$ - see front matter ꢀ 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2005.05.036

2560
A. Ichikawa, H. Ono / Tetrahedron: Asymmetry 16 (2005) 2559–2568
analogue, and found that only (S)-7 caused an increase
in tumor necrosis factor (TNF)-a production. This
prompted us to develop 2-methoxy-2-(aryl)propionic
acids as nonracemizable chiral resolving agents.
2. Results and discussion
Compounds 8–10 are mono-alcohols possessing C8-car-
bon skeletons (Fig. 3); the simple structures of alcohols
8–10 are useful for developing the novel chiral resolving
agents.
MaNP acid 4 and M9PP acid 5 are useful for preparing
enantiopure alcohols, because of their susceptibility to
chiral separation and the advantage of not racemizing
during condensation reactions and HPLC separa-
The enantioresolution of 3-octanol (±)-8 was conducted
using MaNP acid (S)-(+)-4. Both enantiomers of 8 are
ant pheromones. Fujiwhara and Mori synthesized (R)-
(ꢀ)- and (S)-(+)-3-octanol from methyl (R)-3-hydroxy-
1
2–22
tion. Acids 4 and 5 are also useful for determining
the absolute configuration of secondary alcohols using
1
the H NMR anisotropy method.
24
pentanoate and its (S)-isomer, respectively. 3-Octanol
(±)-8 was esterified with MaNP acid (S)-(+)-4 using
Considering the crystalline structure of (1R,2S,5R)-men-
1
1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydro-
chloride (EDC) and 4-dimethylaminopyridine (DMAP)
in CH Cl . The crude products were purified using nor-
mal phase HPLC to afford the two diastereomeric esters
(ꢀ)-11a and (+)-11b in 41% and 43% yields, respectively.
As shown in Figure 4, the separation factor (a value) for
esters (ꢀ)-11a and (+)-11b was 1.45 with the Silica SG80
column.
2
thol M9PP ester, we proposed the conformational
2
2
model shown in Figure 2: (1) the methoxyl and car-
bonyl oxygen atoms are syn-periplanar to each other;
2
2
(
2) the alcohol methine proton is also syn-periplanar
to the ester carbonyl oxygen atom; (3) the methyl group
is syn-periplanar to H-2 in the MaNP ester or H-10 in
the M9PP ester.
1
Figure 5 shows the H NMR chemical shifts of esters
Recently, Seco et al. proposed a new conformational
9
model for MTPA esters; three conformations of similar
populations are present for both (R)- and (S)-MTPA es-
(ꢀ)-11a and (+)-11b, and the Dd {= d[(+)-11b] ꢀ d[(ꢀ)-
1
11a]} values in CDCl . The H NMR signals of esters
3
ters, resulting in smaller Dd values. By contrast, the
MaNP and M9PP esters show large Dd values in H
NMR and large separation factors in HPLC.
(ꢀ)-11a and (+)-11b were assigned from DQF COSY,
1
PS NOESY, and HMBC spectra (600 or 800 MHz,
CDCl ). The positive Dd values were observed for the
3
protons at the 1- and 2-positions of the alcohol moiety
(+0.56 and +0.2, respectively). Conversely, negative
Dd values were observed for the protons at the 4- to
8-positions. Based on the conformational hypotheses
shown in Figure 2, the stereochemistry was repres-
M9PP acid (S)-(+)-5 has been used for the enantioreso-
2
lution of 3-octanol (±)-8 and sulcatol (±)-9 (Fig. 3).
Application examples are still necessary in order to
develop 2-methoxy-2-(aryl)propionic acids as chiral
resolving agents. Here, we report the enantioresolution
of three semiochemicals (3-octanol 8, sulcatol 9, and
1,22
1
7
ented as (S,R)-(ꢀ)-11a and (S,S)-(+)-11b. (See lit.
for the definition of Dd and the assignment of stereo-
chemistry.) The zigzag conformation of the alcohol
moiety explained the largest Dd values at the c-
1-octen-3-ol 10) (Fig. 3) using MaNP acid (S)-(+)-4.
The results were compared to those obtained with
7
M9PP acid (S)-(+)-5 in terms of their HPLC separation
and H NMR anisotropy. We also investigated the
position.
1
stability of the MaNP and M9PP moieties toward
catalytic hydrogenation.
As shown in Scheme 1, the solvolysis of the first-eluted
ester (S,R)-(ꢀ)-11a gave 3-octanol (R)-(ꢀ)-8 {63%,
3
D
0
24
22
D
½
aꢁ ¼ ꢀ8 (c 0.16, CHCl ), lit. : ½aꢁ ¼ ꢀ9.7 (c 0.93,
3
4
0
Syn
Syn
H
H
(
–)-11a
(+)-11b
2
10
9 CH3
1
CH3
20
R1
R2
R1
R2
H C
3
H C
3
O
O
O
O
0
O
H
O
H
Syn
Syn
Syn
Syn
0.0
2.5
5.0
7.5
10.0
min
12.5
15.0
17.5
20.0
(
S)-MαNP ester
(S)-M9PP ester
Figure 4. The HPLC separation of diastereomeric esters formed from
3-octanol (±)-8 and MaNP acid (S)-(+)-4 (Silica SG80, hexane–EtOAc
9:1, UV 300 nm, a = 1.45, T : 1,3,5-tri-tert-butylbenzene).
0
Figure 2. The preferred conformations of (S)-MaNP and (S)-M9PP
esters.
H3C
H3C
CH3 H3C
CH3
H
H
H
OH
H3C
OH
OH
8: 3-Octanol
9: Sulcatol
10: 1-Octen-3-ol
Figure 3. The structures of 3-octanol 8, sulcatol 9, and 1-octen-3-ol 10.

