Application of modified Mosher's method for primary alcohols with a methyl group at C2 position.

Article abstract of DOI:10.1248/cpb.51.448

The absolute configurations of a series of primary alcohols possessing a branched methyl group at C2 position were examined on the basis of a modified Mosher's method proposed by Minale et al. It was revealed that in many cases the absolute configurations

Full text of DOI:10.1248/cpb.51.448

448
Notes
Chem. Pharm. Bull. 51(4) 448—451 (2003)
Vol. 51, No. 4
Application of Modified Mosher’s Method for Primary Alcohols with a
Methyl Group at C2 Position
Masashi TSUDA, Yuki TORIYABE, Tetsuya ENDO, and Jun’ichi KOBAYASHI*
Graduate School of Pharmaceutical Sciences, Hokkaido University; Sapporo 060–0812, Japan.
Received November 28, 2002; accepted January 10, 2003
The absolute configurations of a series of primary alcohols possessing a branched methyl group at C2 posi-
tion were examined on the basis of a modified Mosher’s method proposed by Minale et al. It was revealed that in
many cases the absolute configurations at C2 were assignable from the chemical shift differences of geminal pro-
tons of the methylene attached to the ester linkage in the a-methoxy-a-trifluoromethylphenylacetyl (MTPA) de-
rivatives. The scope and limitation of this method are described.
Key words absolute configuration; modified Mosher’s method; branched primary alcohols
Modified Mosher’s method using a-methoxy-a-trifluo- solute configurations at chiral centers attached to the methyl
romethylphenylacetyl (MTPA) esters has been recognized as group. For example, the absolute configuration at C14 of am-
a useful and reliable method for determination of absolute phidinolide T1 was elucidated on the basis of chemical shift
configurations of secondary alcohols and primary amines.1—3) differences and signal patterns of the geminal protons at C13
The absolute configurations at such methine carbons could of (S)- and (R)-MTPA esters of the C13–C21 segment10)
be determined by the regular arrangement: positive and nega- (Fig. 1). The methylene protons of C13 for the (R)-MTPA
tive chemical shift differences [Dd(dSꢀdR)] of the protons ester were observed as separated double doublet signals at dH
can be found on the right and left sides of the MTPA plane, 4.03 and 4.26 (Dd 0.23), while those for the (S)-MTPA ester
respectively. Nevertheless, it is difficult to assign the absolute appeared at dH 4.09 and 4.12 (Dd 0.03), indicating that ab-
configurations of tertiary and primary alcohols since of the solute configuration at C14 was R. However, this methodol-
irregular arrangements of the Dd values.1,4) Although at- ogy has not been substantiated by examination of compounds
tempts to assign the absolute stereochemistry of C2-chiral with known stereochemistry. Recently, we have applied this
primary alcohols using its MTPA esters have been demon- method for a series of primary alcohols with a C2-branched
strated, there is no conventional method applicable for a lim- methyl whose stereochemistry is known. In this paper we de-
ited amount of natural products.5)
scribe the scope and limitation of this methodology on the
Minale and coworkers have applied a Mosher’s method for basis of the present results.
determination of absolute stereochemistry of a methyl group
at C25 of steroids with a primary hydroxyl group at C26,6,7) Results and Discussion
and reported that the proton signals of the methylene (C26)
A series of primary alcohols (1—14) with a methyl group
attached to the ester linkage in the MTPA derivatives showed (Chart 1), whose absolute configurations are known, were
1
a unique split pattern as follows. In the H-NMR spectra of synthesized or obtained commercially, and they were con-
the (ꢁ)-(R)-MTPA esters, two 26-methylene protons of the verted into the corresponding (S)- and (R)-MTPA esters.
