Anomeric acetates of N-acetylneuraminic acid are useful C-sialyl donors in samarium-mediated reformatsky coupling reactions

Article abstract of DOI:10.1002/anie.200601209

(Chemical Equation Presented) Teaching an old molecule new tricks: A new solution for an expeditious C-sialylation from N-acetylneuraminic acid involves the use of the peracetylated derivative 1, a very common starting material prepared 40 years ago in He

Full text of DOI:10.1002/anie.200601209

Communications
C-Sialylation
DOI: 10.1002/anie.200601209
Anomeric Acetates of N-Acetylneuraminic Acid
are Useful C-Sialyl Donors in Samarium-
Mediated Reformatsky Coupling Reactions**
Adeline Malapelle, Zouleika Abdallah, Gilles Doisneau,
and Jean-Marie Beau*
N-Acetylneuraminic acid (Neu5Ac) occurs in a wide range of
biologically important glycoconjugates, mostly at the terminal
position of oligosaccharides attached to proteins or lipids.[1,2]
It is involved in a large number of intercellular events,[2] and
molecular tools containing this important motif are needed to
devise reagents or probes for biological studies and applica-
tions. The a-glycosidic bond of these terminal sialyl residues
is, however, fragile in vitro under very mild acidic conditions,
and it is cleaved by neuraminidases in vivo. The replacement
of the interglycosidic oxygen atom with a carbon atom
provides C-linked analogues that are stable towards hydrol-
ysis, as required for various applications such as Neu5Ac-
containing antiviral drugs or vaccines.
We have previously established a rapid and stereoselec-
tive assembly of C-glycosides through a samarium diiodide[3]
promoted Barbier reaction with glycosyl 2-pyridylsulfones
without an additive.[4,5] Linhardt and co-workers showed that
the procedure worked equally well with 3, the anomeric 2-
pyridylsulfone of Neu5Ac (Scheme 1),[6] as well as with the
chlorides (such as 4) and phenylsulfones of Neu5Ac and other
2-ulosonic esters.[7]
We have also reported that 2, the anomeric 2-pyridylsul-
fide N-acetyl neuraminic acid derivative, is a useful anionic
precursor in a high-yielding samarium-mediated Reformatsky
approach for stereoselective a-C-sialylation.[8] All these
precursors of the N-acetylneuraminyl–samarium(iii) species
are, in fact, derived from the anomeric acetates 1. In an effort
to simplify further the synthetic sequence, we report herein
that these standard peracetylated intermediates, prepared
40 years ago by Kuhn and co-workers,[9] are practical C-sialyl
donors in samarium-mediated Reformatsky coupling reac-
tions with carbonyl compounds. The possibility of this
approach was suggested by the well-documented a-deoxyge-
nation of esters[10] and acetylated carbohydrate lactones[11]
with samarium diiodide. This procedure was further devel-
[*] A. Malapelle, Dr. Z. Abdallah, Dr. G. Doisneau, Prof. J.-M. Beau
UniversitØ Paris-Sud
Institut de Chimie MolØculaire et des MatØriaux associØ au CNRS
Laboratoire de Synth›se de BiomolØcules
91405 Orsay Cedex (France)
Fax: (+33)1-6985-3715
E-mail: jmbeau@icmo.u-psud.fr
[**] We thank the Minist›re de la Recherche for PhD grants to A.M. and
Z.A.
Supporting information for this article is available on the WWW
under http://www.angewandte.org or from the author.
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Table 1: Samarium-induced coupling of acetates 1 with carbonyl com-
pounds.
oped by Enholm and co-workers for a-deoxygenation/car-
bonyl-addition reactions of benzoylated lactones.[12] In an
application with O-acetylated 2-ulosonates, Hanessian and
Girard have also described an efficient and easy anomeric
deoxygenation procedure by using SmI2.[13] For the success of
all of these reactions, additives were needed (namely,
hexamethylphosphoramide (HMPA)[10–12] or ethylene
glycol[13]).