A. Ichikawa, H. Ono / Tetrahedron: Asymmetry 16 (2005) 2559–2568
2561
0
.84
CH3
.2
–
0.18 –0.5 –0.3 +0.2
1
H3C
1
.2
.2
0.78
H3C
O
CH3
1
.4
CH3
CH3
1
.4
1
–0.3 –0.8
R
1
H
+0.56
H3C
H3C
–0.7
–0.02
O
1.2
.1
.7
O
O
O
O
0
CH3
O
H
O
H 0.4
H3C*
H3CO
4
.79 0.22
4.77 0.5
CH3
.66
0
.9
0
(
S,R)-(–)-11a
(S,S)-(+)-11b
∆δ = δ(R,R) – δ(S,R)
δ[(+)-11b] – δ[(–)-11a]
=
1
Figure 5. The H NMR chemical shift data and Dd values for esters (ꢀ)-11a and (+)-11b (600 MHz, CDCl
3
). The black bars show the relative
intensity of the Dd values.
H C
3
H C
3
CH3
H
CH3
(
S)-(+)-5,
H
NaOMe, MeOH,
reflux
EDC, DMAP,
CH Cl
O
O
O
O
H C
3
2
2
CH3
H
(
S)-(+)-4,
H C
H C
OH
3
3
EDC, DMAP,
CH Cl
H CO
3
H CO
3
2
2
(S,R)-(–)-11a
(R)-(–)-8
(S,R)-(+)-12a
H2, 5% Pd–C,
EtOAc
CH3
H
O
O
H C
3
H
H C
H OC
3
O
O
3
H C
H CO
3
3
(
S,R)-(+)-14b
H2, 5% Pd–C,
EtOAc
(
S,S)-(+)-15a
CH3
CH3
H C
(
S)-(+)-5,
EDC, DMAP,
CH3 CH2Cl2
3
H C
3
H
O
H
NaOMe, MeOH,
reflux
O
O
O
H C
3
H
OH
H C
3
H C
3
H OC
3
H OC
3
(
S,S)-(+)-11b
(S)-(+)-8
(S,S)-(+)-12b
Scheme 1. Preparation of single enantiomer 3-octanol, M9PP esters (+)-12a, and (+)-12b.
1
CHCl )}. 3-Octanol (R)-(ꢀ)-8 was esterified with acids
(Table 1, a = 1.45 and 1.47, respectively) and H NMR
21
3
(
S)-(+)-4 and (S)-(+)-5 to give enantiopure (S,R)-(ꢀ)-
anisotropy. [See lit. for the Dd values of M9PP esters
(S,R)-(+)-12a and (S,S)-(+)-12b.]
2
1
1
1a and (S,R)-(+)-12a,
respectively. Notably, the
retention of the stereochemistry after the solvolysis
was confirmed. The solvolysis of the second-eluted ester
6-Methyl-5-hepten-2-ol 9 (sulcatol) is known as the
aggregation pheromone of the ambrosia beetle, Gnatho-
37
(
(
3
S,S)-(+)-11b gave 3-octanol (S)-(+)-8 {54%, ½aꢁ ¼ þ10
D
2
4
22
25,26
c 0.14, CHCl ), lit. : ½aꢁ ¼ þ10.1 (c 0.82, CHCl )}.
trichus sulcatus.
Sulcatol (±)-9 was esterified with
3
D
-Octanol (S)-(+)-8 was esterified with M9PP acid
3
MaNP acid (S)-(+)-4 using EDC and DMAP in
2
1
(
S)-(+)-5 giving ester (S,S)-(+)-12b.
CH Cl . The crude products were purified by prepara-
2
2
tive HPLC using the prepacked glass column, affording
esters (ꢀ)-13a and (+)-13b in 43% and 37% yields,
respectively. The separation factor (a value) for esters
(ꢀ)-13a and (+)-13b was 1.31 with the Silica SG80 col-
umn (Fig. 6).
We have already reported the enantioresolution of
2
1
3-octanol (±)-8 using M9PP acid (S)-(+)-5. In the case
of 3-octanol (±)-8, acids (S)-(+)-4 and (S)-(+)-5 revealed
nearly equivalent chiral resolving abilities in HPLC

2562
A. Ichikawa, H. Ono / Tetrahedron: Asymmetry 16 (2005) 2559–2568
Table 1. Separation factors for MaNP and M9PP esters
3
-Octanol (±)-8
Sulcatol (±)-9
1-Octen-3-ol (±)-10
MaNP acid (S)-(+)-4
M9PP acid (S)-(+)-5
a = 1.45
a = 1.47
1.31
1.37
1.47
1.52
Silica SG80, hexane/EtOAc, UV 300 nm, a = (T
2
ꢀ T
0
)/(T
1
ꢀ T
0 0
), T : 1,3,5-tri-tert-butylbenzene.
(
±)-9, the observed Dd values of MaNP esters were
22
nearly equal to those of M9PP esters. (See lit. for the
NMR data of sulcatol M9PP esters.)
4
2
0
0
0
(
–)-13a
(
+)-13b
1
sources:
-Octen-3-ol 10 has been isolated from many natural
2
7–30
1-Octen-3-ol 10 was isolated from cattle
odors as a potent olfactory stimulant and attractant
0
.0
2.5
5.0
7.5
10.0
min
12.5
15.0
17.5
20.0
27
for tsetse flies. 1-Octen-3-ol 10 was also reported as
an attractive semiochemical for the foreign grain beetle,
2
9
Figure 6. The HPLC separation of diastereomeric esters formed from
sulcatol (±)-9 and MaNP acid (S)-(+)-4 (Silica SG80, hexane–EtOAc
:1, UV 300 nm, a = 1.31, T : 1,3,5-tri-tert-butylbenzene).
0
Ahasverus advena and the African malaria mosquito,
3
0
Anopheles gambiae. The absolute configuration of 1-
octen-3-ol (ꢀ)-10 was determined as R by empirical
9
2
8
NMR studies. 1-Octen-3-ol (±)-10 was condensed with
MaNP acid (S)-(+)-4 using EDC and DMAP in CH Cl
1
The H NMR signals of esters (ꢀ)-13a and (+)-13b were
2
2
assigned from DQF COSY and PS NOESY spectra
(
to give esters (ꢀ)-14a and (+)-14b in 40% and 43%
yields, respectively. The separation factor for esters
(ꢀ)-14a and (+)-14b was 1.47 with the Silica SG80
column (Fig. 8).