25S isomer were much closer [Dd(dlowꢀdhigh) ca. 0.04] to Chemical shifts of the oxymethylene protons in the (S)- and
each other than those (Dd ca. 0.14) of the 25R isomer, (R)-MTPA esters of each alcohol in CDCl3 were shown in
whereas in the (ꢀ)-(S)-MTPA esters, the mutual relation was Table 1, in which Dd values denoted chemical shift differ-
reverse. During our studies on stereochemistry of marine nat- ences between lower-field protons (dlow) and higher-field
ural products,8—12) we have applied this method for primary ones (dhigh) of the oxymethylenes. The (S)-MTPA esters of
alcohols with a branched methyl at C2, and proposed the ab- compounds 1—5 possessing 2S-configuration had relatively
Fig. 1. Signal Patterns of Methylene Protons at C13 of Bis-(S)- and Bis-(R)-MTPA Esters of C13–C21 Segment of Amphidinolide T1
* To whom correspondence should be addressed. e-mail: jkobay@pharm.hokudai.ac.jp
© 2003 Pharmaceutical Society of Japan

April 2003
449
Fig. 2. Signal Patterns of Methylene Protons at C1 of (S)- and (R)-MTPA
Esters of Primary Alcohol 4
different from other primary alcohols due to the order of pri-
ority between silicon and oxygen atoms.
For compounds 8—12 possessing an unsaturated group
such as carbonyl, conjugated ester, or phenyl group, the dif-
ferences between DdS and DdR were very small except for
that of 8. These observations might result from deshielding
effects by both of the phenyl group of MTPA esters and the
unsaturated moiety. In the cases of the (S)- and (R)-MTPA
esters of compounds 13 and 14 possessing two consecutive
chiral centers at C2 and C3, both DdS and DdR values were
relatively large. Furthermore, the difference between DdS and
DdR in 13 was fairly small (0.03 ppm). These phenomena
were supposed to come from interfere of free-rotation around
the C2–C3 bond, since the methylene protons at C1 of 13
showed a split pattern (d 3.25 and 3.20).
In the present study, we examined the relation between the
absolute configuration and oxymethylene proton chemical
shifts in the MTPA esters of simple primary alcohols (1—14)
with a C2-branched methyl. Like the case of compounds 1—
7, if the differences between DdS and DdR are relatively large
(ꢂ0.10 ppm) they allow the assignment of the absolute con-
figurations at the oxymethine carbons at C2. On the other
hand, like the case of compounds 8—14, if small differences
(ꢃ0.05 ppm) between DdS and DdR are observed, it may be
difficult to predict the absolute configurations by this
method. Particularly, this method could not be applied for
C2-branched primary alcohols with an conjugated group or a
consecutive chiral center at C3 like compounds 13 and 14.
Chart 1
Table 1. Chemical Shifts and Dd Values of Oxymethylene Protons of
MTPA Esters of Primary Alcohols with a Methyl Group at C2-Position (1—
14)
a)
a)
Compd.
MTPA
dlow
dhigh
Ddb)
1
2
S
R
S
R
S
R
S
R
S
R
S
R
S
R
S
R
S
R
S
R
S
R
S
R
S
4.24
4.17c)
4.25
4.16c)
4.24
4.17c)
4.26
4.17c)
4.23
4.15
4.22c)
4.28
4.18
4.24
4.28
4.21c)
4.22
4.22
4.44
4.46
4.52
4.49
4.49
4.52
4.38
4.41
4.27
4.35
4.09
4.10
4.10
4.06
0.15
0.00
0.15
0.00
0.14
0.00
0.20
0.00
0.14
0.05
0.00
0.13
0.00
0.15
0.17
0.00
0.10
0.11
0.08
0.11
0.20
0.15
0.15
0.20
0.06
0.09
0.10
0.26
3
4
5
4.10
4.10
6
4.15
7
4.09
4.11
8
9
4.12
4.11
4.36
4.35
4.32
4.34
4.34
4.32
4.32
4.32
4.17
4.09
10
11
12
13
14
Experimental
General Methods 1H-NMR spectra were recorded on a Bruker ARX-
500 spectrometer. FAB mass spectrum was obtained on a JEOL HX-110
spectrometer using nitrobenzyl alcohol as a matrix.
