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I. Hatial et al. / Tetrahedron Letters 56 (2015) 4275–4279
Table 1
Desilylation of TMS, TBS, and TBDPS
Substrate
Product
Percent yield (method, reaction time)
Si
90
95
(
a, 10 min)
(b, 10 min)
2a
1
a
OSiMe
3
OH
80
90
(
a, 30 min)
(b, 30 min)
1b
2
b
OTBS
OH
55
65
(
c, 12 h)
(d, 12 h)
H
3
CO
H
3
CO
2c
1
c
OTBDPS
OH
67
80
(
c, 24 h)
(d, 24 h)
H
3
C
H
3
C
2d
1d
SiMe
3
80
90
(
a, 10 min)
(b, 10 min)
2e
OTBS
1e OTBS
OSiMe
3
OH
OTBS
7
8
90
(
a, 30 min)
(b, 30 min)
OTBS
1f
2f
a = Na
2
S (1.0 equiv), dry MeOH, 0 °C to rt.
b = Na
c = Na
d = Na
2
S (1.0 equiv), 5% moist MeOH, 0 °C to rt.
2
S (3.0 equiv), dry MeOH, 50 °C.
2
S (3.0 equiv), moist MeOH, 50 °C.
was further confirmed by mass spectrometry (appearance of MH+
peak at m/z 311).
concomitant formation of sulfide as well as silyl deprotection with
this reagent. Thus various TMS-protected propargyl bromides (1g–
Before embarking on to make an elaborate study on the dual
2
1j) were treated with Na S (1.2 equiv)/MeOH, which coupled two
reactivity of Na
ity of different silyl groups with this reagent. Thus various silyl—
protected substrates were treated with Na S/MeOH under different
conditions. The effects of solvent and temperature on this desilyla-
tion reaction were also included in our study. In addition, the scope
of the reaction was extended to other silyl groups like TBS and
TBDPS ethers. Results are summarized in Table 1. Analysis of the
results reveals that both C-TMS and O-TMS underwent efficient
2
S/MeOH, we proceeded to investigate the reactiv-
reactions in one pot to form the sulfides with a free terminal alkyne
in very good yields.
Since the reagent is carrying out two reactions in one pot, it is of
interest to know which step namely desilylation or sulfide forma-
2
tion is occurring first. Thus the bromoenediyne 1g and Na
2
S were
dissolved in MeOH-d in an NMR tube and kept well-shaken at
4
1
0 °C. The H NMR was recorded at different time intervals
(Fig. 1a). Appearance of the methylene signal at d 3.9 with simulta-
neous reduction in intensity of the bromomethylene peak indi-
cated immediate sulfide formation followed by the desilylation
(increase in the signal at d 3.3). It may be pointed out that the acet-
ylenic C–H and the residual protiated methanol peak both
appeared at the same position at d 3.3. However, the integration
under the peak gradually increased with time and became station-
ary after 30 min while the peak for the bromomethyl disappeared
within 5 min (Fig. 1b).
deprotection with Na
2
S (1 equiv) at 0 °C. The reaction took
1
0 min for completion. When carried out at room temperature,
the reaction took an even shorter time (5 min); however, the yield
was slightly less (85% for 1b) as compared to 95% when carried out
at 0 °C. Deprotection of TBS-ether (1c) or TBDPS ether (1d) required
higher temperature and longer reaction time. Typically, these had
to be stirred in methanol at 50 °C for 12 or 24 h respectively. As
regard to the solvent effect, moist methanol (5%) was found to be
best medium affording the highest yield followed by dry methanol
and then THF/water (10%).
The difference in the reaction conditions for C-TMS/O-TMS and
O-TBS allowed us to chemo selectively deprotect the former in the
presence of the latter as shown in Table 1 (conversion of 1e to 2e
and 1f to 2f).
2
We have thus developed a new reagent (Na S/MeOH) for
deprotection of the TMS group attached to alkyne termini. The
method also works for deprotection of O-TMS, O-TBS, and O-
TBDPS. The desilylation method was further explored for chemos-
elective deprotection of alkyl silyl against silyl ether. In general
the method is simple, high yielding, and carried out at 0 °C to
room temperature (for TMS deprotection). The utility of the
reagent has been further extended by carrying two reactions in
After the establishment of Na
2
S/MeOH as an efficient reagent
for silyl deprotection, we turned our attention to study the
Hatial, Ishita