Standard methyl ester formation and peracetylation of
Neu5Ac with acetic anhydride/pyridine provided peracetates
1 as an a/b mixture of ꢀ 1:4 (83% from Neu5Ac; Scheme 1).[9]
Entry Acetate Carbonyl partner (reaction Product: yield[a] (isomer
time)
ratio)
1
2
3
1a
1b
1a
cyclopentanone (0.3 h)
cyclopentanone (2 h)
4-tert-butylcyclohexanone
(0.3 h)
5: 97%
5: 82%
6: 91%
4
1b
4-tert-butylcyclohexanone
(2 h)
3-pentanone (0.3 h)
3-pentanone (2 h)
cyclohexanecarbaldehyde
(0.3 h)
6: 83%
5
6
7
1a
1b
1a
7: 44%[b]
7: 26%[b]
8: 87% (1.25:1)
8
1b
cyclohexanecarbaldehyde
(2 h)
n-octanal (0.3 h)
n-octanal (2 h)
8: 83% (1.25:1)
9
10
1a
1b
9: 39%[b]
9: 33% (1:1)[b]
[a] Yields for isolated products after chromatography on silica gel.
Scheme 1. Synthesis of the Neu5Ac derivatives 1. a) MeOH,
Dowex H+, room temperature, 24 h; b) Ac2O, pyridine, room temper-
ature, overnight; 83% from Neu5Ac; c) HClg, AcOH/AcCl (1:1), room
temperature; d) CsOAc (1.5 equiv), MeCN, room temperature, 74%
from Neu5Ac.
[b] Together with reduction product 36 (40–44%; R1 =H, see Scheme 5).
acetate reduction was however too slow for coupling with an
acyclic ketone such as 3-pentanone or an aliphatic aldehyde
such as n-octanal; these provided the respective coupling
products with much lower efficiency (7: 44 and 26% yield;
Table 1, entries 5 and 6; 9: 39 and 33% yield; Table 1,
entries 9 and 10). In these reactions, reduction of the carbonyl
compound became the major competing pathway.
With these preliminary results on the separate anomers 1,
we proceeded to investigate the use of the more practical 1a,b
synthetic mixture. Some results obtained for the reductive
coupling with the anomeric 2-pyridylsulfide 2[8] are also
reported for comparison (Table 2, Scheme 2).
The SmI2 treatment of 1a,b with the same cyclic carbonyl
compounds provided results essentially identical to those
obtained with the separate anomers in a 2-hour reaction
(entries 3 and 4 in Table 1 and entry 3 in Table 2). Under
identical conditions, sulfide 2 also provided similar results,
although in a very fast reaction, as observed earlier (reduction
time < 1 min; Table 2, entries 2 and 4). Cyclobutanone was
also a good substrate for this reaction and provided the C-
sialyl compound 11 (88 and 96%; Table 2, entries 5 and 6).
Coupling of 1a,b with 1,4-cyclohexanedione (1.4 equiv)
provided 30% of the mono-C-sialyl product 12 (Table 2,
entry 7), whereas sulfide 2 furnished an 89% yield of the
same compound (Table 2, entry 8). Sulfide 2 also provided the
bis-C-sialyl product 13 in a very high yield (98%) when a
limiting amount of the diketone was used (0.45 equiv; Table 2,
entry 9). Good coupling yields were obtained with cyclo-
hexanecarbaldehyde (75 and 90%; Table 2, entries 10 and
11).
The anomers were easily separated by column chromatog-
raphy to allow the examination of their individual behaviors
in the reductive process. For these preliminary studies, larger
amounts of the minor isomer 1a were more conveniently
obtained by cesium acetate treatment of chloride 4, as
described earlier (74% yield from Neu5Ac).[14,15]
Separate treatment of a solution of acetate 1a or 1b in the
presence of cyclopentanone in THF at 208C with a freshly
prepared THF solution of SmI2[16] gave the C-sialyl derivative
5, with yields of 97% and 82%, respectively (Table 1,
entries 1 and 2). In these experiments, reactions occurred at
room temperature in the absence of any additive. However,
the time needed for the reduction depended on the anomeric
configuration of 1. The equatorial acetate in 1a reacted in
about 20 min, whereas the reaction needed about 2 h to go to
completion with the axial acetate in 1b. As was expected and
in agreement with our previously published results, coupling
reactions with a symmetric ketone like cyclopentanone gave 5
as a single diastereomer, with an equatorial orientation of the
À
new C C bond (see below). Coupling with 4-tert-butylcyclo-
hexanone proceeded with equal efficiency (yields of 91% and
83%; Table 1, entries 3 and 4).
