Easy access to derivatives of 2-(hydroxymethyl)propane-1,2,3-triol (isoerythritol) with up to four separately addressable functionalities

Article abstract of DOI:10.1002/ejoc.200200099

5-Methylene-2-oxo[1,3,2]dioxathiane (2) was obtained in 91% yield from 2-methylenepropane-1,3-diol (1) and thionyl chloride. The cyclic sulfite 2 reacts with a variety of nucleophiles to give formally monosubstituted products 3 of the diol 1 in 62-77% yield. Oxidation of 2 with RuCl₃/NaIO₄ yields the diprotected tetraol 5-(hydroxymethyl)-2,2-dioxo[1,3,2]-dioxathian-5-ol (7) in 86% yield, which can be used to easily access tetrafunctional derivatives of 2-(hydroxymethyl)propane-1,2,3-triol (isoerythritol); for example, acetylation with acetic anhydride furnishes in 96% yield the primary acetate 11, which reacts with potassium cyanide and sodium azide to give the 2-cyano- and 2-(azidomethyl)propane-1,2,3-triol monoacetates 12a,b (78 and 82% yield, respectively). Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003.

Full text of DOI:10.1002/ejoc.200200099

FULL PAPER
Easy Access to Derivatives of 2-(Hydroxymethyl)propane-1,2,3-triol
(Isoerythritol) with up to Four Separately Addressable Functionalities
Marko Friedrich,[a] Andrei I. Savchenko,[a] Andreas Wächtler,[b] and Armin de Meijere*[a]
Keywords: Allylic compounds / Alcohols / Sulfur heterocycles / Hydroxylation / Nucleophilic substitution
5-Methylene-2-oxo[1,3,2]dioxathiane (2) was obtained in
91% yield from 2-methylenepropane-1,3-diol (1) and thionyl
pane-1,2,3-triol (isoerythritol); for example, acetylation with
acetic anhydride furnishes in 96% yield the primary acetate
chloride. The cyclic sulfite 2 reacts with a variety of nucleo- 11, which reacts with potassium cyanide and sodium azide
philes to give formally monosubstituted products 3 of the diol to give the 2-cyano- and 2-(azidomethyl)propane-1,2,3-triol
1 in 62−77% yield. Oxidation of 2 with RuCl3/NaIO4 yields monoacetates 12a,b (78 and 82% yield, respectively).
the diprotected tetraol 5-(hydroxymethyl)-2,2-dioxo[1,3,2]-
dioxathian-5-ol (7) in 86% yield, which can be used to easily
( Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
access tetrafunctional derivatives of 2-(hydroxymethyl)pro- Germany, 2003)
Introduction
stitution reaction with sodium p-toluenesulfinate. Despite
the wide use, however, of formal monosubstitution products
of 2-methylenepropane-1,3-diol (1), no general method for
their selective preparation has been described.
Trifunctional building blocks obtained by formal mono-
substitution of one hydroxy group in 2-methylenepropane-
1,3-diol[1] (1) have been applied for a variety of synthetic
purposes. 3-Amino-2-methylenepropan-1-ol has been used
as a starting material in the synthesis of carbapenem anti-
biotics.[2] A monoester of 1 has served as a precursor to
type I and IV cyanolipids,[3] and monocarbonates have
served[4] as bis(allylic) templates for Pd0-catalyzed solid-
phase syntheses of tertiary amines. A monosulfone derived
from 1 can be transformed into a dianion, which reacts with
electrophiles chemoselectively.[5] A diethyl allylmalonate de-
rivative of 1 has been subjected to a ring-closing metathesis
(RCM) reaction.[6] In most cases,[3,4,6] the syntheses were
achieved in moderate yields by the reaction of an appropri-
ate derivative of 1 with 1 equiv. of the reagent and sub-
sequent separation from the disubstitution product. Only a
few examples of selective syntheses of formally monosubsti-
tuted products of 1[7] are known. 4-Methylene[1,2]oxasilol-
anes, generated by radical ring closure of propargyl silyl
ethers, undergo ring opening to formal monosilyl-substi-
tution products of 1, and the cyclic carbonate[8] of 1 —
which has been reported to be accessible from the diol, al-
though without any experimental details having been re-
ported, including the yield[9] — has been used to prepare
the monosulfonyl derivative in a palladium-catalyzed sub-
Results and Discussion
The most frequently applied selective functionalization of
one hydroxy group in a 1,3-diol proceeds via the corre-
sponding cyclic sulfate.[10] Attempts to prepare the cyclic
sulfate of 1 directly by reaction with sulfuryl chloride[11] or
N,NЈ-sulfuryldiimidazole[12] proved to be futile. Routinely,
cyclic sulfates of 1,3-diols are prepared by oxidizing the cor-
responding cyclic sulfite.[13] Indeed, we found that the cyclic
sulfite of 1, 5-methylene-2-oxo[1,3,2]dioxathiane (2), is eas-
ily accessible, and it turned out to react readily with a vari-
ety of nucleophilic reagents in a selective manner.
Treatment of the commercially available 2-methylenepro-
pane-1,3-diol[1] (1) with thionyl chloride in tetrachlorome-
thane gave 5-methylene-2-oxo[1,3,2]dioxathiane (2) in 91%
[a]
Institut für Organische Chemie, Universität Göttingen,
Tammannstrasse 2, 37077 Göttingen, Germany
Fax: (internat.) ϩ 49-551/399475
E-mail: Armin.deMeijere@chemie.uni-goettingen.de
[b]
Merck KGaA, Central Process Development,
64271 Darmstadt, Germany
Scheme 1. Preparation of 5-methylene-2-oxo[1,3,2]dioxathiane (2)
and its reaction with different nucleophiles; for details, see Table 1
E-mail: andreas.waechtler@merck.de
2138
 2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
DOI: 10.1002/ejoc.200200099
Eur. J. Org. Chem. 2003, 2138Ϫ2143

Derivatives of Isoerythritol with up to Four Separately Addressable Functionalities
FULL PAPER
Table 1. Reaction of 5-methylene-2-oxo[1,3,2]dioxathiane (2) in DMF with various nucleophiles
Reagent
Temp. [°C] (time [h])
Product
Nu
Yield (%)
NaN3
80 (0.25)
100 (1)
50 (2.5)
100 (1)
60 (3)
3a
3b
3c
3d
3e
6
N3
NPhth
OPh
OAc
CH(CO2Et)2
CH(CO2Et)2
77
69
KNPhth[a]
NaOPh
69[b]
69[c]
40[d]
47[e]
NaOAc
NaCH(CO2Et)
NaCH(CO2Et)
60 (48)
[a]
[b]
[c]
[d]
Phth ϭ phthalimidoyl.
