Synthesis of syn- and anti-3,5-dihydroxy-6-heptenoates from 2-deoxy-D-ribose: Intermediates for polyols synthesis

Article abstract of DOI:10.1055/s-2003-36801

Syntheses of all four diastereomers of syn- and anti-3,5-dihydroxy-6-heptenoate, proven versatile synthetic intermediates that are enantiomerically pure and functionally differentiated at both ends, have been developed.

Full text of DOI:10.1055/s-2003-36801

LETTER
215
Synthesis of syn- and anti-3,5-Dihydroxy-6-heptenoates from 2-Deoxy-D-
ribose: Intermediates for Polyols Synthesis
Synthesis of
3e
t
y-6-he
e
ptenoates
f
r
rom 2-Deoxy-
D
Z
-ribose akrzewski, Cheuk K. Lau*
Medicinal Chemistry Department, Merck Frosst Centre For Therapeutic Research, 16711 Trans Canada Hwy., Kirkland, Québec,
H9H 3L1, Canada
Fax +1(514)4284900; E-mail: lau@merck.com
Received 10 December 2002
OR
Abstract: Syntheses of all four diastereomers of syn- and anti-3,5-
dihydroxy-6-heptenoate, proven versatile synthetic intermediates
that are enantiomerically pure and functionally differentiated at
both ends, have been developed.
OH OH
O
1a
OR
OR
OR
Key words: 1,3-diols synthesis, tetrahydro-2-furanylacetate, poly-
ols, ring opening, 4-hydroxy-6-vinyltetrahydro-2H-2-pyranone
O
OH OH
O
O
O
OR
1b
I
O
HO
2
Functionalized diols of defined stereochemistry are valu-
able synthetic intermediates in the construction of poly-
ene- and polyether-macrolides such as mycoticins,1
swinholide A,2 halichondrin B3 and spongistatins.4 The
synthetic challenge coupled with the potent pharmacolog-
ical activities of these compounds have led to consider-
able interest in the development of new synthetic methods
for the stereoselective synthesis of both syn- and anti-1,3-
diols.5–12 Most reported stereoselective syntheses of 1,3-
diols are focused on a single isomer of either syn- or anti-
configuartion. Herein, we wish to present a facile and gen-
eral method for preparing all four diastereomers of syn-
and anti- ethyl 3,5-dihydroxy-6-heptenoate 1, proven ver-
satile synthetic intermediates9,10 that are enantiomerically
pure and functionally differentiated at both ends.
OH OH
1c
OH OH
1d
Scheme 1
in 76% combined yield (Scheme 2). The two diastereo-
mers were separated readily using a preparative chiral-
pack AD HPLC column. The β-anomer 2a underwent
reductive ring opening when treated with zinc dust in
25
refluxing ethanol to give the syn-(3R,5S)-diol 1a {[α]D
–21 (c 2.2, CHCl3)} in a modest 41% yield. An improved
yield of 1a was obtained when the 4-hydroxy substituent
of 2a was protected as the tert-butyldimethylsilyl ether 5a
(tert-butyldimethylsilyl chloride, DMAP and Et3N, 86%
yield). Iodotetrahydrofuran 5a underwent reductive ring
opening when treated with zinc dust in refluxing ethanol
to give the mono-protected syn-(3R,5S)-diol 6a in 90%
yield. Compound 6a is a very useful synthetic intermedi-
ate; the two alcohol substituents are differentiated and C1
and C7 are distinctly functionalized. Reaction of 6a with
hydrogen fluoride⋅pyridine in THF gave 1a in 89% yield.
(69% for 3 steps from 2a) The use of hydrogen fluor-
ide⋅pyridine is crucial for the deprotection, since other
fluoride reagents gave very poor yields of the diol 1a.
The method is based on the premise that reductive ring
opening of 2-[4-hydroxy-5-(iodomethyl)tetrahydro-2-
furanyl]acetate 2 of predefined relative and absolute con-
figuration would lead to all four isomers of 1 with unam-
biguous configurations (Scheme 1). 2a and 2b were
prepared quite readily from 2-deoxy-D-ribose using the
methods previously reported from this laboratory.13 Inver-
sion of the chiral center at C4 of 2a and 2b lead to the two
other key intermediates that are required for the prepara-
tion of the four syn- and anti- isomers of 1. The results are
shown in Scheme 2 and Scheme 3.