Cyclohexanecarbaldehyde (2equiv) was also a good
substrate and provided the coupling products 8 in 87% and
83% yield (Table 1, entries 7 and 8). The coupling products
both displayed a standard C2-chair conformation as deter-
5
1
mined by H NMR analysis (J3ax,4, J4,5, and J5,6 values of 10.2,
11.8, and 10.5 Hz for one isomer and of 12.0, 10.5, and 10.5 Hz
for the other). The expected equatorial orientation of the
As noticed above with the separate acetates and n-
octanal, coupling of 1a,b with aldehyde 14 was not practical
(26% yield of 15; Table 2, entry 12) in comparison with the
reaction with sulfide 2, which furnished 15 in 78% yield. The
À
newly formed C C bond at the quaternary center was
3
[17]
indicated by the large values of JC1,H3ax
.
The rate of the
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Table 2: Samarium-induced coupling of acetates 1 and pyridylsulfide 2
with carbonyl compounds. The structural formulae of 12–14 and 16–21
can be found in Scheme 2.
reductive coupling of aldehyde 16 occurring instead to form
diol 17, whereas sulfide 2 supplied the expected compound 18
in 80% yield (Table 2, entries 14 and 15). With the d-
galactose-derived aldehyde 19,[7a] both acetates 1a,b and
sulfide 2 provided the expected compound 20 (in 30 and 82%
yield, respectively, Table 2, entries 16 and 17). When acetates
1a,b are used, the moderate yield is due to the competitive
pinacol coupling of aldehyde 19 to diol 21 (30% yield).
The utility of this coupling process with acetates 1a,b was
validated in a fast elaboration of sialoside analogues 24–26
(Scheme 3). Coupling of 1a,b with ketone 22 provided a
Entry Substrate Carbonyl partner
Product: yield[a] (isomer
ratio)
1
2
3
1a,b[b]
2[c]
1a,b
cyclohexanone
cyclohexanone
4-tert-butylcyclohexa-
none
10: 79%
10: 82%
6: 98%
4
2
4-tert-butylcyclohexa-
none
6: 96%
5
6
7
8
9
1a,b
2
1a,b
2
cyclobutanone
cyclobutanone
11: 88%
11: 96%
12: 30%
12: 89%
13: 98%
1,4-cyclohexanedione[d]
1,4-cyclohexanedione[d]
1,4-cyclohexanedione[e]
2
10
11
12
13
14
15
16
17
1a,b
2
1a,b
2
1a,b
2
1a,b
2
cyclohexanecarbaldehyde 8: 75%
cyclohexanecarbaldehyde 8: 90%[f]
14
14
16
16
19
19
15: 26%[g] (1:1)
15: 78%
(17: 56%)[h]
18: 80% (1:1)
20: 30%[h] (1:1)
20: 82% (1:1)
Scheme 3. Synthesis of sialoside analogues. a) SmI2 (3 equiv), THF,
room temperature, 85%; b) BH3·SMe2 (1.2 equiv), TMSOTf (1.2 equiv),
À788C in CH2Cl2, 4 h, 91%; c) allyltrichloroacetimidate (2 equiv), cat.
TfOH, cyclohexane/CH2Cl2 (2:1), 4 h, 62%; d) K2CO3/MeOH, room
temperature, overnight, 88%. TMSOTf=trimethylsilyl trifluorometha-
nesulfonate.
[a] Yields for isolated products after chromatography on silica gel.
[b] Used as an a/b mixture with a ratio of 1:4; reaction for 2 h at room
temperature. [c] Reaction for about 5 min at room temperature. [d] With
1.4 equivalents of 1,4-cyclohexanedione. [e] With 0.45 equivalents of 1,4-
cyclohexanedione. [f] Results taken from reference [8]. [g] Together with
reduction product 36 (17%; R1 =H, see Scheme 5). [h] Acetates 1a/b
were recovered (53%, entry 14; 14%, entry 16) with reduction product
36 (24%, entry 14; 21%, entry 16).
single compound 23 (85% yield). Reductive opening of the
acetal furnished selectively the equatorial product 24 (91%
yield) which could be allylated to give 25 (62%) and then
deprotected to form 26 (88% yield). Compounds such as 24–
26 constitute valuable building blocks to elaborate multi-
valent sialosides as robust biological probes or potential
inhibitors towards sialic acid binding proteins.[18]
The adequacy of other anomeric substituents was also
briefly examined, with the SmI2-induced coupling with cyclo-
pentanone serving as a reference reaction (Table 3).