800 MHz, CDCl ). The chemical shift and the Dd
3
{
7
= d[(+)ꢀ13b] ꢀ d[(ꢀ)-13a]} values are shown in Figure
. A positive Dd value was observed for the terminal
methyl protons (+0.27), and the negative Dd values were
observed for the protons of the rest of alcohol moiety
1
The H NMR signals of esters (ꢀ)-14a and (+)-14b were
(
Fig. 7). Therefore, the stereochemistry was assigned
1
assigned from DQF COSY spectra (500 MHz, CDCl ).
3
7
as (S,R)-(ꢀ)-13a and (S,S)-(+)-13b.
The Dd {=d[(+)ꢀ14b] ꢀ d[(ꢀ)-14a]} values were pre-
sented in Figure 9, from which the stereochemistry
was assigned as (S,S)-(ꢀ)-14a and (S,R)-(+)-14b.
1
7
The solvolysis of first-eluted ester (S,R)-(ꢀ)-13a gave
26
sulcatol (R)-(ꢀ)-9 {69%, ½aꢁ ¼ ꢀ13 (c 0.19, EtOH),
D
26
23
D
lit. : ½aꢁ ¼ ꢀ14.5 (c 0.74, EtOH)}, together with enan-
The solvolysis of the first-eluted ester (S,S)-(ꢀ)-14a
yielded enantiopure 1-octen-3-ol (S)-(+)-10 {77%,
tiopure MaNP acid (S)-(+)-4 (87%). Sulcatol (R)-(ꢀ)-9
was esterified with the recovered MaNP acid (S)-(+)-4
using EDC and DMAP in CH Cl yielding ester (S,R)-
2
D
6
28
20
D
½aꢁ ¼ þ19 (c 0.18, EtOH), lit. : ½aꢁ ¼ þ20.6 (c 5.3,
2
2
EtOH)}, together with MaNP acid (S)-(+)-4 (95%). 1-
Octen-3-ol (S)-(+)-10 was condensed with recovered
(S)-(+)-4 using EDC and DMAP in CH Cl giving
(
of the second-eluted ester (S,S)-(+)-13b gave sulcatol
ꢀ)-13a only, in 79% yield (Scheme 2). The solvolysis
2
2
2
D
7
26
(
S)-(+)-9 {93%, ½aꢁ ¼ þ15 (c 0.21, EtOH), lit. :
(S,S)-(ꢀ)-14a only (Scheme 3). The catalytic hydrogena-
tion of (S,R)-(+)-14b gave (S,S)-(+)-11b only, in 89%
yield (Scheme 1); therefore, the empirical NMR study
of 1-octen-3-ol 10 was linked to the asymmetric synthe-
23
½
aꢁ ¼ þ14.4 (c 0.998, EtOH)} and MaNP acid (S)-
D
+)-4 (91%). Sulcatol (S)-(+)-9 was esterified with the
(
recovered MaNP acid (S)-(+)-4 using EDC and DMAP
in CH Cl yielding ester (S,S)-(+)-13b only (85%).
2
4,28
2
2
sis of 3-octanol 8.
The separation factor for sulcatol MaNP esters (S,R)-
ꢀ)-13a and (S,S)-(+)-13b was 1.31, while that of
Finally, the enantioresolution of 1-octen-3-ol (±)-10 was
attempted using M9PP acid (S)-(+)-5. 1-Octen-3-ol (±)-
10 was esterified with (S)-(+)-5 using 1,3-dicyclohexyl-
(
M9PP esters was 1.37 (Table 1). In the case of sulcatol
2
2
1
.64
CH3
–0.10 –0.26
H3C
–0.2
0.1
+0.27
CH3
R
1.48
H3C
–
4
.97
1.5
.3
CH3
.87
1
.14
CH3
1.3
.2
–0.5 H
CH3
CH3
–0.04
1
.8
H3C
–0.25
1
O
O
H3C
H3C
O
O
O
O
1
0
4
.71
*
O
H
.90
O
H
4
.86 1.3
H3C
H3C
4
CH3
1.54
H3CO
1
.23
(
S,R)-(–)-13a
(S,S)-(+)-13b
∆δ = δ(R,R) – δ(S,R)
=
δ[(+)-13b] – δ[(–)-13a]
1
Figure 7. The H NMR chemical shift data and Dd values for esters (ꢀ)-13a and (+)-13b (800 MHz, CDCl
3
). The black bars show the relative
intensity of the Dd values.

A. Ichikawa, H. Ono / Tetrahedron: Asymmetry 16 (2005) 2559–2568
2563
H3C
H3C
CH3
1
2
) NaOMe, MeOH,
reflux
) H3O
H
O
OH
O
O
+
H3C
CH3
H
+
+
H3C
H3CO
H3C
H3C
H3CO
EDC, DMAP,
OH
CH Cl2
2
(
S,R)-(–)-13a
(R)-(–)-9
(S)-(+)-4
H3C
H
CH3
1
2
) NaOMe, MeOH,
reflux
CH3
O
OH
O
O
+
) H3O
H3C
H
CH3
CH3
H3C
H3CO
H3C
H3CO
EDC, DMAP,
OH
CH Cl2
2
(
S,S)-(+)-13b
(S)-(+)-9
(S)-(+)-4
Scheme 2. Preparation of the single-enantiomer sulcatol and the reformations of MaNP esters (ꢀ)-13a and (+)-13b.
separation factor for esters (+)-15a and (+)-15b was
1.52 with the Silica SG80 column (Fig. 10).
3
2
1
0
0
0
0
(
–)-14a
(+)-14b
1
The H NMR signals of esters (+)-15a and (+)-15b were
assigned from DQF COSY and HSQC spectra
(800 MHz, CDCl ). The stereochemistry was assigned
3
as (S,S)-(+)-15a and (S,R)-(+)-15b from the Dd
0.0
2.5
5.0
7.5
10.0
min
12.5
15.0
17.5
20.0
1
7
{
= d[(+)-15b] ꢀ d[(+)-15a]} values (Fig. 11).