Plus 6% of disubstitution product 4c. Plus 9% of disubstitution product 4d.
Plus 14% of δ-lactone 6.
[e]
2 equiv. of diethyl sodiomalonate were used, 9% of 3e was also isolated.
yield. This clean transformation of 1 into 2 could be to depend highly on the solvent system used.[19] Routinely, a
achieved only in tetrachloromethane (Scheme 1), because two-phase solvent system is employed to extract the formed
the use of other solvents, as well as the addition of a base, product into the organic phase where it will be protected
led mainly to the formation of oligomers and chlorides. from further oxidation.[17a] In the case of 5-(hydroxy-
Only in tetrachloromethane is the solubility of the evolving methyl)-2,2-dioxo[1,3,2]dioxathian-5-ol (7) — which, be-
hydrogen chloride low enough[14] to prevent these side reac- cause of its high polarity, is soluble in water, but not in a
tions. The reaction of 2 with a number of nucleophiles pro- majority of organic solvents — the best yield of 7 (86%)
ceeded best in dimethylformamide (DMF) to yield the was obtained in a homogeneous mixture (6:1) of aceto-
monosubstitution products
(Scheme 1 and Table 1).
3
cleanly in most cases nitrile and water (Scheme 3, Table 2).[19]
With sodium azide and potassium phthalimide, only the
desired monosubstitution products 3a,b were formed in
good yields. The reactions with sodium phenolate and so-
dium acetate gave the products 3c,d in similar yields, but
they were accompanied by the corresponding disubstitution
products 4c,d (6 and 9%, respectively). When 2 was treated
with the sodium enolate of diethyl malonate 5 at 60 °C for
3 h, a mixture of the expected monosubstitution product 3e
and the δ-lactone 6 was obtained. The latter was apparently
formed by subsequent intramolecular transesterification of
3e. By extending the reaction time to 48 h at 60 °C, the δ-
lactone 6 was isolated in 47% yield (Scheme 2).
Scheme 3. Oxidation of 5-methylene-2-oxo[1,3,2]dioxathiane (2) to
5-(hydroxymethyl)-2,2-dioxo[1,3,2]dioxathian-5-ol (7); for details,
see Table 2
Table 2. Optimization of the solvent system for the oxidation of 2
to yield 7
Entry
Solvents (ratio)
Yield of 7 (%)
1
2
3
4
5
CCl4/MeCN/H2O (3:3:1)[a]
CCl4/MeCN/H2O (1:1:1)
MeCN/H2O (1:1)
MeCN/Et2O/H2O (3:3:1)
MeCN/H2O (6:1)
54
38
41
54
86
Scheme 2. Reaction of 5-methylene-2-oxo[1,3,2]dioxathiane (2)
with diethyl sodiomalonate
[a]
Solvent mixture routinely employed for the oxidation of sulf-
ites.[13]
Thus, the cyclic sulfite 2 of 2-methylenepropane-1,3-diol
(1), which is easily obtained from the diol 1 in high yield,
To demonstrate some possible further selective trans-
can be used to prepare formal monosubstitution products formations, 7 was sequentially treated with various combi-
of 1.[15] These products 3 all contain an allylic alcohol moi- nations of two nucleophiles (PhthNK, NaN3, NaOAc, Na-
ety that is accessible to further elaboration, e.g., by pal- OPh), but the only successful reaction sequence that we
ladium-catalyzed nucleophilic substitution[16] of an appro- achieved was with potassium phthalimide and sodium azide
priate ester derived from them. Even the previously un- in DMF to furnish the phthalimidoazide 9, albeit in only
known δ-lactone 6 is an ester that should be prone to un- 33% yield (Scheme 4). This formal double-substitution
dergo further selective transformations.
product may well have been formed via the epoxide 10.
In an attempt to oxidize the cyclic sulfite 2 to the corre- When the primary hydroxy group was protected by acety-
sponding sulfate by treatment with in situ generated ru- lation with acetic anhydride in pyridine/ethyl acetate, the
thenium tetroxide,[13] we achieved both oxidation of the sul- opening of the cyclic sulfate moiety in the resulting acetate
fur atom and dihydroxylation of the double bond[17] at the 11 with potassium cyanide and sodium azide led to the cor-
same time.[18] The yield of this transformation turned out responding monosubstitution products, with a sulfate group
Eur. J. Org. Chem. 2003, 2138Ϫ2143
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2139

M. Friedrich, A. I. Savchenko, A. Wächtler, A. de Meijere
FULL PAPER
Transfer)]. Chemical shifts in CDCl3 are reported in δ values rela-
tive to tetramethylsilane (δ ϭ 0.00 ppm), with residual CHCl3 (δ ϭ
7.26 ppm) and CDCl3 (δ ϭ 77.0 ppm) used as internal standards
for 1H and 13C NMR spectra, respectively, unless otherwise stated.
IR spectra were recorded with a Bruker IFS 66 instrument, meas-
ured as KBr pellets or oils between KBr plates. Low-resolution EI
mass spectra were obtained with a Varian-MAT 731. Elemental
analyses were performed by the Mikroanalytisches Laboratorium,
Institut für Organische Chemie, Universität Göttingen. Melting
points are uncorrected. TLC analyses were performed using
MachereyϪNagel precoated plates, 0.25 mm Sil G/UV254. Prepara-
tive column chromatography was performed on Merck silica gel 60
(63Ϫ200 µm). All reactions were carried out under dry nitrogen or
argon in oven- and/or flame-dried glassware. Solvents were dried
according to commonly used procedures.
on one primary hydroxy group, that were hydrolyzed upon
aqueous workup to give the monoacetylated triols 12a,b in
78 and 82% yield, respectively.
5-Methylene-2-oxo[1,3,2]dioxathiane (2): A solution of thionyl chlo-
ride (8.33 g, 70.0 mmol) in tetrachloromethane (15 mL) was added
under vigorous stirring to an emulsion of 2-methylenepropane-1,3-
diol (1, 4.15 g, 47.2 mmol) in tetrachloromethane (30 mL) at 0 °C.
When the evolution of hydrogen chloride had ceased after approxi-
mately 30 min, the solution was stirred for an additional 15 min.
Evaporation of the solvent at 0 °C and 5 mbar, followed by kugel-
rohr distillation (b.p. 90Ϫ110 °C/10 Torr) yielded 2 as a colorless
liquid (5.77 g, 43.1 mmol, 91%). IR (film): ν˜ ϭ 3088, 2991, 2938,
2873, 1461, 1446, 1416, 1342, 1300, 1239, 1195, 1177, 982, 958, 926,
870, 759, 717, 692, 663 cmϪ1
.
