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J.R. Zhu et al. / Chinese Chemical Letters 21 (2010) 273–276
Table 1
Desilylating reaction of 1a with Et
3
N (2.0 equiv.) in various solvents systems.
.
Entry
1
2
3
4
5
6
Solvent (v/v)
a
Time
b
Yield (%)
DMSO/H
2 h
2
O (5:1)
DMSO/H
2.5 min
97
2
O (10:1)
DMF/H
40 min
96
2
O (10:1)
CH
2 h
95
3
CN/H
2
O (10:1)
THF/H
6 h
2
O (10:1)
EtOH/H
2
O (10:1)
24 h
95
97
96
a
TLC monitored the substrate disappeared.
Isolated yield.
b
Table 2
Desilylating reaction of 1a with different organic nitrogen bases.
Entry
1
2
3
4
5
6
7
8
9
10
a
Bases
MeNH
2
MeNH
8 min
93
2
(0.1 equiv.) Me
2
N
Piperidine Me
3
N
Et
2
NPh Ph
3
N
Imidazole DBU
DBU (0.05 equiv.)
96
b
Time
Yield
<1 min
96
<1 min 1 h
96 95
10 min 24 h
96 95
48 h
96
5 h
96
<1 min 20 min
97
c
a
The amount of base is 2 equivalents unless noted.
TLC monitored the substrate disappeared.
Isolated yield.
b
c
Elsewise, the reaction rate is also related to the ratio of organic solvent and H O (entries 1 and 2, Table 1).
2
Furthermore, either in anhydrous DMSO or in H O, no reaction happened.
2
Different organic bases were tried in DMSO/H O (10:1, v/v) at room temperature. All of them gave excellent yields
2
in appropriate time (Table 2), including aliphatic amine and aromatic amine, primary amine, secondary amine and
tertiary amine, mono nitrogen base and dinitrogen base. Aliphatic amines (entries 1 and 3, Table 2) took less than an
hour to remove TBDMS completely while aromatic amines (entries 6–8) mostly needed several hours, even longer
time, to do the same. An apparent order of the reaction rate was found: primary amine (entry 1, Table 2) > secondary
amine (entry 3, Table 2) > tertiary amine (entry 5, Table 2) and alkyl-substituted nitrogen base (entries 1, 3 and 5,
Table 2) > aryl-substituted nitrogen base (entries 6 and 7, Table 2), which corresponded to their basicity sequence,
except piperidine (entry 4, Table 2). Piperidine is a stronger base than Me NH (entry 3, Table 2), but with less activity.
2
Furthermore, bulkier base is responsible for a slower reaction rate since the lone electron pair on nitrogen atom is
difficult to be attached to the target. When the lone electron pair of nitrogen atom was conjugated, the basicity of
nitrogen compound will decrease and it will be less efficient for the deprotection reaction, which explained the activity
order of these amines: Me N > imidazole > Et NPh > Ph N.
3
2
3
In aqueous DMSO, even catalytic amount of these bases could push the reaction forward and complete. The
reaction time is in inverse to the amount of base (Table 2). For example, 2 equivalents of MeNH took less than 1 min
2
to remove the TBDMS, and 0.1 equivalent of MeNH needs 8 min. 2 equivalents of DBU took less than 1 min to
2
consume the substrate (entry 9, Table 2), but 0.05 equivalents of it took 20 min (entry 10, Table 2).
We then investigated the substrate scope. Using DBU as the base, this method was successfully applied to a variety
of phenolic TBDMS ethers. The desilylation of 1b–1h in DMSO/H O (10:1, v/v) afforded the corresponding phenols
2
in virtually quantitative and isolated yields (entries 1–5, Table 3). Notably, phenolic TBDMS in compound 1f was
removed but the benzyl TBDMS ether of 1f survived (entry 5, Table 3). And this method did not work with compound
1
g (entry 6, Table 3). This method has good selectivity between phenolic TBDMS ethers and alcoholic TBDMS ethers.
Further, it should be noted that the desilylating reactions of TBDMS ethers 1a–1b and 1e (entry 9 in Table 2, entries 1
and 4 in Table 3) bearing electron-withdrawing groups on the aromatic ring were very fast in comparison with the
desilylating reactions of TBDMS ethers 1d and 1f (entries 3 and 5, Table 3). Phenolic TBDMS ethers bearing electron-
withdrawing groups were deprotected more easily than those bearing electron-donating groups. In compound 1e (entry
Zhu, Jian Rong
