Two novel approaches toward stereoselective introduction of β-hydroxymethyl group at the C-7 position of 5-androstene

Article abstract of DOI:10.1055/s-2006-926356

Two novel approaches to stereoselective introduction of 7β-hydroxymethyl group onto 5-androstene have been developed. In the first approach, coupling of benzyloxymethyl chloride with the 7-carbonyl group of 1 mediated by SmI₂ gives, after deben

Full text of DOI:10.1055/s-2006-926356

PAPER
975
Two Novel Approaches toward Stereoselective Introduction of b-Hydroxy-
methyl Group at the C-7 Position of 5-Androstene
b
Q
-Hydroxymethyl
i
G
roup
ni n Steroids Gu, Yun-Hong Zheng, Yuan-Chao Li*
Institute of Materia Medica, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 555 Zu Cong Zhi Road,
Zhangjiang Hi-Tech Park, Shanghai 201203, P. R. of China
Fax +86(21)50807288; E-mail: ycli@mail.shcnc.ac.cn
Received 28 September 2005; revised 14 November 2005
The first approach to the stereoselective introduction of
Abstract: Two novel approaches to stereoselective introduction of
7
b-hydroxymethyl in androstene was carried out as
7
b-hydroxymethyl group onto 5-androstene have been developed.
shown in Scheme 1. Coupling of benzyloxymethyl chlo-
In the first approach, coupling of benzyloxymethyl chloride with
ride, which is a potential hydroxymethylation reagent,6
the 7-carbonyl group of 1 mediated by SmI gives, after debenzyla-
2
tion, two isomers 4 and 5 respectively, which are stereoselectively with androst-5-en-7-one 1 mediated by SmI afforded 2
2
deoxygenated by means of an ionic hydrogenation to afford 6. The and 3 with a stereo ratio of 1:3.53 in 63% overall yield.
second approach involves the addition of (isopropoxydimethylsi-
These two diastereomers could be separated carefully by
lyl)methyl Grignard reagent (Tamao’s reagent) to the 7-carbonyl
silica gel column chromatography. Reductive cleavage of
group of 1, followed by oxidative cleavage of the silicon–carbon
the benzyl ether of 2 and 3 with radical anion of biphenyl
bond by hydrogen peroxide giving compound 5. Stereoselective
afforded 7a-OH isomer 4 in 84% yield and 7b-OH isomer
5 in 81% yield, respectively.7
deoxygenation of 5 via an ionic hydrogenation also affords 6. The
relative configuration of 6 is confirmed by ROESY studies.
Key words: steroids, stereoselective, 7b-hydroxymethyl, 5-andros- The structural assignments of the 7a-OH and 7b-OH iso-
13
tene, ionic hydrogenation
mers were determined by C NMR spectra. It has been re-
ported that the chemical shift of the C-7 carbon depends
on the orientation of the hydroxyl group; i.e., that an axial
The introduction of 7a-substituted group in steroids has hydroxyl group shields the a-carbon atom more than does
been widely investigated; especially some 7a-methyl de- the corresponding equatorial substituent.4 The axial 7a-
,8
1
–3
rivatives. However, the stereoselective synthesis of 7b- OH isomer 2 and the equatorial 7b-OH isomer 3 showed
1
3
substituted steroids has not been extensively studied. Re-
C NMR signals for C-7 at d = 71.5 and 74.3, respective-
13
cently, we have reported novel stereoselective introduc- ly. Compounds 4 and 5 showed C NMR signals for C-7
tion of 7b-methyl substituent in androstenes. Continuous at d = 72.3 and 73.7, respectively.
4
interests in our laboratories prompt us to synthesize some
Ionic hydrogenation with triethylsilane is an effective
method to reduce tertiary alcohols and has already been
7
b-hydroxymethyl-substituted androstene derivatives.
In 1981, Nickisch et al. reported that 7b-hydroxymethyl used in the stereoselective reduction of hydroxylated ste-
9
derivatives of steroids could be stereoselectively synthe- roids. When a mixture of compound 4 and 5 was treated
sized using 3-(6-chloro-17b-hydroxy-3-oxo-4,6-androst- with triethylsilane and boron trifluoride etherate, the 7-hy-
dien-17a-yl)propionic acid g-lactone as starting material5, droxy group was cleanly reduced affording the desired
but the yield was low (16.6% overall yield in four steps).