Preparation of MTPA Esters To a CH2Cl2 solution (500 ml) of alco-
hols (1 mg) was added 4-dimethylaminopyridine (0.05 mg), triethylamine
(50 ml), and (R)-(ꢀ)- or (S)-(ꢁ)-MTPACl (30 ml) at room temperature, and
stirring was continued for 6 h. N,N-Dimethyl-1,3-propanediamine (30 ml)
was added, and the reaction mixture was stirred for 10 min. After addition of
phosphate buffer, the reaction mixture was evaporated in vacuo. The residue
was subjected to a SiO2 column with hexane/acetone solvent system to af-
ford an MTPA ester.
R
S
R
a) In CDCl3. b) dlowꢀdhigh
.
c) 2H equivalent.
(S)-MTPA Ester of 1: FAB-MS [MꢁH]ꢁ m/z 305; HR-FAB-MS [MꢁH]ꢁ
m/z 305.1360 (Calcd for C15H20F3O3: 305.1364); 1H-NMR (CDCl3) d: 0.909
(3H, t, Jꢄ7.4 Hz), 0.913 (3H, d, Jꢄ6.8 Hz), 1.20 (1H, m), 1.41 (1H, m),
1.76 (1H, m), 3.55 (3H, s), 4.09 (1H, dd, Jꢄ6.7, 10.7 Hz), 4.24 (1H, dd,
Jꢄ5.7, 10.7 Hz), 7.39 (3H, m), and 7.52 (2H, m).
larger Dd values (0.20—0.14) rather than those (0—0.05) of
the (R)-MTPA esters. The typical signal pattern of oxymeth-
ylene protons was shown in Fig. 2. The Dd values observed
for the (S)- and (R)-MTPA esters of 6 with 2R-configuration
were 0 and 0.13, respectively. These results corresponded
well to the Minale’s proposal.6,7) On the other hand, the (S)-
and (R)-MTPA esters of compound 7 possessing 2S-configu-
ration showed opposite pattern: DdS (0) was smaller than
(R)-MTPA Ester of 1: FAB-MS [MꢁH]ꢁ m/z 305; HR-FAB-MS [MꢁH]ꢁ
1
m/z 305.1372 (Calcd for C15H20F3O3: 305.1364); H-NMR (CDCl3) d: 0.89
(3H, t, Jꢄ7.4 Hz), 0.91 (3H, d, Jꢄ6.8 Hz), 1.20 (1H, m), 1.38 (1H, m), 1.77
(1H, m), 3.55 (3H, s), 4.17 (2H, m), 7.40 (3H, m), and 7.52 (2H, m).
(S)-MTPA Ester of 2: FAB-MS [MꢁH]ꢁ m/z 361; HR-FAB-MS [MꢁH]ꢁ
1
m/z 361.2002 (Calcd for C19H28F3O3: 361.1991); H-NMR (CDCl3) d: 0.89
DdR (0.15). Neverthless, the absolute configuration of 7 was (3H, t, Jꢄ7.4 Hz), 0.91 (3H, d, Jꢄ6.8 Hz), 1.30 (10H, m), 1.76 (1H, m),

450
Vol. 51, No. 4
7.51 (2H, m).
3.55 (3H, s), 4.10 (1H, dd, Jꢄ6.7, 10.7 Hz), 4.25 (1H, dd, Jꢄ5.7, 10.7 Hz),
7.39 (3H, m), and 7.52 (2H, m).