Reaction of 2-deoxy-D-ribose with (carbethoxymethyl-
ene)triphenylphosphorane in refluxing THF gave a 91%
crude yield of the triol 3. Treatment of the crude triol with
a catalytic amount of sodium ethoxide in ethanol afforded
a quantitative yield of the tetrahydrofuran 4 as a 1:1 mix-
ture of α- and β-anomers. Reaction of 4 with triphe-
nylphosphine, iodine and pyridine in dioxane gave
selectively the corresponding primary iodides 2a and 2b
Inverting the chiral center at C3 of 2a was accomplished
by using a Mitsunobu reaction. Treating 2a with triphe-
nylphosphine and benzoic acid in the presence of diethyl
azodicarboxylate (DEAD) in THF gave the corresponding
benzoate 7a in 66% yield. Benzoate 7a was then treated
with zinc dust in ethanol at 75 °C to give the mono-pro-
tected anti-(3R,5R)-diol 8a (85%). The benzoate group
was hydrolyzed using potassium carbonate in methanol at
–10 °C to afford the unprotected anti-(3R,5R)-diol 1b
{[α]D25 –29 (c 1.6, CHCl3)} in a 53% yield. Transesterifi-
Synlett 2003, No. 2, Print: 31 01 2003.
Art Id.1437-2096,E;2003,0,02,0215,0218,ftx,en;S06202ST.pdf.
© Georg Thieme Verlag Stuttgart · New York
ISSN 0936-5214

216
P. Zakrzewski, C. K. Lau
LETTER
O
OH
OEt
O
O
Zn, EtOH
OEt
OH
Ph3PCHCO2Et
91%
I
HO
TBSO
OH
O
∆ 90%
OEt
OEt
HO
O
6a
TBSO
OH
5a
3
HO
HF·pyridine
THF
NaOEt, EtOH
TBSCl,
86%
100%
89%
OEt
Et3N
2-DEOXY-D-RIBOSE
O
O
OEt
O
Zn, EtOH
OEt
I
I
HO
OH OH
O
∆
41%
O
I2, PPh3, pyridine
76%
HO
O
O
2a
1a
HO
HO
2a
(3R,5S)
[α]D -21 (c 2.2, CHCl3)
Ph3P, PhCO2H
DEAD 66%
4
25
O
OEt
I
O
OEt
OEt
O
Zn, EtOH
85%
I
HO
2b
BzO
8a
OH
O
O
∆
BzO
7a
K2CO3
Scheme 2
53%
MeOH
-10°C
OMe
cation occurred under the reaction conditions providing
the methyl ester instead of the ethyl ester. The reaction
was much more sluggish in ethanol and the yield of the re-
sulting product was much lower. The other syn- and anti-
1,3-diol diastereomers were then prepared from the α-
anomer 2b using the similar methods. 2b was protected
(86% yield) and converted to the corresponding mono-
protected anti-(3S,5S)-diol 6b with zinc in an 86% yield
as described earlier. The silyl group of the monoprotected
diol 6b was removed with hydrogen fluoride⋅pyridine in
OH OH
1b
O
(3R,5R)
[α]D -29 (c 1.6, CHCl3)
25
O
OEt
OEt
Zn, EtOH
I
∆
O
86%
TBSO
OH
6b
O
TBSO
86%
5b
TBSCl,
Et3N
HF·pyridine
THF
85%
O
OEt
Zn, EtOH
OEt
25
THF to give the unprotected anti-(3S,5S)-diol 1c {[α]D
I
∆ 32%
OH OH
O
O
+27 (c 2.6, CHCl3)} in an 85% yield. Similarly, the unpro-
tected 2b can be converted directly to the corresponding
unprotected anti-diol 1c in 32% yield using zinc dust in
ethanol at 65 °C.
HO
1c
2b
(3S,5S)
Ph3P,
PhCO2H
64%
25
[α]D +27 (c 2.6, CHCl3)
DEAD
OEt
O
Inverting the C3 center of 2b by using a Mitsunobu reac-
tion gave a 64% yield of the corresponding benzoate 7b.
Reaction of 7b with zinc dust in ethanol at 65 °C gave a
57% yield of the desired monoprotected syn (3S,5R)-diol
8b. Attempts to hydrolyze the benzoate group of 8b to the
unprotected diol proved to be difficult. Many different
conditions were tried in an attempt to optimize the yield
of the unprotected syn (3S,5R)-diol 1d {[α]D25 +20 (c 3.0,
CHCl3)}. The best conditions involved treating 8b with
sodium carbonate in methanol at r.t. giving 1d in 13%.