In this paper, we wish to report two simple and highly ste- yield with 96% de, which was determined by integration
7b-hydroxymethyl-5-androstene derivative 6 in 95%
1
reoselective approaches to the introduction of b-hy- of the H NMR of the crude reaction products. The silyl
droxymethyl at the C-7 position of steroids, using 3b,17b- ether groups at C-3 and C-17 of 4 and 5 were also easily
bis(tert-butyldimethylsilyloxy)-5-androsten-7-one (1) as removed under the deoxygenation conditions. The rela-
the starting material. One approach involves the coupling tive configuration of 6 at the C-7 position was determined
of benzyloxymethyl chloride with the 7-carbonyl group by means of ROESY experiments. From the ROESY
mediated by SmI to give two isomers, followed by de- spectrum, the cross peaks between 7-H/9-H and 7-H/14-H
2
benzylation, and the stereoselective deoxygenation of the and the absence of the Overhauser effects between 7-H
7
-hydroxy steroids by means of an ionic hydrogenation. and 8-H (Figure 1) indicated the b orientation of 7-hy-
The other approach includes the addition of Tamao’s re- droxymethyl group in compound 6.
agent to the 7-carbonyl group to give a single isomer, fol-
lowed by oxidative cleavage of the corresponding silicon–
carbon bond, and the stereoselective deoxygenation of the
OH
H
9
14
7
-hydroxy steroid via an ionic hydrogenation.
8
H 7
H
CH2OH
HO
H
SYNTHESIS 2006, No. 6, pp 0975–0978
x
x
.
x
x
.2
0
0
6
Advanced online publication: 27.02.2006
DOI: 10.1055/s-2006-926356; Art ID: F16405SS
Georg Thieme Verlag Stuttgart · New York
Figure 1 The key ROESY correlations of compound 6
©

9
76
Q. Gu et al.
PAPER
OTBS
OTBS
OTBS
a
+
CH2OBn
OH
OH
CH2OBn
TBSO
O
TBSO
TBSO
1
2
3
b
b
OTBS
OTBS
CH2OH
OH
OH
TBSO
TBSO
CH2OH
4
5
c
OH
HO
CH2OH
6
Scheme 1 Reagents and conditions: (a) PhCH OCH Cl, SmI , THF, r.t.; 2 (14%), 3 (49%); (b) Li, biphenyl, THF, –78 °C; 4 (84%), 5 (81%);
2
2
2
(
c) triethylsilane, BF ·Et O, CH Cl , 0 °C, 95%.
3 2 2 2
The second approach towards the stereoselective intro- In summary, we have developed two novel approaches to
duction of 7b-hydroxymethyl in androstene was outlined 7b-hydroxymethyl-substituted 5-androstene derivative 6
in Scheme 2. The (isopropoxydimethylsilyl)methyl Grig- in 96–97% de, starting with 3b,17b-bis(tert-butyldimeth-
nard reagent was used for the first time as a nucleophilic ylsilyloxy)-5-androsten-7-one (1). These two methods
hydroxymethyl anion equivalent by Tamao et al. in will be applicable for stereoselective synthesis of other
1
0,11
1
984.
Androst-5-en-7-one 1 was treated with the Grig- 7b-hydroxymethyl-substituted steroids.
nard reagent in THF at 0 °C to give a single adduct. With-
out purification, the unstable adduct was subjected to
oxidative cleavage of the silicon–carbon bond with hydro-
All melting points were determined on a Büchi 510 melting point
apparatus and are uncorrected. Optical rotations were recorded on a
gen peroxide to give compound 5 in 84% yield (two Jasco DIP-181 polarimeter. IR spectra were recorded on a Nicollet
1
13
steps). Compound 5 was cleanly reduced by treatment Magna FT-IR-750 spectrometer as KBr pellets. H and C NMR
spectra were run on a Bruker AM-400 spectrometer using tetra-
with triethylsilane and boron trifluoride etherate, giving
methylsilane as the internal standard (chemical shifts in d ppm).
compound 6 in 92% yield with 97% de. With regard to the
Mass spectra and high-resolution mass spectra were measured on a
high stereoselectivity in the nucleophilic addition of
Finnigan MAT-95 mass spectrometer. Elemental analysis was per-
Tamao’s reagent to androst-5-en-7-one 1, we suggested
formed at a Carlo Erba 1106 instrument. 3b,17b-Bis(tert-butyldim-
that the addition of relatively bulky (isopropoxydimethyl-
ethylsilyloxy)-5-androsten-7-one (1) was prepared according to
4
silyl)methyl Grignard reagent to the 7-carbonyl group literature. Silica gel 60H (200–300 mesh) manufactured by
would occur from the slightly less hindered a-side, result- Qingdao Haiyang Chemical Group Co. (China) was used for flash
chromatography. Petroleum ether (PE) used refers to the fraction
boiling in the range 60–90 °C.
ing in a single isomer 5 with the 7-hydroxyl function in the
b orientation.