Anomeric a-benzoate 27 did not show an improved
reduction rate compared to that with acetate 1a (reduction in
20 min at room temperature; Table 3, entry 2), whereas the
reaction with ethyl xanthate 28[19] was as fast as with 2-
pyridylsulfide 2 or its corresponding sulfone (less than 1 min
at room temperature; Table 3, entries 3 and 4). Phenylsulfide
29 reacted very slowly (10–20% yield of 5 with 50% of the
starting material recovered after 4 h; Table 3, entry 5) and
methyl glycoside 30 was unreactive under identical condi-
tions, even after a prolonged time in the presence of SmI2
(Table 3, entry 7). Increasing the reducing power of SmI2 by
adding HMPA[20] or 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-
pyrimidinone[21] (DMPU, 8 equiv with respect to SmI2)
restored the reactivity towards phenylsulfide 29; however,
coupling product 5 was obtained in a low yield (25%; Table 3,
Scheme 2. Formulae of some of the compounds given in Table 2.
superiority of sulfide 2 over acetates 1a,b was also revealed by
using the d-mannose-derived aldehyde 16.[4f] No coupling
occurred in the SmI2-induced reaction with 1a,b, with the
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Table 3: Samarium-induced coupling of different Neu5Ac glycosides
with cyclopentanone.
electron transfer within the chelate, which would also be
possible with the reactive pyridylsulfide (as in 2·Sm in
Scheme 4) but not with the phenylsulfide or the unreactive
methyl glycoside (as in 29·Sm and 30·Sm in Scheme 4), unless
HMPA or DMPU were present (phenylsulfide 29 only).
Owing to the behavior of 29 and 30 in the presence of SmI2
without an additive, we would favor electron transfer in the
carbonyl group of the acetate of 1 (as in 1a·Sm in Scheme 4)
rather than in the carbonyl group of the methyl ester (as in
29·Sm/30·Sm in Scheme 4) because in the latter event, enolate
33 could also be formed by cetyl radical reduction (34 to 35)
and b elimination of X (35 to 33; X = SPh or OMe).
Entry
Substrate
X
Reaction time
Yield of 5[a]
1
2
3
4
5
6
7
1a
27
28
2
29
29
30
OAc
20 min
20 min
<1 min
<1 min
4 h
97%
95%
94%
76%
OBz[b]
S(CS)OEt
SPy[c]
SPh
10–20%[d]
25%[f]
n.r.[h]
SPh[e]
OMe[g]
2 h
4 h
Finally, addition of H2O or D2O (8 equiv with respect to
acetates 1) to the reaction mixture before the introduction of
SmI2 strongly interfered with the coupling reaction with
cyclobutanone (Scheme 5). This mostly provided both “pro-
[a] Yields for isolated products after chromatography on silica gel.
[b] Bz=benzoyl. [c] Py=2-pyridyl. [d] 50% of 29 was recovered. [e] With
HMPA or DMPU (8 equiv). [f] Together with reduction product 36 (65%;
R1 =H, see Scheme 5). [g] Experiment done with the b anomer. [h] n.r.=
not recovered. Only 30 was recovered (97%), even when DMPU
(8 equiv) was added.
entry 6), together with the reduction product 36 (R1 = H in
Scheme 4; 65% yield).
The “room-temperature” conditions reported herein and
previously with similar compounds,[6–8] which are possible
with the “anion-sensitive” O-acetyl protecting groups and an
amide proton, may suggest a radical mechanism for the
crucial carbon–carbon bond formation.[22] In this report, the
behavior of the acetylated Neu5Ac derivatives 1, 2, and 27–30
with different anomeric substituents also provides informa-
tion on the possible mechanism. The facile reductive process
of acetates 1, which is possible without an additive, may be
facilitated by the chelation of the two carbonyl groups with
the samarium atom (SmII) with an extra complexation of the
endocyclic O6 atom as shown in Scheme 4.
Scheme 5. Samarium-induced coupling of acetates 1 with cyclobuta-
none in the presence of water (or D2O).
tonation” products 36 and 37 in a ratio of 2:1[24] (62–64%;
70% deuterium incorporation), together with coupling prod-
uct 11 (16–18%). This gives evidence that organosamarium
intermediate 32 or the corresponding enolate 33 could be
generated and be involved in the carbon–carbon bond
forming step, provided that the presence of water does not
alter the mechanism.[22e,25]
In conclusion, we have shown that the reductive samar-
iation of the peracetates of methyl N-acetyl-neuraminate in
the presence of cyclic ketones provides a practical, straight-
forward, and high-yielding solution for stereoselective a-C-
sialylation. Based on experimental evidence, we propose that
the key carbon–carbon bond forming step occurs through an
organosamarium intermediate. This procedure should prove
useful in the fast synthesis of simple molecular modules
containing stable bioactive sialoside mimetics for biological
research.