1H NMR (250 MHz, CDCl3): δ ϭ
2
4.24 [d, J ϭ 12.9 Hz, 2 H, 4(6)-H], 5.14 (s, 2 H, ϭCH2), 5.35 [d,
2J ϭ 12.9 Hz, 2 H, 4(6)-H] ppm. 13C NMR (62.9 MHz, CDCl3,
DEPT): δ ϭ 61.6 [Ϫ, C-4(6)], 114.4 (Ϫ, ϭCH2), 135.5 (Cquat, C-5)
ppm. MS (EI, 70 eV): m/z (%) ϭ 134 (6) [Mϩ], 70 (50), 69 (24), 42
(100), 41 (82). C4H6O3S (134.15): calcd. C 35.81, H 4.51; found C,
36.11, H 4.51.
Scheme 4
Nucleophilic ring opening with a number of nucleophiles
yielded the corresponding open-chain sulfates 13 almost
quantitatively, but the selective hydrolysis of the sulfate
moiety turned out to be difficult in certain cases.[20] Thus,
the sulfate 13 resulting from 11 and sodium p-toluenesul-
fonylamide gave (acetoxymethyl)glycidol (14)[21] unexpec-
tedly as the only product in 38% isolated yield. Apparently,
the p-toluenesulfonylamide moiety is protonated under the
acidic conditions and then acts as a leaving group in an
intramolecular substitution by a hydroxy group. Therefore,
investigations of possible functionalizations of 11 will re-
quire further elaboration.
2-(Azidomethyl)prop-2-en-1-ol (3a): Sodium azide (233 mg,
3.58 mmol) was added to a solution of 2 (400 mg, 2.98 mmol) in
DMF (3 mL), and then the mixture was heated to 80 °C. After
15 min, the reaction was quenched by addition of water (20 mL).
The aqueous phase was extracted with diethyl ether (3 ϫ 10 mL),
the combined organic extracts were washed with water, dried with
anhydrous MgSO4, and concentrated under reduced pressure.
Flash chromatography (25 g of silica gel, light petroleum ether/
ethyl acetate, 65:35, Rf ϭ 0.23) then gave 3a as a colorless liquid
(258 mg, 2.28 mmol, 77%). IR (film): ν˜ ϭ 3270 (OH), 2937, 2877,
2100, 1659, 1455, 1440, 1244, 1068, 1033, 915, 883 cmϪ1. 1H NMR
(250 MHz, CDCl3): δ ϭ 1.72 (s, 1 H, OH), 3.86 (s, 2 H, CH2N3),
4.19 (s, 2 H, 1-H), 5.18 (s, 1 H, 3-H), 5.28 (s, 1 H, 3-H) ppm. 13C
NMR (62.9 MHz, CDCl3, DEPT): δ ϭ 53.3 (Ϫ, CH2N3), 64.0 (Ϫ,
C-1), 114.6 (Ϫ, C-3), 142.7 (Cquat, C-2) ppm. MS (CI, NH3): m/z
Conclusion
The 5-(hydroxymethyl)-2,2-dioxo[1,3,2]dioxathian-5-ol
(7) is a formal derivative of 2-(hydroxymethyl)propane-
1,2,3-triol, also called isoerythritol.[22] Derivatives of iso-
erythritol have come to prominent attention as acyclic
nucleoside analogues[23] and as GABA analogues.[24] With
use of the formal isoerythritol derivative 11, each of the
primary hydroxy functions of isoerythritol may selectively
be addressed.
ϩ
(%) ϭ 148 (72) [M ϩ NH4 ϩ NH3], 131 (100) [M ϩ NH4ϩ].
C4H7N3O (113.11): calcd. C 42.47, H 6.24, N 37.15; found C,
42.67, H 6.18, N 37.00.
N-[2-(Hydroxymethyl)allyl]phthalimide (3b): Potassium phthalimide
(1.38 g, 7.45 mmol) was added to a solution of 2 (500 mg,
3.73 mmol) in DMF (2 mL), and then the resulting suspension was
stirred at 100 °C. After 1 h, the reaction was quenched with water
(14 mL). The aqueous phase was extracted with diethyl ether (3 ϫ
10 mL), and the combined organic extracts were washed with water,
dried with anhydrous MgSO4, and concentrated under reduced
pressure. Flash chromatography (60 g of silica gel, petroleum ether/
ethyl acetate, 70:30, Rf ϭ 0.17) then gave 3b as colorless crystals
(558 mg, 2.57 mmol, 69%), m.p. 83 °C. IR (KBr): ν˜ ϭ 3509 (OH),
Experimental Section
1
General Remarks: H and 13C NMR: Spectra were recorded with
a Bruker AM 250 instrument at 250 MHz (1H) and 62.9 MHz [13C,
3103, 2924, 2799, 1764, 1699, 1435, 1397, 1331, 1174, 1116, 1090,
additional DEPT (Distortionless Enhancement by Polarization 1061, 950, 911, 729, 712 cmϪ1. H NMR (250 MHz, CDCl3): δ ϭ
1
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Derivatives of Isoerythritol with up to Four Separately Addressable Functionalities
2.44 (t, 3J ϭ 6.2 Hz, 1 H, OH), 4.13 (d, 3J ϭ 6.2 Hz, 2 H, CH2OH),
Diethyl 2-[2-(Hydroxymethyl)allyl]malonate (3e) and Ethyl 5-Meth-
FULL PAPER
2
2
4.36 (s, 2 H, 1-H), 5.11 (d, J ϭ 0.5 Hz, 1 H, 3-H), 5.18 (d, J ϭ ylene-2-oxotetrahydropyran-3-carboxylate (6): A suspension of so-
0.5 Hz, 1 H, 3-H), 7.71Ϫ7.76 (m, 2 H), 7.83Ϫ7.88 (m, 2 H) ppm. dium hydride (168 mg, 7.00 mmol) in THF (5 mL) was treated at
13C NMR (62.9 MHz, CDCl3, DEPT): δ ϭ 39.5 (Ϫ, C-1), 64.2 (Ϫ, 0 °C with a solution of diethyl malonate (1057 mg, 6.60 mmol) in
CH2OH), 114.1 (Ϫ, C-3), 123.4 (ϩ), 131.9 (Cquat), 134.2 (ϩ), 142.9 THF (2 mL). After the evolution of hydrogen had ceased, the sol-
(Cquat), 168.3 (Cquat) ppm. MS (EI, 70 eV): m/z (%) ϭ 217 (5) [Mϩ],
vent was removed under reduced pressure, and the resulting diethyl
160 (37), 130 (40), 104 (58), 77 (72), 76 (100) [C6H4ϩ], 50 (50), 41 sodiomalonate was dissolved in DMF (5 mL). This solution was
(45). C12H11NO3 (217.22): calcd. C 66.35, H 5.10, N 6.45; found added to a solution of 5-methylene[1,3,2]dioxathian-2-one (2,
C, 66.13, H 4.93, N 6.38.
