The presence of PhS and I groups at positions 1 and 2 in
compound 3 makes such substrates appropriate for glycal
preparation under anionic or radical conditions. Initially, we
treated the 1-thioglycoside 5 with a Zn-Cu couple following
the Fischer-Zach method as modified by Bredenkamp14 and
obtained a quantitative yield of the D-allal 6 (entry 1, Table
1). The use of zinc in the presence of vitamin B12,15 a very
Scheme 1
Table 1. Optimization of the Synthesis of the Glycal 6 from
the 2-Deoxy-2-iodo-1-thioglycoside 5
yield
(%)
entrya
conditions
SePh, TePh, etc.) and the reducing agent (modifications of
the initial Zn reagents, (Cp2TiCl)2, Cr(EDTA), Al-Hg,
lithium naphthalenide, potassium-graphite, SmI2, etc.) used
for glycal generation.10 When appropriate groups are present
at positions 1 and 2, the reaction can be performed under
radical conditions.10 These methods are limited to readily
available pyranoses. Glycals have also been recently prepared
by ring-closing metathesis11 and via tungsten- and molyb-
denum-promoted alkynol endo cycloisomerization.12
1b
2
3
4
5
6
7
8
9g
Zn-Cu, THF-AcOH 20:1, NaOAc, 0 °C to rt, 6 h 100
Zn, B12, NH4Cl, MeOH-CH3CN 3:1, rt, 45 min
n-BuLi, THF, -78 °C, 1 h
2LNc (1 M), THF, -78 °C, 4.5 h
2TiCl4, 4LiAlH4, THF, reflux, 2 h
2NaI, acetone, 0 °C to reflux, 40 h
SmI2, THF-HMPA, rt, 15 h
94
41
94
85d
e
15f
91
h
Bu3SnH, AIBN, toluene, reflux, 30 min
t-BuOK, THF, 0 °C to reflux, 10.5 h
In a previous report,13 we described a new route to
glycosides that makes use of a new kind of glycosyl donor,
2-deoxy-2-iodo-thioglycosides, which are synthesized from
pentoses through a short synthetic route that involves
olefination and iodonium-ion-mediated 6-endo cyclization
(Scheme 2). As an extension of this work, we envisioned an
a A 2:5 R/â mixture was used unless otherwise indicated. b A 1:9 R/â
mixture was used. c LN ) lithium naphthalenide. d Benzyl-deprotected
glycals were detected by TLC. e 100% of starting material was recovered.
f 49% of starting material was recovered. g A 2:5 R/â mixture was used.
h 87% of starting material was recovered.
efficient reduction system, also afforded an excellent yield
of 6 but in a shorter reaction time (entry 2). The reaction of
5 with BuLi only gave a modest yield of the glycal 6 (entry
3); however, when 5 was treated with lithium naphthalenide
(LN),16 the yield increased to 94% (entry 4). When 5 was
treated with TiCl4/LiAlH4,17 the glycal 6 was obtained in
85% yield (entry 5).
Scheme 2
The reaction of 5 with NaI left the starting material
unaltered even after 40 h of heating (entry 6). Phenyl
(10) Somsak, L. Chem ReV. 2001, 101, 81-135
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L. J. Org. Chem. 2000, 65, 6061-6068.
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thioglycosides that would allow the preparation of D-allal
and D-gulal derivatives.
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