Figure 8. The HPLC separation of diastereomeric esters formed from
-octen-3-ol (±)-10 and MaNP acid (S)-(+)-4 (Silica SG80, hexane–
EtOAc 92:8, UV 300 nm, a = 1.47, T : 1,3,5-tri-tert-butylbenzene).
The solvolysis of the first fraction (S,S)-(+)-15a yielded
26
1
1-octen-3-ol (S)-(+)-10 {80%, ½aꢁ ¼ þ19 (c 0.21,
D
EtOH)} and M9PP acid (S)-(+)-5 (82%). 1-Octen-3-ol
0
(
DMAP, and CSA in CH Cl giving ester (S,S)-(+)-15a
S)-(+)-10 was condensed with (S)-(+)-5 using DCC,
carbodiimide (DCC), DMAP, and (+)-10-camphorsulf-
onic acid (CSA) in CH Cl affording esters (+)-15a
and (+)-15b in 37% and 43% yields, respectively. The
2
2
(Scheme 4). The catalytic hydrogenation of (S,S)-(+)-
1
15a gave ester (S,R)-(+)-12a in 70% yield (Scheme 1).
2
2
2
0
.82
3
+0.21
5
.08
H
CH
–0.15 –0.4 –0.3
3
H
+0.28
H
1
.2
5.66
H
H C
1
.2
5.14
3 H
CH3
1.5
CH
–0.3 –0.6
S
H
1
O
.1
H 5.45
H+0.48
–
0.04
H C
3
H3C
1.2
O
O
O
O
H
O
0
.8
4
.80
*
O
H
O
H
H
0.5
H C
3
5
.25
5.21
CH3
4
.66
0.9
0
.67
H CO
3
(S,S)-(–)-14a
(S,R)-(+)-14b
∆δ = δ(R,S) – δ(S,S)
δ[(+)-14b] – δ[(–)-14a]
=
1
Figure 9. The H NMR chemical shift data and Dd values for esters (ꢀ)-14a and (+)-14b (500 MHz, CDCl
3
). The black bars show the relative
intensity of the Dd values.
H3C
1
) NaOMe, MeOH,
reflux
) H3O
H
HO
O
O
O
+
2
3
H C
+
H
H3C
H3CO
H3C
H3CO
EDC, DMAP,
CH Cl
OH
2
2
(
S,S)-(–)-14a
(S)-(+)-10
(S)-(+)-4
Scheme 3. Preparation of the single-enantiomer 1-octen-3-ol and reformation of MaNP ester (ꢀ)-14a.

2564
A. Ichikawa, H. Ono / Tetrahedron: Asymmetry 16 (2005) 2559–2568
1
ters and M9PP esters had similar Dd values on H NMR
(Figs. 9 and 11).
200
(
+)-15a
(+)-15b
1
100
The MaNP and M9PP moieties caused similar H NMR
anisotropy in the alcohol part of the esters. The confor-
mational models shown in Figures 2 and 5 could explain
these results: The two benzene rings that exist in both
acids are important for the recognition of the alcohol
chirality. A similar conformational model has been pro-
posed for the 2NMA ester. The chiral resolving ability
of M9PP acid (S)-(+)-5 was slightly superior to that of
MaNP acid (S)-(+)-4 in HPLC (Table 1).
0
0
.0
2.5
5.0
7.5
10.0
min
12.5
15.0
17.5
20.0
Figure 10. The HPLC separation of diastereomeric esters formed from
-octen-3-ol (±)-10 and M9PP acid (S)-(+)-5 (Silica SG80, hexane–
EtOAc 9:1, UV 300 nm, a = 1.52, T : 1,3,5-tri-tert-butylbenzene). Only
in the case of 1-octen-3-ol M9PP esters, were the separated diastereo-
mers mixed again, and analyzed by HPLC.
9
1
0
3. Conclusion
The solvolysis of the second fraction (S,R)-(+)-15b
2
D
7
yielded 1-octen-3-ol (R)-(ꢀ)-10 {82%, ½aꢁ ¼ ꢀ19 (c
MaNP and M9PP acids are recyclable and effective for
HPLC separation and H NMR anisotropy: (1) both
2
8
20
D
1
0
.23, EtOH), lit. : ½aꢁ ¼ ꢀ20.2 (c 7.3, EtOH)}, and
M9PP acid (S)-(+)-5 (49%). 1-Octen-3-ol (R)-(ꢀ)-10
the acids could resolve the alcohol enantiomers via ester-
ification; (2) successive NMR analyses assigned the ste-
reochemistry of MaNP and M9PP esters; and (3)
solvolysis of the esters yielded enantiopure alcohols
and acids. The method using the MaNP and M9PP
acids was applicable to 1-octen-3-ol, an allylic alcohol.
The MaNP and M9PP moieties were stable against cat-
alytic hydrogenation. Clearly, enantioresolution using
was esterified with M9PP acid (S)-(+)-5 yielding ester
(
S,R)-(+)-15b (76%).
The separation factor for 1-octen-3-ol MaNP esters
S,S)-(ꢀ)-14a and (S,R)-(+)-14b was 1.47, while that of
M9PP esters (S,S)-(+)-15a and (S,R)-(+)-15b was 1.52
Table 1). In the case of 1-octen-3-ol (±)-10, MaNP es-
(
(
+
0.22
–
–
0.2
0.3
0
.80
–
0.19 –0.4
H C
H
+0.28
H C
5.08
H
3
3
H
1
.2 1.4
1
1
.2
5.15
5.64
H
–0.4 –0.6 H S
CH3
1.5
H
CH3
+0.44
H
H
O
–0.05
.1
O
O
H C
3
5
.42 H C
3
O
1
.2
.8
O
O
H
0
*
4
.80
O
H
.28
O
H
H C
H
0.5
.23
3
5
CH3
.61
5
4
.71
H CO
3
0
.8
0
(
S,S)-(+)-15a
(S,R)-(+)-15b
∆δ = δ(R,S) – δ(S,S)
δ[(+)-15b] – δ[(+)-15a]
=
1
Figure 11. The H NMR chemical shift data and Dd values for esters (+)-15a and (+)-15b (800 MHz, CDCl
intensity of the Dd values.