The major product in this reaction is ethyl (3S,5S)-3-hy-
droxy-5-methoxyhept-6-enoate 9 which was isolated in a
52% yield. Eventually, the benzoate 7b was hydrolyzed
with sodium carbonate in methanol at r.t. and the resulting
intermediate was treated with zinc dust in refluxing etha-
nol to give the desired unprotected syn-(3S,5R)-diol 1d in
a 43% yield.
OEt
Zn, EtOH
I
BzO
OH
8b
Na2CO3
MeOH
rt
O
∆ 57%
O
BzO
43%
7b
1. K2CO3, MeOH
2. Zn, EtOH, ∆
52%
OEt
OMe
OMe OH
O
OH OH
O
9
1d
(3S,5R)
25
[α]D +20 (c 3.0, CHCl3)
Scheme 3
+6.5}.14 Treatment of the unprotected anti-(3R,5R)-diol
1b under the same conditions generated the corresponding
chiral lactone 10b {[α]D25 –38 (c 1.0, CHCl3)} in a yield
of 55%. Similarly, the monoprotected anti-(3S,5S)-diol 1c
To illustrate the synthetic utility of these diols, the mono-
protected syn-(3R,5S)-diol 6a was converted to the lac-
tone 10a {[α]D25 +47 (c 1.0, CHCl3)} in 71% yield by the
treatment of 6a with hydrogen fluoride in acetonitrile and
water (Scheme 4). Lactone 10a is a key intermediate in
the synthesis of compactin.10 Silylation of 10a yield the
25
was converted into the lactone 10c {[α]D +38 (c 1.3,
CHCl3)} in 56% yield.
In summary, starting from commercially available 2-
deoxy-D-ribose, four functionalized syn- and anti-1,3-diol
diastereomers were obtained in high overall yields in a
limited number of steps. These diols can be potential in-
termediates in the synthesis of many natural products.
25
known intermediate 11 {mp = 63–64 °C and [α]D +6.7
25
(c 6.3, CHCl3). Literature mp = 61–62 °C and [α]D
Synlett 2003, No. 2, 215–218 ISSN 0936-5214 © Thieme Stuttgart · New York

LETTER
Synthesis of 3,5-Dihydroxy-6-heptenoates from 2-Deoxy-D-ribose
217
Ethyl (3R,5S)-3,5-dihydroxy-6-heptenoate (1a): To a solution of
ethyl (3R,5S)-5-{[1-(tert-butyl)-1,1-dimethylsilyl]oxy}-3-hy-
O
OR
OR'
HF/CH3CN/H2O
O
droxy-6-heptenoate 6a (1.22 g, 4.02 mmol in anhydrous THF (20
mL) at 0 °C was added a solution of hydrogen fluoride⋅pyridine
complex (4.8 mL). The reaction was warmed to r.t. and stirred for 1
h. Saturated sodium bicarbonate was added until there was no more
carbon dioxide liberated. The mixture was extracted twice with
EtOAc and the combined organic layers were washed with brine
and dried (MgSO4). The title compound (0.676 g, 89%) was isolated
by column chromatography (45–50% EtOAc–hexane). Compound
O
OR OH
25
6a R = TBS, R' = Et (3R,5S)
1b R = H, R' = Me (3R,5R)
71%
55%
10a
10b
[α]D +47 (c 1.0, CHCl
R = H, (4R,6S)
R = H, (4R,6R)
25
[α]D -38 (c 1.0, CHCl3
25
1c R = H, R' = Et (3S,5S)
56%
[α]D +38 (c 1.3, CHC
10c
R = H, (4S,6S)
m.p. = 63-64 °C (Lit.14 = 61-62 °C)
11
R = TBDPS
25
14
[α]D +6.7 (c 6.3, CHCl )
3 (Lit. +6.5)
(4R,6S)
25
1a exhibits: [α]D –21 (c 2.2, CHCl3). 1H NMR (300 MHz,
Scheme 4
CD3COCD3): δ 1.20 (t, 3 H, J = 7.1 Hz, CH3), 1.63 (m, 2 H, C4-H2),
2.44 (m, 2 H), 4.08 (q, 2 H, J = 7.1 Hz, CH2-O), 4.21 (m, 3 H), 4.30
(m, 1 H), 5.00 (dt, 1 H, J = 10.4 Hz, 1.4 Hz, CH2=), 5.21 (dt, 1 H,
J = 17.0 Hz, 1.5 Hz, CH2=), 5.86 (m, 1 H, CH=). 13C NMR (75.5
MHz, CD3COCD3): δ 14.1, 42.8, 43.8, 60.2, 67.6, 71.7, 113.4,
142.2, 171.7. Exact mass calcd for C9H17O4 (M + 1): 189.1127;
found: 189.1128.