737 mg, 5.50 mmol) in DMF (2.5 mL), and then the reaction mix-
ture was stirred at 60 °C. After 3 h, the reaction was quenched with
water (50 mL). The aqueous phase was extracted with diethyl ether
(3 ϫ 10 mL), and the combined organic extracts were washed with
water, dried with anhydrous MgSO4, and concentrated under re-
duced pressure. Flash chromatography (50 g of silica gel, hexane/
ethyl acetate, 75:25) gave two fractions. Fraction I (Rf ϭ 0.19) pro-
vided diethyl 2-[2-(hydroxymethyl)allyl]malonate (3e) as a colorless
liquid (505 mg, 2.19 mmol, 40%). IR (film): ν˜ ϭ 3448 (OH), 3081,
2984, 2938, 2874, 1734, 1653, 1466, 1447, 1393, 1370, 1335, 1234,
1153, 1036, 908, 860, 790 cmϪ1. 1H NMR (250 MHz, CDCl3): δ ϭ
1.26 (t, 3J ϭ 7.1 Hz, 6 H) 1.75 (br. s, 1 H, OH), 2.69 (d, 3J ϭ
2-(Phenoxymethyl)prop-2-en-1-ol (3c) and 3-Phenoxy-2-(phenoxy-
methyl)propene (4c): A suspension of sodium hydride (64.4 mg,
2.68 mmol) in THF (3 mL) was cooled to 0 °C and treated with
phenol (253 mg, 2.69 mmol). After the evolution of hydrogen had
ceased, the solvent was evaporated under reduced pressure, and the
resulting sodium phenolate was dissolved in DMF (2 mL). This
solution was added to a solution of 2 (300 mg, 2.24 mmol) in DMF
(1 mL), and the reaction mixture was stirred at 50 °C. After 2.5 h,
the reaction was quenched with water (20 mL). The aqueous phase
was extracted with diethyl ether (3 ϫ 10 mL), and the combined
organic extracts were washed with water, dried with anhydrous
MgSO4, and concentrated under reduced pressure. Flash chroma-
tography (30 g of silica gel, petroleum ether/ethyl acetate, 75:25)
yielded two fractions. Fraction I (Rf ϭ 0.22) provided 3c as a color-
less liquid (255 mg, 1.55 mmol, 69%). IR (film): ν˜ ϭ 3346 (OH),
3064, 3040, 2923, 2868, 1599, 1587, 1496, 1457, 1400, 1241, 1172,
3
7.8 Hz, 2 H, 1-H), 3.65 (t, J ϭ 7.8 Hz, 1 H, CHCO2Et), 4.10 (br.
s, 2 H, CH2OH), 4.22 (q, 3J ϭ 7.1 Hz, 4 H), 4.93 (s, 1 H, 3-H),
5.10 (s, 1 H, 3-H) ppm. 13C NMR (62.9 MHz, CDCl3, DEPT): δ ϭ
14.0 (ϩ), 31.7 (Ϫ, C-1), 50.7 (ϩ, CHCO2Et), 61.5 (Ϫ, CO2CH2),
65.8 (Ϫ, CH2OH), 112.4 (Ϫ, C-3), 145.1 (Cquat, C-2), 169.0 (Cquat
,
CO2Et) ppm. MS (EI, 70 eV): m/z (%) ϭ 230 (1) [Mϩ], 185 (35),
160 (90), 139 (40), 111 (100), 82 (27), 67 (20), 55 (22), 41 (15).
C11H18O5 (230.26): calcd. C 57.38, H 7.88; found C 57.12, H 7.62.
Fraction II (Rf ϭ 0.29) provided ethyl 5-methylene-2-oxotetrahydro-
pyran-3-carboxylate (6) as a colorless liquid (141 mg, 766 µmol,
14%). IR (film): ν˜ ϭ 3085, 2986, 2939, 1735, 1660, 1467, 1444,
1079, 1060, 1031, 916, 754, 691 cmϪ1 1H NMR (250 MHz,
.
CDCl3): δ ϭ 1.74 (s, 1 H, OH), 4.27 (s, 2 H, 1-H), 4.60 (s, 2 H,
CH2OPh), 5.29 (s, 2 H, 3-H), 6.92Ϫ7.00 (m, 3 H), 7.26Ϫ7.32 (m,
2 H) ppm. 13C NMR (62.9 MHz, CDCl3, DEPT): δ ϭ 63.9 (Ϫ, C-
1), 68.9 (Ϫ, CH2OPh), 113.7 (Ϫ, C-3), 114.6 (ϩ), 121.0 (ϩ), 129.4
(ϩ), 144.1 (Cquat, C-2), 158.4 (Cquat) ppm. MS (EI, 70 eV): m/z
(%) ϭ 164 (30) [Mϩ], 145 (29), 133 (32), 131 (23), 95 (30), 94 (100)
[C6H6Oϩ], 77 (20), 43 (18), 41 (30). C10H12O2·0.5H2O (173.21):
calcd. C 69.34, H 7.57; found C 69.16, H 7.63. Fraction II (Rf ϭ
0.67) provided 4c as a colorless liquid (21 mg, 87 µmol, 6%). 1H
NMR (250 MHz, CDCl3): δ ϭ 4.65 (s, 4 H, 3-H), 5.42 (s, 2 H, 1-
H), 6.90Ϫ7.02 (m, 6 H, Ph-H), 7.25Ϫ7.37 (m, 4 H, Ph-H) ppm.
13C NMR (62.9 MHz, CDCl3, DEPT): δ ϭ 68.5 (Ϫ, C-3), 114.7
(ϩ), 115.7 (Ϫ, C-1), 121.00 (ϩ), 129.4 (ϩ), 140.4 (Cquat, C-2), 158.5
(Cquat) ppm. C16H16O2 (240.30): calcd. C 79.97, H 6.71; found C
79.74, H 7.02.
1379, 1345, 1244, 1203, 1149, 1042, 913, 857, 831, 749 cmϪ1 1H
.
