A carbohydrate synthesis employing a photochemical decarbonylation

Article abstract of DOI:10.1016/S0040-4039(01)01874-3

A new route to the aldopentoses, ribose and lyxose, and the aldohexoses, talose and gulose, has been developed using chiral building blocks containing a bicyclo[3.2.1]octane framework by employing a photochemical decarbonylation reaction as the key step.

Full text of DOI:10.1016/S0040-4039(01)01874-3

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 42 (2001) 8661–8664
A carbohydrate synthesis employing a photochemical
decarbonylation
Kohei Kadota and Kunio Ogasawara*
Pharmaceutical Institute, Tohoku University, Aobayama, Sendai 980-8578, Japan
Received 20 September 2001; revised 5 October 2001; accepted 9 October 2001
Abstract—A new route to the aldopentoses, ribose and lyxose, and the aldohexoses, talose and gulose, has been developed using
chiral building blocks containing a bicyclo[3.2.1]octane framework by employing a photochemical decarbonylation reaction as the
key step. © 2001 Elsevier Science Ltd. All rights reserved.
We have developed an efficient method for the prepara-
tion of the enantiopure bicyclic enones containing a
bicyclo[3.2.1]octane framework, levoglucosenone 1,1,2
and an isolevoglucosenone derivative 2,3,4 having an
oxymethyl functionality, in both enantiomeric forms
from non-carbohydrate precursors (Fig. 1). Photolysis
of a monocyclic pyranone has been reported5 to furnish
an epimeric mixture of ring-contracted tetrahydrofuran
derivatives with extrusion of the carbonyl functionality.
Although only one such example appears in the litera-
ture, we nevertheless thought that by using a photolytic
decarbonylation reaction, we could perhaps develop a
diastereocontrolled route to carbohydrates from these
bicyclic enones without inducing epimerization, given
their rigid framework and inherent convex-face selectiv-
ity. We report here a new diastereocontrolled synthesis
of two aldopentoses from the enone (−)-1 and two
aldohexoses from the enone (+)-2.
sponding acetonide 6, [h]2D9 −199 (c 1.1, CHCl3). During
the conversion, both reduction and dihydroxylation
occurred diastereoselectively from the convex-face of
the molecule owing to its sterically biased framework.
On sequential alkaline methanolysis and oxidation with
tetrabutylammonium perruthenate (TPAP),7 the ace-
tonide 6 furnished the ketone 7, mp 82°C, [h]2D9 −177 (c
1.0, CHCl3), having an exo-acetonide functionality.
The overall yield of 7 from (−)-1 was 55% in five steps.
The same intermediate 4, on the other hand, was first
treated with m-chloroperbenzoic acid (m-CPBA) to
give, diastereoselectively, the exo-epoxide 8, mp 68°C,
[h]2D9 −151 (c 0.8, CHCl3). Upon exposure to boron
trifluoride, the epoxide 8 furnished the acetate mixture
from which the single triol 10 having a 1,2-endo-glycol
moiety was obtained by alkaline methanolysis. The
observed regio- and diastereoselective epoxide-opening
may be explained by the intervention of the dioxole-
nium intermediate 9 arising from participation of the
neighboring acetoxy functionality.8 Under standard
acid-catalyzed ketalization conditions with 2,2-
dimethoxypropane, the triol 10 furnished selectively the
single endo-acetonide 11, mp 159°C, [h]2D9 −49.2 (c 1.1,
CHCl3), leaving the exo-hydroxy functionality intact.
Oxidation of 11 with TPAP afforded the ketone 12, mp
The synthesis began with the diastereoselective 1,2-
reduction6 of levoglucosenone (−)-1 to give the endo-
alcohol 3. After acetylation, the allyl acetate
4
generated was dihydroxylated diastereoselectively under
catalytic osmylation conditions to give the exo-diol 5,
[h]2D9 −149 (c 1.4, CHCl3), which, on acid-catalyzed
reaction with 2,2-dimethoxypropane afforded the corre-
O
O
O
O
O
O
O
O
O
O
TBSO
TBSO
O
O
(–)-2
(–)-1
(+)-1
(+)-2
Figure 1.
* Corresponding author. E-mail: konol@mail.cc.tohoku.ac.jp
0040-4039/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(01)01874-3

