The reaction of O-isopropylidene pentodialdo-1,4-furanoses with lithium diisopropylamide

Article abstract of DOI:10.1016/S0008-6215(99)00165-2

Three O-isopropylidene group-protected pentose aldehydes (methyl 2,3-O-isopropylidene-β-D-ribo-pentodialdo-1,4-furanoside (1), methyl 2,3-O-isopropylidene-α-D-lyxo-pentodialdo-1,4-furanoside (2), and 3-O-benzyl-1,2-O-isopropylidene-α-D-xylo-pentodialdo-1,4-furanose (3)) were treated at -30°C with lithium diisopropylamide (LDA) and the mixtures obtained were reduced with LiAlH₄. The products, obtained in moderate yields, proved that deacetonation occurred followed by aldol reactions between aldehydes 1-3 and acetone. Copyright (C) 1999 Elsevier Science Ltd.

Full text of DOI:10.1016/S0008-6215(99)00165-2

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Carbohydrate Research 321 (1999) 105–109
Note
The reaction of O-isopropylidene
pentodialdo-1,4-furanoses with lithium diisopropylamide
Halszka Ste˛powska, Aleksander Zamojski *
Institute of Organic Chemistry, Polish Academy of Sciences, Ul. Kasprzaka 44, PL-01-224 Warsaw, Poland
Received 7 April 1999; accepted 16 June 1999
Abstract
Three O-isopropylidene group-protected pentose aldehydes (methyl 2,3-O-isopropylidene-b-
1,4-furanoside (1), methyl 2,3-O-isopropylidene-a- -lyxo-pentodialdo-1,4-furanoside (2), and 3-O-benzyl-1,2-O-iso-
propylidene-a- -xylo-pentodialdo-1,4-furanose (3)) were treated at −30 °C with lithium diisopropylamide (LDA)
D-ribo-pentodialdo-
D
D
and the mixtures obtained were reduced with LiAlH4. The products, obtained in moderate yields, proved that
deacetonation occurred followed by aldol reactions between aldehydes 1–3 and acetone. © 1999 Elsevier Science Ltd.
All rights reserved.
Keywords: O-Isopropylidene-pentodialdo-1,4-furanoses; Lithium diisopropylamide (LDA); Aldol reaction
We decided to investigate whether pentose
terminal aldehydes methyl 2,3-O-isopropyli-
When performing chain-elongation reac-
tions on monosaccharide terminal aldehydes
dene-b-
methyl 2,3-O-isopropylidene-a-
dialdo-1,4-furanoside (2), and 3-O-benzyl-1,2-
O-isopropylidene-a- -xylo-pentodialdo-1,4-fur
D
-ribo-pentodialdo-1,4-furanoside (1),
(protected pentodialdo-1,4-furanoses or hexo-
dialdo-1,5-pyranoses) with alkoxymethylmag-
nesium chlorides, we often came across side
products originating from aldehydes inverted
at the a position [1–3]. The formation of these
products was interpreted by assuming inver-
sion of configuration at the a position of
aldehydes due to the basicity of the medium
resulting from an excess of Grignard reagent
followed by the normal addition reaction.
D
-lyxo-pento-
D
anose (3) will undergo configuration inversion
at C-4 in the presence of a strong base. To this
end, solutions of aldehydes 1–3 in tetrahydro-
furan were treated with lithium diisopropy-
lamide (LDA, 4 molar excess) at −30 °C, the
products were reduced in situ with LiAlH4,
and isolated. When aldehyde 1 was reacted
* Corresponding author. Tel.: +48-22-632-7030; fax: +
48-22-632-6681.
E-mail address: awzam@ichf.edu.pl (A. Zamojski)
0008-6215/99/$ - see front matter © 1999 Elsevier Science Ltd. All rights reserved.
PII: S0008-6215(99)00165-2

106
H. Ste˛powska, A. Zamojski / Carbohydrate Research 321 (1999) 105–109
dropped to 13.1% and that of 8 rose to 45%.
The presence of 7 was not detected in either
reaction mixture.
