10.1002/ejoc.202000707
European Journal of Organic Chemistry
COMMUNICATION
4[b]
DMSO
24
10
TIPS (1a)
2b (100 mol%)
To examine the fluoride reactivity of aryltrifluoroborate, we
first chose potassium p-tolyltrifluoroborate 2a, which is
commercially
available,
as
the
electron
neutral
5[b]
6[b]
DMSO
DMSO
24
4
8
TBS (1b)
MePh2Si
(1d)
2b (100 mol%)
2a (100 mol%)
phenyltrifluoroborate, and we attempted to promote a desilylation
reaction with a series of benzyl silyl ethers (Table 1). The silyl
88
ethers
1a-c,
which
are
derived
from
3-[(4-
nitrobenzoyl)amino]benzyl alcohol and protected by TIPS, TBS,
and TBDPS groups for each, were treated with 100 mol%
trifluoroborate 2a in DMSO at 37 C. The resulting desilylation
7[c]
MePh2Si
(1d)
DMSO
33
24
24
24
24
86
3
2a (16.7 mol%)
2a (100 mol%)
2a (100 mol%)
2a (100 mol%)
2a (100 mol%)
o
reaction gave the alcohol 3 in negligible yield (Entry 1-3). We then
tried the desilylation reaction on 1a,b by using potassium p-
methoxyphenyltrifluoroborate 2b as the electron rich
phenyltrifluoroborate, which is also commercially available,
producing 3 in improved yields, 10% and 8%, respectively (Entry
4 and 5). As a moderately fluoride-sensitive silyl group, the
MePh2Si group-protected benzyl alcohol derivative 1d was
subjected to this desilylation reaction. Treatment of the silyl ether
1d with trilfluoroborate 2a in DMSO at 37 oC cleaved the MePh2Si
group to give the alcohol 3 in 88% yield after 4 h (Entry 6). The
desilylation was performed at lower concentration (5 mM) to avoid
overreaction of the desilylated product with trifluoroborate. When
the reaction was carried out with 0.56 mmol of 1 and 2a, according
to monitoring by TLC, it was confirmed that the desilylation under
this conditions was also compatible with large scale. Moreover,
when a catalytic amount (16.7 mol%) of trifluoroborate 2a was
loaded, the desilylation was completed and the corresponding
alcohol 3 was obtained in 86% yield (Entry 7). The catalytic
desilylation of 1d was investigated in 50, 33, and 25 mol% loading
of 2a, the product 3 was obtained in 88% after reaction for 6 h,
84% after reaction for 10 h, and 77% after reaction for 24 h by
HPLC ananlysis, for each. However, CHCl3 and THF were not
applicable to this desilylation due to the poor solubility of
potassium aryltrifluoroborate in these organic solvents, giving the
alcohol 3 in 3% and 7% yields, respectively (Entry 8 and 9). In
order to neutralize the hydrogen fluoride that was likely to be
generated by the hydrolysis of potassium trifluoroborate, the
desilylation was performed in phosphate buffer saline containing
DMSO (pH 7.4) (Entry 10). Although it was expected that the
electron neutral aryltrifluoroborate 2a would not be not stable in
aqueous solution and appeared to be nonreactive, the desilylation
of 1d proceeded and the alcohol 3 was obtained in 38% yield.
However, the trifluoroborate 2a demonstrated poor reactivity in
anhydrous DMSO, producing 3 in trace amounts (Entry 11). This
suggested that a small amount of water works as a reactant in this
desilylation reaction.
8[b]
MePh2Si
(1d)
CHCl3
THF[e]
[e]
9[b]
MePh2Si
(1d)
7
10[d]
11[b]
MePh2Si
(1d)
DMSO/P
BS (1:2)
Anhydrou
s DMSO
38
MePh2Si
(1d)
Trace
[a] The reaction was performed with a 50 mM solution of 1. [b] The reaction was
performed with a 5 mM solution of 1. [c] The reaction was performed with a 30
mM solution of 1 and 5 mM solution of 2a. [d] The reaction was performed with
a 10 mM solution of 1. [e] The solvent contained 1% DMSO. [f] Yield was
calculated by HPLC analysis.
To further explore the unique fluoride reactivity of the electron
neutral p-tolyltrifluoroborate 2a and the electron rich p-
methoxyphenyltrifluoroborate 2b, a substrate analysis of various
MePh2Si ethers was carried out (Table 2). Although this
desilylation in 50 mol% loading of trifluoroborate 2a also gave the
alcohol 3 excellent yield (Table 1), the desilylation was carried out
by using 100 mol% of 2, by considering low reactive substrates,
including amino acid derivatives and secondary silyl ethers. The
2-naphthylmethyl silyl ether 4 reacted with 100 mol% electron
neutral trifluoroborate 2a in DMSO at 37 oC. After 33 h, the alcohol
PD4 was obtained in 71% yield. Subsequently, desilylation was
examined under the same conditions. The (E)-cinnamyl silyl ether
5 could be desilylated by 2a to give the alcohol PD5 in excellent
yield. The liner alkyl silyl ethers 6 and 7 were treated with 2a,
giving the corresponding alcohols PD6 and PD7 in 80% and 18%
yields, respectively. It was expected that PD7 would be trapped
by the boron after quenching the reaction with brine. Thus,
isolation of PD7 by silica gel column chromatography led to
decrease the yield. In addition, it was difficult to calculate the yield
by HPLC analysis due to the low UV absorption. Treatment of 8,
which has a pyrene and is a useful fluorophore, with 2a afforded
the alcohol PD8 in 60% yield. Use of the electron rich
trifluoroborate 2b completed the desilylation of 8 within 2 h and
PD8 was obtained in quantitative yield. This desilylation reaction
of 9, which has a free aromatic amino group, produced PD9 in
68% yield, without interfering with the trifluoroborate. The
heteroaromatic ring-containing silyl ether 10, and the amide bond-
embedded silyl ether 11 were compatible with this desilylation,
giving PD10 in 98% yield and PD11 in 96% yield. The desilylation
of the MePh2Si group-protected N-Fmoc-L-serine 12 and 13
resulted in the production of PD12 and PD13 in low yields, due to
the cleavage of the Fmoc group. The MePh2Si group-protected N-
Boc-L-serine 14 tolerated this desilylation to afford PD14 in 39%
yield with recovery of 14 in 48% yield. The desilylation by using
Table 1. Desilylation by potassium phenyltrifluoroborate derivatives
Si
Entry
ArBF3K
Solvent
Time
(h)
Yield
of 3
(%)[f]
1[a]
2[a]
3[a]
DMSO
DMSO
DMSO
24
24
24
1
1
3
TIPS (1a)
TBS (1b)
2a (100 mol%)
2a (100 mol%)
2a (100 mol%)
TBDPS (1c)
2
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