Methyl (3R,5R)-3,5-dihydroxy-6-heptenoate (1b): [α]D25 –29 (c 1.6,
CHCl3). 1H NMR (300 MHz, CD3COCD3): δ 1.59 (m, 2 H, C4-H2),
2.44 (m, 2 H, C2-H2), 3.61 (s, 3 H, CH3-O), 3.97 (d, 1 H, J = 1.9 Hz,
OH), 3.98 (d, 1 H, J = 1.6 Hz, OH), 4.32 (m, 2 H), 5.01 (dt, 1 H, J
= 10.5 Hz, 1.4 Hz, CH2=), 5.22 (dt, 1 H, J = 17.0 Hz, 1.6 Hz, CH2=),
5.90 (m, 1 H, CH=). 13C NMR (75.5 MHz, CD3COCD3): δ 42.8,
44.0, 51.1, 65.5, 69.3, 112.8, 142.8, 172.3. Exact mass calcd for
C8H15O4 (M + 1): 175.0970; found: 175.0971.
Ethyl 2-[(2R,4S,5S)-4-hydroxy-5-(iodomethyl)tetrahydro-2-fura-
nyl]acetate (2a) and ethyl 2-[(2S,4S,5S)-4-hydroxy-5-(iodometh-
yl)tetrahydro-2-furanyl]acetate (2b): To a solution of ethyl 2-[4-
hydroxy-5-(hydroxymethyl)tetrahydro-2-furanyl]acetate 4 (13.5 g,
66.3 mmol) in 1,4-dioxane (250 mL) was added pyridine (10.5 g,
133 mmol), iodine (25.2 g, 99.4 mmol), and triphenylphosphine
(27.8 g, 106 mmol) successively and the reaction mixture was
stirred at r.t. for 1.5 h. MeOH was added to the mixture and the sol-
vents were removed under vacuum. The residue was dissolved in
EtOAc and washed with distilled water, aqueous sodium dithionite
(0.1 g/mL), brine, and dried (MgSO4). The solvents were removed
under vacuum and the title compounds (1:1 mixture of diastere-
omers 2a and 2b) (13.6 g, 65%) were isolated by column chroma-
25
Ethyl (3S,5S)-3,5-dihydroxy-6-heptenoate (1c): [α]D +27 (c 2.6,
tography
(40%
EtOAc–hexane).
Subsequent
column
CHCl3). 1H NMR (300 MHz, CD3COCD3): δ 1.20 (t, 3 H, J = 7.1
Hz, CH3), 1.59 (m, 2 H), 2.43 (m, 2 H), 3.97 (m, 2 H), 4.08 (q, 2 H,
J = 7.1 Hz, CH2-O), 4.32 (m, 2 H), 5.00 (dt, 1 H, J = 10.5 Hz, 1.8
Hz, CH2=), 5.22 (dt, 1 H, J = 17.2 Hz, 1.8 Hz, CH2=), 5.90 (m, 1 H,
CH=). 13C NMR (75.5 MHz, CD3COCD3): δ 14.1, 43.0, 44.0, 60.2,
65.5, 69.3, 112.8, 142.8, 171.8. Exact mass calcd for C9H17O4 (M +
1): 189.1127; found: 189.1128.
chromatography on preparative chiralpack AD HPLC column (30%
EtOAc–hexane) separated the two isomeric title compounds. Com-
pound 2a exhibits: [α]D25 –10.8 (c 6.0, CHCl3). 1H NMR (300 MHz,
CD3COCD3): δ 1.21 (t, 3 H, J = 7.1 Hz, CH3), 1.96 (m, 2 H), 2.55
(m, 2 H), 3.25 (d, 2 H, J = 5.6 Hz, CH2-I), 3.75 (dt, 1 H, J = 5.0, 2.4
Hz), 4.09 (q, 2 H, J = 7.1 Hz, CH2-O), 4.20 (m, 1 H), 4.29 (d, 1 H,
J = 4.1 Hz, OH), 4.51 (m, 1 H). Exact mass calcd for C9H16O4I (M
+ 1): 315.0093; found: 315.0093. Anal. calcd for C9H15O4I: C,
34.41; H, 4.81. Found: C, 34.10; H, 4.73. Compound 2b exhibits:
[α]D –1.1 (c 2.3, CHCl3). H NMR (300 MHz, CD3COCD3): δ
1.21 (t, 3 H, J = 7.1 Hz, CH3), 1.76 (m, 1 H), 2.44 (m, 1 H), 2.62 (m,
2 H), 3.29 (m, 2 H, CH2-I), 3.80 (m, 1 H), 4.08 (q, 2 H, J = 7.1 Hz,
CH2-O), 4.23 (m, 1 H), 4.37 (d, 1 H, J = 4.4 Hz, OH), 4.47 (m, 1 H).
