Synthesis of 1,2-trans C-glycosyl compounds by reductive samariation of glycosyl iodides

Article abstract of DOI:10.1039/b006455f

Reductive samariation of per-O-trimethylsilyl or benzyl glycopyranosyl iodides in the presence of carbonyl compounds provides the corresponding 1,2-trans-C-glycosyl compounds in good yields.

Full text of DOI:10.1039/b006455f

Synthesis of 1,2-trans C-glycosyl compounds by reductive samariation of
glycosyl iodides
Nicolas Miquel, Gilles Doisneau and Jean-Marie Beau*
Laboratoire de Synthèse de Biomolécules, UMR CNRS 8614, Institut de Chimie Moléculaire, Université Paris-Sud,
F-91405 Orsay Cedex, France. E-mail: jmbeau@icmo.u-psud.fr
Received (in Liverpool, UK) 3rd August 2000, Accepted 16th October 2000
First published as an Advance Article on the web
Table 1 SmI2-induced coupling of silylated glycopyranosyl iodides with
Reductive samariation of per-O-trimethylsilyl or benzyl
carbonyl compoundsa
glycopyranosyl iodides in the presence of carbonyl com-
pounds provides the corresponding 1,2-trans-C-glycosyl
Entry
Substrate
Conditions
C-Glycoside (yield)b
compounds in good yields.
1
2
3
4
5
1
1
1
1
Cyclohexanone
Pentan-3-one
IsoButyraldehyde
n-Octanal
3a (85%)
3b (58%)
3c (71%; 10+1c)
3d (72%; 4+1c)
4 (61%)d
Numerous synthetic methods have been developed for the
preparation of C-glycosyl compounds, analogues of glycosides
in which the interglycosidic oxygen atom has been replaced by
a carbon atom.1 Recent work in our laboratory has focused on a
direct method for the synthesis of C-glycosyl compounds
derived from neutral hexoses by the reductive samariation of
anomeric 2-pyridyl sulfones in the presence of carbonyl
compounds (Barbier procedure).2 While the procedure is
efficient with the manno series,3 it is unsatisfactory with the
gluco- or the galactopyranosyl series2 because of too high a
level of the competing b-elimination (an elimination–C–C bond
formation ratio of approximately 1+1). We now report an
unexpected solution to this problem starting from glycosyl
iodides as efficient C-glycosyl donors in reductive samariation
experiments. These glycosyl halides, first prepared by the
reaction of glycosyl bromides with sodium iodide4 and rarely
used as electrophilic O-glycosyl donors,5 can be prepared from
methyl glycosides, glycosyl acetals and glycosyl acetates,6
hemiacetals7 or trimethylsilyl glycosides.8 Either a rapid
synthesis of structurally simple C-glycosyl compounds from
commercial free sugars via the per-O-trimethylsilyl glycosyl
iodides,8 or a multi-step construction of more complex C-
glycosyl compounds with the more practical per-O-benzyl
iodides is possible.
D
-Glucose
Cyclohexanone
a See Scheme 1 for the reaction conditions. b Isolated yields from the free
sugar after chromatography on silica gel. c Diastereomer ratio at the
exocyclic asymmetric center. d The only other byproduct is the protonation
product, 1,5-anhydro-2,3,4,6-tetra-O-acetyl-D-glucohexitol.
step, pyridine which suffered a samarium(III)-induced ring
opening was replaced by 2,6-lutidine. This one-pot four-step
procedure from the persilylated sugars (steps ii–v, Scheme 1)
provided only the a-products 3a–d as determined by 1H-NMR
analysis of the crude acetylated reaction mixtures, in yields of