(R)-MTPA Ester of 9: FAB-MS [MꢁH]ꢁ m/z 389; HR-FAB-MS [MꢁH]ꢁ
1
(R)-MTPA Ester of 2: FAB-MS [MꢁH]ꢁ m/z 361; HR-FAB-MS [MꢁH]ꢁ
m/z 389.1579 (Calcd for C19H24F3O5: 389.1576); H-NMR (CDCl3) d: 0.97
1
(3H, d, Jꢄ6.8 Hz), 1.29 (3H, t, Jꢄ7.0 Hz), 2.12 (2H, m), 2.24 (1H, m), 3.54
(3H, s), 4.11 (1H, dd, Jꢄ5.7, 10.9 Hz), 4.18 (2H, q, Jꢄ7.0 Hz), 4.22 (1H, dd,
Jꢄ5.9, 10.9 Hz), 5.78 (1H, d, Jꢄ15.5 Hz), 6.85 (1H, m), 7.41 (3H, m), and
7.51 (2H, m).
m/z 361.1990 (Calcd for C19H28F3O3: 361.1991); H-NMR (CDCl3) d: 0.89
(3H, t, Jꢄ7.4 Hz), 0.91 (3H, d, Jꢄ6.8 Hz), 1.20 (10H, m), 1.77 (1H, m),
3.55 (3H, s), 4.16 (2H, m), 7.40 (3H, m), and 7.52 (2H, m).
(S)-MTPA Ester of 3: FAB-MS [MꢁH]ꢁ m/z 389; HR-FAB-MS [MꢁH]ꢁ
(S)-MTPA Ester of 10: FAB-MS [MꢁH]ꢁ m/z 335; HR-FAB-MS
[MꢁH]ꢁ m/z 335.1114 (Calcd for C15H18F3O5: 335.1106); 1H-NMR
(CDCl3) d: 1.24 (3H, d, Jꢄ6.8 Hz), 2.58 (1H, m), 3.55 (3H, s), 3.67 (3H, s),
4.36 (1H, dd, Jꢄ5.4, 10.8 Hz), 4.44 (1H, dd, Jꢄ5.8, 10.8 Hz), 7.41 (3H, m),
and 7.51 (2H, m).
1
m/z 389.2312 (Calcd for C21H32F3O3: 389.2303); H-NMR (CDCl3) d: 0.89
(3H, t, Jꢄ7.4 Hz), 0.91 (3H, 3H, d, Jꢄ6.8 Hz), 1.30 (14H, m), 1.76 (1H, m),
3.55 (3H, s), 4.10 (1H, dd, Jꢄ6.7, 10.7 Hz), 4.24 (1H, dd, Jꢄ5.7, 10.7 Hz),
7.39 (3H, m), and 7.52 (2H, m).
(R)-MTPA Ester of 3: FAB-MS [MꢁH]ꢁ m/z 389; HR-FAB-MS [MꢁH]ꢁ
(R)-MTPA Ester of 10: FAB-MS [MꢁH]ꢁ m/z 335; HR-FAB-MS
[MꢁH]ꢁ m/z 335.1101 (Calcd for C15H18F3O5: 335.1106); 1H-NMR
(CDCl3) d: 1.25 (3H, d, Jꢄ6.9 Hz), 2.59 (1H, m), 3.55 (3H, s), 3.67 (3H, s),
4.35 (1H, dd, Jꢄ5.3, 10.9 Hz), 4.46 (1H, dd, Jꢄ5.8, 10.9 Hz), 7.41 (3H, m),
and 7.51 (2H, m).
1
m/z 389.2308 (Calcd for C21H32F3O3: 389.2303); H-NMR (CDCl3) d: 0.90
(3H, t, Jꢄ7.4 Hz), 0.91 (3H, 3H, d, Jꢄ6.7 Hz), 1.30 (14H, m), 1.77 (1H, m),
3.55 (3H, s), 4.17 (2H, m), 7.40 (3H, m), and 7.52 (2H, m).