8662
K. Kadota, K. Ogasawara / Tetrahedron Letters 42 (2001) 8661–8664
83°C, [h]2D9 −78.9 (c 1.1, CHCl3), which is diastereo-
meric with 7. The overall yield of 11 from (−)-1 was
20% in six steps (Scheme 1).
functionality, which was oxidized with TPAP to give
the ketone 16, [h]2D7 +6.0 (c 1.2, CHCl3). The overall
yield of 16 from (+)-2 was 66% in six steps.
Similarly, the isolevoglucosenone counterpart (+)-2 was
transformed into the diastereomeric ketones, 16 having
an exo-acetonide functionality, and 20 having an endo-
acetonide functionality, respectively, in a diastereocon-
trolled manner.
On the other hand, the same intermediate 13 was
sequentially acetylated and epoxydized with m-CPBA
to give the exo-epoxide 17, [h]2D9 +30.8 (c 1.1, CHCl3).
On exposure to boron trifluoride followed by alkaline
methanolysis, the epoxide 17 furnished the single triol
19, [h]2D8 +1.7 (c 1.1, CHCl3), presumably through the
transient intermediate 18. On acid-catalyzed reaction
with 2,2-dimethoxypropane followed by oxidation with
TPAP, the triol 19 furnished the ketone 20 accompa-
Thus, (+)-2 was first reduced to the endo-alcohol 13
which furnished the single triol 14, mp 102°C, [h]D30
+25.9 (c 0.8, CHCl3), on catalytic osmylation. The
acid-catalyzed reaction of 14 with 2,2-dimethoxy-
propane afforded the secondary alcohol 15, mp 122°C,
[h]3D0 +40.5 (c 0.6, CHCl3), having an exo-acetonide
nied by
a trace of inseparable impurities. The
overall yield of 20 from (+)-2 was 41% in six steps
(Scheme 2).
O
O
O
OH
O
O
O
O
O
v
O
iv
O
iii
OH
OAc
i
OR
OAc
O
O
O
O
O
O
3:R = H
7
6
5
(–)-1
ii
4:R = Ac
vi
–
OBF3
OH
O
O
O
X
viii
vii
O
O
+
O
O
O
O
O
O
OAc
OH
OH
O
O
Me
11:X = OH,H
12: X = O
10
ix
9
8
Scheme 1. Reagents and conditions: (i) NaBH4–CeCl3, MeOH; (ii) Ac2O, pyridine, CH2Cl2 (81%, two steps); (iii) OsO4 (cat.),
4-methylmorpholine N-oxide (NMO), aq. THF (85%); (iv) 2,2-dimethoxypropane, pyridinium p-toluenesulfonate (PPTS), toluene,
reflux (100%); (v) (a) K2CO3, MeOH, (b) TPAP (cat.), NMO, CH2Cl2 (80%); (vi) m-CPBA, CH2Cl2 (65%); (vii) BF3–Et2O, then
NaOMe, MeOH; (viii) 2,2-dimethoxypropane, PPTS, toluene, reflux (52%, three steps); (ix) TPAP (cat.), NMO, CH2Cl2 (71%).
O
O
OH
O
OH
OH
O
O
O
O
O
O
OH
iii
iv
PO
i
ii
O
OH
O
PO
O
O
PO
O
PO
O
PO
O
(+)-2
13
14
15
16
P = TBS
v,vi
–
F3BO
O
OH
O
OAc
O
O
viii, ix
PO
O
O
O
vii
OH
+
O
O
O
O
PO
O
PO
O
OH
PO
O
Me
20
17
18
19
Scheme 2. Reagents and conditions: (i) NaBH4–CeCl3, MeOH (99%); (ii) OsO4 (cat.), NMO, aq. THF (85%); (iii) 2,2-
dimethoxypropane, PPTS, toluene, reflux (87%); (iv) TPAP (cat.), NMO, CH2Cl2 (91%); (v) Ac2O, pyridine, CH2Cl2 (93%); (vi)
m-CPBA, CH2Cl2 (76%); (vii) BF3–Et2O, then TBS–Cl, Et3N, DMAP (cat.), CH2Cl2, then NaOMe, MeOH; (viii) 2,2-
dimethoxypropane, PPTS, toluene, reflux (74%, four steps); (ix) TPAP (cat.), NMO, CH2Cl2 (79%).

