Recent results in synthetic glycochemistry with iron salts at Orsay-Gif - Carbohydrate Chemistry: Chemical and Biological Approaches - page 133

several steps for the introduction of the protecting groups and for the
post-coupling conversion to the 2-acetamido substituent found in the
natural products. To date, these reliable methods are the most frequently
used for the ecient synthesis of glycoconjugates containing a b- D -N-
acetyl glucosamine residue.
This chemistry was developed because the direct b-glycosylation of N-
acetyl- D -glucosamine is dicult. Indeed, it is well established that it leads
to the intermediate formation of the 1,2-O,N-oxazoline 2 which is a poorly
reactive glycosyl donor to form the b-glycoside (Scheme 19). Glycosylation
with the long known 59 and relatively unreactive glycosyl acetate donors, is
a straightforward alternative to methods using donors with much better
leaving groups at the anomeric position. Following the earlier report
using anhydrous iron( III ) chloride in excess, 8 (Scheme 1) other promoters
were recently studied for the synthesis of glycosides of GlcNAc, directly or
via the isolated 1,2-O,N-oxazolines: stoichiometric cupric salts 60 or acidic
conditions. 61,62 Activation using an excess of FeCl 3 (producing the a-
anomer under anomerization conditions) 12 was previously described for
anomeric ester donors incorporating a C-2 amide functionality (N-acetyl,
N-phthaloyl, N-chloroacetyl glycosyl acetate donors) 9,63 via the oxazoli-
nium cations (such as 76) as well as for other sugar donors having a C-2
ester participatory group. 10b,10c,11
Mild reaction conditions using catalytic triflates of rare earth metals
were also developed. 52,64-66 This was based on the better Lewis acid
properties of the catalysts, their ready availability and easy handling. An
alternative is the use iron( III ) triflate. In carbohydrate chemistry, iron( III )
triflate has only been used for oxidative C-C bond cleavage, 67
thioglycosylation of peracetylated glycosides 68 and type I Ferrier re-

arrangement of glucal. 69
Iron( III ) triflate is readily prepared by oxidative dissolution of iron
powder in the presence of triflic acid in DMSO under oxygen at atmos-
pheric pressure. This provides a stable and non-hygroscopic solvate
Fe(OTf) 3 6.2DMSO. 70 In our current program to develop new methods
for the preparation of oligomers of GlcNAc, 71,72 we studied the glycosy-
lation of stable and commercially available peracetate donor 1 using
catalytic amounts of Fe(OTf) 3 6.2DMSO. 73
Glucose derivative 77 was selected as a test alcohol for the glycosyla-
tion. Due to the low reactivity of the acetate donor, it proceeded better
under microwave irradiation 65 for a more ecient and faster glycosyla-
tion. The best catalytic loading of Fe(OTf) 3 6.2DMSO or Fe(OTf) 3 was 15
mol%. The reagent was far superior to Fe(NTf 2 ) 3 or FeCl 3 in the formation
of glycoside 78 (entries 1-3 vs. 4-5, 82-98 vs. 51-31%, Table 1) and
compares well with the rare earth triflates. 64-66
The addition of 2,4,6-tri-tert-butylpyrimidine (TTBP, 2 equiv) provided
the optimized procedure to perform the glycosylation (entry 3; 98% yield
of 78). These conditions can be extended to other glycosyl acceptors
(Table 3). The use of TTBP also allowed the glycosylation of a silylated
acceptor 79 (TBDPS protecting group), with the donor 1 and the
formation of b-(1

3) linked disaccharide 80 in 70% yield without
degradation (entry 1). The method was tested in the synthesis of a

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