(S)-MTPA Ester of 4: FAB-MS [MꢁH]ꢁ m/z 345; HR-FAB-MS [MꢁH]ꢁ
1
m/z 345.1665 (Calcd for C18H24F3O3: 345.1677); H-NMR (CDCl3) d: 0.90
(S)-MTPA Ester of 11: FAB-MS [MꢁH]ꢁ m/z 353; HR-FAB-MS
[MꢁH]ꢁ m/z 353.1370 (Calcd for C19H20F3O3: 353.1364); 1H-NMR
(CDCl3) d: 1.30 (2H, d, Jꢄ6.9 Hz), 3.19 (1H, m), 3.43 (3H, s), 4.32 (1H, dd,
Jꢄ7.0, 10.8 Hz), 4.52 (1H, dd, Jꢄ6.7, 10.8 Hz), and 7.20—7.42 (10H, m).
(R)-MTPA Ester of 11: FAB-MS [MꢁH]ꢁ m/z 353; HR-FAB-MS
[MꢁH]ꢁ m/z 353.1360 (Calcd for C19H20F3O3: 353.1364); 1H-NMR
(CDCl3) d: 1.41 (2H, d, Jꢄ6.9 Hz), 3.17 (1H, m), 3.40 (3H, s), 4.34 (1H, dd,
Jꢄ6.8, 11.0 Hz), 4.49 (1H, dd, Jꢄ7.5, 11.0 Hz), and 7.19—7.39 (10H, m).
(S)-MTPA Ester of 12: FAB-MS [MꢁH]ꢁ m/z 353; HR-FAB-MS
[MꢁH]ꢁ m/z 353.1362 (Calcd for C19H20F3O3: 353.1364); 1H-NMR
(CDCl3) d: 1.41 (2H, d, Jꢄ6.9 Hz), 3.17 (1H, m), 3.40 (3H, s), 4.34 (1H, dd,
Jꢄ6.8, 11.0 Hz), 4.49 (1H, dd, Jꢄ7.5, 11.0 Hz), and 7.19—7.39 (10H, m).
(R)-MTPA Ester of 12: FAB-MS [MꢁH]ꢁ m/z 353; HR-FAB-MS
[MꢁH]ꢁ m/z 353.1366 (Calcd for C19H20F3O3: 353.1364); 1H-NMR
(CDCl3) d: 1.30 (2H, d, Jꢄ6.9 Hz), 3.19 (1H, m), 3.43 (3H, s), 4.32 (1H, dd,
Jꢄ7.0, 10.8 Hz), 4.52 (1H, dd, Jꢄ6.7, 10.8 Hz), and 7.20—7.42 (10H, m).
(S)-MTPA Ester of 13: FAB-MS [MꢁH]ꢁ m/z 391; HR-FAB-MS
[MꢁH]ꢁ m/z 391.1736 (Calcd for C19H26F3O5: 391.1732); 1H-NMR
(CDCl3) d: 0.92 (3H, d, Jꢄ7.1 Hz), 1.30 (3H, s), 1.34 (3H, s), 1.45 (1H, m),
1.55 (1H, m), 1.87 (1H, m), 3.55 (3H, s), 3.66 (1H, m), 3.83 (1H, m), 3.89
(1H, m), 4.32 (1H, dd, Jꢄ3.9, 10.7 Hz), 4.38 (1H, dd, Jꢄ5.5, 10.7 Hz), 7.40
(3H, m), and 7.52 (2H, m).
(3H, d, Jꢄ6.7 Hz), 1.00 (3H, t, Jꢄ7.4 Hz), 1.88 (1H, m), 1.98 (2H, q,
Jꢄ7.4 Hz), 2.09 (2H, m), 3.55 (3H, s), 4.06 (1H, dd, Jꢄ6.3, 10.9 Hz), 4.26
(1H, dd, Jꢄ5.1, 10.9 Hz), 4.69 (1H, s), 4.79 (1H, s), 7.40 (3H, m), and 7.52
(2H, m).
