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stabilize the resulting glycosidic linkages. The latter feature
would provide synthetic chemists more flexibility to conquer
target molecules, and the introduction of the desired 2-deoxy
function(s) in the later stage could significantly improve the
overall efficiency of the synthesis.
Table 1. Optimization of visible-light-mediated deiodination.
The most widely used deiodination reaction involves the
toxic organotin-mediated radical reduction (Scheme 2a).[14] De-
spite the development of several improved methods to avoid
the use of potentially explosive initiators and toxic hydrogen
atom donors,[15] the successful applications of those methods
Entry
Conditions
Yield [%][a]
1
2
3
4
5
6
7
8
9
nBu3N (10 equiv), 1.5 h
nBu3N (2 equiv), 3 h
DIPEA (10 equiv), 1.5 h
DIPEA (2 equiv), 1.5 h
nBu3N (10equiv), HCOOH( 10 equiv), 1.5 h
nBu3N (2 equiv), Hantzsch ester (2 equiv), 1.5 h
nBu3N (2 equiv), p-toluenethiol (2 equiv), 1.5 h
DIPEA (2 equiv), p-toluenethiol (2 equiv), 1.5 h
DIPEA (2 equiv), p-toluenethiol (1 equiv), 1.5 h
p-toluenethiol (5 equiv), 4 h
84
69
80
60
86
91
93
95
42
39
10
[a] Isolated yield after purification by column chromatography on SiO2.
DIPEA=N,N-diisopropylethylamine.
In view of the synthetic potential of deiodination, the scope
of this newly uncovered protocol in 2-deoxy-a-glycoside syn-
thesis was next explored. As summarized in Table 2, from the
known corresponding glycosyl acetates 9a–d,[6b,25] a-linked 2-
iodo-2-deoxy glycosides 10a–p were accessed under the
modified Roush’s conditions in good to excellent yield with ex-
clusive stereochemistry. The optimal deiodination condition
from Table 1 (entry 8) was adopted to examine the scope of
functionalization of the C-2-position of newly formed glyco-
sides. The visible-light-mediated reduction was found to
reduce mono-/di-, primary, or/and secondary iodides within
two hours, and the desired 2-deoxy-a-di-, tri-, and pentasac-
charides 11 a–p were obtained with good to excellent yields.
Both glycosylation and deiodination demonstrated excellent
functional-group tolerance, in which thioether 11 k (S-glyco-
side), thioester 11 h, ester, benzylideneacetals, acetonide, silyl-
ether, ally ether, glycan, and benzyl ethers remained un-
touched.[26] We were also delighted to discover the remarkable
chemoselectivity during the reduction between alkyl iodide
and alkyl bromide 11 n, which was difficult to achieve under
conventional conditions.[8a]
Scheme 2. Reductive deiodinations.
in the synthesis of complex targets were rare.[16] Recently, stud-
ies on visible-light-induced photocatalytic reactions have re-
ceived considerable attention.[17] In 2012, Stephenson[18a] and
Lee[18b] reported a highly efficient way to remove an iodo-
group by using a photocatalyst and readily available amine
under visible-light irradiation, respectively (Scheme 2b).[19] We
envisioned that the combination of such an advance with
Roush’s strategy[10] would be beneficial to solve the challeng-
ing problem involving the synthesis of 2-deoxy sugars. Herein,
we report an efficient way to prepare 2-deoxy-a-glycoside by
glycosylation of 2-iodo-glycosyl acetate and subsequent
visible-light-mediated
(Scheme 2c).[20,21]
tin-free
reductive
deiodination
Initially, we selected the deiodination of the known 2-deoxy-
2-iodo-a-mannosyl disaccharide 7 as the model study. An en-
couraging result was obtained upon submitting 7 to irradiation
by a 1 W blue LED with fac-[Ir(mppy)3] (fac-[Ir(mppy)3]=fac-
tris[2-(p-tolyl)pyridinato-C2,N’]iridium(III)) (1.5 mol%) as a photo-
sensitizer or catalyst in Stephenson reported conditions
(Table 1, entries 1–6).[18a,22] Early studies revealed that the blend
of nBu3N (2 equiv) and Hantzsch ester (2 equiv) in the presence
of the fac-[Ir(mppy)3] (1.5 mol%) in CH3CN might reduce secon-
dary iodide efficiently within a couple of hours (entry 6). Subse-
quent optimization revealed that the replacement of expensive
Hantzsch ester with inexpensive p-toluenethiol afforded an ex-
cellent yield (entries 7, 8).[23] Other thiols were also tested for
the reduction and were found to be inferior to p-toluene-
thiol.[23] In the absence of the reducing reagent (amine), the re-
duction became less efficient and the 2-deoxyl glycoside 8 was
isolated with 39% yield (entry 10). Although the role of p-
toluenethiol in this transformation is not fully understood at
this moment, it may act as a hydrogen-atom shuttle, electron
donor, or hydrogen donor.[24]
Compared to the conventional deiodination conditions,
these photoinduced dieodination reaction conditions displayed
a great advantage (Table 3). Among the reported methods, the
combination of Bu3SnH and AIBN exhibited the best efficiency,
which produced 2-deoxy disaccharide 8 in 81% yield (Table 3,
entry 1).[16a] Na2S2O4 (entry 2) VA-061 and H3PO2 (entry 3), and
Et3B (entry 4)[16b–d] also generated 8 in moderate yields. Howev-
er, the rest conditions showed lesser efficiency under the cur-
rent circumstance.[16e–i]
To further demonstrate the synthetic potential of this meth-
odology in the construction of complex targets, we decided to
synthesize 2-dexoy-a-tetrasaccharide 14 containing four a-link-
ages by two routes (Scheme 3). The diiododisaccharide 10j un-
derwent a sequential removal of benzylideneactetal (90%),
TMSOTf-mediated glycosylation (70%), and global reduction
Chem. Eur. J. 2014, 20, 17319 – 17323
17320
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