Rhodium-catalyzed decarbonylation of aldoses

Article abstract of DOI:10.1021/jo7017729

(Chemical Equation Presented) A catalytic procedure is described for decarbonylation of unprotected aldoses to afford alditols with one less carbon atom. The reaction is performed with the rhodium complex Rh(dppp)₂Cl in a refluxing diglyme-DMA solution. A slightly improved catalyst turnover is observed when a catalytic amount of pyridine is added. Under these conditions most hexoses and pentoses undergo decarbonylation into the corresponding pentitols and tetrols in isolated yields around 70%. The reaction has been applied as the key transformation in a five-step synthesis of L-threose from D-glucose.

Full text of DOI:10.1021/jo7017729

Rhodium-Catalyzed Decarbonylation of Aldoses
and co-workers exploited this transformation with stoichiometric
amounts of Wilkinson’s catalyst (Rh(PPh3)3Cl). The decarbo-
5
nylation was performed in N-methyl-2-pyrrolidinone (NMP) at
Rune Nygaard Monrad and Robert Madsen*
1
3
30 °C and afforded alditols in isolated yields ranging from
7% to 87%. The high temperature is due to the fact that only
Center for Sustainable and Green Chemistry, Building 201,
Department of Chemistry, Technical UniVersity of Denmark,
DK-2800 Lyngby, Denmark
5
a minute amount of the aldose is present as the free aldehyde
in solution. Ketohexoses underwent decarbonylation under the
same conditions, but in this case the main product was furfuryl
alcohol since ketohexoses are easily dehydrated into 5-hy-
rm@kemi.dtu.dk
6
droxymethylfurfural. The reactions are stoichiometric since Rh-
ReceiVed August 14, 2007
(PPh3)3Cl is converted into Rh(CO)(PPh3)2Cl, which will not
perform the decarbonylation unless the temperature is raised to
about 200 °C. However, if additives are added the decarbony-
lation of D-glucose can be achieved with 5-10% of Rh(PPh3)3-
7
Cl in an NMP solution. The additives are either diphenylphos-
8
phoryl azide, sodium azide (both at 50 °C for 24 h), or a 1,ω-
bis(diphenylphosphino)alkane (alkane ) ethane, butane, hexane,
at 130 °C for 24 h). In all cases, the conversion was rather slow
and only a 30-49% HPLC yield of D-arabinitol was obtained
A catalytic procedure is described for decarbonylation of
unprotected aldoses to afford alditols with one less carbon
atom. The reaction is performed with the rhodium complex
7
in 24 h.
Earlier work has shown that catalytic decarbonylations of
aldehydes can be carried out with rhodium catalysts containing
Rh(dppp)
2
Cl in a refluxing diglyme-DMA solution. A
9
a bidentate phosphine ligand. The complex Rh(dppp)2Cl (dppp
slightly improved catalyst turnover is observed when a
catalytic amount of pyridine is added. Under these conditions
most hexoses and pentoses undergo decarbonylation into the
corresponding pentitols and tetrols in isolated yields around
)
1,3-bis(diphenylphosphino)propane) has been shown to
9
decarbonylate simple aldehydes in neat solution. Unfortunately,
Rh(dppp)2Cl is not very soluble in organic solvents and has
only found limited use as a decarbonylation catalyst. Recently,
70%. The reaction has been applied as the key transformation
we reinvestigated the application of Rh(dppp) Cl in this reaction
2
in a five-step synthesis of L-threose from D-glucose.
and found that the decarbonylation of a wide range of aldehydes
could be effectively achieved in refluxing diglyme and that the
active catalyst could be generated in situ from commercially
available RhCl3‚3H2O and dppp.
Herein, we describe the catalytic decarbonylation of unpro-
tected aldoses by the use of Rh(dppp)2Cl. The reaction gives
easy access to a number of chiral polyols which can be used as
building blocks for further synthesis. Furthermore, the decar-
bonylation has been applied as the key step in a concise
synthesis of L-threose from D-glucose.
