Tetrahedron Letters
Co2(CO)6-propargyl cation mediates glycosylation reaction by using
thioglycoside
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Meng-jie Xia, Wang Yao, Xiang-bao Meng, Qing-hua Lou , Zhong-jun Li
State Key Laboratory of Natural and Biomimetic Drugs, Department of Chemical Biology, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China
a r t i c l e i n f o
a b s t r a c t
Article history:
We discovered that the cobalt-propargyl cation can mediate the glycosylation reaction by activating the
thioglycoside donor. The glyco-oxacarbenium cation was formed by transferring the thio-aglycone to the
cobalt-propargyl cation that was generated from the cobalt-propargylated acceptor in situ via the activat-
ing with Lewis acid. The reactivity of the donor (Armed or dis-armed) and the amount of the Lewis acid
control the releasing rate of the cobalt-propargyl group.
Received 5 April 2017
Revised 4 May 2017
Accepted 5 May 2017
Available online 6 May 2017
Ó 2017 Elsevier Ltd. All rights reserved.
Keywords:
Nicholas reaction
Glysosylation
CAS bond cleavage
Cobalt propargyl cation
Glycosylation reaction is the key step in the chemical synthesis
of complex oligosaccharides of biological importance. The thiogly-
cosides are useful glycosylation donors since they can be promoted
by several thio-reactive species1,2 The combination of Lewis acids
and thio-reactive additives plays a critical role in the glycosylation
reaction. It controls the formation rate of glyco-oxacarbenium
cation as well as the stereoselectivity of the 1, 2-cis linkage. Thus,
a comprehensive screening of the reaction conditions is always
essential for the success of a glycosylation coupling. In the mean-
time, novel promoting conditions for glycosylation with thioglyco-
sides are still needed.
Co2(CO)6-propargyl complex discovered by Nicholas and co-
workers3 has been used as key precursor for propargyl modifica-
tion4 The feature of the Co2(CO)6-stabilized propargylic cation
makes it an excellent electrophilic species when activated by Lewis
or Brønsted acids. Decades ago, Mukai et al. reported an
intramolecular aglycan delivery (IAD) strategy (Scheme 1a) medi-
ated by a Co2(CO)6-proparyl cationic intermediate to induce the
formation of the glyco-oxacarbenium species from an easily acti-
vated O-acyl donor5 However, the activating sequence in this reac-
tion was not demonstrated clearly, since the two cationic species:
the glyco-oxacarbenium cation as well as the Co2(CO)6-propargyl
cation, could be both activated by the Lewis acid. Thus, the role
of the Co2(CO)6-propargyl cation played in this transformation is
still need to be explored. Moreover, utilization of the Co2(CO)6-
propargyl cation in carbohydrate chemistry was poorly
investigated.
Herein, we firstly disclosed a Co2(CO)6-propargyl cation induced
glycosylation reaction by using thioglycoside as donor (Sche-
me 1b). Mechanism study shows that Co2(CO)6-propargyl cation
is an indispensable auxiliary in activating the thioglycoside.
The attempt to investigate Co2(CO)6-propargyl cation induced
glycosylation reaction initiated from the unexpected observation
of 1, 6-anhydro-glucoside 3a when p-methyl thiophenol-2, 3, 4-
tribenzyl-6-O-Co2(CO)6-propynyl-b-D-glucopyranoside 2 was trea-
ted with BF3ÁOEt2 in CH2Cl2 (Scheme 2). Instead of the desired 6-
OH product 3b6 that was normally formed from the acid-hydroly-
sis of the O-propargyl bond, 3a was unexpectedly isolated in 86%
after a short reaction time (15 min). The formation of 3a indicated
that the CAS bond was cleaved under the giving condition. In con-
sideration of the fact that 1 was inert to BF3ÁOEt2 treatment with-
out other additives,7 Co2(CO)6-propargyl cation formed in situ by
Lewis acid activation was hypothesized to act as a thio-reactive
auxiliary to induce the cleavage of the CAS bond, thereby, we envi-
sion that the Co2(CO)6-propargyl complex could facilitate a glyco-
sylation reaction via promoting the thioglycosides donor.
To investigate the conceived novel glycosylation reaction, we
established a model reaction by using 4 as donor and Co2(CO)6-
propargylated glucoside 5 as acceptor (Table 1). A wide range of
promoters, solvents and temperatures were subsequently
screened. Among all the tested Lewis acid promoters, BF3ÁOEt2,
TfOH and TMSOTf were found to be able to accomplish the trans-
formation, which afforded disaccharide 4a in good to excellent
yields (entry 1, 6 and 7). SnCl4 only gave the product in 17% (entry
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Corresponding authors.
0040-4039/Ó 2017 Elsevier Ltd. All rights reserved.