OTBS
OTBS
OH
a, b
c
OH
CH2OH
TBSO
O
TBSO
HO
2
CH OH
1
5
6
Scheme 2 Reagents and conditions: (a) (isopropoxydimethylsilyl)methyl chloride, Mg, THF, 0 °C; (b) H O , KHCO , KF, MeOH, THF, r.t.,
2
2
3
8
4% (for 2 steps); (c) triethylsilane, BF ·Et O, CH Cl , 0 °C, 92%.
3 2 2 2
Synthesis 2006, No. 6, 975–978 © Thieme Stuttgart · New York

PAPER
b-Hydroxymethyl Group in Steroids
977
3
b,17b-Bis(tert-butyldimethylsilyloxy)-7b-benzyloxymethylan-
drost-5-en-7a-ol (2) and 3b,17b-Bis(tert-butyldimethylsilyloxy)-
a-benzyloxymethylandrost-5-en-7b-ol (3)
sulting green solution was cooled to –78 °C, and then 2 (200 mg,
0.31 mmol) in anhyd THF (3 mL) was added dropwise at the same
temperature. After stirring the mixture for 1 h at –78 °C, aq sat.
7
Powdered samarium (1.22 g, 8.11 mmol) was added to a dry 150-
mL round-bottomed flask equipped with a stirring bar. The flask
was simultaneously flushed with argon and flamed dry. Anhyd THF
NH Cl solution (40 mL) was added. The organic layer was separat-
4
ed. The aqueous layer was extracted with EtOAc (3 × 80 mL). The
combined extracts were washed with brine, dried (Na SO ), and
2
4
(
75 mL) was added to the cooled flask. The vigorously stirred slurry
evaporated in vacuo. The residue was chromatographed using PE–
EtOAc (10:1) as eluent to give 4 (145 mg, 84%), which was recrys-
tallized from n-hexane to give an analytical sample: white solid; mp
80–82 °C; [a]D –29.8 (c = 0.80, acetone).
IR (KBr): 3433, 2933, 2856, 1632 cm–1.
of samarium metal in THF was cooled to 0 °C, and neat di-
iodomethane (0.61 mL, 7.57 mmol) was added. The green slurry
was stirred at 0 °C for 30 min, then allowed to warm to r.t., and vig-
orously stirred for an additional hour. A mixture of 1 (1.00 g, 1.88
mmol) and chloromethyl benzyl ether (0.52 mL, 3.74 mmol) in an-
hyd THF (15 mL) was added dropwise to the resulting deep blue so-
lution of 0.1 M SmI at r.t. After the initial dark blue color of the
SmI solution turned yellow, the reaction was quenched with 0.1 N
HCl (30 mL), and then extracted with EtOAc (3 × 80 mL). The
combined extracts were washed sequentially with aq sat. Na S O ,
2
0
1
H NMR (300 MHz, DMSO-d ): d = 0.05 [d, 6 H, J = 3.6 Hz,
6
(
CH ) Si], 0.06 [s, 6 H, (CH ) Si], 0.76 (s, 3 H, 18-CH ), 0.89 [s, 9
3 2 3 2 3
2
H, (CH ) CSi], 0.90 [s, 9 H, (CH ) CSi], 0.98 (s, 3 H, 19-CH ), 2.84
3
3
3 3
3
2
(
br s, 1 H, 7-OH), 3.31 (d, 1 H, J = 10.5 Hz, 7-CH OH), 3.41 (d, 1
2
H, J = 10.5 Hz, 7-CH OH), 3.51–3.63 (m, 2 H, 3-H, 17-H), 5.34 (s,
2
2
2
3
1
H, 6-H).
aq sat. NaHCO , and brine, dried (Na SO ) and concentrated in vac-
uo. The crude mixture was chromatographed using PE–EtOAc
(
3
2
4
13
C NMR (100 MHz, DMSO-d ): d = –5.0, –4.7, –4.7, –4.6, 11.5,
6
25:1) as eluent to give 2 (0.17 g, 14%) as a colorless oil and 3 (0.60
1
4
8.0, 18.3, 21.4, 25.9, 27.1, 31.3, 32.7, 36.9, 37.3, 37.5, 37.6, 43.1,
4.1, 45.2, 46.5, 69.1, 72.3, 72.4, 82.1, 128.6, 144.3.
g, 49%) as a white solid, which was recrystallized from n-hexane.