The results of the LDA treatment (−30 °C,
1 h, then LiAlH4) of the aldehyde 2 were
similar, i.e., 1,3-disubstituted acetone 9 was
the main product (17.1%), accompanied by
stereoisomeric octuloses 10 (11.8%) and the
alcohol 5 (12%). The behaviour of the alde-
hyde 3 was different. From the reaction, a
single product 11 (21%) was isolated to which
the structure of substituted ‘diacetone alcohol’
was assigned on the basis of analytical and
spectral data.
with LDA for 15 min, the only isolated
product was methyl 2,3-O-isopropylidene-b-
D
-ribofuranoside (4, 85.6%) as expected. Simi-
larly, methyl 2,3-O-isopropylidene-a- -lyxo-
furanoside (5, 79.1%) was obtained from com-
pound 2.
D
However, prolongation of the reaction time
of aldehydes with the base to 1 h substantially
changed the outcome of the reactions, and
furanoside 4 was formed in 7.4% yield starting
with compound 1 and two other products, 6
and 7, were isolated. The structure of 1,3-di-
Deacetalation of monosaccharide benzyli-
dene and isopropylidene derivatives under the
influence of strong bases (BuLi or LDA) was
extensively studied by Klemer et al. [4–7] (see
also Ref. [8]) and interesting unsaturated or
deoxy-keto sugar derivatives have been ob-
tained. Incorporation of the base ligand (butyl
group) to some of the products, but not of the
released acetone, was observed. For the cleav-
age of acetone from aldehydes 1 and 2, the
elimination shown in 12 seems to be more
plausible than Klemer’s proposals [6]. Deacet-
onation of the aldehyde 3 can be interpreted
as shown in 131. Furthermore, it seems that
the deacetonated aldehydes are unstable and
undergo further (self ?) condensations to poly-
meric materials. The results described here
might be regarded as a caveat when perform-
ing reactions of isopropylidene acetal-contain-
ing sugar aldehydes in the presence of strong
bases. On the other hand, the results did not
prove the facile inversion of configuration at a
C-(methyl 2,3-O-isopropylidene-a- -talo-pen-
L
tofuranos-5-yl)acetone was assigned to the
major product 6 (19.6%) on the basis of ana-
lytical, spectral and synthetic (vide infra) data.
The third product, 7 (7.1%), was identified as
a 4:1 mixture of the a-
L
-talo and b- -allo
D
stereoisomers of methyl 6,8-dideoxy-2,3-O-
isopropylidene-octofuranosid-7-ulose.
Formation of products 6 and 7 points to the
deacetonation of the substrate and a follow-
up aldol reaction between the aldehyde 1 and
the liberated acetone. However, it must be
added that we did not succeed in isolation of
the deacetonated sugar products in this and
other cases (vide infra).
In order to substantiate the structures of the
acetone-derived products 6 and 7, a solution
of 1 was treated again at −30 °C with LDA
(1 h), but this time acetone was added to the
solution. When the molar ratio 1:acetone was
1:2, product 6 was, in fact, obtained in 24.4%
yield. Another product was also isolated and
the structure of a substituted ‘diacetone alco-
hol’ 8 (24.4%) was assigned. When the ratio
1:acetone was changed to 1:0.5, the yield of 6
1 We thank a Referee for this suggestion.

H. Ste˛powska, A. Zamojski / Carbohydrate Research 321 (1999) 105–109
107
LDA were carried out according to the same
method.
1,3-Di-C-(methyl 2,3-O-isopropylidene-h-
talo-pentofuranos-5-yl)acetone
L
-
(6).—Yield
0.155 g (19.6%); white solid, mp 151–152 °C;
[h]D −34.6° (c 1.8, CHCl3); IR wmax (KBr):
1
3417, 2944, 1710, 1378, 1091, 868 cm−1; H
position of pentodialdo-1,4-furanoses, at least
when LDA was present as the base.
NMR (CDCl3): l 4.96 (s, 1 H, H-1), 4.86 (d, 1
H, J 6.0 Hz, H-3), 4.48 (d, 1 H, J 6.0 Hz,
H-2), 4.20–4.08 (m, 2 H, H-4, H-5), 3.40 (s, 3
H, OCH3), 2.75–2.66 (m, 2 H, H-6a, H-6b),
1.47, 1.32 (2 s, 6 H, (CH3)2C). 13C NMR
(CDCl3): l 208.4 (CO), 112.3 ((CH3)2C), 109.9
(C-1), 90.1 (C-4), 85.5 (C-2), 80.4 (C-3), 68.5
(C-5), 55.7 (OCH3), 46.6 (C-6), 26.3, 24.7
((CH3)2C). HRMS (LSIMS): m/z 485.2003
[M+Na]+. Calcd for C21H34O11Na: 485.1999.
