SHORT COMMUNICATION
DOI: 10.1002/ejoc.201300123
Application of the 2-Nitrobenzyl Group in Glycosylation Reactions: A Valuable
Example of an Arming Participating Group
Szymon Buda,[a] Patrycja Gołebiowska,[a] and Jacek Mlynarski*[a]
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Keywords: Carbohydrates / Glycosylation / Protecting groups / Stereoselectivity
The application of the o-nitrobenzyl (oNBn) group is demon-
strated. This practical methodology allows the stereocon-
trolled synthesis of glucosides with a 1,2-trans linkage. This
new ether-type arming group can broadly extend the con-
cept of the use of participating groups in glycosylation reac-
tions. Easy protection and deprotection of the oNBn group
further confirms its usefulness in synthesis.
Introduction
The synthesis and application of carbohydrate derivatives
is still the subject of enormous interest because of the re-
markable biological relevance of carbohydrate units.[1] Most
carbohydrates found in nature exist as polysaccharides,
glycosides, or glycoconjugates, and thus, particular effort
has been constantly devoted to the stereoselective genera-
tion of the O-glycosidic bond between carbohydrate resi-
dues and the aglycon. Various methodologies and ideas are
now available for the efficient and stereocontrolled synthesis
of structurally defined complex oligosaccharides, but this
field still deserves additional attention.[2] The most com-
monly used strategy for the synthesis of glycosidic bonds
involves the coupling of a fully protected donor bearing a
leaving group at its anomeric center with a suitably pro-
tected glycosyl acceptor.
The most reliable method for stereoselective glycosyl-
ation is still based on the neighboring group participation
of the 2-O-acyl functionality [Scheme 1, III, benzoyl (Bz)].
An alcohol acceptor can attack the anomeric center from
only one face to provide the 1,2-trans-glycoside. The pres-
ence of an ester-type substituent that electronically deacti-
vates the donor is necessary for the stereocontrolled forma-
tion of the anomeric bond. Application of an ether-type
substituent [e.g., I, benzyl (Bn)], which electronically acti-
vates the donor molecule, in many cases leads to a mixture
of two stereoisomers that differ in the configuration of the
anomeric center.
Scheme 1. Application of the ether- and ester-type participating
groups in glycosylation reactions.
The above concept is fundamental for the stereocon-
trolled synthesis of the glycosidic bond, and the use of an
electron-rich ether-type neighboring group (Scheme 1, II)
has been only scantly mentioned in the literature. Examples
of heterocyclic thiophen-2-yl[3] and picolinyl[4] substituents
have been presented, whereas successful examples of substi-
tuted benzyl ethers have never been deeply explored. This
concept, however, seems to have great potential, and the
use of stereocontrolling benzyl-type groups may have many
advantages that include (1) the use of an activated (armed)
donor that allows for milder reaction conditions and
(2) easy one-step deprotection of all benzyl-type groups af-
ter the reaction.
Now, we present our contribution to the field by demon-
strating the successful application of o-nitrobenzyl (oNBn)
as an arming participating group to control glucosidic bond
formation. This concept was initially investigated by using
phenyl thioglucoside (1), which is frequently used as a glyc-
osyl donor in glycoside synthesis.[5] We assumed that neigh-
boring group participation of the 2-O-oNBn protecting
group would give a more stable acetoxonium ion, which
would provide the β-glycosides after alcohol attack from
only one face to afford 1,2-trans-glucosides (Scheme 2).
[a] Faculty of Chemistry, Jagiellonian University
Ingardena 3, 30-060 Krakow, Poland
E-mail: jacek.mlynarski@gmail.com
Homepage: www.jacekmlynarski.pl
Supporting information for this article is available on the
3988
© 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2013, 3988–3991