+
MS (EI): m/z (%) = 563 ([M – 1] , 2), 533 (100), 489 (10), 401 (12),
75 (16).
2
2
0
Oil; [a]D –23.8 (c = 2.20, n-hexane).
–
1
Anal. Calcd for C32
H, 10.68.
H O Si : C, 68.03; H, 10.70. Found: C, 68.52;
60 4 2
IR (KBr): 3471, 2955, 2856, 1664 cm .
1
H NMR (400 MHz, CDCl ): d = 0.01 [(d, 6 H, J = 3.6 Hz,
CH ) Si], 0.06 [s, 6 H, (CH ) Si], 0.69 (s, 3 H, 18-CH ), 0.87 [s, 9
3
(
3 2 3 2 3
3b,17b-Bis(tert-butyldimethylsilyloxy)-7a-hydroxymethylan-
drost-5-en-7b-ol (5)
H, (CH ) CSi], 0.89 [s, 9 H, (CH ) CSi], 0.94 (s, 3 H, 19-CH ), 3.20
3
3
3 3
3
(
d, 1 H, J = 9.2 Hz, 7-CH OBn), 3.49 (d, 1 H, J = 9.2 Hz, 7-
2
Method A: Under similar conditions as above, 3 (200 mg, 0.31
mmol) was debenzylated to afford a residue which was chromato-
graphed on silica gel. Elution with PE–EtOAc (10:1) gave 5 (140
mg, 81%), which was recrystallized from n-hexane to give an ana-
CH OBn), 3.49–3.57 (m, 2 H, 3-H, 17-H), 4.53 (s, 2 H, CH Ph),
5
2
2
.48 (s, 1 H, 6-H), 7.29–7.37 (m, 5 H, C H ).
6 5
1
3
C NMR (100 MHz, CDCl ): d = –4.8, –4.6, –4.5, 11.3, 17.9, 18.1,
3
2
0
lytical sample; white solid; mp 148–150 °C; [a]D –28.0 (c = 0.93,
acetone).
1
4
1
8.2, 20.9, 25.8, 25.9, 27.0, 30.7, 32.0, 36.5, 36.7, 37.1, 37.8, 42.4,
3.7, 44.4, 45.9, 71.5, 71.8, 73.3, 76.4, 81.3, 126.2, 127.6, 127.6,
28.3, 138.3, 144.5.
IR (KBr): 3429, 2955, 2933, 2856, 1637 cm–1.
+
+
MS (EI): m/z (%) = 654 (M , 2), 636 ([M – H O] , 22), 533 (100),
5
1
2
H NMR (300 MHz, DMSO-d ): d = 0.03 [d, 6 H, J = 3.0 Hz,
6
15 (20), 401 (16), 91 (39), 73 (27).
(
CH ) Si], 0.05 [s, 6 H, (CH ) Si], 0.71 (s, 3 H, 18-CH ), 0.87 [s, 9
3 2 3 2 3
+
H, (CH ) CSi], 0.88 [s, 9 H, (CH ) CSi], 1.04 (s, 3 H, 19-CH ), 3.51
HRMS (EI): m/z calcd for C H O Si [M] : 654.4500; found:
6
3 3 3 3 3
3
9
66
4
2
(
(
d, 2 H, J = 3.6 Hz, 7-CH OH), 3.55–3.63 (m, 2 H, 3-H, 17-H), 5.28
s, 1 H, 6-H).
54.4463.
2
3
13
C NMR (100 MHz, DMSO-d ): d = –5.0, –4.7, –4.6, 10.9, 18.2,
6
2
0
Mp 114–116 °C; [a]D –32.1 (c = 1.90, n-hexane).
18.2, 18.8, 21.1, 25.8, 27.0, 31.3, 32.5, 36.9, 37.4, 37.5, 42.5, 42.9,
43.9, 44.3, 46.4, 66.6, 72.6, 73.7, 81.8, 129.1, 142.2.