(R)-MTPA Ester of 4: FAB-MS [MꢁH]ꢁ m/z 345; HR-FAB-MS [MꢁH]ꢁ
1
m/z 345.1672 (Calcd for C18H24F3O3: 345.1677); H-NMR (CDCl3) d: 0.93
(3H, d, Jꢄ6.7 Hz), 1.00 (3H, t, Jꢄ7.4 Hz), 1.87 (1H, m), 1.96 (2H, q,
Jꢄ7.4 Hz), 2.08 (2H, m), 3.55 (3H, s), 4.17 (2H, m), 4.66 (1H, s), 4.78 (1H,
s), 7.40 (3H, m), and 7.52 (2H, m).
(S)-MTPA Ester of 5: FAB-MS [MꢁH]ꢁ m/z 391; HR-FAB-MS [MꢁH]ꢁ
1
m/z 391.1728 (Calcd for C19H26F3O5: 391.1732); H-NMR (CDCl3) d: 0.93
(3H, d, Jꢄ6.7 Hz), 1.25 (3H, t, Jꢄ7.2 Hz), 1.19 (1H, m), 1.37 (1H, m), 1.59
(1H, m), 1.68 (1H, m), 1.87 (1H, m), 2.25 (2H, t, Jꢄ7.5 Hz), 3.55 (3H, s),
4.10 (1H, dd, Jꢄ6.0, 10.7 Hz), 4.11 (2H, q, Jꢄ7.2 Hz), 4.23 (1H, dd, Jꢄ3.1,
10.7 Hz), 7.40 (3H, m), and 7.52 (2H, m).
(R)-MTPA Ester of 5: FAB-MS [MꢁH]ꢁ m/z 391; HR-FAB-MS [MꢁH]ꢁ
1
m/z 391.1737 (Calcd for C19H26F3O5: 391.1732); H-NMR (CDCl3) d: 0.93
(3H, d, Jꢄ6.8 Hz), 1.25 (3H, t, Jꢄ7.2 Hz), 1.17 (1H, m), 1.36 (1H, m), 1.57
(1H, m), 1.69 (1H, m), 1.86 (1H, m), 2.24 (2H, dt, Jꢄ2.1, 7.0 Hz), 3.55 (3H,
s), 4.10 (1H, dd, Jꢄ6.3, 10.9 Hz), 4.14 (2H, q, Jꢄ7.2 Hz), 4.15 (1H, dd,
Jꢄ5.1, 10.7 Hz), 7.40 (3H, m), and 7.47 (2H, m).
(S)-MTPA Ester of 6: FAB-MS [MꢁH]ꢁ m/z 391; HR-FAB-MS [MꢁH]ꢁ
(R)-MTPA Ester of 13: FAB-MS [MꢁH]ꢁ m/z 391; HR-FAB-MS
[MꢁH]ꢁ m/z 391.1735 (Calcd for C19H26F3O5: 391.1732); 1H-NMR
(CDCl3) d: 0.90 (3H, d, Jꢄ6.9 Hz), 1.36 (6H, s), 1.46 (1H, m), 1.55 (1H, m),
1.89 (1H, m), 3.55 (3H, s), 3.69 (1H, m), 3.85 (1H, m), 3.90 (1H, m), 4.32
(1H, dd, Jꢄ3.9, 10.7 Hz), 4.41 (1H, dd, Jꢄ5.5, 10.7 Hz), 7.40 (3H, m), and
7.52 (2H, m).
1
m/z 391.1741 (Calcd for C19H26F3O5: 391.1732); H-NMR (CDCl3) d: 0.97
(3H, d, Jꢄ6.9 Hz), 1.33 (3H, s), 1.37 (3H, s), 1.63 (2H, m), 2.09 (1H, m),
3.45 (1H, t, Jꢄ7.0 Hz), 3.55 (3H, s), 4.02 (1H, dd, Jꢄ5.9, 7.8 Hz), 4.13 (1H,
m), 4.22 (2H, m), 7.41 (3H, m), and 7.52 (2H, m).