Extending or shortening the carbon chain in unprotected
aldoses has been a subject in carbohydrate chemistry for more
10
1
than a century. Although many methods are known for chain
2
elongation of aldoses there are only a few procedures for
shortening the carbon chain. The Ruff degradation converts salts
3
of aldonic acids into one carbon shorter aldoses. The reaction
is performed with hydrogen peroxide in the presence of iron-
(III) or copper(II) salts and often occurs in a moderate yield.
The initial experiments were performed with D-glucose as
the substrate. It soon became clear that the decarbonylation could
not be achieved with an in situ generated catalyst. When glucose,
RhCl3‚3H2O, and dppp were mixed in refluxing diglyme the
reaction immediately turned black due to precipitation of
rhodium metal. Our earlier work has shown that Rh(III) is
Another oxidative degradation reaction converts aldoses into
4
salts of aldonic acids with loss of one carbon atom. This
reaction is carried out with molecular oxygen in an alkaline
solution and gives rise to a good yield in most cases. Moreover,
these procedures for shortening the carbon chain both involve
stoichiometric amounts of inorganic salts.
Aldoses are aldehydes that can undergo a C-H insertion
reaction with a metal followed by decarbonylation. This
transformation converts Cn aldoses into Cn-1 alditols. Andrews
10
reduced to Rh(I) by dppp, but glucose is also a reducing agent
and is probably responsible for the further reduction to Rh(0).
It was also attempted to form the active catalyst by mixing
RhCl3‚3H2O and dppp in refluxing diglyme and then adding
glucose. However, these experiments mainly led to decomposi-
tion of the carbohydrate. As a result, it was decided to use a
preformed catalyst, Rh(dppp)2Cl, which can be prepared in two
(1) Gy o¨ rgyde a´ k, Z.; Pelyv a´ s, I. F. Monosaccharide Sugars: Chemical
Synthesis by Chain Elongation, Degradation, and Epimerization; Academic
Press: San Diego, CA, 1998.
(2) For recent examples, see: (a) Palmelund, A.; Madsen, R. J. Org.
Chem. 2005, 70, 8248. (b) Hotchkiss, D.; Soengas, R.; Simone, M. I.; van
Ameijde, J.; Hunter, S.; Cowley, A. R.; Fleet, G. W. J. Tetrahedron Lett.
(5) Andrews, M. A.; Gould, G. L.; Klaeren, S. A. J. Org. Chem. 1989,
54, 5257.
(6) Andrews, M. A. Organometallics 1989, 8, 2703.
(7) Beck, R. H. F.; Elseviers, M.; Lemmens, H. O. J. EP 0716066A1,
1996.
2
2
2
004, 45, 9461. (c) Hunter, D. F. A.; Fleet, G. W. J. Tetrahedron: Asymmetry
003, 14, 3831. (d) Jørgensen, M.; Iversen, E. H.; Madsen, R. J. Org. Chem.
001, 66, 4625.
(3) (a) Hourdin, G.; Germain, A.; Moreau, C.; Fajula, F. J. Catal. 2002,
2
6
09, 217. (b) Ji rˇ i cˇ n y´ , V.; Stan eˇ k, V. Collect. Czech. Chem. Commun. 1995,
0, 863.
(8) O’Connor, J. M.; Ma, J. J. Org. Chem. 1992, 57, 5075.
(9) Doughty, D. H.; Pignolet, L. H. J. Am. Chem. Soc. 1978, 100, 7083.
(10) Kreis, M.; Palmelund, A.; Bunch, L.; Madsen, R. AdV. Synth. Catal.
2006, 348, 2148.
(4) (a) Hendriks, H. E. J.; Kuster, B. F. M.; Marin, G. B. Carbohydr.
Res. 1991, 214, 71. (b) Humphlett, W. J. Carbohydr. Res. 1967, 4, 157.
10.1021/jo7017729 CCC: $37.00 © 2007 American Chemical Society
9
782
J. Org. Chem. 2007, 72, 9782-9785
Published on Web 11/03/2007

TABLE 1. Decarbonylation of D-Glucose into D-Arabinitol
amount of
Rh(dppp)2Cl, %
reaction
time, h
isolated
yield, %
entry
additive
none
1
2
3
4
5
6
7
10
5
5
5
5
9
11
9.5
9
9.5
9.5
8
71
44
39
51
55
58
71
none
7% AcOH
15% AcOH
6% pyridine
13% pyridine
6% pyridine
5
8
FIGURE 1. CO evolution during the course of the decarbonylation
see the Experimental Section for details).
