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chemoselectivity associated with these deprotections, while
unexpected, is noteworthy. Complete removal of the DPMS
residue in 2a could be achieved within 4 h at a concentration
of 0.25 M with virtually no deprotection of the TBS, TIPS, or
TBDPS ethers (entries 2, 4 and 5) under identical reaction
conditions (entry 3). As expected, the TMS ether is especially
labile and is hydrolyzed. Deprotections of the other silyl ethers
did eventually take place, requiring 72 h to reach completion.
Similar results were obtained in the case of allylic educt 4a. On
the other hand, phenolic DPMS ethers do not participate in this
deprotection chemistry, perhaps adding to the selectivity of this
Table 1. Deprotection of citronellyldiphenylmethylsilyl ether 1a using
sulfonyl fluorides.
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
[a]
Entry
R
Yield [%]
4
9
1
2
3
4
5
6
n-C H -
0
2
PhCH -
86
17
0
94
90
Ph-
4-propylphenyl-
perfluorobutyl-
4-nitrophenyl-
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
[9]
[a] Isolated Yields. 0.5 mmol scale reaction.
method. However, all types of silyl protected propargylic
alcohols underwent facile deprotection upon treatment with
SuFEx reagents.
As part of our ongoing efforts to assist with the “switch” of
organic synthesis from an organic solvent to a water-based
discipline using nanoreactors derived from newly engineered
fluoride exchange) reagents in click chemistry called for a 1:1
[8]
mixture of acetonitrile/water as reaction medium, n-propanol
was selected due to its relatively benign nature and lower cost
relative to acetonitrile. Benzylsulfonyl fluoride (entry 2), as well
as sulfonyl fluorides bearing electron-withdrawing groups, such
as 4-nitrobenzenesulfonyl fluoride (entry 6), led to very efficient
desilylation of model substrate 1a. Another especially effective
SuFEx reagent is perfluorobutanesulfonyl fluoride (entry 5). By
contrast, the typical alkyl or aryl analogs (entries 1, 3, and 4)
were either sluggish or gave little-to-no conversion after 16 h
under otherwise identical conditions. From this study, perfluor-
obutanesulfonyl fluoride was chosen for its high reactivity as
well as its substantially lower cost compared to its 4-nitro-
phenyl- or benzyl- analogs.
[10]
and benign surfactants, it has been found that fluoride ion is
reluctant towards entering the hydrophobic micellar inner core,
thereby all but eliminating the option to cleave silyl ethers in
this manner “in water.” This was attributed to the highly
favorable status of hydrated fluoride ion, and hence, silyl ether
cleavage appeared to require a “dry” source of this ion to be
available in an aqueous micellar medium. This led us to
examine a lipophilic SuFEx reagent in the presence of nano-
micelles, where a water-stable sulfonyl fluoride might release
fluoride in return for the oxygen in an alcohol, all taking place
[
11]
within the inner hydrophobic core of a micellar environment.
Hence, as an alternative set of reaction conditions, we
investigated the effectiveness of a SuFEx reagent within
Notwithstanding the effectiveness of a SuFEx reagent to
desilylate a DPMS ether, the main question surrounding
selectivity remained. As illustrated in Tables 2a and 2b, the
[12]
micelles derived from TPGS-750-M (Figure 2).
Use of this
Table 2. (a) Chemoselectivity of perfluorobutanesulfonyl fluoride towards
alkyl silyl ethers.
Figure 2. Structure of designer surfactant TPGS-750-M.
[a]
entry
Silyl ether [SiR
3
]
Yield [%]
1
2
3
4
5
TMS
TIPS
DPMS
TBS
TBDPS
95
0 (86)
91
[
b]
surfactant medium may broaden the scope of substrates, in
particular those with solubility and/or reactivity issues in water/
alcohol mixtures.
As shown in Scheme 1 (results in blue), various primary
alcohols derived from DPMS ethers containing a wide variety of
functional groups are amenable, leading to good-to-excellent
yields of deprotected alcohols. These include nitro (16b),
benzylic (6b, 9b, 10b) propargylic (5b), allylic (4b, 7b, 11b,
[b]
0 (89)[
b]
0 (84)
*R-SuFEx=n-C
4 9 2
F SO F; [a] Isolated yields. [b] Isolated yields after 72 h.
0
.5 mmol scale.
(b) Chemoselectivity of perfluorobutanesulfonyl fluoride towards allylic
silyl ethers.
1
3b, 15b) heteroaromatic (2b, 9b, 16b), and alkyl (1–3b, 12b,
[a]
17–19b). Notable cases include the tolerance exhibited by
several basic nitrogen-containing educts affording product
alcohols 2, 9, 14 and 16, as well as an allylic cyclopropane
leading to product 3. Secondary alcohols were also depro-
tected, although there was a noticeable increase in reaction
time, likely a steric effect. Diol-containing substrates also
exhibited selectivity towards the DPMS ether, as both TBS and
Entry
Silyl ether [SiR
3
]
Yield [%]
1
2
3
TIPS
DPMS
TBS
0
83
trace
4 9 2
*R-SuFEx=n-C F SO F; [a] Isolated yields; 0.5 mmol scale.
ChemCatChem 2019, 11, 1–6
2
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