Anal. Calcd for C21H34O11: C, 54.54; H, 7.41.
Found: C, 54.32; H, 7.58.
1. Experimental
General methods.—1H NMR spectra were
recorded with a Varian AC-200 (200 MHz)
spectrometer using CDCl3 as solvent. 13C
NMR spectra were recorded in the DEPT
mode. High-resolution mass spectra (HRMS)
were measured in the FAB+ ion mode with an
AMD-604 mass spectrometer. IR spectra were
recorded with a Perkin–Elmer 1640 FT-IR
spectrometer. Optical rotations were measured
with a Jasco DIP-360 automatic polarimeter
at 2492 °C. Melting points were determined
with a Kofler apparatus and are not corrected.
Reaction of methyl 2,3-O-isopropylidene-i-
Methyl 6,8-dideoxy-2,3-O-isopropylidene-h-
L
-talo- and -i- -allo-octofuranosid-7-uloses
D
(7a,b).—Yield 0.031 g (7.1%): 7a+7b; white
foam; NMR data are taken from the spectra
of a 4:1 mixture of L:D isomers. Configuration
1
assignments are based on analogy of H and
13C NMR signals (H-1, C-1,2,3) with methyl
D-ribo-pentodialdo-1,4-furanoside (1) with
6-O-allyl-2,3-O-isopropylidene-b-
D
-allo- and -
lithium diisopropylamide (LDA).—To a stirred
solution of LDA (6.9 mmol) in THF (15 mL)
at −30 °C under an argon atmosphere, a
a- -talo-furanosides [3].
L
1
7a: H NMR (CDCl3): l 4.96 (s, 1 H, H-1),
4.88 (d, 1 H, J 5.6 Hz, H-3), 4.58 (d, 1 H, J
5.6 Hz, H-2), 4.18–4.08 (m, 2 H, H-4, H-5),
3.40 (s, 3 H, OCH3), 2.72–2.64 (m, 2 H, H-6a,
H-6b), 2.22 (s, 3 H, CH3CO), 1.47, 1.32 (2 s, 6
H, (CH3)2C). 13C NMR (CDCl3): l 207.5
(CO), 112.2 ((CH3)2C), 109.9 (C-1), 90.0 (C-
4), 85.4 (C-2), 80.4 (C-3), 68.4 (C-5), 55.6
(OCH3), 46.3 (C-6), 30.8 (CH3CO), 26.3, 24.7
((CH3)2C). IR wmax (KBr): 3458, 2944, 1714,
1375, 1089, 867 cm−1. Anal. Calcd for
C12H20O6 (260.28): C, 55.37; H, 7.74. Found:
C, 55.36; H, 7.90.
solution of methyl 2,3-O-isopropylidene-b- -
D
ribo-pentodialdo-1,4-furanoside (1) [9,10]
(0.346 mg, 1.7 mmol) in THF (5 mL) was
added dropwise. The reaction mixture was
stirred at this temperature for 1 h, then
LiAlH4 (33 mg, 0.85 mmol) was added in one
portion and stirring was continued for 15 min.
The reaction was quenched with water (2 mL).
The mixture was then filtered through Celite
pad, the filtrate was dried (Na2SO4), concd
under reduced pressure, and the crude product
was chromatographed on Silica Gel with
3.5:1.5 then 1:1 hexane–EtOAc to give 4
(0.026 g, 7.4%), the mixture of stereoisomeric
7 (0.031 g, 7.1%, a 4:1 ratio of L:D isomers)
and the main product 6 (0.155 g, 19.6%).