(
TABLE 2. Decarbonylation of Pentoses and Hexoses
steps from RhCl3‚3H2O.11 The reaction with this catalyst gave
D-arabinitol as the main product, but the decarbonylation was
still accompanied by significant decomposition due to the poor
solubility of glucose in diglyme. Several cosolvents were
investigated and it was found that smaller amounts of water,
NMP, or N,N-dimethylacetamide (DMA) gave rise to a homo-
geneous reaction mixture. Unfortunately, water forms an azeo-
trope with diglyme with a boiling point of 99 °C, which is much
lower than the boiling point of diglyme (162 °C). The decar-
bonylation requires a rather high temperature in order to proceed
at a reasonable rate and the reactions in diglyme-water mixtures
proceeded too slowly and were highly dependent on the
diglyme-water ratio and the scale. NMP was used in the earlier
decarbonylations with Rh(PPh3)3Cl5 and we have shown that
reaction
isolated
yield, %
entry
aldose
methoda time, h
alditol
1
2
3
4
5
6
7
8
9
D-arabinose
D-arabinose
D-ribose
D-ribose
D-xylose
A
B
A
B
A
B
A
B
A
9
6.5
8
6.5
8
7.5
9
erythritol
erythritol
erythritol
erythritol
D-threitol
D-threitol
D-arabinitol
D-arabinitol
5-deoxy-
L-arabinitol
5-deoxy-
L-arabinitol
D-arabinitol
D-arabinitol
1-acetylamino-
1-deoxy-
D-arabinitol
1-acetylamino-
1-deoxy-
68
70
71
76
70
74
69
72
66
D-xylose
D-mannose
D-mannose
L-rhamnose
8
11
-7
simple aldehydes could be decarbonylated in NMP with a
10 L-rhamnose
B
10
71
catalyst generated from RhCl3‚3H2O and dppp.10 Glucose also
11
12
13
D-galactose
D-galactose
N-acetyl-
A
B
A
9
8
16
39
56
42
underwent decarbonylation with Rh(dppp)2Cl in a diglyme-
NMP mixture, but it was difficult to remove the high-boiling
NMP (bp 202 °C) in the workup. DMA (bp 165 °C), on the
other hand, was easier to remove and gave similar results as
NMP. We therefore selected a mixture of diglyme and DMA
for the decarbonylations of monosaccharides. The progress of
the reaction could be monitored by measuring the evolution of
carbon monoxide (Figure 1). The solvents were removed in the
workup by diluting the reaction with water and washing the
mixture with dichloromethane. This afforded D-arabinitol in 71%
isolated yield from D-glucose with 10% of Rh(dppp)2Cl (Table
-D-glucosamine
14
N-acetyl-
D-glucosamine
B
14.5
40b
-
D-arabinitol
a
A: 10% Rh(dppp)2Cl. B: 8% Rh(dppp)2Cl, 6% pyridine. b 15% of
pyridine was used.
to incomplete conversion and decomposition (Table 1, entry 2
and Figure 1). It is known, however, that the mutarotation of
1
, entry 1). The major byproduct was 1,4-anhydro-D-arabinitol,
1
3
aldoses can be accelerated by acid or base. Therefore, several
experiments were performed in the presence of acetic acid or
pyridine (Table 1, entries 3-6). Both additives had a beneficial
effect and made it possible to obtain higher yields with a shorter
reaction time. Pyridine gave the best result and it was therefore
decided to carry out the decarbonylation in the presence of 6%
of pyridine (Figure 1). Under these conditions complete conver-
sion of glucose was achieved with 8% of Rh(dppp)2Cl in 8 h
which was isolated in 20% yield and characterized as the
corresponding triacetate. Only traces were observed of 2,5-
anhydro-D-arabinitol (1,4-anhydro-D-lyxitol) and both anhydro
sugars are probably formed from the parent arabinitol due to
the high reaction temperature. It was not possible to obtain 1,4-
anhydro-D-arabinitol as the major product by increasing the
reaction time since these experiments were accompanied by
significant decomposition.
