Tetrahedron Letters
A mild and efficient method for the selective cleavage
of primary p-methoxybenzyl protecting group
of saccharides by Co2(CO)8–Me2PhSiH–CO system
Peng-zhan Qian a, Wang Yao a, Lu-bai Huang a, Xiang-bao Meng a,b, Zhong-jun Li a,b,
⇑
a The State Key Laboratory of Natural and Biomimetic Drugs, Department of Chemical Biology, School of Pharmaceutical Sciences, Peking University, Beijing 100191, PR China
b National Research Center for Carbohydrate Synthesis, Jiangxi Normal University, Nanchang 330022, PR China
a r t i c l e i n f o
a b s t r a c t
Article history:
A mild and efficient method to selectively cleave p-methoxybenzyl (PMB) ether with a catalytic amount
of Co2(CO)8, hydrosilane and CO (1 atm) is presented. The cleavage reaction shows regioselectivity to
primary O-PMB of a variety of permethoxybenzylated saccharides and chemoselectivity to O-Bn,
sulfur-containing group and common ester protecting groups.
Received 18 June 2015
Revised 12 July 2015
Accepted 16 July 2015
Available online 21 July 2015
Ó 2015 Elsevier Ltd. All rights reserved.
Keywords:
Co2(CO)8
Cleavage
p-Methoxybenzyl
Regioselectivity
p-Methoxybenzyl (PMB) group is frequently used in organic
synthesis for the protection of hydroxyl groups, especially in the
synthesis of oligosaccharides.1 Various methods have been devel-
oped to cleave PMB ether.2,3 Recent advances include selective cat-
alytic hydrogenolysis,4 oxidative cleavage,5 and the use of new
Lewis acids such as AgSbF6 and POCl3.3,6,7 Some other studies also
focus on transforming PMB to other functional groups directly.8
However, few protecting groups are stable under Lewis acid or
oxidative conditions, especially in carbohydrate manipulations,
and groups like thiol can greatly inhibit the reaction process during
Pd catalyzed reaction. Therefore, it is necessary to explore milder
conditions.
hydrosilane determines the reaction rate of the cleavage process.
Therefore, five hydrosilanes were firstly screened in the presence
of 2.0 equiv of Co2(CO)8 in benzene under balloon pressure of CO
at 50 °C (Table 1, entries 1–6).
As shown in Table 1, Me2PhSiH afforded the desired primary
alcohol 1b in a higher yield than Et3SiH, EtMe2SiH, EtOMe2SiH,
and (EtO)2MeSiH after the acid–labile silyl ether was hydrolyzed
with a mixture of AcOH/H2O/THF13 at RT (entries 1–6).14,15 In order
to probe the potential similarity of mechanism between the
de-OPMB and de-OBn process which we reported previously,9,10
triethylsilyl ether intermediate 1c (Table 1, entry 1) which is stable
to silica gel chromatography (see SI). Solvents, temperature, and
equivalents of Co2(CO)8 were then screened.16 Optimal result was
achieved using 0.5 equiv of Co2(CO)8 and 20 equiv of Me2PhSiH
in refluxing CH2Cl2 (entry 11), which yielded the de-6-O-PMB
product (1b) in 86%. Lowering the temperature or reducing the
equivalent of Me2PhSiH can decrease the yield of 1b, while a large
amount of 1a was not consumed after stirring for 48 h (entries 12
and 14).
It was reported that O-Bn group can be readily cleaved under
the Co2(CO)8–HSiMe2Ph–CO system (Co2(CO)8: 0.1–0.2 equiv,
HSiMe2Ph: 6–20 equiv),10 which utilized less amount of Co2(CO)8
compared with the optimized condition given in Table 1 (entry
11). Thus, the tolerance of secondary O-benzyl group in the pres-
ence of primary O-PMB ether (compound 2a) under the optimized
reaction condition was investigated. As shown in Table 2, when 2a
Previous
work
in
our
laboratory
has
identified
Co2(CO)8–hydrosilane–CO system as an effective method for the
selective cleavage of benzyl ether.9,10 Various substrates have been
tested to show its broad applications and high functional groups
tolerance.10 Since PMB ether is similar to benzyl ether, we presume
this mild method is also applicable for the selective cleavage of
PMB ether. Based on these considerations, a model reaction was
established using 1a as the substrate to investigate the reaction
conditions (Table 1).
Hydrosilane is proposed to react with Co2(CO)8 first to form an
active catalytic species Co(CO)4SiR3 in situ.9–12 The reactivity of
⇑
Corresponding author.
0040-4039/Ó 2015 Elsevier Ltd. All rights reserved.