The reactions of methyl 2,3-O-isopropyli-
1
7b: H NMR (CDCl3): l 4.98 (s, 1 H, H-1),
4.82 (d, 1 H, J 5.5 Hz, H-3), 4.39 (d, 1 H, J
5.5 Hz, H-2), 4.12–4.01 (m, 2 H, H-4, H-5),
3.47 (s, 3 H, OCH3), 2.75–2.67 (m, 2 H, H-6a,
H-6b), 2.20 (s, 3 H, CH3CO), 1.47, 1.32 (2 s, 6
H, (CH3)2C). 13C NMR (CDCl3): l 206.6
(CO), 112.1 ((CH3)2C), 110.4 (C-1, 89.8 (C-4),
85.3 (C-2), 82.1 (C-3), 67.9 (C-5), 55.8
(OCH3), 47.6 (C-6), 30.6 (CH3CO), 26.3, 24.7
((CH3)2C).
dene-a-
[11] and 3-O-benzyl-1,2-O-isopropylidene-a-
-xylo-pentodialdo-1,4-furanose (3) (obtained
by the method used for 2 from 3-O-benzyl-
1,2-O-isopropylidene-a- -glucofuranose) with
D
-lyxo-pentodialdo-1,4-furanoside (2)
D
D

108
H. Ste˛powska, A. Zamojski / Carbohydrate Research 321 (1999) 105–109
(s, 3 H, OCH3), 3.38, 3.26 (ABq, 2 H, H-6a,
Methyl
dene-9-C-methyl-h-
6,8,10-trideoxy-2,3-O-isopropyli-
-talo-decofuranosid-7-
H-6b), 2.23 (s, 3 H, CH3CO), 1.47, 1.31 (2 s, 6
H, (CH3)2C). 13C NMR (CDCl3): l 214.1
(CO), 106.7 (C-1), 85.2, 80.8, 80.2 (C-2, C-3,
C-4), 66.8 (C-5), 54.7 (OCH3), 46.5 (C-6), 30.9
(CH3CO), 25.9, 24.5 ((CH3)2C). IR wmax (film):
3487, 2938, 1715, 1374, 1091, 861 cm−1. Anal.
Calcd for C12H20O6 (260.28): C, 55.37; H,
7.74. Found C, 55.21; H, 7.95.
L
ulose (8).—Yield 39.5%; colourless oil (from
13
the C NMR spectrum of 8, a minute admix-
ture of the b- -allo stereoisomer can be dis-
D
cerned (\1:8); we did not succeed in its
isolation); [h]D −33.6° (c 1.4 CHCl3); IR wmax
(film): 3427, 2974, 1700, 1379, 1093, 869
cm−1. 1H NMR (CDCl3): l 4.96 (s, 1 H, H-1),
4.85 (d, 1 H, J 5.9 Hz, H-3), 4.58 (d, 1 H, J
5.9 Hz, H-2), 4.17–4.06 (m, 2 H, H-4, H-5),
3.70–3.51 (m, 2 H, CH2), 3.41 (s, 3 H, OCH3),
2.80–2.59 (m, 2 H, H-6a, H-6b), 1.47, 1.32 (2
s, 6 H, (CH3)2C), 1.28 (s, 6 H, (CH3)2ꢀCOH.
13C NMR (CDCl3): l 211.2 (CO), 109.9 (C-1),
90.2, 85.5, 80.2 (C-2, C-3, C-4), 68.6 (C-5),
55.7 (OCH3), 54.5 (CH2), 46.9 (C-6), 29.4, 29.3
(CH3)2CꢀOH), 26.3, 24.7 ((CH3)2C). HRMS
(LSIMS): m/z 341.1568 [M+Na]+. Calcd for
C15H26O7Na: 341.1576.
