M. Adinolfi et al. / Tetrahedron Letters 44 (2003) 6479–6482
6481
labile protecting groups such as trityl,12 TBDMS,13
primary acetonides.14 In all cases these deprotections
are conducted in wet solvents, and therefore anhydrous
conditions required in the present glycosidation proce-
dure should be important for the preservation of the
acid labile functionalities.
In conclusion, in this paper we report the feasible use of
the very acid labile dimethoxytrityl group in glycosida-
tion reactions. In addition, the installation of this steri-
cally demanding protecting group at the primary
position of the donor in combination with the use of a
suitable solvent allows the achievement of very high
selectivity in the synthesis of a-glycosides with a variety
of acceptors.
Supplementary material. Experimental procedures for
preparation of donors 2 and 3, glycosidations, and
spectral (1H and 13C NMR) data of disaccharides 8–13
are available.
Acknowledgements
Scheme 1. Synthesis of donors 2 and 3.
This work was supported by MIUR (Programmi di
Ricerca di Interesse Nazionale 2001 e 2002) and by a
grant (to M.S.) from Universita` Federico II di Napoli
(Progetto Giovani Ricercatori).
Indeed, glycosidations with donor 2 in ether mixtures
(entries 2, 6, 7 and 8) proceeded in all cases in high
yields. In addition, exclusive formation of the a-
anomers could be detected in all cases in the limits of
the NMR analysis. Interestingly, no appreciable detrityl-
ation process was observed despite the prolonged reac-
tion times, consistently with the extreme mildness of the
activation conditions. In order to confirm the sterical
effect of the bulky dimethoxy trityl group of the donor,
the coupling between donor 2 and the primary acceptor
4 was next examined in the nitrile solvent mixture
acetonitrile/propionitrile 4:1 which was previously
shown3 to address the selectivity of glycosidations with
armed imidates toward b-selectivity,11 especially with a
more reactive primary acceptor (see entry 3). As
expected, in this case (entry 4) an equally high yield was
achieved, and the b-selectivity was sensibly decreased
(b:a 1.7:1) by the 6-O-protecting group of the donor
which renders much more difficult the access of the
nucleophilic acceptor from the b-side. It should be
outlined that also with this alternative solvent mixture
no appreciable detritylation process was detected.
References
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It should be noted that several reports are concerned
with the lanthanide triflates mediated removal of acid