Exact mass calcd for C9H16O4I (M + 1): 315.0093; found: 315.0093.
Anal. calcd. for C9H15O4I: C, 34.41; H, 4.81. Found: C, 34.22; H,
5.01.
25
Ethyl (3S,5R)-3,5-dihydroxy-6-heptenoate (1d): [α]D +20 (c 3.0,
CHCl3). 1H NMR (300 MHz, CD3COCD3): δ 1.20 (t, 3 H, J = 7.1
Hz, CH3), 1.63 (m, 2 H, C4-H2), 2.44 (m, 2 H, C2-H2), 4.08 (q, 2 H,
J = 7.1 Hz, CH2-O), 4.21 (m, 3 H, C3-H, OH), 4.31 (m, 1 H, C5-H),
5.02 (dt, 1 H, J = 10.4 Hz, 1.4 Hz, CH2=), 5.21 (dt, 1 H, J = 17.0 Hz,
1.5 Hz, CH2=), 5.86 (m, 1 H, CH=). 13C NMR (75.5 MHz,
CD3COCD3): δ 14.1, 42.8, 43.8, 60.1, 67.6, 71.7, 113.3, 142.3,
171.7. Exact mass calcd for C9H17O4 (M + 1): 189.1127; found:
189.1128.
25
1
Ethyl (3R,5S)-5-{[1-(tert-butyl)-1,1-dimethylsilyl]oxy}-3-hydroxy-
6-heptenoate (6a): To a solution of ethyl 2-[(2R,4S,5S)-4-{[1-(tert-
butyl)-1,1-dimethylsilyl]oxy}-5-(iodomethyl)tetrahydro-2-fura-
nyl]acetate 5a (7.2 g, 16.8 mmol) in anhydrous EtOH (100 mL) was
added zinc dust (9.60 g, 147 mmol) portionwise and the reaction
mixture was refluxed for 2.5 h. The mixture was cooled to r.t.,
EtOAc was added, and it was filtered through a short pad of Celite.
The solvents were removed under vacuum and the residue was dis-
solved in EtOAc. The EtOAc solution was then washed with hydro-
chloric acid (0.2 N), distilled water, brine, and dried (MgSO4). The
title compound (4.56 g, 90%) was isolated by column chromatogra-
(4R,6S)-4-Hydroxy-6-vinyltetrahydro-2H-2-pyranone (10a): Ethyl
(3R,5S)-5-{[1-(tert-butyl)-1,1-dimethylsilyl]oxy}-3-hydroxy-6-
heptenoate 6a (0.252 g, 0.83 mmol) was dissolved in a previously
prepared solution of 5% aqueous hydrogen fluoride in MeCN (1.6
M HF, 8.5 mL). The reaction mixture was stirred at r.t. for 2.75 h.
Distilled water was added and the mixture was extracted twice with
EtOAc. The combined organic layers were washed with brine and
dried (MgSO4). The title compound (0.084 g, 71%) was isolated by
column chromatography (75% EtOAc–hexane). Compound 10a ex-
hibits: [α]D25 +47 (c 1.0, CHCl3). 1H NMR (300 MHz, CD3COCD3):
δ 1.85 (m, 1 H), 2.00 (m, 1 H), 2.49 (m, 1 H), 2.69 (dd, 1 H, J = 17.0
Hz, 4.6 Hz), 4.32 (m, 1 H), 4.43 (d, 1 H, J = 2.9 Hz, OH), 5.12 (m,
1 H), 5.17 (d, 1 H, J = 10.5 Hz), 5.31 (d, 1 H, J = 17 Hz), 5.93 (m,
1 H, CH=). 13C NMR (75.5 MHz, CD3COCD3): δ 36.2, 38.9, 62.4,
76.2, 115.9, 137.7, 169.6. Exact mass calcd for C7H11O3 (M + 1):
143.0708; found: 143.0709.