This scheme of tight complexation might increase the
reducing ability of SmI2, as most chelating agents do,[23] or
facilitate the first electron transfer. It would allow a fast
Experimental Section
23: A freshly prepared 0.1m solution of SmI2 in THF (100 mL,
10 mmol of SmI2) was added to a stirred THF (10 mL) solution
mixture of acetates 1a,b (1.77 g, 3.32mmol) and ketone 22 (1.00 g,
6.64 mmol) at 208C under Ar. After the mixture had been stirred for
2h, saturated aqueous NH 4Cl was added and the reaction mixture
was extracted three times with CH2Cl2. The combined organic phases
were washed twice with water, dried with Na2SO4, and evaporated to
dryness. Flash chromatography on silica gel (toluene/acetone, 1:1)
gave 23 (1.78 g, 85%): 1H NMR (CDCl3, 360 MHz): d = 5.62(d,
J(NH,5) = 9.5 Hz, 1H, NH), 5.52(ddd, J(8,7) = 8.1, J(8,9b) = 6.6,
J(8,9a) = 2.5 Hz, 1H, H-8), 5.39 (dd, J(7,8) = 8.1, J(7,6) = 1.1 Hz, 1H,
H-7), 4.84 (ddd, J(4,3ax) = 11.2, J(4,5) = 10.4, J(4,3eq) = 4.5 Hz, 1H,
H-4), 4.43 (dd, J(9a,9b) = 12.4, J(9a,8) = 2.5 Hz, 1H, H-9a), 4.22–3.97
Scheme 4. The proposed complexation scheme for efficient electron
transfer and formation of the organosamarium intermediate (in 33:
Y=OAc from 32 or Y=I from 35). L=ligand.
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Communications
(m, 2H, H-5,6), 4.21 (dd, J(9b,9a) = 12.4, J(9b,8) = 6.6 Hz, 1H, H-9b),
[12] a) E. J. Enholm, S. Jiang, Tetrahedron Lett. 1992, 33, 6069;
b) E. J. Enholm, S. Jiang, Heterocycles 1992, 34, 2 2 47; c) E. J.
Enholm, S. Jiang, K. Aboud, J. Org. Chem. 1993, 58, 4061.
[13] S. Hanessian, C. Girard, Synlett 1994, 863.
[14] A. Marra, P. Sinaþ, Carbohydr. Res. 1989, 190, 317.
[15] A. Lubineau, J. Le Gallic, J. Carbohydr. Chem. 1991, 10, 263.
[16] P. Girard, J.-L. Namy, H. B. Kagan, J. Am. Chem. Soc. 1980, 102,
2693.
4.05 (m, 4H, O(CH2)2O), 3.89 (s, 3H, COOCH3), 2.95 (s, 1H, OH),
2.58 (dd, J(3eq,3ax) = 12.8, J(3eq,4) = 4.5 Hz, 1H, H-3eq), 2.27, 2.22,
2.15, and 2.12 (4s, 12H, OCOCH3), 1.96 (s, 3H, NCOCH3), 1.94 (dd,
J(3ax,3eq) = 12.8, J(3ax,4) = 11.2Hz, 1H, H-3ax), 1.93–1.60 ppm (m,
8H, CH2 of cyclohexyl); 13C NMR (CDCl3, 90 MHz): d = 170.8, 170.7,
170.5, 170.1, 169.9, and 169.8 (4OCOCH3, NCOCH3, COOCH3),
108.1 (C of cyclohexyl), 85.7 (C2), 74.1 (COH), 73.1, 70.3, 68.7, 67.7
(C4, C6, C7, C8), 64.9, 63.9 (OCH2CH2O), 62.9 (C9), 52.2 (CH3O),
49.0 (C5), 32.9 (C3), 29.9, 29.7, 29.2, and 28.9 (4CH2 of cyclohexyl),
22.9, 21.1, 20.7, 20.6, and 20.5 ppm (4CH3OCO, CH3CON); MS (ES):
m/z 654 [M + Na]+; HR-MS (ES): calcd for C28H41NaNO15: 654.2368;
found: 654.2383.