–
1
IR (KBr): 3440, 2956, 2856, 1667 cm .
+
1
MS (EI): m/z (%) = 564 (M , <1), 533 (100), 489 (38), 265 (22), 75
H NMR (300 MHz, CDCl ): d = 0.01 [s, 6 H, (CH ) Si], 0.08 [s, 6
3
3 2
(
39).
H, (CH ) Si], 0.69 (s, 3 H, 18-CH ), 0.88 [s, 9 H, (CH ) CSi], 0.90
3
2
3
3 3
[
7
s, 9 H, (CH ) CSi], 1.05 (s, 3 H, 19-CH ), 3.42 (d, 1 H, J = 9.0 Hz,
-CH OBn), 3.46–3.55 (m, 2 H, 3-H, 17-H), 3.56 (d, 1 H, J = 9.0
2
3
3
3
Anal. Calcd for C H O Si : C, 68.03; H, 10.70. Found: C, 68.09;
H, 10.98.
3
2
60
4
2
Hz, 7-CH OBn), 4.52 (d, 1 H, J = 12.6 Hz, CH Ph), 4.60 (d, 1 H,
J = 12.6 Hz, CH Ph), 5.31 (s, 1 H, 6-H), 7.30–7.38 (m, 5 H, C H ).
2
2
Method B: Under N , a portion (2 mL) of a solution of (isopropoxy-
2
2
6
5
dimethylsilyl)methyl chloride (1.70 mL, 9.44 mmol) in anhyd THF
(10 mL) was added to Mg turnings (0.24 g, 10.00 mmol). To the
stirred mixture was added a few drops of 1,2-dibromoethane at r.t.
and an exothermic reaction started in several min. The remaining
solution was added dropwise over 30 min at such a rate as to main-
tain a gently exothermic reaction. After the addition was complete,
the grey mixture was refluxed for 45 min and then cooled to 0 °C.
A solution of 1 (1.00 g, 1.88 mmol) in anhyd THF (15 mL) was add-
ed dropwise at the same temperature over 30 min. The mixture was
1
3
C NMR (100 MHz, CDCl ): d = –4.5, –4.2, –4.1, 11.1, 18.4, 18.5,
3
1
4
1
9.3, 21.0, 26.2, 26.2, 27.0, 31.1, 32.3, 36.7, 37.6, 37.6, 42.2, 42.7,
3.9, 44.5, 46.4, 72.7, 73.7, 74.3, 74.6, 81.6, 127.6, 127.8, 127.9,
28.6, 138.6, 143.2.
+
+
MS (EI): m/z (%) = 654 (M , 1), 636 ([M – H O] , 20), 533 (100),
4
2
01 (16), 91 (33), 73 (23).
Anal. Calcd for C H O Si : C, 71.50; H, 10.15. Found: C, 71.35;
H, 10.38.
3
9
66
4
2
stirred at 0 °C for another 2 h, and aq sat. NH Cl solution (30 mL)
4
was added at the same temperature. The organic layer was separat-
ed. The aqueous layer was extracted with EtOAc (3 × 60 mL). The
combined organic extracts were washed with brine, dried (Na SO ),
3
b,17b-Bis(tert-butyldimethylsilyloxy)-7b-hydroxymethylan-
drost-5-en-7a-ol (4)
2
4
Freshly activated lithium wire (2–3 cm) was added to a solution of
biphenyl (1.10 g, 7.13 mmol) in anhyd THF (20 mL) at 0 °C under
argon. The solution was vigorously stirred at 0 °C for 1.5 h. The re-
and evaporated in vacuo to give an unstable single adduct as a col-
orless oil; R 0.47 (PE–EtOAc, 15:1). To a stirred mixture of color-
f
less crude adduct, MeOH (10 mL), THF (10 mL), KHCO (0.28 g,
3
Synthesis 2006, No. 6, 975–978 © Thieme Stuttgart · New York

9
78
Q. Gu et al.
PAPER
+
+
2
.80 mmol) and KF (0.33 g, 5.68 mmol), was added 30% aq H O
MS (EI): m/z (%) = 320 (M , 4), 302 ([M – H O] , 4), 289 (76), 271
2
2
2
solution (1.10 mL, 9.71 mmol) dropwise at r.t. The mixture was
stirred at r.t. for 7 h until no starting material remained. Aq sat.