(Table 1, entry 7).
The decarbonylation still required a rather high catalyst
loading due to the tiny amount of the free aldehyde at
The reaction was then applied to a number of other monosac-
charides (Table 2). The experiments were performed in the
presence and in the absence of pyridine to illustrate the effect
of the added base. The pentoses generally reacted slightly faster
than the hexoses (Table 2 and Figure 1). Arabinose, ribose,
xylose, mannose, and rhamnose gave similar yields as glucose
1
2
equilibrium. A lower catalyst loading gave a lower yield due
(
11) (a) van der Ent, A.; Onderdelinden, A. L. Inorg. Synth. 1990, 28,
0. (b) James, B. R.; Mahajan, D. Can. J. Chem. 1979, 57, 180.
12) Glucose exists as a mixture of the free aldehyde (0.019%), the
9
(
hydrated aldehyde (0.022%), two pyranose forms (98.6%), and two furanose
forms (1.29%) in an aqueous solution at 82 °C; see: Maple, R. R.;
Allerhand, A. J. Am. Chem. Soc. 1987, 109, 3168.
(13) Isbell, H. S.; Pigman, W. AdV. Carbohydr. Chem. Biochem. 1969,
24, 13.
J. Org. Chem, Vol. 72, No. 25, 2007 9783

one step.19 Unfortunately, when we applied this procedure to 1
we only obtained 3 in 40-50% yield, which is much lower
than the 91% yield for the two-step procedure. Aldehyde 3
crystallizes as the dimer, but slowly equilibrates in aqueous
solution to form the monomer. Contrary to the unprotected
aldoses, aldehyde 3 is easy to dissolve in pure diglyme. Again,
it was not possible to conduct the decarbonylation with an in
situ generated catalyst from RhCl3‚3H2O and dppp since this
experiment only led to precipitation of rhodium metal. However,
when aldehyde 3 was submitted to 2% of Rh(dppp)2Cl, clean
decarbonylation occurred into 1,2-O-isopropylidene-â-L-threo-
furanose (4). Subsequent removal of the acetal then afforded
L-threose in an overall yield of 71% from D-glucose. L-Threose
is a syrup and exists as an almost equal mixture of the R- and
the â-anomer together with a small amount of the hydrate of
the aldehyde.
SCHEME 1
In conclusion, we have developed a catalytic procedure for
decarbonylation of unprotected and partially protected carbo-
hydrate aldehydes. This transformation will open new possibili-
ties for using carbohydrates as chiral starting materials in
synthetic chemistry.
while the yields with galactose and N-acetylglucosamine were
lower. Galactose is less soluble in diglyme-DMA than the other
aldoses while N-acetylglucosamine is known to decarbonylate
5
slowly due to coordination with the N-acetyl group. The long
Experimental Section
reaction time and the high temperature did result in some
decomposition of N-acetylglucosamine during the course of the
reaction. In all cases, however, the addition of pyridine gave a
faster transformation and made it possible to use slightly less
of the rhodium catalyst. As in the case of the initial experiments
with glucose, the major byproducts were Cn-1 1,4-anhydroaldi-
tols. For example, 1,4-anhydro-D-arabinitol was isolated in 20%
yield from the experiment in entry 8 while 1,4-anhydro-5-deoxy-
L-arabinitol was obtained in 17% yield from the reaction in
entry 10.
General Procedure for Decarbonylation of Unprotected
Aldoses. To the aldose (400-650 mg, 2.78 mmol) were added Rh-
2
dppp) Cl (214 mg, 0.22 mmol), DMA (3 mL), diglyme (20 mL),
and freshly distilled pyridine (14.5 µL, 0.18 mmol). The mixture
was thoroughly degassed under high vacuum and then stirred at
reflux (162 °C) under a nitrogen atmosphere until TLC (acetone/
(
BuOH/H O ) 5:4:1) showed full conversion to the corresponding
2
alditol (6-16 h). The solution was cooled to room temperature
followed by addition of water (50 mL). The mixture was washed
with CH
2
Cl
2
(4 × 50 mL) and the combined organic phases were
The reaction can also be applied to partially protected
carbohydrate substrates. We envisioned that the tetrose L-threose
could be prepared from D-glucose in a few steps by using the
decarbonylation as the key step. L-Threose is a useful chiral
starting material,14 but is not available from natural sources. It
has previously been prepared by oxidative degradation of other
carbohydrates15 and from L-tartaric acid. However, none of
these routes takes advantage of the most abundant carbohydrate,
D-glucose.