NMR (250 MHz, CDCl3): δ ϭ 1.26 (t, 3J ϭ 7.1 Hz, 3 H) 2.84 (dd,
2J ϭ 16.1, 3J ϭ 6.9 Hz, 1 H, 4-H), 3.05 (dd, 2J ϭ 16.1, 3J ϭ 8.5 Hz,
3
3
1 H, 4-H), 3.66 (dd, J ϭ 8.5, J ϭ 6.9 Hz, 1 H, 3-H), 4.19Ϫ4.31
(m, 2 H, CH2Me), 4.79 (s, 2 H, 6-H), 5.11Ϫ5.14 (m, 2 H, ϭCH2)
ppm. 13C NMR (62.9 MHz, CDCl3, DEPT): δ ϭ 14.0 (ϩ), 29.3
(Ϫ, C-4), 47.2 (ϩ, C-3), 62.1 (Ϫ), 71.9 (Ϫ, C-6), 113.4 (Ϫ, ϭCH2),
135.7 (Cquat, C-5), 167.6 (Cquat), 168.0 (Cquat) ppm. MS (EI, 70 eV):
m/z (%) ϭ 184 (3) [Mϩ], 138 (17), 111 (100), 82 (17), 67 (20), 55
(12). C9H12O4 (184.19): calcd. C 58.69, H 6.57; found C 58.92, H
6.55. According to the procedure above — starting with sodioma-
lonate, prepared as described above from diethyl malonate (721 mg,
2-(Acetoxymethyl)prop-2-en-1-ol (3d) and 1,3-Diacetoxy-2-methyl-
enepropane (4d): Sodium acetate (367 mg, 4.47 mmol) and 18-
crown-6 (6.0 mg, 23 µmol) was added to a solution of 2 (300 mg,
2.24 mmol) in DMF (3 mL). The reaction mixture was stirred for
1 h at 100 °C. The mixture was cooled to room temp. and then
hydrolyzed with water (10 mL). The aqueous phase was extracted
with ethyl acetate (3 ϫ 10 mL), and the combined organic extracts
were washed with water, dried with anhydrous MgSO4, and concen-
trated under reduced pressure. Flash chromatography (20 g of silica
gel, petroleum ether/ethyl acetate, 50:50) yielded two fractions.
Fraction I (Rf ϭ 0.45) provided 3d as a colorless liquid (201 mg,
1.55 mmol, 69%). IR (film): ν˜ ϭ 3433 (OH), 3095, 2936, 2875,
4.50 mmol) in DMF (4.5 mL), and compound
2 (300 mg,
2.24 mmol) in DMF (1 mL) — the reaction mixture after 48 h was
diluted with EtOAc (50 mL) and poured into 10% aqueous H2SO4
(50 mL). The organic phase was washed with H2O (30 mL), brine
(30 mL), and dried with MgSO4. Evaporation of the solvent and
chromatography (30 g of silica gel, hexane/ethyl acetate, 75:25) gave
two fractions. Fraction I (Rf ϭ 0.19) provided diethyl 2-[2-
(hydroxymethyl)allyl]malonate (3e) as a colorless liquid (45 mg, 196
µmol, 9%). Fraction II (Rf ϭ 0.29) provided ethyl 5-methylene-2-
oxotetrahydropyran-3-carboxylate (6) as a colorless liquid (193 mg,
1.05 mmol, 47%).
1744, 1660, 1455, 1376, 1243, 1029, 951, 916, 844 cmϪ1. H NMR
1
(250 MHz, CDCl3): δ ϭ 1.91 (br. s, 1 H, OH), 2.10 (s, 3 H, COCH3) 5-(Hydroxymethyl)-2,2-dioxo[1,3,2]dioxathian-5-ol (7): A solution
4.14 (s, 2 H, 1-H), 4.64 (s, 2 H, CH2OAc), 5.18 (s, 1 H, 3-H), 5.24 of ruthenium() chloride (15 mg, 72 µmol) and sodium periodate
(s, 1 H, 3-H) ppm. 13C NMR (62.9 MHz, CDCl3, DEPT): δ ϭ 20.9 (1.59 g, 7.45 mmol) in water (10 mL) was added to a solution of 5-
(ϩ, COCH3), 63.7 (Ϫ, C-1), 64.7 (Ϫ, CH2OAc), 114.4 (Ϫ, C-3), methylene-2-oxo[1,3,2]dioxathiane (2, 500 mg, 3.73 mmol) in aceto-
143.3 (Cquat, C-2), 171.0 (Cquat, COMe) ppm. MS (CI, NH3): m/z nitrile (60 mL) at 0 °C. After 3 min, the mixture was filtered
(%) ϭ 165 (15) [M ϩ NH4 ϩ NH3], 148 (100) [M ϩ NH4ϩ], 131 through Celite (1 cm), and the solvent was evaporated under re-
ϩ
(5) [M ϩ Hϩ]. Fraction II (Rf ϭ 0.65) provided 4d as a colorless duced pressure. Flash chromatography (15 g of silica gel, light
liquid (35 mg, 203 µmol, 9%). Spectral data are in agreement with
petroleum ether/EtOAc, 35:65, Rf ϭ 0.26) gave 7 as colorless crys-
tals (591 mg, 86%), m.p. 94Ϫ96 °C. IR (KBr): ν˜ ϭ 3399 (OH),
those reported previously.[15b]
Eur. J. Org. Chem. 2003, 2138Ϫ2143
www.eurjoc.org
 2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
2141

M. Friedrich, A. I. Savchenko, A. Wächtler, A. de Meijere
FULL PAPER
2959, 1453, 1391, 1354, 1316, 1197, 1152, 1111, 1032, 997, 979,
2252, 1737, 1727, 1378, 1249, 1151, 989, 836 cmϪ1 1H NMR
.
921, 901, 847, 806, 782, 690 cmϪ1
.