1
10b: H NMR (CDCl3): l 4.88 (s, 1 H,
H-1), 4.82 (dd, 1 H, J 6.0, 3.8 Hz, H-3), 4.55
(d, 1 H, J 6.0 Hz, H-2), 4.42–4.36 (m, 1 H,
H-5), 3.78 (dd, 1 H, J 3.8, 7.8 Hz, H-4), 3.34
(s, 3 H, OCH3), 3.28, 3.22 (ABq, 2 H, H-6a,
H-6b), 2.22 (s, 3 H, CH3CO), 1.43, 1.26 (2 s, 6
H, (CH3)2C). 13C NMR (CDCl3): l 212.4
(CO), 107.1 (C-1), 84.8, 81.1, 79.5 (C-2, C-3,
C-4), 66.0 (C-5), 54.5 (OCH3), 47.2 (C-6), 30.8
(CH3CO), 25.9, 24.6 ((CH3)2C)
3-O-Benzyl-6,8,10-trideoxy-1,2-O-isopropyl-
idene-9-C-methyl-h- -gluco-decapyranosulos-
D
1,3-Di-C-(methyl 2,3-O-isopropylidene-h-
manno-pentofuranosid-5-yl)acetone (9).—
D-
7-ulose (11).—Yield 0.166 g (21%); colourless
oil; (the gluco configuration of 11 was based
13
Yield 0.086 (17.1%); white foam; [h]D +49.3°
(c 0.9, CHCl3); IR wmax (film): 3457, 2937,
on the close analogy of its C NMR spectral
data with other compounds of the same
configuration [3]; [h]D −29.0° (c 2.1, CHCl3);
IR wmax (film): 3493, 2987, 2936, 1710, 1374,
1711, 1373, 1090, 863 cm−1
;
1H NMR
(CDCl3): l 4.87 (s, 1 H, H-1), 4.82 (dd, 1 H, J
5.9, 3.7 Hz, H-3), 4.58 (d, 1 H, J 5.9 Hz, H-2),
4.47 (m, 1 H, J 4.1, 8.3 Hz, H-5), 3.81 (dd, 1
H, J 3.7, 8.3 Hz, H-4), 3.30 (s, 3 H, OCH3),
2.92 (dd, 1 H, J 4.1, 16.9 Hz, H-6a), 2.76 (dd,
1 H, J 8.3, 16.9 Hz, H-6b), 1.47, 1.32 (2 s, 6
H, (CH3)2C). 13C NMR (CDCl3): l 207.5
(CO), 107.0 (C-1), 84.8, 81.2, 79.5 (C-2, C-3,
C-4), 66.0 (C-5), 54.6 (OCH3), 47.4 (C-6),
25.9, 24.6 ((CH3)2C). HRMS (LSIMS): m/z
485.2001[M+Na]+. Calcd for C21H34O11Na:
485.1999.
Methyl 6,8-dideoxy-2,3-O-isopropylidene-i-
-gulo- and -h-
uloses (10a,b).—Yield 0.033
10a+10b; colourless oil; (NMR data are
taken from a 6:1 mixture of L:D isomers.
Configuration assignments are based on anal-
ogy with methyl 6-O-alkyl-2,3-O-isopropyli-
1
1076, 887, 740 cm−1. H NMR (CDCl3): l
5.91 (d, 1 H, J 3.8 Hz, H-1), 4.82, 4.64 (ABq,
2 H, CH2Ph), 4.59 (d, 1 H, J 3.8 Hz, H-2),
4.44 (m, 1 H, H-5), 4.08 (d, 1 H, J 2.8 Hz,
H-3), 4.01 (dd, 1 H, J 2.8, 8.6 Hz, H-4), 1.95
(dt, 1 H, J 2.3, 4.8, 13.9 Hz, H-6a), 1.83 (dd,
1 H, J 2.3, 13.9 Hz, H-6b), 1.54–1.38 (m, 2 H,
CH2), 1.31 (s, 6 H, (CH3)2CꢀOH), 1.47, 1.23
(2 s, 6 H, (CH3)2C). 13C NMR (CDCl3): l
209.5 (CO), 104.9 (C-1), 82.9, 82.7, 80.8 (C-2,
C-3, C-4), 72.7 (CH2PH), 62.9 (CH), 62.8
(C-5), 45.1 (C-6), 41.2 (CH2), 30.9, 29.3
((CH3)2CꢀOH), 26.7, 26.2 ((CH3)2C). HRMS
(LISIMS): m/z 417.1874 [M+Na]+. Calcd
for C21H30O7Na: 417.1889. Anal. Calcd for
C21H30O7: C, 63.94; H, 7.67. Found: 63.95, H,
7.74.
L
D
-manno-octofuranosid-7-
(11.8%):
g
dene-b-
L
-gulo- and a- -manno-furanosides
D
[3]).
Acknowledgements
1
10a: H NMR (CDCl3): l 4.96 (s, 1 H,
H-1), 4.73 (dd, 1 H, J 5.9, 3.6 Hz, H-3), 4.58
(d, 1 H, J 5.9 Hz, H-2), 4.54–4.43 (m, 1 H,
H-5), 3.86 (dd, 1 H, J 3.6, 5.5 Hz, H-4), 3.33
Support of this work by the State Commit-
tee for Scientific Research (grant no. 3 TO9A
066 12) is gratefully acknowledged.

H. Ste˛powska, A. Zamojski / Carbohydrate Research 321 (1999) 105–109
109
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