Stereoselective double alkylation of the acetoacetate ester α-carbon on a D-glucose-derived template: Application to the synthesis of enantiopure cycloalkenones bearing an asymmetric quaternary carbon

Article abstract of DOI:10.1055/s-2007-967934

The previously developed D-glucose derivative, i.e., methyl 6-deoxy-2,3-di-O-(tert-butyldimethylsilyl)-α-D-glucopyranoside, served as a significant stereocontrolling element for the diastereoselective alkylation of the α-carbon in its acetoacetate at C-4

Full text of DOI:10.1055/s-2007-967934

LETTER
399
Stereoselective Double Alkylation of the Acetoacetate Ester a-Carbon on a
D-Glucose-Derived Template: Application to the Synthesis of Enantiopure
Cycloalkenones Bearing an Asymmetric Quaternary Carbon
S
tereose
l
ective
D
oub
u
le Alkylation
k
of anAceto
o
acetate
E
ster
a
-Car
K
bon ozawa, Yoko Akashi, Kumiko Takiguchi, Daisuke Sasaki, Daisuke Sawamoto, Ken-ichi Takao,
Kin-ichi Tadano*
Department of Applied Chemistry, Keio University, Hiyoshi, Yokohama 223-8522, Japan
Fax +81(45)5661571; E-mail: tadano@applc.keio.ac.jp
Received 11 November 2006
has been extensively investigated by the use of a transi-
tion-metal catalyst,5 an organocatalyst6 or chiral auxilia-
ries.7
Abstract: The previously developed D-glucose derivative, i.e.,
methyl 6-deoxy-2,3-di-O-(tert-butyldimethylsilyl)-a-D-glucopyra-
noside, served as a significant stereocontrolling element for the
diastereoselective alkylation of the a-carbon in its acetoacetate at
C-4 with two types of alkyl halides. The thus obtained doubly
alkylated acetoacetate moiety bearing both methyl and allyl groups
was efficiently converted into functionalized cycloalk-2-en-1-one
derivatives by means of an intramolecular aldol strategy. Further-
more, the synthetic utility of the cycloalkenones was exemplified
through the 1,4-addition to the thus obtained cyclopentenone
derivative.
We are interested in the use of the D-glucose-derived
chiral template 1 for the stereoselective construction of an
asymmetric quaternary carbon. We herein report the high-
ly stereoselective quaternization of the a-carbon in the 4-
O-acetoacetyl derivative of 1 by a double C-alkylation
strategy and the utilization of the resulting differentially
a-dialkylated acetoacetate for the synthesis of two cyclo-
alk-2-en-1-ones, both incorporating an asymmetric qua-
ternary carbon, connecting with 1. The starting 4-
acetoacetate 58 was prepared by the acylation of 1 with
2,2,6-trimethyl-1,3-dioxin-4-one in refluxing o-xylene
(Scheme 1). The acetoacetate 5 exists as a 3:1 mixture of
1,3-diketo and keto–enol forms. The C-methylation at the
a-carbon of this mixture 5 occurred by using K2CO3 as a
base with methyl iodide at 40 °C. The C-methylated prod-
uct 6 exists as a 5:2:2 mixture of three tautomeric forms,
as detected on the basis of 1H NMR analysis. We did not
characterize each form in this mixture but, rather, used the
second alkylation directly. We explored the second alky-
lation with benzyl bromide as an electrophile. After the
examination of several bases, we found that sodium meth-
oxide was the most effective base for this reaction.9 As a
result, the benzylated product 7 was obtained as a single
Key words: D-glucose derivatives, chiral auxiliary, double alkyla-
tion, asymmetric quaternization, intramolecular aldol reactions
In relation to the development of stereoselective carbon–
carbon bond-forming reactions realized in a chiral en-
vironment, we have been using sugar-based templates as
effective chiral auxiliaries.1 As a result, we have found
that a D-glucose derivative, i.e., methyl 6-deoxy-2,3-di-O-
(tert-butyldimethylsilyl)-a-D-glucopyranoside (1),2 pre-
pared from methyl a-D-glucopyranoside in six steps,
served as an effective chiral template for a variety of
carbon–carbon bond-forming reactions by using its 4-O-
propionyl ester (2),3 4-O-acryloyl ester (3),4 and 4-O-crot-
onyl ester (4)2,3a (Figure 1).