1H NMR (250 MHz, (250 MHz, [D6]DMSO): δ ϭ 2.02 (s, 3 H, COCH3), 2.63 (s, 2 H,
2
[D6]DMSO): δ ϭ 3.34 (s, 2 H, CH2OH), 4.42 [d, J ϭ 10.6 Hz, 2
2-H), 3.25Ϫ3.42 (m, 2 H, CH2OH), 3.90 (d, 2J ϭ 11.2 Hz, 1 H,
CH2OAc), 4.00 (d, 2J ϭ 11.2 Hz, 1 H, CH2OAc), 5.07 (t, 3J ϭ
H, 4(6)-H], 4.79 [d, 2J ϭ 10.6 Hz, 2 H, 4(6)-H], 5.24 (br. s, 1 H,
OH), 5.73 (br. s, 1 H, OH) ppm. 13C NMR (62.9 MHz, [D6]DMSO, 5.7 Hz, 1 H, CH2OH), 5.40 (s, 1 H, 2-OH) ppm. 13C NMR
DEPT): δ ϭ 62.4 (Ϫ, CH2OH), 66.4 (Cquat, C-5), 79.0 [Ϫ, C-4(6)] (62.9 MHz, [D6]DMSO, DEPT): δ ϭ 20.9 (ϩ), 24.00 (Ϫ, C-2), 64.1
ppm. MS (CI, NH3): m/z (%) ϭ 403 (3) [2 M ϩ NH3 ϩ NH4ϩ], (Ϫ, CH2OH), 66.2 (Ϫ, CH2OAc), 71.6 (Cquat, C-3), 118.4 (Cquat
,
386 (10) [2 M ϩ NH4ϩ], 236 (22) [M ϩ2 NH3 ϩ NH4ϩ], 219 (100) CN), 170.4 (Cquat) ppm. MS (CI, NH3): m/z (%) ϭ 364 (5) [2 M ϩ
[M ϩ NH3 ϩ NH4ϩ], 202 (16) [M ϩ NH4ϩ]. C4H8O6S (184.16):
NH4ϩ], 191 (100) [M ϩ NH4ϩ]. An analytical sample was obtained
by kugelrohr distillation, b.p. 140Ϫ150 °C/0.01 Torr.
calcd. C 26.09, H 4.38; found C 26.20, H 4.32.
C7H11NO4·0.5H2O (182.17): calcd. C 46.15, H 6.64; found C 46.72,
H 6.34.
N-[2-(Azidomethyl)-2,3-dihydroxypropyl]phthalimide (9): Potassium
phthalimide (185 mg, 1.0 mmol) was added to a solution of 5-(hyd-
roxymethyl)-2,2-dioxo[1,3,2]dioxathian-5-ol (7, 94 mg, 0.51 mmol) 2-(Azidomethyl)-2,3-dihydroxypropyl Acetate (12b): A solution of
in DMF (1.5 mL), and the resulting mixture was stirred at
60 °C for 4 h and then at 100 °C for 2 h. Sodium azide (65 mg,
1.0 mmol) was then added and the mixture was stirred at 100 °C.
After 2 h, the reaction was quenched by adding a mixture of water
and brine (1:1, 20 mL). The aqueous phase was extracted with ethyl
acetate (3 ϫ 10 mL), and the combined organic extracts were
washed with brine, dried with anhydrous MgSO4, and concentrated
under reduced pressure. The solid residue (129 mg) was recrys-
11 (154 mg, 0.68 mmol) and sodium azide (65 mg, 1.00 mmol) in
DMF (3 mL) was stirred at 25 °C for 16 h. The solvent was evapo-
rated under reduced pressure and the residue was dissolved in a
mixture of THF and Et2O (1:1.5, 10 mL). Water (5 drops) and
concentrated sulfuric acid (1 drop) were added, and the mixture
was stirred at ambient temperature for 1 h. Neutralization with
solid NaHCO3, filtration, evaporation of the solvent, and sub-
sequent kugelrohr distillation gave 12b as a colorless liquid
tallized from ether/hexane to provide 9 as colorless crystals (45 mg, (106 mg, 0.56 mmol, 82%), b.p. 120Ϫ130 °C/0.01 Torr. IR (film):
33%), m.p. 80Ϫ81 °C. IR (KBr): ν˜ ϭ 3478, 3400, 3333, 3099, 3045, ν˜ ϭ 3420 (OH), 2943, 2886, 2107, 1728 (CO), 1445, 1378, 1243,
3029, 2182, 2104, 1776, 1701, 1402, 1384, 1236, 1038, 922, 909, 1118, 1047, 992, 927, 795 cmϪ1. 1H NMR (250 MHz, [D6]DMSO):
1
3
888, 726, 714 cmϪ1. H NMR (250 MHz, CDCl3): δ ϭ 2.90 (br. s, δ ϭ 2.01 (s, 3 H, COCH3), 3.24 (s, 2 H), 3.33 (d, J ϭ 5.6 Hz, 2
2
2
2 H, 2 OH), 3.39 (d, J ϭ 12.7 Hz, 1 H), 3.49 (s, 2 H, CH2N3), 3.50
(d, J ϭ 12.6 Hz, 1 H), 3.83 (d, J ϭ 14.6 Hz, 1 H, CH2OH), 3.90
H, 3-H), 3.88 (d, J ϭ 11.1 Hz, 1 H, 1-H), 3.97 (d, J ϭ 11.1 Hz,
1 H, 1-H), 4.86 (t, J ϭ 5.6 Hz, 1 H, 3-OH), 5.12 (s, 1 H, 2-OH)
2
3
(d, 2J ϭ 14.6 Hz, 1 H, CH2OH), 7.74Ϫ7.78 (m, 2 H), 7.86Ϫ7.90 ppm. 13C NMR (62.9 MHz, [D6]DMSO, DEPT): δ ϭ 21.0 (ϩ),
(m, 2 H) ppm. 13C NMR (62.9 MHz, CDCl3, DEPT): δ ϭ 41.5 (Ϫ, 53.8 (Ϫ), 62.9 (Ϫ, C-3), 65.3 (Ϫ, C-1), 73.9 (Cquat, C-2), 170.51
CH2N3), 55.3 (Ϫ, C-1), 63.9 (Ϫ, C-3), 75.1 (Cquat, C-2), 123.8 (ϩ), (Cquat) ppm. MS (CI, NH3): m/z (%) ϭ 396 (34) [2 M ϩ NH4ϩ],
131.5 (Cquat), 134.6 (ϩ), 169.5 (Cquat, CϭO) ppm. MS (CI, NH3): 207 (100) [M ϩ NH4ϩ]. C6H11N3O4 (189.17): calcd. C 38.10, H
m/z (%) ϭ 294 (100) [M ϩ NH4ϩ], 237 (20). C12H12N4O4 (276.25):
5.86; found C 37.89, H 5.71.
calcd. C 52.17, H 4.38; found C 52.55, H 4.27.