58–85% from the commercial free sugar after silica gel column
chromatography. The only identified byproduct was the 1,5-an-
hydromannohexitol (reprotonation product) in about 10%,
presumably arising from traces of HI present in the starting
glycosyl iodides. With the two aldehydes tested (entries 3 and 4,
Table 1), a mixture of diastereomers were produced with
selectivities (10+1 and 4+1, respectively) in line with the results
previously obtained with anomeric 2-pyridyl sulfones.2
D-
Glucose provided C-glycosyl compound 4 by the same
sequence of reactions (entry 5). Noteworthy is the absence of
elimination products, particularly striking in the gluco series.
While this procedure is well suited for the rapid conversion of
commercial sugars to simple 1,2-trans-C-glycopyranosyl com-
pounds, more elaborated synthetic schemes would require
protecting groups more stable than trimethylsilyl groups. We
therefore tested the benzylated mannopyranosyl iodide availa-
ble by TMSI treatment in DCM at rt of either the glycosyl
acetate 55 or the trimethylsilyl glycoside 6 (entries 1 and 2,
Table 2). Reductive samariation as reported above in the
presence of cyclohexanone provided comparable results. The
same one-pot transformation (i, TMSI; ii, SmI2, cyclohexanone)
on the trimethylsilyl glycosides derived from glucose 7,
galactose 8 and fucose 9 also provided an unprecedented level
of C-glycosylation for these series (72–75% yield), obviously to
the detriment of the competing elimination reaction. For these
three substrates, it was necessary to conduct the samariation
step in the presence of one equiv. of 2,6-lutidine which greatly
reduces the amount of the competing protonation leading to the
1,5-anhydro sugars. As usual, the 1,2-trans compounds were the
only detectable C-glycosylation products, as indicated by the
values of the H1–H2 coupling constants in the 1H-NMR spectra
(9.2 Hz for 11 and 9.3 Hz for 12 and 13 in a chair conformation
of the pyranose ring). These results significantly differ from
those obtained from anomeric 2-pyridyl sulfones.2 Substitution
of the 2-pyridyl sulfone group by an iodine atom in an otherwise
identical structure resulted, under identical conditions, in an
improvement of the C-glycosylation reaction at a synthetically
Silylation of -mannopyranose 1 and treatment of a DCM
D
solution of the per-O-silylated derivative with iodotrimethyl-
silane (TMSI) according to the procedure of Uchiyama and
Hindsgaul8 provided anomeric iodide 2 which, after solvent
removal, was successively treated with the carbonyl compound
(2 equiv.) and a THF solution of SmI2 (2.2 equiv.) at rt (Scheme
1 and Table 1). On completion of the reaction, indicated by the
disappearance of the blue color of SmI2 in approximately 1.5 h,
the products were desilylated by addition of acidic MeOH and
analyzed as their acetylated compounds. For the acetylation
Scheme 1 Reagents and conditions: i, TMSCl, Et3N, DMF, 0 °C; ii, 1.1
equiv. of TMSI, CH2Cl2, 25 °C, 0.5 h; iii, 2 equiv. of carbonyl compound,
2.2 equiv. of SmI2, THF, 25 °C, 1.5 h; iv, MeOH, 1 M HCl, (3+1, v/v), 25°C;
v, Ac2O, 2,6-lutidine, 25 °C.
DOI: 10.1039/b006455f
Chem. Commun., 2000, 2347–2348
This journal is © The Royal Society of Chemistry 2000
2347