One of the highlights in current organic synthesis is the
development of the enantioselective construction of an
all-carbon asymmetric quaternary carbon center. For this
subject, the asymmetric induction of a quaternary carbon
1
diastereomer (based on H NMR analysis) in 75% yield.
We recognized that the order of this sequential alkylation
is essential for the observed high diastereoselectivity.
When the two alkylations were carried out in the order of
benzylation and methylation, the diastereomeric ratio for
the doubly alkylated product 7 was significantly changed,
with a decrease in the formation of 7.10 The absolute ste-
reochemistry of the newly introduced stereogenic carbon
in 7, i.e., the R-configuration as depicted, was established
by the following experiment. Treatment of 7 with hydra-
zine hydrate in EtOH at 140 °C provided a known pyrazo-
line derivative 811 in 88% yield.12 The sugar template 1
was also recovered in 87% yield. We then explored the al-
lylation of 6 for the second alkylation. The allylation pro-
ceeded with complete diastereoselectivity by using allyl
bromide as an electrophile, providing 9 in 80% yield as a
single diastereomer. The configuration of the new quater-
nary carbon in 9 was confirmed to be R, as depicted, on
the basis of converting 9 into a pyrazoline derivative 10 by
treatment of 9 with hydrazine hydrate as in the case of 7.13
O
O
HO
TBSO
O
O
TBSO
TBSO
TBSO
OMe
1
OMe
2
O
O
O
O
TBSO
O
O
TBSO
TBSO
OMe
TBSO
OMe
3
4
Figure 1 Previously used substrates for stereoselective carbon–
carbon bond-forming reactions
SYNLETT 2007, No. 3, pp 0399–0402
1
5.
0
2.
2
0
0
7
Advanced online publication: 07.02.2007
DOI: 10.1055/s-2007-967934; Art ID: U13306ST
© Georg Thieme Verlag Stuttgart · New York

400
I. Kozawa et al.
LETTER
We had experienced analogous high diastereoselectivi- >20:1 diastereomeric ratio. The newly introduced stereo-
ties, which were realized using the 4-O-acyl substrates 2– genic center at the allylic position was established after
4 for a variety of carbon–carbon bond-forming reactions. removal of the sugar template from 13. The hydride re-
We had also explained that these stereoselectivities were duction of 13 using excess DIBAL-H eventually removed
effectively brought by the existence of a bulky OTBS the sugar template, providing a 2-cyclopentenol deriva-
group installed at C-3 of 2–4, which disturbs the approach tive 1415,16 in a virtually enantiopure form, and the sugar
of reactive species to the reaction site installed at C-4 from template 1 was recovered.17
the front side, i.e., the side shielded by the OTBS group.
O
In the present case, base-mediated deprotonation from 6 is
likely to result in the exclusive formation of Z-enolate, as
shown in Scheme 2.3 In this transition state, the 3-O-TBS
group hinders the approach of the electrophile from the
front side. Consequently, the alkyl halides predominantly
approached from the rear side of the enolate as depicted.
Although we could not determine the geometry of the in-
termediary enolate by spectroscopic means, the aforemen-
tioned argument is most likely to explain the observed
diastereoselectivity in the second alkylation step.