Sodium 2-(Acetoxymethyl)-2-hydroxy-3-azidopropyl Sulfate (13b):
Sodium azide (29 mg, 446 µmol) was added to a solution of 11
(100 mg, 442 µmol) in DMF (5 mL), and the mixture was stirred
at room temp. for 1 h. Evaporation of the solvent gave 13b as a
5-Hydroxy-2,2-dioxo[1,3,2]dioxathian-5-ylmethyl Acetate (11): Pyri-
dine (607 mg, 7.67 mmol) and acetic anhydride (783 mg,
7.67 mmol) were added to a solution of 7 (706 mg, 3.83 mmol) in
anhydrous EtOAc (10 mL), and the mixture was stirred at room colorless solid (129 mg, 442 µmol, 100%). IR (KBr): ν˜ ϭ 3467
temp. for 20 h. Evaporation of the solvent under reduced pressure,
followed by filtration through silica gel (15 g; light petroleum ether/
EtOAc, 50:50, Rf ϭ 0.44) gave the title compound mixed with pyri-
dine. Evaporation of the pyridine under reduced pressure (10Ϫ3
mbar) overnight gave 11 as colorless crystals (832 mg, 3.68 mmol,
96%), m.p. 67Ϫ68 °C. IR (KBr): ν˜ ϭ 3378 (OH), 2957, 1717 (CO),
(OH), 2113, 1734 (CO), 1662, 1457, 1387, 1254, 1137, 1071, 1049,
1
1015, 936, 829 cmϪ1. H NMR (250 MHz, [D6]DMSO): δ ϭ 2.03
(s, 3 H), 3.28 (s, 2 H, 3-H), 3.72 (s, 2 H, 1-H), 3.88 (d, 2J ϭ 9.8 Hz,
2
1 H, CH2OAc), 3.97 (d, J ϭ 9.8 Hz, 1 H, CH2OAc), 5.51 (s, 1 H,
OH) ppm. 13C NMR (62.9 MHz, [D6]DMSO, DEPT): δ ϭ 20.9
(ϩ), 53.9 (Ϫ, CH2N3), 65.2 (Ϫ, C-1), 67.4 (Ϫ, CH2OAc), 72.8
1465, 1405, 1386, 1321, 1268, 1197, 1175, 1109, 1058, 1009, 988, (Cquat, C-2), 170.4 (Cquat) ppm. MS (ESI): anions: m/z (%) ϭ 269
941, 823, 776, 706 cmϪ1 1H NMR (250 MHz, [D6]DMSO): δ ϭ (100) [AϪ], 560 (84) [M ϩ AϪ]; cations: m/z (%) ϭ 314 (16) [M ϩ
.
2.05 (s, 3 H), 4.04 (s, 2 H), 4.49 [d, 2J ϭ 11.2 Hz, 2 H, 4(6)-H],
Naϩ], 605 (54) [2 M ϩ Naϩ], 896 (100) [3 M ϩ Naϩ].
2
4.75 [d, J ϭ 11.2 Hz, 2 H, 4(6)-H], 6.10 (br. s, 1 H, OH) ppm. 13C
Sodium 2-(Acetoxymethyl)-2-hydroxy-3-[(tolylsulfonyl)amino]propyl
Sulfate (13c): Sodium p-toluenesulfonamide (44 mg, 221 µmol) was
added to a solution of 11 (50 mg, 221 µmol) in THF (5 mL), and
the mixture was stirred at room temp. for 15 h. Evaporation of the
solvent gave 13c (94 mg, 221 µmol, 100%) as a colorless solid. IR
(KBr): ν˜ ϭ 3500 (OH), 3359, 3261, 1739 (CO), 1653, 1599, 1528,
NMR (62.9 MHz, [D6]DMSO, DEPT): δ ϭ 20.8 (ϩ), 63.9 (Ϫ), 65.0
(Cquat, C-5), 77.8 [Ϫ, C-4(6)], 170.2 (Cquat) ppm. MS (CI, NH3): m/
z (%) ϭ 470 (10) [2 M ϩ NH4ϩ], 261 (43) [M ϩ NH3 ϩ NH4ϩ],
244 (100) [M ϩ NH4ϩ]. C6H10O7S (226.20): calcd. C 31.86, H 4.46;
found C 32.20, H 4.35.
3-(Acetoxymethyl)-3,4-dihydroxybutyronitrile (12a): A solution of
11 (50 mg, 221 µmol) and potassium cyanide (16 mg, 246 µmol) in
DMF (1.5 mL) was stirred at 25 °C for 18 h. The solvent was eva-
porated under reduced pressure, and the residue was dissolved in
THF (5 mL). Water (8 µL) and concentrated sulfuric acid (12 µL)
were added, and the mixture was stirred at room temp. for 1 h.
Neutralization by addition of solid NaHCO3, filtration, and evap-
oration of the solvent, followed by flash chromatography (5 g of
silica gel, light petroleum ether/EtOAc, 25:75, Rf ϭ 0.15) gave 12a
1457, 1388, 1307, 1257, 1161, 1097, 1070, 1005, 904, 817, 704 cmϪ1
1H NMR (250 MHz, [D6]DMSO): δ ϭ 2.02 (s, 3 H), 2.34 (s, 3 H),
.
2
2
2.76 (d, J ϭ 6.9 Hz, 1 H, 3-H), 2.78 (d, J ϭ 6.9 Hz, 1 H, 3-H),
3.76 (d, 2J ϭ 11.2 Hz, 1 H, 1-H), 3.84 (d, J ϭ 11.2 Hz, 1 H, 1-H),
2
2
2
4.01 (d, J ϭ 12.1 Hz, 1 H, CH2OAc), 4.25 (d, J ϭ 12.1 Hz, 1 H,
3
CH2OAc), 6.90 (br. s, 1 H, OH), 7.32 (d, J ϭ 8.1 Hz, 2 H), 7.68
(d, 3J ϭ 8.1 Hz, 2 H) ppm. 13C NMR (62.9 MHz, [D6]DMSO,
DEPT): δ ϭ 20.8 (ϩ), 21.2 (ϩ), 48.8 (Ϫ, C-3), 56.2 (Cquat, C-2),
63.4 (Ϫ, C-1), 66.0 (Ϫ, CH2OAc), 125.8 (ϩ), 129.4 (ϩ), 141.7
as a colorless liquid (30 mg, 78%). IR (film): ν˜ ϭ 3387 (OH), 2937, (Cquat), 142.5 (Cquat), 170.3 (Cquat) ppm. MS (ESI): anions: m/z
2142  2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim www.eurjoc.org
Eur. J. Org. Chem. 2003, 2138Ϫ2143

Derivatives of Isoerythritol with up to Four Separately Addressable Functionalities
FULL PAPER
[11]
(%) ϭ 397 (100) [AϪ], 525 (17), 696 (22), 816 (8) [M ϩ AϪ]; cations:
m/z (%) ϭ 443 (54) [M ϩ Naϩ], 622 (86), 741 (76), 861 (100) [2 M
ϩ Naϩ].
Cf.: P. D. Bragg, J. K. N. Jones, J. C. Turner, Can. J. Chem.
1959, 37, 1412Ϫ1416.
Cf.: T. J. Tewson, M. Sonderlind, Carbohydr. Chem. 1985, 4,
529Ϫ543.