3
). The black bars show the relative
H C
3
1
2
) NaOMe, MeOH,
reflux
) H3O
H
HO
O
O
O
+
H C
3
H C
H CO
3
H C
3
H
+
+
3
3
OH
H CO
DCC, DMAP,
CSA, CH2Cl2
(S,S)-(+)-15a
(S)-(+)-10
(S)-(+)-5
CH3
1
2
) NaOMe, MeOH,
reflux
) H3O
H
HO
O
O
O
+
CH3
H C
H C
3
H
3
3
OH
H3CO
H CO
EDC, DMAP,
CH2Cl2
(S,R)-(+)-15b
(R)-(–)-10
(S)-(+)-5
Scheme 4. Preparation of single-enantiomer 1-octen-3-ol and re-formation of M9PP esters (+)-15a and (+)-15b.

A. Ichikawa, H. Ono / Tetrahedron: Asymmetry 16 (2005) 2559–2568
2565
MaNP and M9PP acids is useful for the small-scale syn-
thesis of natural products and the preparation of single
enantiomer agrochemicals and pharmaceuticals.
128.55, 126.38, 125.72, 125.68, 125.48, 124.59, 81.50,
76.46, 50.80, 32.91, 31.33, 26.58, 23.83, 22.22, 21.68,
13.89, 9.54; IR (KBr, neat): m
2934, 2860, 1746,
252, 1139, 1114, 806, 780 cm ; LC–MS (API-ESI,
max
ꢀ
1
1
CH CN–H O 24:1): m/z 365 ([M+Na] , 100), 311 (2),
+
3
2
33
4. Experimental
199 (10); ½aꢁ ¼ þ15 (c 0.72, EtOH).
D
4
.1. General
4.2.3. 3-Octanol (R)-(ꢀ)-8. A mixture of ester (S,R)-
(
ꢀ)-11a (67 mg) and 28% NaOMe/MeOH (1.5 mL)
The NMR spectra were obtained using a Bruker (Rhein-
stetten, Germany) Avance800, a Bruker DRX600, or a
Bruker Avance500 in CDCl3 with tetramethylsilane
was refluxed for 7 h under argon. The solution was di-
luted with ice water, and extracted with CH Cl twice.
2
2
The organic layer was washed with brine, dried over
anhydrous Na SO , and concentrated in vacuo. The
crude product was chromatographed over silica gel with
(
TMS) as an internal standard. The IR spectra were re-
2
4
corded as thin films (neat) mounted on KBr plates with
a Perkin–Elmer (Norwalk, CT) 1760X or a Shimadzu
CH Cl to give 3-octanol (R)-(ꢀ)-8 (16 mg, 63%):
2
2
3
0
(
Kyoto, Japan) FTIR-8200. The MS data were obtained
½aꢁ ¼ ꢀ8 (c 0.16, CHCl ).
D
3
with an Agilent (Palo Alto, CA) 1100 LC/MSD system.
The optical rotations were determined on a JASCO
4.2.4. 3-Octanol (S)-(+)-8. Ester (S,S)-(+)-11b (68 mg)
was similarly hydrolyzed with 28% NaOMe/MeOH
(1.5 mL) yielding 3-octanol (S)-(+)-8 (14 mg, 54%):
(
Tokyo, Japan) DIP1000 spectropolarimeter. Wakogel
C-200 (Wako Pure Chemical Industries, Osaka, Japan)
was used for the open column chromatography. HPLC
was performed using the Shimadzu LC10AT VP systems
equipped with: (1) diode array detector–refractive index
detector, (2) UV–vis detector. The CIG prepacked silica
gel and ODS columns (Kusano Scientific Instrument,
Tokyo, Japan) were used for preparative HPLC. A Sil-
ica SG80 column (4.6 mmB · 250 mm, Shiseido, Tokyo,
Japan) was used for analytical HPLC.
37
½aꢁ ¼ þ10 (c 0.14, CHCl3).
D
4.2.5. Preparation of MaNP ester (S,R)-(ꢀ)-11a from
(R)-(ꢀ)-3-octanol. 3-Octanol (R)-(ꢀ)-8 (8 mg) pre-
pared above was esterified with MaNP acid (S)-(+)-4
(21 mg) using EDC (40 mg) and DMAP (55 mg) in
CH Cl (0.5 mg). The crude product was chromato-
2
2
graphed over silica gel giving ester (S,R)-(ꢀ)-11a
(10 mg, 48%), which was identical with the authentic
sample.
4
.2. Enantioresolution of (±)-3-octanol using MaNP acid
A mixture of MaNP acid (S)-(+)-4 (49 mg), EDC
4.2.6. Preparation of M9PP ester (S,R)-(+)-12a from
(R)-(ꢀ)-3-octanol. 3-Octanol (R)-(ꢀ)-8 (8 mg) pre-
pared above was similarly esterified with M9PP acid
(S)-(+)-5 (11 mg) yielding ester (S,R)-(+)-12a (13 mg,
(
(
81 mg), DMAP (109 mg), and 3-octanol (±)-8
120 lL) in CH Cl2 (0.75 mL) was allowed to stand
2
for 16 h. The mixture was chromatographed over silica
gel with CH Cl . The diastereomeric esters obtained
were separated by HPLC on silica gel (hexane–EtOAc
2
1
84%), which was identical with the authentic sample.
2
2
47:3), giving the first eluted ester (S,R)-(ꢀ)-11a (30 mg,
41%) and the second eluted ester (S,S)-(+)-11b (31 mg,
43%).
4.2.7. Preparation of M9PP ester (S,S)-(+)-12b from (S)-
(+)-3-octanol. 3-Octanol (S)-(+)-8 (7 mg) prepared
above was similarly esterified with M9PP acid (S)-(+)-
5 (10 mg) yielding ester (S,S)-(+)-12b (12 mg, 86%),
21
which was identical with the authentic sample.