extracted with water (2 × 10 mL). The combined aqueous phases
were concentrated and the residue co-concentrated with EtOH. The
resulting residue was further purified by either flash column
chromatography (CH
phase column chromatography (H
2
Cl
2
/MeOH/H
2
O ) 4:1:0 to 65:25:4) or reverse
2
O). The reaction could also be
monitored by measuring the evolution of carbon monoxide. In this
case, the reaction flask was connected to a burette filled with water.
The bottom of the burette was further connected to a water reservoir
with a large surface area. At rt (25 °C) full conversion of the aldose
corresponds to 68 mL of carbon monoxide.
16
The synthesis of L-threose began by converting glucose into
D-Arabinitol. White crystals. R
f
0.49 (acetone/BuOH/H
2
O ) 5:4:
diisopropylidene glucofuranose 117 (Scheme 1). The more labile
5
22
D
20
19
D
1). [R]
Mp 98-99 °C (MeOH) (lit. mp 101-102 °C (EtOH)). H NMR
300 MHz, D O) δ 3.86 (ddd, J ) 2.0, 5.3, 7.3 Hz, 1H), 3.77 (dd,
J ) 2.7, 11.5 Hz, 1H), 3.68 (ddd, J ) 2.7, 6.2, 8.8 Hz, 1H), 3.58
O)
: C, 39.47;
-10.3 (c 0.2, MeOH) (lit. [R]
-12 (c 1, MeOH)).
21
1
,6-O-isopropylidene acetal was selectively hydrolyzed in
(
2
aqueous acetic acid followed by evaporation of the solvent. The
crude triol 2 was then subjected to periodate cleavage to afford
aldehyde 3.18 Previously, periodic acid (H5IO6) in dry ether has
been shown to affect acetal hydrolysis and glycol cleavage in
(
m, 3H), 3.50 (dd, J ) 2.0, 8.3 Hz, 1H). 13C NMR (75 MHz, D
2
5 12 5
δ 72.3, 71.8, 71.7, 64.5, 64.4. Anal. Calcd for C H O
H, 7.95. Found: C, 39.55; H, 7.65.
Erythritol. White crystals. R
). Mp 116-117 °C (MeOH/heptane) (lit. mp 120-121 °C). H
NMR (300 MHz, D O) δ 3.74-3.65 (m, 2H), 3.62-3.49 (m, 4H).
C NMR (75 MHz, D O) δ 73.3, 64.0. Anal. Calcd for C
C, 39.34; H, 8.25. Found: C, 39.05; H, 8.00.
D-Threitol. White crystals. R 0.52 (acetone/BuOH/H
f
0.47 (acetone/BuOH/H O ) 5:4:
2
(
14) For recent examples, see: (a) Evans, D. A.; Cee, V. J.; Siska, S. J.
22
1
1
J. Am. Chem. Soc. 2006, 128, 9433. (b) Li, F.; Schwardt, O.; J a¨ ger, V.
Synthesis 2006, 2173. (c) F u¨ rstner, A.; Wuchrer, M. Chem. Eur. J. 2006,
2
13
2
4 10 4
H O :
1
2, 76. (d) Wu, T.; Froeyen, M.; Kempeneers, V.; Pannecouque, C.; Wang,
J.; Busson, R.; De Clercq, E.; Herdewijn, P. J. Am. Chem. Soc. 2005, 127,
056. (e) Achmatowicz, M.; Hegedus, L. S. J. Org. Chem. 2004, 69, 2229.
15) (a) Isbell, H. S.; Frush, H. L. Carbohydr. Res. 1979, 72, 301 (from
5
f
2
O ) 5:4:
-7.0 (c 0.9, MeOH)).