Cf.: Y. Gao, K. B. Sharpless, J. Am. Chem. Soc. 1988, 110,
7538Ϫ7539.
A. Kruis, H. Hausen, in: Landolt-Börnstein, 6th ed., vol. 4c,
Springer, Heidelberg, 1976, pp. 36Ϫ257.
The overall yields achieved with this sequence (40Ϫ77%) far
exceed those obtained starting with 2-(chloromethyl)allyl chlo-
ride, which has been converted in two steps into 2-(chloro-
methyl)allyl alcohol in 23% overall yield.
[12]
[13]
[14]
[15]
[2-(Hydroxymethyl)oxiranyl]methyl Acetate (14): H2O (1.0 µL, 55.5
µmol) and concentrated sulfuric acid (0.92 mg, 9.41 µmol) were
added to a solution of 13c (40 mg, 95.4 µmol) in THF (1 mL), and
then the mixture was stirred at room temp. for 1 h. Neutralization
with solid NaHCO3, filtration, evaporation of the solvent, and sub-
sequent flash chromatography (2 g of silica gel, petroleum ether/
EtOAc, 25:75) gave 14 as a colorless liquid (5.3 mg, 36.3 µmol,
38%), the spectra of which are in agreement with the ones reported
in the literature.[21]
[15a]
Cf.: O. B.
Chalova, G. P. Chistoedova, T. K. Kiladze, E. V. Germash, E.
A. Kantor, D. L. Rakhmankulov, Zh. Prikl. Khim. 1988, 61,
934Ϫ937 (Chem. Abstr. 1989, 110, 38603b). For a recent syn-
[15b]
thetic application of 2-(chloromethyl)allyl alcohol, see:
A.
Fürstner, H. Weintritt, J. Am. Chem. Soc. 1998, 120,
Acknowledgments
2817Ϫ2825.
[16]
B. M. Trost, R. Braslau, J. Org. Chem. 1988, 53, 532Ϫ537.
This work was supported by E. Merck KGaA, Darmstadt, and the
Fonds der Chemischen Industrie, Frankfurt. We are grateful to Dr.
Burkhard Knieriem (Göttingen) for his careful proofreading of the
final manuscript.
[17] [17a] T. K. M. Shing, V. W.-F. Tai, E. K. W. Tam, Angew. Chem.
1994, 106, 2408Ϫ2409; Angew. Chem. Int. Ed. Engl. 1994, 33,
[17b]
2312Ϫ2313.
T. K. M. Shing, E. K. W. Tam, V. W.-F. Tai,
I. H. F. Chung, Q. Jiang, Chem. Eur. J. 1996, 2, 50Ϫ57.
Two examples have been reported of osmium tetroxide me-
diated dihydroxylation of unsymmetrical methylenepropane-
[18]
[1] [1a]
On a larger scale, diol 1 was prepared from dihydroxyace-
tone dimer adapting a procedure published for the use of tri-
methylsilyl, instead of tert-butyldimethylsilyl, protecting
groups; cf.: J. E. Baldwin, R. M. Adlington, D. G. Marquess,
A. R. Pitt, M. J. Porter, A. T. Russell, Tetrahedron 1996, 52,
2537Ϫ2556. [1b] For the preparation of 1,3-bis(trimethylsiloxy)-
acetone, see: W. Klis, P. W. Erhardt, Synth. Commun. 2000, 30,
4027Ϫ4038. [1c] T. Ehlis, D. Hueglin, J. F. Roeding, WO Patent
2001/085124, 2001 (Chem. Abstr. 2001, 135, 376517).
diol bis(ethers) to form the corresponding isoerythritol deriva-
[18a]
tives:
V. E. Marquez, R. Sharma, S. Wang, N. E. Lewin,
P. M. Blumberg, Biorg. Med. Chem. Lett. 1998, 13, 1757Ϫ1762.
[18b]
For an enantioselective preparation of a diol, see:
E. J.
Corey, A. Guzman-Perez, M. C. Noe, J. Am. Chem. Soc. 1995,
117, 10805Ϫ10816.
T. K. M. Shing, E. K. W. Tam, Tetrahedron Lett. 1999, 40,
2179Ϫ2180.
Cf.: T. Ozturk, N. Saygili, S. Ozkara, M. Pilkington, C. R. Rice,
D. A. Tranter, F. Turksoj, J. D. Wallis, J. Chem. Soc., Perkin
Trans. 1 2001, 407Ϫ414.
T. Itoh, H. Ohara, Y. Takagi, N. Kanda, K. Uneyama, Tetra-
hedron Lett. 1993, 34, 4215Ϫ4218.
2-(Hydroxymethyl)glycerol has been prepared previously by the
so-called formose reaction (i.e., self-condensation of formal-
[19]
[20]
[2]
M. Anada, N. Watanabe, S. Hashimoto, Chem. Commun.
1998, 1517Ϫ1518.
M. Nishizawa, K. Adachi, Y. Hayashi, J. Chem. Soc., Chem.
[3]
[21]
[22]
Commun. 1984, 1637Ϫ1638.
[4]
´
´
Z. Flegelova, M. Patek, J. Org. Chem. 1996, 61, 6735Ϫ6738.
[5]
´
D. A. Alonso, C. Najera, J. Sansano, Tetrahedron 1994, 50,
6603Ϫ6620.
T. A. Kirkland, R. H. Grubbs, J. Org. Chem. 1997, 62,
7310Ϫ7318.
M. Journet, M. Malacria, J. Org. Chem. 1992, 57, 3085Ϫ3093.
The cyclic carbonate of 1 has been prepared also by a retro-
DielsϪAlder reaction of an appropriate norbornene derivative;
cf.: T. Takata, M. Igarashi, T. Endo, J. Polym. Sci., Part A:
Polym. Chem. 1991, 29, 781Ϫ784.
I. Shimizu, Y. Ohashi, J. Tsuji, Tetrahedron Lett. 1984, 25,
5183Ϫ5186.
[6]
dehyde), but was obtained as a mixture with three other main
[22a]
products.
Cf.: T. Matsumoto, M. Komiyama, S. Inoue,
[7]
[8]
[22b]
Chem. Lett. 1980, 839Ϫ842.
Y. Shigemasa, T. Ueda, H.
Saimoto, Bull. Chem. Soc. Jpn. 1990, 63, 389Ϫ394.
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K. K. Ogilvie, N. Nguyen-ba, R. G. Hamilton, Can. J.
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Received February 22, 2002
[9]
[24]
[10]
Cf.: B. B. Lohray, Synthesis 1992, 1035Ϫ1052.
Eur. J. Org. Chem. 2003, 2138Ϫ2143
www.eurjoc.org
 2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
2143