O
O
O
O
O
Xc
Xc
O
O
a
b
Xc
O
CHO
9
11
12
OH
OH
O
d
c
Xc
12
OH
+
O
1
13
14
Scheme 3 Synthesis of a cyclopent-2-en-1-one derivative 12 and
removal of the sugar template. Reagents and conditions: (a) O3 (3%
O3 in O2), CH2Cl2, –78 °C, then PPh3, 95%; (b) DBU, DMF, 50 °C,
69%:(c) DIBAL-H, CH2Cl2, –78 °C, 79%, dr > 20:1; (d) DIBAL-H
(3 equiv, then 2 equiv), CH2Cl2, –78 °C to 0 °C, 61% for 14 and 59%
for 1 (recovery of 13, 20%).
Xc
O
O
O
HO
TBSO
a
b
Xc
O
TBSO
OMe
5
1
O
N
NH
O
O
O
R
We also explored the synthesis of the cyclohexenone ho-
mologue of 12, i.e. compound 18. This task was accom-
plished uneventfully by the analogous intramolecular
aldol condensation strategy used for the synthesis of 12
(Scheme 4). The Wittig carbon-elongation reaction of al-
dehyde 11 with the ylide prepared from Ph3PCH2OCH3Cl
provided an E/Z-mixture of methyl vinyl ether 15. Acid
hydrolysis of this mixture 15 afforded the one-carbon-
elongated aldehyde 16. When 16 was treated with DBU in
toluene at room temperature, the expected intramolecular
aldol reaction proceeded smoothly to afford the b-hydrox-
ylated cyclohexanone 17. Acetylation of 17 followed by
treatment of the resulting acetate with triethylamine
provided 18 in 74% from 16. 1,2-Hydride reduction of the
cyclohexenone 18 under Luche conditions18 provided
allylic alcohol 1919 virtually as a single product.20 Treat-
ment of 19 with excess DIBAL-H (two additions of a 5.0
equiv of DIBAL-H at –18 °C) resulted in the removal of
the sugar template, providing cyclohexenol bearing an
asymmetric quaternary carbon center 2021 in 83% yield.22
d
c
Xc
Xc
O
O
O
1
+
R
6
8 R = Bn
10 R = allyl
7 R = Bn
9 R = allyl
Scheme 1 Asymmetric quaternization of the a-carbon of acetoace-
tate 5. Reagents and conditions: (a) 2,2,6-trimethyl-1,3-dioxin-4-one,
o-xylene, reflux, 93%; (b) MeI, K2CO3, acetone, 40 °C, quantitative-
ly; (c) for 7: BnBr, MeONa, THF, –78 °C to r.t., 75%; for 9: allyl
bromide, MeONa, THF, 80%; (d) N2H4·H2O, EtOH, 140 °C (sealed
tube); 88% for 8 (87% for 1); quantitative yield for 10 (60% for 1).
We next investigated the synthetic utility of the differen-
tially a-disubstituted acetoacetate moiety in 9 as an enan-
tiopure building block. As one example for this aim, we
explored the transformation of 9 into a differentially 5,5-
disubstituted cyclopent-2-en-1-one 12 (Scheme 3). Ozo-
nolysis of the double bond in 9 followed by work-up with
PPh3 provided aldehyde 11, which was subjected to a
DBU-mediated intramolecular aldol condensation. The
desired cyclopentenone 1214 was obtained in 65% yield
over two steps. Then, the DIBAL-H reduction of 12 was
carried out at –78 °C, producing allylic alcohol 13 with a
To demonstrate the synthetic utility of the enantiopure
cycloalkenones 12 and 18, we explored the diastereo-
selectivity in the 1,4-additions of carbon nucleophiles to
RX
base
RX
O
O
M
O
O
O
R
O
Xc
O
Xc
O
O
O
O
TBSO
OMe
Si
6
7 R = Bn
9 R = allyl
RX
Scheme 2 A plausible transition state for the second alkylation of 6
Synlett 2007, No. 3, 399–402 © Thieme Stuttgart · New York

LETTER
Stereoselective Double Alkylation of the Acetoacetate Ester a-Carbon
401
O
O
O
O
O
O
Xc
Xc
O
Xc
O
b
O
a
c
11
HO
15
17
OHC
16
OMe
OH
OH
O
O
O
Xc
Xc
O
f
OH
d
e
O
17
+
1
20
18
19
Scheme 4 Synthesis of a cyclohex-2-en-1-one derivative 18 and removal of the sugar template from 18. Reagents and conditions:
(a) Ph3PCH2OMeCl, NaHMDS, THF, r.t., 84%; (b) CF3CO2H–H2O–CH2Cl2 (1:1:5), 0 °C, 96%; (c) DBU, toluene, r.t., dr = 1.3:1; (d) 1) Ac2O–
pyridine (1:1), r.t.; 2) Et3N, CH2Cl2, r.t., 74% from 16; (e) NaBH4, CeCl3·7H2O, MeOH–CH2Cl2 (1:1), –78 °C, 81%; (f) DIBAL-H (total
10 equiv), –18 °C to r.t., 83% for 20.