25
phy (15% EtOAc–hexane). Compound 6a exhibits: [α]D –7.2 (c
2.8, CHCl3). 1H NMR (300 MHz, CD3COCD3): δ 0.04 (s, 3 H, CH3-
Si), 0.08 (s, 3 H, CH3-Si), 0.89 (s, 9 H, CH3-C-Si), 1.19 (t, 3 H, J =
7.1 Hz, CH3), 1.59 (m, 1 H), 1.76 (m, 1 H), 2.37 (dd, 1 H, J = 15.0
Hz, 8.3 Hz), 2.48 (dd, 1 H, J = 15.0 Hz, 4.5 Hz), 3.81 (d, 1 H, J =
5.0 Hz, OH), 4.08 (m, 3 H, C3-H, CH2-O), 4.39 (m, 1 H), 5.06 (d, 1
H, J = 10.4 Hz, CH2=), 5.21 (d, 1 H, J = 17.0 Hz, CH2=), 5.87 (m,
1 H, CH=). 13C NMR (75.5 MHz, CD3COCD3): δ –5.0, –4.48, 14.1,
18.2, 25.8, 42.8, 45.6, 60.1, 65.6, 72.3, 114.2, 141.8, 171.7. Exact
mass calcd for C15H31O4Si (M + 1): 303.1992; found: 303.1991.
(4R,6R)-4-Hydroxy-6-vinyltetrahydro-2H-2-pyranone
(10b):
[α]D25 –38 (c 1.0, CHCl3). 1H NMR (300 MHz, CD3COCD3): δ 1.58
(m, 1 H), 2.33 (m, 1 H), ), 2.37 (dd, 1 H, J = 16.7 Hz, 7.0 Hz), 2.83
(ddd, 1 H, J = 16.7 Hz, 5.6 Hz, 1.1 Hz), 4.30 (m, 1 H), 4.76 (m, 1
H), 5.18 (dt, 1 H, J = 10.5 Hz, 1.3 Hz), 5.33 (dt, 1 H, J = 17.2 Hz,
1.4 Hz), 5.94 (m, 1 H, CH=). 13C NMR (75.5 MHz, CD3COCD3): δ
Synlett 2003, No. 2, 215–218 ISSN 0936-5214 © Thieme Stuttgart · New York

218
P. Zakrzewski, C. K. Lau
LETTER
38.6, 39.8, 63.5, 77.3, 116.2, 137.1, 170.2. Exact mass calcd for
C7H11O3 (M + 1): 143.0708; found: 143.0709.
(4) Pettit, G. R.; Chicacz, Z. A.; Gao, F.; Herald, C. L.; Boyd,
M. R.; Schmidt, J. M.; Hooper, J. N. A. J. Org. Chem. 1993,
58, 1302.
(5) Eh, M.; Kalesse, M. Synlett 1995, 837.
(6) Kumar, A.; Dittmer, D. C. J. Org. Chem. 1994, 59, 4760.
(7) Harada, T.; Shintani, T.; Oku, A. J. Am. Chem. Soc. 1995,
117, 12346.
(8) Solladie, G.; Wilb, N.; Bauder, C.; Bonini, C.; Viggiani, L.;
Chiummiento, L. J. Org. Chem. 1999, 64, 5447.
(9) Mohr, P. Tetrahedron Lett. 1992, 33, 2455.
(10) Scialdone, M. A.; Johnson, C. R. Tetrahedron Lett. 1995, 36,
43.
(11) Smith, A. B. III; Pitram, S. M. Org. Lett. 1999, 1, 2001.
(12) Enders, D.; Hundertmark, T. Tetrahedron Lett. 1999, 40,
4169.
25
(4S,6S)-4-Hydroxy-6-vinyltetrahydro-2H-2-pyranone (10c): [α]D
+38 (c 1.3, CHCl3). 1H NMR (300 MHz, CD3COCD3): δ 1.58 (m, 1
H), 2.33 (m, 2 H), 2.83 (m, 1 H), 4.30 (m, 1 H, C4-H, OH), 4.75 (m,
1 H, C6-H), 5.18 (m, 1 H, CH=C-C6), 5.33 (m, 1 H, CH=C-C6),
5.92 (m, 1 H, CH=C6). 13C NMR (75.5 MHz, CD3COCD3): δ 38.6,
39.8, 63.5, 77.3, 116.2, 137.1, 170.1. Exact mass calcd for C7H11O3
(M + 1): 143.0708; found: 143.0709.
References
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Synlett 2003, No. 2, 215–218 ISSN 0936-5214 © Thieme Stuttgart · New York