K. Kadota, K. Ogasawara / Tetrahedron Letters 42 (2001) 8661–8664
8663
Having obtained the two pairs of diastereomeric
ketones bearing an acetonide functionality in a diastere-
ocontrolled manner, we next carried out their conver-
The structure of 22 was confirmed by its conversion
into
-lyxose, [h]D29 −12.9 (c 0.3, H2O) [lit.:12 [h]2D3 +13 (c
0.92, H2O) for the -enantiomer], by deacetonization
with 90% trifluoroacetic acid. The product obtained in
95% yield was identical in all respects with an authentic
material.
D
L
sion
into
carbohydrates
by
employing
the
photochemical decarbonylation.
Irradiation of the ketone 7 having an exo-acetonide
functionality was first examined. Since 7 was found to
be insoluble in a saturated hydrocarbon solution which
is presumed to be the most suitable solvent for decar-
bonylation, irradiation was carried out in methanol in a
Pyrex tube using a Rayonet Photochemical Reactor
(lamp 300 nm).9 After 2 h irradiation, the starting
material disappeared to generate a single product which
was discernible on TLC. However, the yield of the
decarbonylation product assigned as 21, mp 59°C, [h]D29
−72.1 (c 0.8, CHCl3), was only 40% after purification
by silica gel column chromatography. It was found that
the decarbonylation reaction of 7 also proceeded in
toluene, which afforded the same product in a com-
parable yield of 38%. On stirring with 90% trifl-
uoroacetic acid10 at room temperature, compound 21
Likewise both of the diastereomeric ketones, 16 and 20,
furnished the corresponding decarbonylation products,
23 and 24, cleanly, in comparable moderate yields via
the same photolytic treatment. Thus, the ketone 16, on
irradiation in hexane for 1.5 h, afforded decarbonyla-
tion product 23, [h]3D0 +0.1 (c 1.3, CHCl3), in 41% yield,
while the ketone 20 afforded 24, [h]2D8 −42.1 (c 1.2,
CHCl3), in 40% yield. On sequential desilylation with
trifluoroacetic acid in aq. THF at 0°C and deacetoniza-
tion with 90% trifluoroacetic acid at room temperature,
compound 23 furnished
L
-talose, [h]3D0 −18.2 (c 0.7,
-gulose, [h]3D0 +20.0 (c
H2O) [lit.:13 [h]D28 −17.6 (c 1.01, H2O)], in 73% yield,
while compound 24 furnished
L
0.5, H2O) [lit.:3 [h]D31 +20.9 (c 1.01, H2O)], in 72%
yield.14 In the photolysis reaction, the three substrates
besides 12 exhibited a clear-cut single spot on TLC to
give the decarbonylation product as a sole product
though the yield did not exceed 41% (Scheme 3).
furnished
D
-ribose, [h]2D9 −21.2 (c 0.4, H2O) [lit.:11 [h]D
-enantiomer], in 90% yield. In
−22.6 (H2O) for the
L
contrast to 7, irradiation of 12, the diastereomer of 7,
afforded a mixture of products from which the decar-
bonylation product 22, [h]2D8 −92.6 (c 0.8, CHCl3), was
obtained in 11% yield after separation by silica gel
column chromatography.
In conclusion, we have developed a new route to two
aldopentoses and two aldohexoses starting from readily
CHO
O
O
OH
O
O
ii
i
O
OH
OH
OH
O
O
O
O
7
21
D-ribose
CHO
O
ii
HO
HO
O
i
O
O
O
O
O
O
O
OH
OH
D-lyxose
22
12
CHO
OH
O
O
O
O
O
O
OH
O
i
ii
OH
TBSO
O
TBSO
O
HO
OH
16
23
L-talose
CHO
O
O
HO
HO
O
i
ii
O
O
O
O
TBSO
O
TBSO
O
OH
HO
24
OH
20
L-gulose
Scheme 3. Reagents and conditions: (i) hw (300 nm) (for 7: MeOH, 40%; for 12: hexane–THF (40:1), 11%; for 16: hexane, 41%;
for 20: hexane, 40%); (ii) 90% CF3CO2H, rt (for 21, 90% and for 22, 95%) (a) CF3CO2H, 80% aq. THF, 0°C, (b) 90% CF3CO2H,
rt (for 23, 73% and for 24, 72%).

8664
K. Kadota, K. Ogasawara / Tetrahedron Letters 42 (2001) 8661–8664
accessible enantiopure precursors containing a rigid
dioxabicyclo[3.2.1]octane framework by employing a
photochemical decarbonylation reaction as the key
step.
7. Ley, S. V.; Norman, J.; Griffith, W. P.; Marsden, S. P.
Synthesis 1994, 639.
8. Prystas, M.; Gustafsson, H.; Sorm, F. Coll. Czech. Chem.
Commun. 1971, 36, 1487.
9. For a typical procedure: A solution of 7 (60 mg, 0.3 mmol)
in MeOH (30 ml) in a Pyrex tube was irradiated at room
temperature for 2 h using a Rayonet Photochemical
Reactor (Lamp 300 nm). After evaporation of the solvent
under reduced pressure, the residue was chromatographed
(SiO2, 2.5 g, elution with Et2O–hexane 1:3 v/v) to give 21
(20.5 mg, 40%) as colorless needles, mp 59°C, [h]2D9 −72.1
(c 0.8, CHCl3).
10. Ko, S. Y.; Lee, A. W. M.; Masamune, S.; Reed, III, L. A.;
Sharpless, K. B.; Walker, F. J. Tetrahedron 1990, 46, 245.
11. Austin, W. C.; Humoller, F. L. J. Am. Chem. Soc. 1934,
56, 1152.
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1. Taniguchi, T.; Nakamura, K.; Ogasawara, K. Synlett 1996,
971.
2. Kadota, K.; Kurusu, Y.; Taniguchi, T.; Ogasawara, K.
Adv. Synth. Catal. 2001, 343, 618.
3. (a) Takeuchi, M.; Taniguchi, T.; Ogasawara, K. Synthesis
1999, 341; (b) Takeuchi, M.; Taniguchi, T.; Ogasawara, K.
Chirality 2000, 12, 338.
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14. Carbohydrates obtained are depicted using the Fischer
projection for brevity.