1
4
(
.2.1. 3-Octanol MaNP ester (S,R)-(ꢀ)-11a. H NMR
600 MHz, CDCl ): d 8.45 (1H, m), 7.83 (1H, m), 7.82
3
(
1H, m), 7.61 (1H, dd, J = 7, 1 Hz), 7.48–7.43 (3H, m),
4.3. Enantioresolution of (±)-sulcatol using MaNP acid
4
1
.79 (1H, m), 3.11 (3H, s), 2.00 (3H, s), 1.4 (2H, m),
.2 (8H, m), 0.84 (3H, t, J = 7 Hz), 0.22 (3H, t,
A mixture of MaNP acid (S)-(+)-4 (50 mg), EDC
(77 mg), DMAP (103 mg), and sulcatol (±)-9 (95 lL)
in CH Cl (0.5 mL) was allowed to stand for 16 h. The
1
3
J = 7.5 Hz); C NMR (151 MHz): d 173.89, 135.37,
1
1
2
2
7
3
0
34.02, 131.45, 129.29, 128.56, 126.32, 125.64, 125.62,
25.42, 124.62, 81.57, 76.57, 50.87, 33.10, 31.60, 26.32,
4.81, 22.49, 21.74, 13.97, 8.52; IR (KBr, neat): mmax
934, 2860, 1746, 1727, 1254, 1139, 1114, 806,
2
2
crude products were chromatographed over silica gel
with CH Cl . The diastereomeric esters obtained were
2
2
separated by HPLC on silica gel (hexane–EtOAc 9:1)
giving the first eluted ester (S,R)-(ꢀ)-13a (32 mg, 43%)
and the second eluted ester (S,S)-(+)-13b (27 mg, 37%).
ꢀ
1
80 cm ; LC–MS (API-ESI, CH CN–H O 24:1): m/z
3
2
+
31
D
65 ([M+Na] , 100), 311 (2), 199 (11); ½aꢁ ¼ ꢀ12 (c
.68, EtOH).
1
4
.3.1. Sulcatol MaNP ester (S,R)-(ꢀ)-13a. H NMR
1
4
.2.2. 3-Octanol MaNP ester (S,S)-(+)-11b. H NMR
(800 MHz, CDCl ): d 8.40 (1H, m), 7.84 (1H, m), 7.82
3
(
(
7
2
600 MHz, CDCl ): d 8.48 (1H, m), 7.83 (1H, m), 7.81
1H, br d, J = 8 Hz), 7.60 (1H, dd, J = 7, 1 Hz), 7.48–
(1H, dt, J = 8, 1 Hz), 7.61 (1H, dd, J = 7, 1 Hz), 7.46
(2H, m), 7.45 (1H, m), 4.97 (1H, m), 4.90 (1H, m),
3.11 (3H, s), 1.99 (3H, s), 1.8 (2H, m), 1.64 (3H, br d,
J = 1 Hz), 1.48 (3H, br s), 1.5 (1H, m), 1.3 (1H, m),
0.87 (3H, d, J = 6 Hz); C NMR (126 MHz): d
173.77, 135.39, 134.03, 132.06, 131.26, 129.30, 128.63,
126.27, 125.62, 125.51, 125.23, 124.65, 123.34, 81.55,
3
.43 (3H, m), 4.77 (1H, sept, J = 6 Hz), 3.09 (3H, s),
.00 (3H, s), 1.4 (2H, m), 1.1 (2H, m), 0.9 (2H, m),
.78 (3H, t, J = 7.5 Hz), 0.7 (2H, m), 0.66 (3H, t,
1
3
0
1
3
J = 7 Hz), 0.5 (1H, m), 0.4 (1H, m); C NMR
(151 MHz): d 173.88, 135.20, 134.04, 131.53, 129.33,

2566
A. Ichikawa, H. Ono / Tetrahedron: Asymmetry 16 (2005) 2559–2568
7
1.94, 50.96, 35.67, 25.65, 23.85, 21.79, 19.36, 17.56; IR
20 h. The crude products were chromatographed over
silica gel with CH Cl . The diastereomeric esters ob-
tained were separated by HPLC on silica gel (hexane–
EtOAc 9:1), giving the first eluted ester (S,S)-(ꢀ)-14a
(23 mg, 40%) and the second eluted ester (S,R)-(+)-14b
(
KBr, neat): mmax 2974, 2932, 1744, 1727, 1251, 1132,
2
2
ꢀ
1
1 LC–MS (API-ESI,
CH CN–H O 19:1): m/z 363 ([M+Na] , 100), 309 (4),
123, 1065, 806, 780 cm
;
+
3
2
25
1
99 (31); ½aꢁD ¼ ꢀ37 (c 0.54, EtOH).
(25 mg, 43%).
1
4
.3.2. Sulcatol MaNP ester (S,S)-(+)-13b. H NMR
(
(
800 MHz, CDCl ): d 8.44 (1H, br d, J = 8 Hz), 7.82
1H, m), 7.81 (1H, br d, J = 8 Hz), 7.59 (1H, dd, J = 7,
1
3
4
.4.1. 1-Octen-3-ol MaNP ester (S,S)-(ꢀ)-14a.