(
22
23
23
1). [R]
D
-7.5 (c 0.5, MeOH) (lit. [R]
D
L-ascorbic acid). (b) Morgenlie, S. Acta Chem. Scand. 1972, 26, 2146 (from
L-sorbose). (c) Perlin, A. S. Methods Carbohydr. Chem. 1962, 1, 68 (from
L-arabinitol).
24
1
Mp 89-91 °C (MeOH) (lit. mp 90-91 °C (BuOH)). H NMR
(
16) (a) Chattopadhyay, A.; Dhotare, B. Tetrahedron: Asymmetry 1998,
, 2715. (b) Nakaminami, G.; Edo, H.; Nakagawa, M. Bull. Chem. Soc.
Jpn. 1973, 46, 266.
(19) Wu, W.-L.; Wu, Y.-L. J. Org. Chem. 1993, 58, 3586.
(20) Lewis, D. J. Chem. Soc., Perkin Trans. 2 1991, 197.
(21) Richtmyer, N. K. Carbohydr. Res. 1970, 12, 135.
(22) Trenner, N. R.; Bacher, F. A. J. Am. Chem. Soc. 1949, 71, 2352.
(23) Kitajima, J.; Ishikawa, T.; Tanaka, Y.; Ida, Y. Chem. Pharm. Bull.
1999, 47, 988.
9
(
17) Schmidt, O. T. Methods Carbohydr. Chem. 1963, 2, 318.
(18) Gautam, D.; Kumar, D. N.; Rao, B. V. Tetrahedron: Asymmetry
2
006, 17, 819.
9
784 J. Org. Chem., Vol. 72, No. 25, 2007

(
300 MHz, D
2
O) δ 3.69-3.51 (m, 6H). 13C NMR (75 MHz, D
2
O)
: C, 39.34; H, 8.25. Found:
1H), 4.04 (d, J ) 2.8 Hz, 1H), 3.92 (dd, J ) 2.9, 9.8 Hz, 1H), 3.68
13
δ 72.9, 63.9. Anal. Calcd for C
C, 39.19; H, 8.05.
4
H
10
O
4
(dd, J ) 1.0, 9.8 Hz, 1H), 1.32 (s, 3H), 1.19 (s, 3H). C NMR (50
MHz, CD OD) δ 112.7, 106.7, 86.4, 75.9, 73.9, 27.1, 26.4.
3
5-Deoxy-L-arabinitol. Colorless syrup. R
f
0.68 (acetone/BuOH/
Anal. Calcd for C
7.47.
7 12 4
H O : C, 52.49; H, 7.55. Found: C, 52.79; H,
22
22
H
H
2
O ) 5:4:1). [R]
D
+11.7 (c 3.8, MeOH). [R]
D
+13.1 (c 0.5,
25
23
1
2
O) (reported for the enantiomer [R]
D
-10.6 (H
2
O)). H NMR
L-Threose. 1,2-O-Isopropylidene-â-L-threofuranose (4) (100 mg,
0.62 mmol) was dissolved in 30% aqueous AcOH (10 mL) and
heated to reflux for 4 h. The liquids were removed in vacuo and
the residue was purified by reverse-phase column chromatography
(
3
300 MHz, D O) δ 3.85-3.74 (m, 2H), 3.64-3.53 (m, 2H), 3.38-
2
13
.28 (m, 1H), 1.17 (d, J ) 6.4 Hz, 3H). C NMR (75 MHz, D
2
O)
δ 74.6, 70.7, 67.1, 63.1, 18.3. Anal. Calcd for C H O : C, 44.11;
H, 8.88. Found: C, 43.85; H, 8.59.
5 12 4
eluting with H
2
O to give L-threose (74 mg, 99%) as a colorless oil
1
-Acetylamino-1-deoxy-D-arabinitol. White crystals. R
acetone/BuOH/H +23.5 (c 0.5, H O) (lit.