Table 2 SmI2-induced coupling of benzylated glycopyranosyl iodides with
cyclohexanone
The utility of this new procedure has been demonstrated in a
fast synthesis of the carbon-linked mimic of the -glucopyr-
anosyl(b1?6)- -mannopyranoside dimer 17 (Scheme 2). Re-
D
D
ductive samariation of iodide 14 in the presence of aldehyde
1510† provided the b-C-dimer 16 in 66% yield. Only one isomer
was detected at the exocyclic asymmetric center. Methyl
xanthate formation and radical reduction furnished the methyl-
ene-linked dimer which was debenzylated and characterized as
its per-O-acetyl derivative 17.‡
In summary, we have shown that the silylated or benzylated
glycopyranosyl iodides are useful C-glycosyl donors for the
synthesis of 1,2-trans C-glycosyl compounds. Work is in
progress to delineate a precise mechanism for the transforma-
tion.§
Notes and references
† Aldehyde 15 was prepared from methyl 2,3,4,6 tetra-O-benzyl-a-D-
mannopyranoside in an overall yield of 54% by the following five-step
sequence of reactions: i, Ac2O, CF3COOH, (4+1), 25 °C, 1 h; ii, MeONa,
MeOH, 25 °C, 12 h; iii, 1.4 equiv. PPh3, 4 equiv. I2, imidazole, toluene, 70
°C, 1 h; iv, 1.4 equiv. Bu4NCN, DMF, 0 to 25 °C, 3 h; v, 3 equiv. DIBAL-H,
CH2Cl2,, 278 °C, 0.5 h.
‡ Selected data for 17: [a]2D0 = + 22 (c = 0.2, CHCl3); 1H NMR (CDCl3,
400 MHz, atom numbering of a tridecopyranoside) d = 5.29 (dd, 1H, J 9.8,
3.5, H-3), 5.26 (dd, 1H, J 3.5, 1.5, H-2), 5.18, 5.10, 5.04, 4.89 (4 t, 4H, J 9.5,
H-4,9,10,11), 4.65 (d, 1H, J 1.5, H-1), 4.25 (d, 1H, J 12, 5.2, H-13), 4.10
(dd, 1H, J 12, 2.1, H-13A), 3.70 (ddd, 1H, J 10, 9.5, 2, H-12), 3.64 (ddd, 1H,
J 10, 5, 2, H-5), 3.40 (ddd, 1H, H-8), 3.36 (s, 3H, OMe), 2.16, 2.11, 2.08,
2.06, 2.04, 2.02 and 2.00 (7 s, 21H, OAc), 1.9–1.8 and 1.5–1.4 (2 m, 4H, H-
6,6A,7,7A); MS (ES): m/z
= 671 [M + Na]; HR-MS (ES), calcd for
C28H40NaO17 [M + Na]: 671.2163, found: 671.2166.
§ We do not yet have a reasonable explanation for the significant differences
between the behavior of anomeric iodides and anomeric 2-pyridyl sulfones.
It is possible that there is a change in the electron transfer mechanism (inner
vs. outer sphere ET) on going from anomeric 2-pyridyl sulfones to anomeric
iodides inducing a change in the product distribution (C–C bond formation
vs. elimination).
1 M. H. D. Postema, C-Glycoside Synthesis, CRC Press, Boca Raton, FL,
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Scheme 2 Reagents and conditions: i, 1.1 equiv. of TMSI, CH2Cl2, 25 °C,
0.5 h; ii, 1.1 equiv. of 15, 2.2 equiv. of SmI2, THF, 25 °C, 0.25 h, 66% from
7; iii, 1.5 equiv. of NaH, CS2, CH3I, 25 °C, 3 h, 96%; iv, 1.5 equiv. of
Bu3SnH, cat. AIBN, toluene, 95 °C, 2.5 h, 89%; v, H2, Pd/C, MeOH, Ac2O,
py, 94%.
9 F. Machrouhi, B. Hamann, J.-L. Namy and H. B. Kagan, Synlett, 1996,
633 and references cited therein; P. Girard, J.-L. Namy and H. B. Kagan,
J. Am. Chem. Soc., 1980, 102, 2693.
10 For another synthesis of aldehyde 15 see: H. B. Boren, K. Eklind, P. J.
Garegg, B. Lindberg and A. Pilotti, Acta Chem. Scand., 1972, 26,
4143.
useful level (72 vs. 39% yield in the gluco series) with a
concomitant decrease in the elimination reaction. We also
noticed a further improvement by incorporating catalytic
amounts of NiI2 with SmI2,9 and conducting the coupling
reaction at 210 °C (80% of 11, entry 4).
2348
Chem. Commun., 2000, 2347–2348