(R)-MTPA Ester of 6: FAB-MS [MꢁH]ꢁ m/z 391; HR-FAB-MS [MꢁH]ꢁ
1
m/z 391.1729 (Calcd for C19H26F3O5: 391.1732); H-NMR (CDCl3) d: 0.98
(S)-MTPA Ester of 14: FAB-MS [MꢁH]ꢁ m/z 347; HR-FAB-MS
[MꢁH]ꢁ m/z 347.1829 (Calcd for C18H26F3O3: 347.1834); 1H-NMR
(CDCl3) d: 0.84 (9H, m), 1.07 (1H, m), 1.18 (1H, m), 1.27 (1H, m), 1.36
(1H, m), 1.47 (1H, m), 1.80 (1H, m), 3.55 (3H, s), 4.17 (1H, dd, Jꢄ7.5,
10.8 Hz), 4.27 (1H, dd, Jꢄ5.6, 10.8 Hz), 7.40 (3H, m), and 7.52 (3H, m).
(R)-MTPA Ester of 14: FAB-MS [MꢁH]ꢁ m/z 347; HR-FAB-MS
[MꢁH]ꢁ m/z 347.1838 (Calcd for C18H26F3O3: 347.1834); 1H-NMR
(CDCl3) d: 0.83 (9H, m), 1.08 (1H, m), 1.18 (1H, m), 1.28 (1H, m), 1.35
(1H, m), 1.48 (1H, m), 1.80 (1H, m), 3.55 (3H, s), 4.09 (1H, dd, Jꢄ7.6,
10.8 Hz), 4.35 (1H, dd, Jꢄ5.6, 10.8 Hz), 7.40 (3H, m), and 7.52 (3H, m).
(3H, d, Jꢄ6.9 Hz), 1.33 (3H, s), 1.37 (3H, s), 1.64 (1H, m), 2.10 (1H, m),
3.45 (1H, t, Jꢄ7.5 Hz), 3.55 (3H, s), 4.03 (1H, dd, Jꢄ6.0, 7.9 Hz), 4.14 (1H,
m), 4.15 (1H, dd, Jꢄ6.3, 10.8 Hz), 4.28 (1H, dd, Jꢄ5.7, 10.8 Hz), 7.40 (3H,
m), and 7.52 (2H, m).
(S)-MTPA Ester of 7: FAB-MS [MꢁH]ꢁ m/z 421; HR-FAB-MS [MꢁH]ꢁ
m/z 421.2016 (Calcd for C20H32F3O4Si: 421.2022); 1H-NMR (CDCl3) d:
0.00 (6H, s), 0.89 (12H, m), 1.96 (1H, m), 3.45 (2H, m), 3.55 (3H, s), 4.18
(2H, m), 7.41 (3H, m), and 7.52 (2H, m).
(R)-MTPA Ester of 7: FAB-MS [MꢁH]ꢁ m/z 421; HR-FAB-MS [MꢁH]ꢁ
m/z 421.2026 (Calcd for C20H32F3O4Si: 421.2022); 1H-NMR (CDCl3) d:
0.00 (6H, s), 0.88 (12H, m), 1.95 (1H, m), 3.46 (2H, m), 3.55 (3H, s), 4.09
(1H, dd, Jꢄ5.9, 7.8 Hz), 4.24 (1H, dd, Jꢄ5.7, 10.8 Hz), 7.41 (3H, m), and
7.52 (2H, m).
Acknowledgments This work was partly supported by a Grant-in-Aid
for Scientific Research from the Ministry of Education, Culture, Sports, Sci-
ence, and Technology of Japan.