12 and 18 (Scheme 5). In the case of the cyclopentenone dr = 1.6:1 on the basis of the 1H NMR analysis of the in-
derivative 12, Me2CuLi as a carbon nucleophile attacked separable mixture (82% combined yield); R = i-Pr, dr =
in a 1,4-addition fashion with remarkable diastereoselec- 5.3:1 (48% combined yield); the configurations of the
tivity, providing 21 as a single adduct. The configuration newly created stereogenic centers for these adducts were
at newly introduced b-carbon in 21 was confirmed to be not determined]. Therefore, the superiority of 12 to 18 as
1
depicted by H NMR analysis, including a NOE experi- the substrate for the 1,4-addition of carbon nucleophiles is
ment, which revealed that two methyl groups on the cy- obvious.
clopentanone 21 are in a cis relationship.23 To evaluate the
role of the sugar template for effecting the stereoselectiv-
ity in the 1,4-addition to 12, we explored the 1,4-addition
of racemic 5-carboethoxy-5-methyl-2-cyclopenten-1-one
In conclusion, we have demonstrated the highly stereose-
lective quaternization of the a-carbon of acetoacetate ester
installed at C-4 of the sugar template 1. One of the doubly
alkylated products (9) thus obtained serves as a versatile
building block. For example, compound 9 was trans-
formed into cycloalk-2-en-1-ones 12 and 18, both bearing
a methyl and an alkoxycarbonyl group at C-5 and C-6, re-
spectively, by means of an intramolecular aldol strategy.
The synthetic utility of 12 was enhanced by the highly
stereoselective 1,4-addition of carbon nucleophiles to 12.
(racemic 22). The racemic 22 was prepared according to a
previous report.24 The 1,4-addition of a methyl nucleo-
phile to the racemic 22 under the same conditions used for
12 quantitatively provided the 1,4-adduct, racemic 23, as
an approximately 1:1 diastereomeric mixture. These re-
sults suggested the remarkable role of the sugar template
part in 12 as a stereocontrolling element for the exclusive
The further synthetic utilization of 12 and 18 for stereo-
diastereoselectivity observed in the 1,4-addition of carbon
selective carbon–carbon bond-forming reactions is our
nucleophiles to 12. Although we cannot propose a distinct
current concern.
transition-state model to account for these high stereose-
lectivities, further utilization of 12, such as the elaboration
References and Notes
of the enone part, is to be expected. On the other hand, the
1,4-addition of two alkylcuprates (R = Me or i-Pr) to the
cyclohexenone derivative 18 provided the corresponding
1,4-adducts 24. In contrast to the case of 12, the diastereo-
selectivities observed in 24 were low to modest [R = Me,
(1) Totani, K.; Takao, K.; Tadano, K. Synlett 2004, 2066.
(2) Munakata, R.; Totani, K.; Takao, K.; Tadano, K. Synlett
2000, 979.