[17] a) J. Haverkamp, T. Spoormaker, L. Dorland, J. F. G. Vliegen-
thart, J. Am. Chem. Soc. 1979, 101, 4851; b) D. W. Norbeck, J. B.
Kramer, P. A. Lartey, J. Org. Chem. 1987, 52, 2174.
[18] a) D. Zanini, R. Roy, J. Am. Chem. Soc. 1997, 119, 2088, and
references therein; b) G. B. Sigal, M. Mammen, G. Dahmann,
G. M. Whitesides, J. Am. Chem. Soc. 1996, 118, 3789.
[19] A. Marra, P. Sinaþ, Carbohydr. Res. 1989, 187, 35.
[20] J. Inanaga, M. Ishikawa, M. Yamaguchi, Chem. Lett. 1987, 1485.
[21] E. Hasegawa, D. P. Curran, J. Org. Chem. 1993, 58, 5008.
[22] For mechanistic studies, see: a) H. B. Kagan, J.-L. Namy, P.
Girard, Tetrahedron 1981, 37, 175; b) J.-L. Namy, J. Collin, C.
Bied, H. B. Kagan, Synlett 1992, 733; c) G. A. Molander, L. S.
Harring, J. Org. Chem. 1990, 55, 6171; d) D. P. Curran, T. L.
Fevig, M. J. Totleben, Synlett 1990, 773; e) D. P. Curran, X. Gu,
W. Zhang, P. Dowd, Tetrahedron 1997, 53, 9023.
Received: March 27, 2006
Revised: June 13, 2006
Published online: August 9, 2006
Keywords: carbohydrates · glycosides · metalation · samarium ·
.
sialic acids
[23] E. Prasad, R. A. Flowers II, J. Am. Chem. Soc. 2002, 124, 6357,
and references therein.
[1] Sialic Acids: Chemistry, Metabolism and Function (Ed.: R.
Schauer), Cell Biology Monograph Series, Vol. 10, Springer,
Vienna, 1982.
[2] a) R. Schauer in Carbohydrates in Chemistry and Biology, Vol. 3
(Eds.: B. Ernst, G. W. Hart, P. Sinaþ), Wiley-VCH, Weinheim,
2000, pp. 227 – 243; b) M. L. Allende, R. L. Proia, Curr. Opin.
Struct. Biol. 2002, 12, 587; c) P. R. Crocker, Curr. Opin. Struct.
Biol. 2002, 12, 609.
[24] These results parallel the reduction results of Hanessian and
Girard[13] when they used SmI2 with ethylene glycol, which
provided the two isomers 36 (R1 = H) and 37 (R2 = H) in a ratio
of 4:1. However, when the reduction of 1 or 2 was carried out
without any other electrophile, addition of a proton source (H2O
or ethylene glycol) after the reduction event provided only
product 36 (R1 = H).
[3] For selected recent reviews on the use of SmI2 in organic
synthesis, see: a) D. J. Edmonds, D. Johnston, D. J. Procter,
Chem. Rev. 2004, 104, 3371; b) H. B. Kagan, Tetrahedron 2003,
59, 10351; c) P. G. Steel, J. Chem. Soc. Perkin Trans. 1 2001, 2 72 7;
d) A. Krief, A.-M. Laval, Chem. Rev. 1999, 99, 745; e) G. A.
Molander, C. R. Harris, Tetrahedron 1998, 54, 3321; f) G. A.
Molander, C. R. Harris, Chem. Rev. 1996, 96, 307.
[25] As further evidence, the reaction performed in [D8]THF without
an electrophile provided after treatment product 36 without
deuterium incorporation (R1 = H). This indicates that this
compound arises from the protonation of an organosamarium
intermediate or the corresponding enolate.
[4] Neutral hexoses: a) D. MazØas, T. Skrydstrup, O. Doumeix, J.-M.
Beau, Angew. Chem. 1994, 106, 1457; Angew. Chem. Int. Ed.
Engl. 1994, 33, 1383; b) D. MazØas, T. Skrydstrup, J.-M. Beau,
Angew. Chem. 1995, 107, 990; Angew. Chem. Int. Ed. Engl. 1995,
34, 909; c) T. Skrydstrup, D. MazØas, M. Elmouchir, G.
Doisneau, C. Riche, A. Chiaroni, J.-M. Beau, Chem. Eur. J.
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