Recent results in synthetic glycochemistry with iron salts at Orsay-Gif - Carbohydrate Chemistry: Chemical and Biological Approaches - page 127

The result of this FeCl 3 6H 2 O-cascade of transformations is a very
concise and highly flexible preparation of antiviral zanamivir analogues.
This synthetic route has also potential for the fast generation of dihy-
dropyrans of this type for other applications.
4 Tandem catalysis with iron( III ) chloride hexahydrate
Tandem catalysis refers to the use of a single catalyst which promotes the
sequential transformation of a substrate via two or more mechanistically
distinct processes in a single reaction vessel. Applied to carbohydrates,
this should make multi-step routes, such as chemical oligosaccharide
syntheses, faster. We explain how iron( III ) chloride hexahydrate, acting as
a Lewis acid, is appropriate to catalyze one-pot regioselective protection
of carbohydrates.
4.1 One-pot regioselective functionalization of glucopyranosides:
acetalation /reductive etherification
The construction of complex carbohydrate oligomers remains a chal-
lenging task in terms of stereoselective formation of glycosidic bonds.
The elaboration of monomeric or dimeric building blocks (glycosyl
donors and acceptors) typically requires lengthy multi-step sequences
decreasing the eciency of the overall synthesis. The streamlined syn-
thesis of these units can be achieved by means of tandem procedures, in
which several transformations occur in one-pot, thus reducing the
number of chemical steps and the time-consuming isolation and puri-
fication of intermediates. 38
In this context, a one-pot regioselective protection of persilylated
monosaccharides, using copper( II ) triflate 39 as a single catalyst was able
to promote acetalation-reductive etherification-acylation reactions. 40 In
the same way, the easy to handle, cheap and environment-friendly
FeCl 3 6H 2 O complex was a very ecient catalyst to promote regioselec-
tive acetalation and reductive etherification on glucopyranosides. 41
Hence, treatment of per-O-silylated a-methyl- D -glucopyranoside 50 with
benzaldehyde (3 equiv) and triethylsilane (1.1 equiv) in the presence of
5 mol% of FeCl 3 6H 2 OinaCH 2 Cl 2 /CH 3 CN solvent mixture led to 3-O-
benzyl-4,6-O-benzylidene- D -glucopyranoside 52 in a 77% yield (entry 1,
Table 1). The regioselectivity of the reductive etherification was deter-
mined through chemical correlation after acetylation of the hydroxyl
function. Compound 52 was also isolated in a similar yield using an-
hydrous iron( III ) chloride as catalyst, indicating that the hexahydrate
catalyst does not generate hydrogen chloride as a possible catalytic species.
Other iron salts such as Fe(acac) 3, (FeCl 3 ) 2 (TMEDA) 3 , Fe(NO 3 ) 3 9H 2 Oor
the iron( II )chloridehydratedcomplexFeCl 2 4H 2 Oprovidedeitherlower
yields or were inecient. The above optimized procedure could then be
successfully applied to thioglucopyranosides (such as 51), useful building
blocks for glycosylation reactions.
This two-step process can be followed by either an acylating reaction,
providing the fully protected glycosyl derivatives, or by a reductive
cleavage of the 4,6-O-benzylidene acetal furnishing the O-4 alcohol as