Intramolecular Tishchenko reactions of protected hexos-5-uloses: A novel and efficient synthesis of L-idose and L-altrose

Article abstract of DOI:10.1055/s-1999-3156

Protected t-butyl esters of aldonic acids with the rare L-ido and L- altro configuration can be effectively obtained by a diastereoselective Tishchenko reaction of hexos-5-uloses induced by t-BuOSmI₂. These compounds can be easily converted int

Full text of DOI:10.1055/s-1999-3156

336
LETTER
Intramolecular Tishchenko Reactions of Protected Hexos-5-uloses: a Novel
and Efficient Synthesis of L-Idose and L-Altrose
M. Adinolfi, G. Barone, F. De Lorenzo, A. Iadonisi*
Dipartimento di Chimica Organica e Biologica, Università degli Studi Federico II, Via Mezzocannone 16, I-80134 Napoli, Italy
Fax +39 0815521217; E-mail iadonisi@unina.it
Received 13 November 1998
preparation of 2,3,4,6-tetra-O-benzyl-hexos-5-uloses, we
Abstract: Protected t-butyl esters of aldonic acids with the rare
explored the proposed path.
L-ido and L-altro configuration can be effectively obtained by a
diastereoselective Tishchenko reaction of hexos-5-uloses induced
by t-BuOSmI2. These compounds can be easily converted into the
corresponding protected lactones and free sugars.
Aldulose 6 was first generated from 2,3,4,6-tetra-O-benz-
yl-D-glucitol 5 through a double Swern oxidation, and
then treated with tBuOSmI2 (5 eq.) following a one-pot
procedure.6 Under these conditions t-butyl ester 7, pos-
sessing the desired L-ido configuration, was obtained in
place of lactone 8. Lactonization of 7 was easily accom-
plished in a further step by acid treatment (Scheme 2).
Key words: Tishchenko reaction, trivalent samarium reagents,
L-idose, L-altrose, aldonic acids t-butyl esters
During our synthetic studies toward the monosaccharide
caryose1 the fully diastereoselective formation of 2,3,4-
tri-O-benzyl-6-deoxy-L-iditono-1,5-lactone 3 rather than
the expected pinacolic condensation2 to the desired diol 4
was observed when 2,3,4-tri-O-benzyl-6-deoxy-D-xylo-
hexos-5-ulose 2, obtained by Swern oxidation of alditol 1,
was treated with an old commercial solution of SmI2 in
THF (Scheme 1).
Scheme 2
However, disappointing yields were achieved (35% of 7
from 5 after 36 h at r.t. or 25% after 2 h at reflux), prob-
ably due to interference of triethyl ammonium salts pro-
duced by the Swern oxidation in the reaction. As a matter
of fact, when the salts were removed by centrifugation un-
der argon prior to the Tishchenko step only 2.5 eq of
tBuOSmI2 in THF at room temperature (12 hours) were
needed to afford almost pure t-butyl ester 7 (1H NMR).7,9
This compound was directly submitted to lactonization,
reduction and debenzylation10 to give L-idose with an
overall 65% yield from 5.9, 11
Scheme 1
Actually, the use of trivalent samarium reagents, and in
particular t-BuOSmI2, for the conversion of 1,5-ketoalde-
hydes into d-lactones through an intramolecular Tish-
chenko oxidoreduction had been already reported by
Uenishi.3 Interestingly however, lactone 3 presented the
opposite configuration at its 5 position with respect to al-
ditol 1 from which it was generated. Thus an intramolec-
ular Tishchenko reaction could be potentially exploited as
the key-step for a straightforward synthesis of rare L-sug-
ars such as Lidose, L-gulose and L-altrose starting from
suitably protected alditols easily obtained from D-glucose,
D-mannose and D-galactose, respectively. These rare L-
sugars are synthetic targets of current interest.4 Taking ad-
vantage of our recently reported5 general approach for the
The optimized procedure was then applied to protected D-
mannitol 10 and D-galactitol 13. In the first case we ob-
served that the Tishchenko reaction furnished almost ex-
clusively t-butyl ester 11 having the manno configuration
as demonstrated by its conversion into a product having
spectroscopic properties identical with authentic 2,3,4,6-
tetra-O-benzyl-D-mannopyranose 12 (Scheme 3).
Synlett 1999, No. 3, 336–338 ISSN 0936-5214 © Thieme Stuttgart · New York