(S)-MTPA Ester of 8: FAB-MS [MꢁH]ꢁ m/z 389; HR-FAB-MS [MꢁH]ꢁ
1
m/z 389.1574 (Calcd for C19H24F3O5: 389.1576); H-NMR (CDCl3) d: 0.96
References
(3H, d, Jꢄ6.8 Hz), 1.28 (3H, t, Jꢄ7.0 Hz), 2.05 (1H, m), 2.65 (2H, t,
Jꢄ7.3 Hz), 3.55 (3H, s), 4.11 (1H, dd, Jꢄ6.8, 10.8 Hz), 4.16 (2H, q,
Jꢄ7.0 Hz), 4.28 (1H, dd, Jꢄ5.7, 10.8 Hz), 5.83 (1H, d, Jꢄ11.6 Hz), 6.17
(1H, m), 7.40 (3H, m), and 7.51 (2H, m).
1) Ohtani I., Kusumi T., Kashman Y., Kakisawa H., J. Am. Chem. Soc.,
113, 4092—4095 (1991).
2) Kusumi T., Hamada T., Ishitsuka M. O., Ohtani I., Kakisawa H., J.
Org. Chem., 57, 1033—1035 (1992).
3) Kusumi T., Fukushima T., Ohtani I., Kakisawa H., Tetrahedron Lett.,
32, 2939—2942 (1991).
4) Latypov S. K., Ferreiro M. J., Quiñoá E., Riguera R., J. Am. Chem.
Soc., 120, 4741—4751 (1998).
5) Yasuhara F., Yamaguchi S., Tetrahedron Lett., 47, 4085—4088 (1977).
6) De Riccardis F., Minale L., Riccio R., Giovannitti B., Iorizzi M., Debi-
tus C., Gazz. Chim. Ital., 123, 79—86 (1993).
7) Finamore E., Minale L., Riccio R., Rinaldo G., Zollo F., J. Org. Chem.,
56, 1146—1153 (1991).
(R)-MTPA Ester of 8: FAB-MS [MꢁH]ꢁ m/z 389; HR-FAB-MS [MꢁH]ꢁ
1
m/z 389.1576 (Calcd for C19H24F3O5: 389.1576); H-NMR (CDCl3) d: 0.97
(3H, d, Jꢄ6.8 Hz), 1.28 (3H, t, Jꢄ7.0 Hz), 2.05 (1H, m), 2.65 (2H, t,
Jꢄ7.3 Hz), 3.55 (3H, s), 4.16 (2H, q, Jꢄ7.0 Hz), 4.21 (2H, m), 5.82 (1H, d,
Jꢄ11.6 Hz), 6.16 (1H, m), 7.40 (3H, m), and 7.51 (2H, m).
(S)-MTPA Ester of 9: FAB-MS [MꢁH]ꢁ m/z 389; HR-FAB-MS [MꢁH]ꢁ
1
m/z 389.1581 (Calcd for C19H24F3O5: 389.1576); H-NMR (CDCl3) d: 0.96
(3H, d, Jꢄ6.8 Hz), 1.29 (3H, t, Jꢄ7.0 Hz), 2.08 (2H, m), 2.27 (1H, m), 3.54
(3H, s), 4.12 (1H, dd, Jꢄ5.4, 10.8 Hz), 4.19 (2H, q, Jꢄ7.0 Hz), 4.22 (1H, dd,
Jꢄ5.8, 10.8 Hz), 5.80 (1H, d, Jꢄ15.5 Hz), 6.87 (1H, m), 7.40 (3H, m), and

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451
8) Fontana A., Ishibashi M., Kobayashi J., Tetrahedron, 54, 2041—2048
11) Kobayashi J., Kubota T., Endo T., Tsuda M., J. Org. Chem., 66, 134—
(1998).
142 (2001).
9) Shigemori H., Sato Y., Kagata T., Kobayashi J., J. Nat. Prod., 62,
12) Kubota T., Tsuda M., Kobayashi J., Org. Lett., 3, 1363—1366 (2001).
13) Kubota T., Tsuda M., Kobayashi J., J. Org. Chem., 67, 1651—1656
(2002).
372—374 (1999).
10) Tsuda M., Endo T., Kobayashi J., J. Org. Chem., 65, 1349—1352
(2000).