(3) (a) Totani, K.; Asano, S.; Takao, K.; Tadano, K. Synlett
2001, 1772. (b) Asano, S.; Tamai, T.; Totani, K.; Takao, K.;
Tadano, K. Synlett 2003, 2252. (c) Sasaki, D.; Sawamoto,
D.; Takao, K.; Tadano, K.; Okue, M.; Ajito K.,
Heterocycles, 2007, 72, in press.
(4) (a) Nagatsuka, T.; Yamaguchi, S.; Totani, K.; Takao, K.;
Tadano, K. Synlett 2001, 481. (b) Nagatsuka, T.;
Yamaguchi, S.; Totani, K.; Takao, K.; Tadano, K. J.
Carbohydr. Chem. 2001, 20, 519. (c) Tamai, T.; Asano, S.;
Totani, K.; Takao, K.; Tadano, K. Synlett 2003, 1865.
(5) Some recent prominent papers on this subject: (a) Trost, B.
M.; Pissot-Soldermann, C.; Chen, I.; Schroeder, G. M. J.
Am. Chem. Soc. 2004, 126, 4480. (b) Trost, B. M.; Xu, J. J.
Am. Chem. Soc. 2005, 127, 2846. (c) Mohr, J. T.; Behenna,
D. C.; Harned, A. M.; Stoltz, B. M. Angew. Chem. Int. Ed.
2005, 44, 6924.
O
O
O
O
a
Xc
Xc
12
O
CH3
O
O
H3C
21
3.3% NOE
O
21
O
O
O
O
Xc
a
b
O
OEt
OEt
18
R
racemic 22
racemic 23
as a 1:1 mixture
24 R = Me or i-Pr
Scheme 5 1,4-Additions of alkylcuprates to 12 and 18. Reagents
and conditions: (a) MeLi (6 equiv), CuI (3 equiv), Et2O, –78 °C, 74%
for 21; quantitatively for racemic 23; (b) for R = Me same as (a); for
R = i-Pr, i-PrMgBr (6 equiv), CuBr·SMe2 (3 equiv), Et2O, –78 °C.
(6) Some recent prominent papers on this subject: (a) Bella,
M.; Jørgensen, K. A. J. Am. Chem. Soc. 2004, 126, 5672.
(b) Wilson, R. M.; Jen, W. S.; MacMillan, D. W. C. J. Am.
Chem. Soc. 2005, 127, 11616.
Synlett 2007, No. 3, 399–402 © Thieme Stuttgart · New York

402
I. Kozawa et al.
LETTER
(7) A recent review on this subject: Arya, P.; Qin, H.
Tetrahedron 2000, 56, 917.
1360 cm–1. HRMS (EI): m/z calcd for C22H39O7Si2 [M+ –
t-Bu]: 471.2234; found: 471.2233.
(8) All new compounds were fully characterized by spectral
means (1H NMR and 13C NMR, IR, and HRMS). Yields
refer to isolated products after purification by column
chromatography on silica gel.
(15) (1S,5S)-5-Hydroxymethyl-5-methyl-2-cyclopenten-1-ol
(14): TLC: Rf = 0.44 (EtOAc); [a]D23 +65.6 (c 0.14, CHCl3).
1H NMR (300 MHz, CDCl3): d = 1.09 (s, 3 H), 1.98 (d, 1 H,
J = 17.1 Hz), 2.48 (dd, 1 H, J = 17.1, 2.1 Hz), 3.63, 3.70 (2
d, each 1 H, J = 11.1 Hz), 4.44 (br s, 1 H), 5.74–5.76 (m, 1
H), 5.95–5.97 (m, 1 H). 13C NMR (68 MHz, CDCl3): d =
24.0, 41.9, 45.2, 68.3, 85.4, 131.6, 134.9. IR (neat): 3250,
3060, 2930, 1730, 1460 cm–1. HRMS (EI): m/z calcd for
C7H12O2 [M+]: 128.0837; found: 128.0841
(16) (a)(1S,5R)-5-Hydroxymethyl-5-methyl-2-cyclopenten-1-ol,
the 5-epimer of 14, is a known compound that was
synthesized by Kato and co-workers using a chiral acetal-
mediated asymmetric alkylation, see ref. 16b. The 1H NMR
and 13C NMR spectra of the 5-epimer were distinctly
different from those of 14. Furthermore, the NOE
experiment of the 5-epimer revealed a 2.9% signal
enhancement for the methylene of the hydroxymethyl group
at C-5 when the proton at C-1 (H-1) was irradiated. On the
other hand, the irradiation of H-1 in 14 resulted in a 1.3%
signal enhancement of the methyl protons at C-5. (b) Kato,
K.; Suzuki, H.; Tanaka, H.; Miyasaka, T.; Baba, M.;
Yamaguchi, K.; Akita, H. Chem. Pharm. Bull. 1999, 47,
1256.