LETTER
A Novel and Efficient Synthesis of L-Idose and L-Altrose
337
Scheme 4
Scheme 3
Acknowledgement
Financial support by MURST (PRIN 1997-98: Chemistry of Orga-
nic Compounds of Biological Interest) and by CNR is acknowled-
ged. NMR spectra were performed at the Centro di Metodologie
Chimico-Fisiche of Università di Napoli Federico II.
In the case of galacto precursor 13, the sequence of Swern
oxidation/Tishchenko reaction afforded a 5:1 mixture of
t-butyl esters 149 and 15 having the L-altro and D-galacto
configuration, respectively. The subsequent lactonization
afforded an unseparable mixture of compounds 169 and 17
(78% overall yield from 13) which was submitted to re-
duction with DIBAL. The resulting epimeric hemiacetals
could be separated by silica gel chromatography to yield
the L-altro and D-galacto derivatives 189 and 19 (65 and
12% yield from 13, respectively). Debenzylation of 18 af-
forded L-altrose11 free from any detectable (NMR)
amount of 1,6-anhydro-b-L-altropyranose though the
deprotection implied an acid treatment.4a
References and Notes
(1) Adinolfi, M.; Barone, G.; Iadonisi, A.; Mangoni, L.; Manna,
R. Tetrahedron 1997, 53, 11767.
(2) Molander G. A.; Kenny, C. J. Org. Chem. 1988, 53, 2132.
(3) Uenishi, J.; Masuda, S.; Wakabayashi, S. Tetrahedron Lett.
1991, 32, 5097.
(4) a) So, Y. K.; Lee, A. W. M.; Masamune, S.; Reed III, L. A.,
Sharpless, K. B., Walker, F. J. Tetrahedron 1990, 46, 245.
b) Dondoni, A.; Marra, A.; Massi, A. J. Org. Chem. 1997, 62,
6261 and references therein.
A possible explanation of the observed diastereoselectiv-
ities of the Tishchenko step can be based on the model
proposed by Uenishi.3 However, the extensive presence of
benzyloxy groups on the chain of the studied sugar deriv-
atives must be considered. As shown in Scheme 4, the
conversion of galacto derivative 13 to ester 14 can occur
through the samarium complex B rather than A, both com-
plexes being stabilized by further coordination of samari-
um to the oxygen atoms of the adjacent benzyloxy
substituents, but the latter being disfavoured by some
eclipsing of 1-O-t-Bu and 2-OBn groups. Similarly, inter-
mediate C should be favoured over intermediate D in the
reversion of manno derivative 10 to manno ester 11, and
intermediate F over intermediate E in the conversion of
gluco derivative 5 to L-ido ester 7.
(5) Adinolfi, M.; Barone, G.; Iadonisi, A.; Mangoni, L. Tetra-
hedron Lett. 1998, 39, 2021.
(6) Isolation of aldulose 6 was avoided because of the easy hydra-
tion of hexos-5-uloses (ref. 5 and 7). However, the pure alde-
hyde form can be obtained (Boiron, A.; Zillig, P.; Faber, D.;
Giese, B. J. Org. Chem. 1998, 63, 5877) by removing water
over molecular sieves.
(7) In a typical procedure compound 5 (162 mg, 0.3 mmol) was
submitted to Swern oxidation in THF at -60 °C as previously
reported,5 but in a centrifugation tube closed with a rubber
septum. The clear solution obtained after centrifugation was
transferred via cannula with an argon stream to a 0.1 M THF
solution of t-BuOSmI28 (7.5 mL, 0.75 mmol) and stirred at r.t.
for 12 hours. The reaction mixture was added with few drops
of acetic acid and filtered through a short column of 1:1 Celite/
Florisil to remove the samarium salts and to give almost pure
7. This compound was directly submitted to lactonization (1:1
CF3COOH/CH2Cl2, 0°C, 30 min). Usual work-up and chro-
matography on Florisil (CHCl3) gave pure 8 (122 mg, 76%