O ) 5:4:1). [R]22
O)). Mp 142-143 °C (MeOH) (lit. mp 146.5-
47.5 °C). H NMR (300 MHz, D O) δ 3.81 (t, J ) 6.7 Hz, 1H),
f
0.49
consisting of a 14:11:5 mixture of the R- and â-furanose forms
26
22
(
[
2
D
2
and the hydrate. R
f
0.57 (acetone/BuOH/H
2
O ) 5:4:1). [R]
D
+12.3
O)). H NMR (300 MHz,
2
D O) δ 5.33 (d, J ) 4.2 Hz), 5.17 (d, J ) 1.1 Hz), 4.94 (d, J ) 6.3
2
2
26
15b
1
R]
D
+23 (H
2
(c 2.0, H
2
O) (lit. [R]
D
+12 (c 1, H
2
1
1
3
1
3
7
4
2
1
3
.67 (dd, J ) 2.6, 11.4 Hz, 1H), 3.57 (ddd, J ) 4.4, 7.8, 7.7 Hz,
H), 3.48 (dd, J ) 6.2, 11.5 Hz, 1H), 3.32 (d, J ) 8.5 Hz, 1H),
Hz), 4.50-3.36 (m, 4H). C NMR (75 MHz, D
103.4, 81.9, 76.4, 74.3; â-anomer: δ 97.9, 77.4, 76.1, 71.8;
hydrate: δ 91.0, 74.5, 72.1, 64.2. Anal. Calcd for C : C, 40.00;
H, 6.71. Found: C, 40.74; H, 6.72. HRMS calcd for C Na
2
O), R-anomer: δ
.25-3.11 (m, 2H), 1.85 (s, 3H). 13C NMR (75 MHz, D
O) δ 175.4,
: C,
2
4 8 4
H O
1.7, 71.7, 69.1, 63.9, 43.3, 22.8. Anal. Calcd for C
3.52; H, 7.83; N, 7.25. Found: C, 43.67; H, 7.56; N, 7.18.
,2-O-Isopropylidene-â-L-threofuranose (4). To 1,2-O-isopro-
pylidene-R-D-xylo-pentodialdo-1,4-furanose (3) (500 mg, 2.66
mmol) were added Rh(dppp) Cl (51 mg, 0.053 mmol) and a
7
H
15NO
5
4 8 4
H O
+
1
13
[M + Na] m/z 143.0320, found m/z 143.0327. H and C data
are in accordance with literature values.28
1
2
Acknowledgment. Financial support from the Lundbeck
Foundation is gratefully acknowledged. The Center for Sustain-
able and Green Chemistry is sponsored by the Danish National
Research Foundation.
degassed solution of diglyme (10 mL). The mixture was thoroughly
degassed and then stirred at reflux (162 °C) in a preheated oil bath
for 26 h. The solvent was removed under high vacuum at 70 °C to
give a black residue, which was purified by flash column chroma-
tography eluting with ether/pentane ) 2:3 to 4:1 to afford 4 (366
Supporting Information Available: General experimental
methods, characterization of 1,4-anhydro-D-arabinitol and 1,4-
anhydro-5-deoxy-L-arabinitol, synthesis of 2 and 3, and copies of
NMR spectra. This material is available free of charge via the
Internet at http://pubs.acs.org.
mg, 86%) as white crystals. R
f
0.35 (EtOAc/heptane ) 3:2). [R]22
5b
D
1
+
8
13.1 (c 0.8, acetone) (lit. [R] +13 (c 1, acetone)). Mp 80-
D
1 °C (ether) (lit.1
5b,27
mp 84-85 °C (ether/hexane)). H NMR (300
1
MHz, CD
3
OD) δ 5.78 (d, J ) 3.7 Hz, 1H), 4.35 (d, J ) 3.7 Hz,
JO7017729
(24) Birkinshaw, J. H.; Stickings, C. E.; Tessier, P. Biochem. J. 1948,
4
2, 329.
(25) B ´ı lik, L.; Petru sˇ , L.; Zemek, J. Chem. ZVesti 1978, 32, 242.
26) Jones, J. K. N.; Perry, M. B.; Turner, J. C. Can. J. Chem. 1962, 40,
(27) Francisco, C. G.; Le o´ n, E. I.; Mart ´ı n, A.; Moreno, P.; Rodr ´ı guez,
M. S.; Su a´ rez, E. J. Org. Chem. 2001, 66, 6967.
(
5
03.
(28) Serianni, A. S.; Barker, R. J. Org. Chem. 1984, 49, 3292.
J. Org. Chem, Vol. 72, No. 25, 2007 9785