(9) We examined the following bases for the second
benzylation, which was carried out in THF. The yield of 7
using NaHMDS (–78 °C to r.t.), 18%; using LiHMDS
(–18 °C to r.t.), 35%; and using NaH (–78 °C to r.t.), 74%.
(10) The yield of the first benzylation (BnBr, EtONa, THF, 0 °C
to r.t.) was 97%. The conditions and yields of the second
methylation for the two diastereomers, i.e., 7 and its epimer
at the a-carbon, were as follows: a) MeI and KHMDS in
THF at –18 °C to r.t., 46% and 10%; b) EtONa as the base at
–78 °C to r.t., 64% and 16%; c) MeONa as the base at –78 °C
to r.t., 63% and 14%. In all cases, the major product was 7.
(11) (a) (4R)-4-Benzyl-3,4-dimethyl-2-pyrazolin-5-one (8):
[a]D22 –186 (c 1.24, CHCl3). For the reported [a]D for 8
[a]D15 –186 (c 1.24, CHCl3) see ref. 11b. In this paper, the
Vallribera group reported the asymmetric construction of a
quaternary carbon using D-ribolactone acetonide or its
cyclohexanone ketal as a sugar-based chiral template. Their
sugar templates also served as good stereocontrolling
elements, which provided the doubly a-alkylated (both Me
and Bn) acetoacetates installed at C-5 in the sugar templates
in 56–69% yield with 80:20 to 75:25 diastereomeric ratios in
favor of the respective R-isomer. Thus, the diastereo-
selectivities observed in their cases were lower than those in
ours with the use of the pyranose-type template 1.
(b) Moreno-Mañas, M.; Trepat, E.; Sebastián, R. M.;
Vallribera, A. Tetrahedron: Asymmetry 1999, 10, 4211.
(12) We also synthesized the S-antipode of 8 from the minor a-
dialkylated acetoacetate obtained by the reverse double
alkylation of 5 with the same alkyl halides followed by the
analogous pyrazoline formation used for the case of 7. The
synthesized S-isomer possessed the following optical
rotation: [a]D21 +180 (c 0.30, CHCl3).
(13) (a) We synthesized the antipode of 10, i.e., (S)-10, as
follows. As a substrate for the pyrazoline formation,
enantioenriched ethyl (S)-2-acetyl-2-methyl-4-pentenoate
was prepared at first by the a-allylation of racemic ethyl 2-
methyl-acetoacetate using L-valine tert-butyl ester as a
chirality inducer, according to a known procedure reported
by Koga and co-workers, see ref. 13b. The thus obtained a-
disubstituted acetoacetate ester was then treated with
N2H4·H2O, providing enantioenriched (S)-10. The
(17) We explored the removal of the sugar template from 12
directly by methanolysis (MeONa in MeOH). In this case,
compound 12 was quantitatively recovered. The removal of
the sugar template from the protected forms of the allylic
alcohol 13 as its TBS or MOM ethers was also fruitless. For
these ethers, saponification or hydride attack resulted in the
recovery of the starting material.
(18) Gemal, A. L.; Luche, J. L. J. Am. Chem. Soc. 1981, 103,
5454.