from 5).
In summary, Tishchenko reaction of hexos-5-uloses has
been shown to proceed in a highly stereoselective fashion.
The reaction has been exploited as the key-step of a con-
venient synthesis of L-idose and L-altrose and leads to use-
ful synthons such as t-butyl esters of aldonic acids.
(8) Namy, J. L.; Souppe, J.; Collin, J.; Kagan, H. B. J. Org. Chem.
1984, 49, 2045.
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338
M. Adinolfi et al.
LETTER
(9) Selected physical data. 7: 1H NMR (400 MHz, CDCl3) d 1.48
(9H, s, -C(CH3)3), 2.50 (1H, d, exchanges with D2O, JOH,H-5
14: 1H NMR (250 MHz, CDCl3) d 1.46 (9H, s, -C(CH3)3), 3.60
(1H, dd, J6a,6b = 10.9 Hz, J5,6a = 3.5 Hz, H-6a), 3.67 (1H, dd,
=
7.1 Hz, 5-OH), 3.36 (1H, dd, J6a,6b = 9.7 Hz, J5,6a = 6.1 Hz, H-
6a), 3.47 (1H, dd, J5,6b = 6.3 Hz, H-6b), 3.75 (1H, m, H-5),
3.89 (1H, dd, J4,5 = 2.9 Hz, J3,4 = 6.9 Hz, H-4), 4.15 (1H, d, J2,3
= 3.5 Hz, H-2), 4.37-4.87 (4 x benzylic CH2), 7.15-7.40 (aro-
matic protons). 13C NMR d 28.2 (-C(CH3)3), 69.4, 71.3, 72.9,
73.2, 74.9, 77.1 78.2, 78.4, 80.3, 82.1 (C-2, C-3, C-4, C-5, C-
6 and 4 x benzylic CH2 and -C(CH3)3), 127.5-128.6 (aromatic
CH), 137.2-138.3 (quaternary aromatic carbons), 169.7 (C-1).
8: 1H NMR (400 MHz, CDCl3) d 3.65 (1H, dd, J6a,6b = 10.0 Hz,
J5,6b = 7.0 Hz, H-6b), 3.79 (1H, t, J3,4 = J4,5 = 5.8 Hz, H-4), 4.11
(1H, dd, J2,3 = 4.6 Hz, H-3), 4.14 (1H, m, 5-H), 4.26 (1H, d, H-
2), 4.35-4.80 (4 x benzylic CH2), 7.15-7.40 (aromatic pro-
tons).
16: 1H NMR (250 MHz, CDCl3) d 3.71 (2H, d, J5,6 = 4.8 Hz,
H-6), 4.05 (1H, dd, J3,4 = 2.2 Hz, J4,5 = 5.9 Hz, H-4), 4.18 (1H,
dd, J2,3 = 5.9 Hz, H-3), 4.28 (1H, d, H-2), 4.55-5.00 (4 x ben-
zylic CH2 and H-5), 7.15-7.40 (aromatic protons). 13C NMR d
68.7, 72.1, 72.5, 72.8, 73.5, 73.5, 74.5, 75.6, 78.1 (C-2, C-3,
C-4, C-5, C-6 and 4 x benzylic CH2), 128-129 (aromatic CH),
137.3-137.7 (quaternary aromatic carbons), 168.8 (C-1).
18 was obtained as an anomeric mixture. Selected data:
1H NMR (250 MHz, CDCl3, exchanged with D2O) anomeric
protons at 5.05 (1H, d, J = 1.4 Hz) and 5.10 (1H, bs). 13C NMR
(DEPT) d 67.1, 72.2, 72.5, 72.7, 74.6, 74.6, 74.8, 76.8 (C-2,
C-3, C-4, C-5), 69.3, 69.4, 71.9, 72.0, 72.2, 73.2, 73.2, 73.6,
73.6, 74.1 (C-6 and 4 x benzylic CH2), 91.9 and 93.1 (C-1).
(10) Rao, V. S.; Perlin, A. S. Carbohydr. Res. 1980, 83, 175.
(11) L-idose and L-altrose prepared by the above procedure dis-
played 1H and 13C NMR spectra as reported.12, 13
J5,6a = 5.3 Hz, H-6a), 3.79 (1H, dd, J5,6b = 5.6 Hz, H-6b), 3.79
(1H, t, J3,4 = J4,5 = 1.7 Hz, H-4), 3.93 (1H, dd, J2,3 = 6.6 Hz, H-
3), 4.17 (1H, d, H-2), 4.32-5.07 (4 x benzylic CH2 and H-5),
7.2-7.5 (aromatic protons). 13C NMR d 67.9, 71.3, 72.4, 73.3,
73.5, 75.2, 75.9, 78.5, 79.9 (C-2, C-3, C-4, C-5 and C-6 and 4
x benzylic CH2), 128-129 (aromatic CH), 137.3-137.7 (qua-
ternary aromatic carbons), 169.4 (C-1).
9 was obtained as an anomeric mixture. 1H NMR (400 MHz,
CDCl3) anomeric protons at d 4.94 (1H, d, J = 2.3 Hz) and 5.18
(1H, d, J = 2.8 Hz). 13C NMR (DEPT) d 66.6, 71.9, 72.5, 73.3,
73.8, 74.5, 74.5, 75.7 (C-2, C-3, C-4, C-5), 68.2, 68.4, 72.2,
72.2, 72.3, 72.3, 72.4, 72.8, 72.9 and 72.9 (C-6 and 4 x benzy-
lic CH2), 91.7 and 93.2 (C-1).
(12) Angyal, S.; Pickles, V.A. Aust. J. Chem. 1972, 25, 1695.
(13) Bock, K.; Pedersen C. Adv. Carbohydr. Chem. Biochem.
1990, 41, 27.
Synlett 1999, No. 3, 336–338 ISSN 0936-5214 © Thieme Stuttgart · New York