Na S O solution (25 mL) was added with stirring over 15 min until
(100), 253 (82), 159 (48), 91 (35).
Anal. Calcd for C H O : C, 74.96; H, 10.06. Found: C, 74.53; H,
2
0
32
3
2
2
3
1
0.19.
Method B: Under similar conditions as above, 5 (200 mg, 0.35
mmol) was reacted with Et SiH and BF ·OEt to afford a residue,
a negative starch-iodide test was observed. The mixture was ex-
tracted with EtOAc (3 × 80 mL). The combined organic extracts
were washed with brine, dried (Na SO ), and evaporated in vacuo
3
3
2
2
4
which was chromatographed on silica gel. Elution with PE–EtOAc
3:1) gave 6 (104 mg, 92%).
to give a residue which was chromatographed on silica gel. Elution
with PE–EtOAc (10:1) gave 5 (0.89 g, 84% for two steps).
(
3
b,17b-Dihydroxy-7b-hydroxymethylandrost-5-ene (6)
Method A: A mixture of 4 and 5 (200 mg, 0.35 mmol) was dissolved
in CH Cl (10 mL) and cooled to 0 °C. To the solution was added
References
2
2
(1) Solo, A. J.; Caroli, C.; Darby, M. V.; McKay, T.;
Et SiH (0.35 mL, 2.17 mmol), and then BF ·OEt (0.45 mL, 3.55
3
3
2
Slaunwhite, W. D.; Hebborn, P. Steroids 1982, 40, 603.
2) Gompel, A.; Chaouat, M.; Jacob, D.; Perrot, J.-Y.;
mmol) was added dropwise. After stirring the mixture for 1 h, aq
0% Na CO (5 mL) was added and the aqueous layer was extracted
(
1
2
3
Kloosterboer, H. J.; Rostene, W. Fertil. Steril. 2002, 78, 351.
(3) Kendle, K. E. J. Reprod. Fertil. 1978, 52, 373.
(4) Zheng, Y.-H.; Li, Y.-C. J. Org. Chem. 2003, 68, 1603.
with CH Cl . The combined CH Cl layers were washed with brine,
dried (Na SO ), and evaporated in vacuo. The residue was chro-
matographed with PE–EtOAc (3:1) to give 6 (108 mg, 95%), which
was recrystallized from acetone to give an analytical sample; white
2
2
2
2
2
4
(
5) Nickisch, K.; Laurent, H.; Wiechert, R. Tetrahedron Lett.
1981, 22, 3833.
2
0
solid; mp 181–183 °C; [a]D –15.1 (c = 1.13, MeOH).
(6) Imamoto, T.; Takeyama, T.; Yokoyama, M. Tetrahedron
–
1
Lett. 1984, 25, 3225.
7) Shimshock, S. J.; Waltermire, R. E.; DeShong, P. J. Am.
Chem. Soc. 1991, 113, 8791.
8) Eggert, H.; VanAntwerp, C. L.; Bhacca, N. S.; Djerassi, C.
J. J. Org. Chem. 1976, 41, 71.
9) Tedesco, R.; Fiaschi, R.; Napolitano, E. J. Org. Chem. 1995,
60, 5316.
IR (KBr): 3311, 2928, 2874, 1635 cm .
(
(
(
1
H NMR (400 MHz, CD OD): d = 0.76 (s, 3 H, 18-CH ), 1.00 (s, 3
3
3
H, 19-CH ), 3.22 (dd, 1 H, J = 7.2, 3.2 Hz, 7-CH OH), 3.36–3.44
3
2
(
m, 1 H, 3-H), 3.55 (t, 1 H, J = 8.0 Hz, 17-H), 3.68 (dd, 1 H,
J = 10.8, 3.2 Hz, 7-CH OH), 5.38 (s, 1 H, 6H).
2
1
3
C NMR (100 MHz, CD OD): d = 12.4, 20.1, 22.9, 27.3, 31.2,
3
3
8
3.0, 34.8, 37.4, 38.8, 39.0, 43.5, 45.3, 46.1, 52.9, 54.1, 67.0, 72.5,
2.7, 126.2, 143.8.
(10) Tamao, K.; Ishida, N. Tetrahedron Lett. 1984, 25, 4245.
(11) Tamao, K.; Ishida, N.; Ito, Y.; Kumada, M. Org. Synth.
1991, 69, 96.
Synthesis 2006, No. 6, 975–978 © Thieme Stuttgart · New York