the acceptor 7 giving a 70% yield of trisaccahride 8 (Scheme
1) in apparent contravention of the armed-disarmed concept.
Scheme 3. Synthesis of the R-SBox Donor 13
Scheme 1. Trisaccharide Synthesis
compared to the more downfield shift of this carbon
resonance in the N-glycosides (δ ∼178), consistent with the
thiocarbonyl nature of the latter system. These assignments
were confirmed by the UV spectra, which showed the
anticipated differences between 2-alkylthiobenzoxazoles and
N-alkylbenzoxazol-2-thiones.9
A rationale was advanced based on the differential
stabilization of a fully developed positive charge (oxacar-
benium ion) at the anomeric center by the protecting groups
at O2 and/or O6, and on the changing ability of the “O5
lone pair” to eject the leaving group from the anomeric center
according to the nature of the O6 protecting group.5 It
occurred to us that the at first sight unusual reactivity patterns
of Figure 1 and Scheme 1 are better explained on the basis
of classical anchimeric assistance, and, if so, that they would
be dependent on the anomeric configuration. We report here
on the results of our investigation and confirm that neighbor-
ing group participation is the underlying cause of the
observed reactivity sequence.
A series of reactions were then conducted in which donors
1, 2, 4, 11, and 13 were activated with Cu(OTf)2 in
dichloromethane at room temperature in the presence of 5
Å molecular sieves10 and 1,2;3,4-di-O-isopropylidene-R-D-
galactopyranose, essentially according to the original condi-
tions. The results obtained with donors 1, 2, and 4 (Table 1)
conform to the pattern reported previously (Figure 1). Thus,
the perbenzyl donor 1 was the most reactive and was
consumed within 2 h (Table 1, entry 1), whereas the
perbenzoyl system 4 required 14 h (Table 1, entry 2). The
2-O-benzyl-3,4,6-tri-O-benzoyl-â-SBox derivative 2 was
recovered in 85% yield after 14 h in a reaction that afforded
only 14% of the anticipated glycoside (Table 1, entry 3).
Turning to the R-SBox donors 11 and 13, the 2-O-benzyl-
3,4,6-tri-O-benzoyl-R-SBox system 11 showed comparably
poor reactivity to its â-anomer (Table 1, entry 4), whereas
the per-O-benzoyl R-SBox donor 13 was completely un-
reactive under these conditions (Table 1, entry 5).
The R-analogue (11) of 2 was synthesized from the known
bromide 96 by hydrolysis to the pyranose and subsequent
Mitsunobu reaction with benzoxazolethiol (Scheme 2).
Scheme 2. Synthesis of the R-SBox Donor 8
The complete contrast in reactivity of the R- and â-
anomers of the perbenzoyl donors 4 and 13 (Table 1, entries
2 and 5) is informative, especially when viewed alongside
the very similar reactivity of the two anomers of the 2-O-
benzyl-3,4,6-O-benzyl system 2 and 11 (Table 1, entries 3
and 4). We conclude that the enhanced reactivity of donor 4
with respect to its R-isomer 13 is simply a manifestation of
the weak promoting system (copper(II) triflate) being assisted
by participation of the 2-O-benzoate ester. Thus, unlike the
case of the fully armed per-O-benzyl ether, the promoter is
unable to cause departure of the anomeric leaving group from
the formally more disarmed donor 4 without participation
by the ester group. When participation is stereoelectronically
prevented, as in the case of 13, no reaction occurs at all.
The 2-O-benzyl-3,4,6-O-benzoyl systems, both of which are
In a similar manner 2,3,4,6-tetra-O-benzoyl-D-glucopyra-
nose 127 was transformed into a separable mixture of the R-
and â-SBox glycosides 13 and 4, and the R-NBox glycoside
14 (Scheme 3). The â-SBox donors 1 and 2 were prepared
according to the literature protocols.8
The identity of donors 11 and 13 as the R-SBox deriva-
tives, as opposed to the corresponding NBox derivatives (e.g.,
14), was determined by inspection of the 13C NMR spectra
in which C2 of the benzoxazole is found around δ 160 as
(5) Kamat, M. N.; Demchenko, A. V. Org. Lett. 2005, 7, 3215-3218.
(6) Lichtenthaler, F. W.; Ko¨hler, B. Carbohydr. Res. 1994, 258, 77-
85.
(7) Sebesan, S.; Neira, S. Carbohydr. Res. 1992, 223, 169-185.
(8) Demchenko, A. V.; Kamat, M. N.; De Meo, C. Synlett 2003, 1287-
1290.
(9) Zinner, H.; Peseke, K. Chem. Ber. 1965, 98, 3515-3519.
(10) Without commenting on the reason, we note that reactions conducted
in the presence of 4 rather than 5 Å molecular sieves were much slower
with donors 1 and 4, and prohibitively so with donors 2, 11, and 13.
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Org. Lett., Vol. 9, No. 21, 2007