H
NMR (500 MHz, CDCl ): d 8.38 (1H, m), 7.84 (1H,
3
1
Hz), 7.47 (1H, m), 7.45 (1H, m), 7.44 (1H, m), 4.86
1H, m), 4.71 (1H, br t, J = 7 Hz), 3.09 (3H, m), 1.98
m), 7.82 (1H, br d, J = 8 Hz), 7.63 (1H, dd, J = 7,
(
(
(
1
6
Hz), 7.48–7.42 (3H, m), 5.45 (1H, ddd, J = 17, 11,
Hz), 5.25 (1H, m), 4.80 (1H, dt, J = 11, 1 Hz), 4.66
3H, br s), 1.54 (3H, br d, J = 1 Hz), 1.3 (3H, m), 1.23
C
1
3
3H, br s), 1.2 (1H, m), 1.14 (3H d, J = 6 Hz);
(
1
1H, dt, J = 17, 1 Hz), 3.13 (3H, s), 2.00 (3H, s), 1.55–
.40 (2H, m), 1.25–1.05 (6H, m), 0.82 (3H, t,
NMR (126 MHz): d 173.79, 135.14, 134.05, 131.71,
1
1
2
1
31.44, 129.40, 128.62, 126.39, 125.70, 125.68, 125.35,
24.58, 123.22, 81.45, 71.92, 50.86, 35.61, 25.54, 23.22,
1.68, 19.71, 17.35; IR (KBr, neat): mmax 2973, 2932,
13
J = 7 Hz); C NMR (126 MHz, CDCl ): d 173.39,
3
1
1
5
35.78, 135.40, 134.03, 131.25, 129.34, 128.63, 126.33,
25.63, 125.52, 125.32, 124.68, 116.25, 81.67, 75.53,
1.02, 33.96, 31.39, 24.54, 22.43, 21.91, 13.94; IR
ꢀ1
743, 1734, 1250, 1133, 1122, 1066, 806, 780 cm ; LC–
+
MS (API-ESI, CH CN–H O 19:1): m/z 363 ([M+Na] ,
3
1
2
(
KBr, neat): mmax 2934, 2860, 1747, 1730, 1250, 1134,
27
00), 309 (2), 199 (8); ½aꢁD ¼ þ52 (c 0.46, EtOH).
ꢀ1
1121, 806, 779 cm
2
EtOH).
; LC–MS (API-ESI, CH CN–H O
3
2
+
28
D
4:1): 363 ([M+Na] , 100), 144 (6); ½aꢁ ¼ ꢀ5 (c 0.58,
4
.3.3. Sulcatol (R)-(ꢀ)-9. A mixture of ester (S,R)-(ꢀ)-
1
3a (73 mg) and 28% NaOMe/MeOH (1.5 mL) was re-
fluxed for 6 h under argon. The solution was diluted
with ice water, and extracted with CH Cl three times.
1
4
.4.2. 1-Octen-3-ol MaNP ester (S,R)-(+)-14b.
H
2
2
NMR (500 MHz, CDCl ): d 8.45 (1H, m), 7.86–7.80
2H, m), 7.59 (1H, dd, J = 7, 1 Hz), 7.49–7.43 (3H, m),
.66 (1H, ddd, J = 17, 11, 6 Hz), 5.21 (1H, m), 5.14
1H, dt, J = 17, 1 Hz), 5.08 (1H, dt, J = 11, 1 Hz), 3.10
The organic layer was washed with brine, dried over
anhydrous Na SO , and concentrated in vacuo. The
crude product was chromatographed over silica gel with
3
(
5
(
(
(
2
4
CH Cl to give sulcatol (R)-(ꢀ)-9 (19 mg, 69%):
2
2
2
6
3H, s), 2.00 (3H, s), 1.30–1.15 (2H, m), 0.95–0.72
4H, m), 0.67 (3H, t, J = 7 Hz), 0.60–0.40 (2H, m);
½
aꢁ ¼ ꢀ13 (c 0.19, EtOH). The aqueous layer was acid-
D
ified with 2 M HCl and extracted with CH Cl three
13
C
2
2
NMR (126 MHz, CDCl ): d 173.39, 136.16, 135.04,
34.04, 131.50, 129.41, 128.58, 126.43, 125.74, 125.69,
25.40, 124.58, 116.57, 81.44, 75.36, 50.84, 33.64,
times. The organic layer was washed with brine, dried
over anhydrous Na SO , and concentrated in vacuo giv-
3
1
1
3
2
2
4
ing MaNP acid (S)-(+)-4 (43 mg, 87%). The chiral
1.12, 23.70, 22.19, 21.60, 13.87; IR (KBr, neat): mmax
HPLC analysis (Chiralcel OD-RH, CH CN–H O 13:7)
of the (S)-MaNP acid methyl ester (prepared using
3
2
932, 2860, 1747, 1730, 1250, 1136, 1123, 806,
779 cm ; LC–MS (API-ESI, CH CN–H O 24:1): 363
2
ꢀ
1
2
3
2
M
revealed that (S)-(+)-4 recovered was enantiopure.
trimethylsilyldiazomethane
ether solution)
3
+
28
D
([M+Na] , 100); ½aꢁ ¼ þ9 (c 0.63, EtOH).
4
.3.4. Sulcatol (S)-(+)-9. Ester (S,S)-(+)-13b (60 mg)
was similarly hydrolyzed with 28% NaOMe/MeOH
1.5 mL) yielding sulcatol (S)-(+)-9 (21 mg, 93%):
4
.4.3. 1-Octen-3-ol (S)-(+)-10. (S,S)-(ꢀ)-14a (104 mg)
was similarly hydrolyzed with 28% NaOMe/MeOH
1.5 mL) yielding 1-octen-3-ol (S)-(+)-10 (30 mg, 77%):
(
(
27
26
½
aꢁ ¼ þ15 (c 0.21, EtOH), and enantiopure MaNP acid
D
S)-(+)-4 (37 mg, 91%).
½aꢁ ¼ þ19 (c 0.18, EtOH), and MaNP acid (S)-(+)-4
D
(
(67 mg, 95%). The chiral HPLC analysis of (S)-MaNP
acid methyl ester revealed that acid (S)-(+)-4 recovered
was enantiopure.
4
(
.3.5. Preparation of MaNP ester (S,R)-(ꢀ)-13a from
R)-(ꢀ)-sulcatol. Sulcatol (R)-(ꢀ)-9 (10 mg) was simi-
larly converted to MaNP ester (S,R)-(ꢀ)-13a (21 mg,
9%), which was identical with the authentic sample
described above.