(19) The configuration of newly introduced allylic carbinol
carbon in 19 as depicted was confirmed by the NOE
experiment in which a significant (7.3%) signal
enhancement of the proton at the allylic carbinol carbon was
observed when the adjacent methyl group was irradiated.
(20) The DIBAL-H reduction of 18 (1.5 equiv, CH2Cl2, –78 °C)
also provided 19 as a single product in a less effective yield
of 63%.
(21) The observed dextrorotatory property for 20 {[a]D21 +138,7
(c 0.355, CHCl3)} confirmed the absolute stereochemistry of
20. For the reported enantioenriched 20 (94% ee), [a]D
+104.1 (c 0.95, CHCl3) was reported, see: Mikami, K.;
Motoyama, Y.; Terada, M. J. Am. Chem. Soc. 1994, 116,
2812.
(22) In this case, the sugar template 1 was recovered in 19%
yield. Under the harsh DIBAL-H reduction of 19, the silyl
group at C-2 in 1 was unexpectedly deprotected to a large
extent. Thus, the 3-O-TBS derivative was obtained in a
significant yield of 75%.
(23) We also examined the 1,4-addition using n-Bu2CuLi under
analogous conditions as those used for the Me2CuLi
addition. The 1,4-addition proceeded with complete
stereoselectivity to provide a single 1,4-adduct in 75% yield.
Unfortunately, we could not establish the configuration at
the b-carbon of this adduct unambiguously from 1H NMR
spectral analysis.
(24) (a) Sato, K.; Suzuki, S.; Kojima, Y. J. Org. Chem. 1967, 32,
339. (b) Lee, K.-H.; Mar, E.-C.; Okamoto, M.; Hall, I. H. J.
Med. Chem. 1978, 21, 819. (c) Practically, we prepared
racemic 22 by the Ito–Saegusa oxidation of 2-methyl-2-
(carboethoxy)cyclopentanone for the introduction of the
C=C bond.
comparison of the sign and magnitude of the optical rotatory
property for (S)-10 {[a]D27 +128 (c 0.49, CHCl3)} with our
(R)-10 {[a]D26 –123 (c 0.78, CHCl3)} clearly established the
R-configuration for the new stereogenic carbon center in 9.
(b) Ando, K.; Takemasa, Y.; Tomioka, K.; Koga, K.
Tetrahedron 1993, 49, 1579.
25
(14) Compound 12: TLC: Rf = 0.50 (EtOAc–hexane, 1:3); [a]D
+64.1 (c 1.49, CHCl3). 1H NMR (300 MHz, CDCl3): d =
0.09, 0.10 (2 s, each 6 H), 0.84, 0.91 (2 s, each 9 H), 1.05 (d,
3 H, J = 6.3 Hz), 1.42 (s, 3 H), 2.53, 3.45 (2 ddd, each 1 H,
J = 19.2, 2.2, 2.2 Hz), 3.33 (s, 3 H), 3.56–3.64 (m, 1 H), 3.66
(dd, 1 H, J = 8.7, 3.5 Hz), 3.87 (t, 1 H, J = 8.7 Hz), 4.60 (d,
1 H, J = 3.5 Hz), 4.72 (dd, 1 H, J = 9.8, 8.7 Hz), 6.17 (ddd,
1 H, J = 5.6, 2.2, 2.2 Hz), 7.74 (ddd, 1 H, J = 5.6, 2.2, 2.2
Hz). 13C NMR (68 MHz, CDCl3): d = –4.2 × 2, –3.2, –2.6,
17.5, 17.9, 18.5, 21.9, 26.0 × 3, 26.2 × 3, 42.1, 53.7, 54.8,
65.3, 72.0, 74.6, 78.2, 99.8, 131.5, 163.0, 170.3, 205.8. IR
(neat): 2950, 2850, 2750, 2710, 1730, 1715, 1590, 1450,
Synlett 2007, No. 3, 399–402 © Thieme Stuttgart · New York