4
.4.4. Preparation of MaNP ester (S,S)-(ꢀ)-14a from
S)-(+)-1-octen-3-ol. 1-Octen-3-ol (S)-(+)-10 (2 mg)
prepared above was esterified with MaNP acid (S)-(+)-
(60 mg) using EDC (121 mg) and DMAP (121 mg)
in CH Cl (0.5 mL). The crude product was chromato-
7
(
4
4
(
.3.6. Preparation of MaNP ester (S,S)-(+)-13b from (S)-
+)-sulcatol. Sulcatol (S)-(+)-9 (8 mg) was similarly
2
2
graphed over silica gel (1st CH Cl ; 2nd hexane/EtOAc)
2
2
converted to MaNP ester (S,S)-(+)-13b (18 mg, 85%),
which was identical with the authentic sample described
above.
giving ester (S,S)-(ꢀ)-14a (5 mg, 94%).
4
14b. Ester (S,R)-(+)-14b (30 mg) and 5% palladium–
.4.5. Hydrogenation of MaNP ester (S,R)-(+)-
4.4. Enantioresolution of (±)-1-octen-3-ol using MaNP
acid
carbon (11 mg) were stirred in EtOAc (2 mL) under
H for 3 h. The suspension was filtered through Celite,
2
A mixture of MaNP acid (S)-(+)-4 (39 mg), EDC
and concentrated in vacuo. The crude product was chro-
matographed on silica gel (Kieselgel 60, EtOAc) giving
ester (S,S)-(+)-11b (27 mg, 89%).
(
103 mg), DMAP (130 mg), and 1-octen-3-ol (±)-10
120 lL) in CH Cl (0.5 mL) was allowed to stand for
(
2
2

A. Ichikawa, H. Ono / Tetrahedron: Asymmetry 16 (2005) 2559–2568
2567
4.5. Enantioresolution of (±)-1-octen-3-ol using M9PP
acid
a silica gel cartridge (Wako Presep-C Silica Gel) and a
column chromatography (silica gel, hexane/EtOAc) giv-
ing ester (S,S)-(+)-15a (20 mg, 47%).
1
M9PP acid (S)-(+)-5 (53 mg) using DCC (112 mg),
-Octen-3-ol (±)-10 (120 lL) was similarly esterified with
4.5.5. 1-Octen-3-ol (R)-(ꢀ)-10. Ester (S,R)-(+)-15b
(85 mg) was hydrolyzed with 28% NaOMe/MeOH
(1.5 mL) giving 1-octen-3-ol (R)-(ꢀ)-10 (23 mg, 82%):
DMAP (123 mg), and CSA (26 mg) in CH Cl (0.5 mL)
2
2
yielding the first eluted ester (S,S)-(+)-15a (27 mg, 37%)
and the second eluted ester (S,R)-(+)-15b (32 mg, 43%).
2
7
½aꢁ ¼ ꢀ19 (c 0.23, EtOH), and M9PP acid (S)-(+)-5
D
(30 mg, 49%).
1
4
.5.1. 1-Octen-3-ol M9PP ester (S,S)-(+)-15a.
H
4
.5.6. Preparation of M9PP ester (S,R)-(+)-15b from
NMR (800 MHz, CDCl ): d 8.72 (1H, br d, J = 8 Hz),
3
(R)-(ꢀ)-1-octen-3-ol. 1-Octen-3-ol (R)-(ꢀ)-10 (10 mg)
was esterified with M9PP acid (S)-(+)-5 (25 mg) using
EDC (103 mg) and DMAP (127 mg) in CH Cl (0.6
2
mL). The crude product was chromatographed over
silica gel (1st CH Cl ; 2nd hexane/EtOAc) giving ester
8
.66 (1H, br d, J = 8 Hz), 8.44 (1H, dd, J = 8, 1 Hz),
7.91 (1H, br d, J = 8 Hz), 7.90 (1H, br s), 7.67 (1H,
ddd, J = 8, 7, 1 Hz), 7.63 (1H, ddd, J = 8, 7, 1 Hz),
2
7
1
4
3
.61 (1H, ddd, J = 8, 7, 1 Hz), 7.55 (1H, ddd, J = 8, 7,
Hz), 5.42 (1H, ddd, J = 17, 11, 6 Hz), 5.28 (1H, m),
.80 (1H, dt, J = 11, 1 Hz), 4.71 (1H, dt, J = 17, 1 Hz),
.16 (3H, s), 2.07 (3H, s), 1.52–1.40 (2H, m), 1.21–1.10
2
2
(
S,R)-(+)-15b (23 mg, 76%).
1
3
4
.5.7. Hydrogenation of M9PP ester (S,S)-(+)-
5a. Ester (S,S)-(+)-15a (20 mg) and 5% palladium–
(
6H, m), 0.80 (3H, t, J = 7 Hz); C NMR (201 MHz,
1
carbon (13 mg) were stirred in EtOAc (2 mL) under
CDCl ): d 173.45, 135.74, 133.76, 130.91, 130.82,
3
1
1
5
30.69, 130.08, 129.09, 127.22, 127.12, 126.85, 126.71,
26.41, 126.02, 122.94, 122.45, 116.50, 81.57, 75.72,
1.03, 33.92, 31.37, 24.59, 22.41, 21.93, 13.91; IR
H for 6 h. The suspension was filtrated, and purified
2
using HPLC (silica gel, hexane/EtOAc) giving ester
S,R)-(+)-12a (14 mg, 70%).
Acknowledgements
(
(
KBr, neat): m
2932, 2859, 1746, 1730, 1250, 1127,
max
ꢀ
50, 731 cm ; LC–MS (API-ESI, CH CN–H O 9:1):
3 2
28
1
7
4
0
+
13 ([M+Na] , 100), 359 (24), 249 (11); ½aꢁ ¼ þ32 (c
D
.49, EtOH).
The authors are indebted to Ms. Ikuko Maeda for
obtaining the NMR spectra.
1
4
.5.2. 1-Octen-3-ol M9PP ester (S,R)-(+)-15b.
H
NMR (800 MHz, CDCl ): d 8.71 (1H, br d, J = 8 Hz),
3
8
.66 (1H, br d, J = 8 Hz), 8.50 (1H, dd, J = 8, 1 Hz),
.91 (1H, br d, J = 8 Hz), 7.86 (1H, br s), 7.67 (1H,
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2
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3
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(
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1
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