8

PROTECTION FOR THE ALKYNE ⫺CH

Trialkylsilylacetylenes, 927
Trimethylsilyl, 928
(3-Cyanopropyl)dimethylsilyl, 930
Triethylsilyl, 930
t-Butyldimethylsilyl, 930
Thexyldimethylsilyl, 930
Benzyldimethylsilyl, 931
Dimethyl[1,1-dimethyl-3-(tetrahydro-2H-pyran-2-yloxy)propylsilyl, 931
Biphenyldimethylsilyl, 931
Triisopropylsilyl, 931
Biphenyldiisopropylsilyl, 931
2-(2-Hydroxypropyl), 932
Hydroxymethyl, 932

Protection of an acetylenic hydrogen is often necessary because of its acidity. The

bulk of a silane can protect an acetylene against catalytic hydrogenation because
of rate differences between an olefin (primary or secondary) vs. the more hindered
protected alkyne.1 Trialkylsilylacetylenes are often used as a convenient method for
introduction of an acetylenic unit because they tend to be easily handled liquids or
solids as opposed to gaseous acetylene.

Trialkylsilylacetylenes

Formation
1. Trialkylsilanes are usually formed by addition of a lithium or Grignard re-
agent to the silyl chloride,2 and thus discussions related to formation of the

Greene’s Protective Groups in Organic Synthesis, Fourth Edition, by Peter G. M. Wuts and
Theodora W. Greene
Copyright © 2007 John Wiley & Sons, Inc.

927
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928 PROTECTION FOR THE ALKYNE ⫺CH

silyl acetylene bond will be kept to a minimum. Silyl acetylenes are prepared
from the alkynylcopper(I) reagents in the presence of PPh3, Zn, or TMEDA in
CH3CN at 100⬚C, 36–98% yield.3 It is interesting to note that the reaction can
be reversed to give the alkynylcopper(I) reagent in the presence of CuCl and
1,3-dimethyl-2-imidazolidinone.4
R3SiCl, CH3CN, Ph3P
Zn, TMEDA, 100°C

36–98%
R Cu R SiR3

CuCl, DMI

2. Et2NSiR3, ZnCl2, 1,4-dioxane, 100⬚C, 68–97% yield. This method works for
the TMS, TES, and the SiMe2Ph derivatives but does not work to introduce a
TBDMS group.5
3. TMSCl, Zn(OTf)2, TEA, CH2Cl2, 75–99% yield. The TES and (i-Bu)3Si de-
rivatives can also be formed using this method but the triphenylsilylalkyne
could not be formed.6

Trimethylsilylalkyne (TMS⫺alkyne)

Cleavage
1. KF, MeOH, 50⬚C, 89% yield.7,8
2. AgNO2, 2,6-lutidine, 90% yield.9
3. AgNO3, MeOH, H2O, 24⬚C, cool to 0⬚C, add KCN, then HCl, 96% yield.10,11
The reduced electron density of the propargylic alkyne directs the electro-
philic silver to the other alkyne and activates it for cleavage. These conditions
also resulted in the removal of a primary TBDMS group.12 AgOTf can also be
used, but other inert salts such as AgCl are ineffective.13 A procedure that does
not require the use of cyanide has been developed. The process uses water as a
cosolvent with acetone. Since nitric acid is generated in the reaction, TBDMS
ethers were also cleaved.14
TMS TMS
HO HO

O O
OH OH

OTIPS OTIPS
TMS H

4. AgNO3, KI, ⬎82% yield. These conditions resulted in partial cleavage of a

secondary TES group as well.15
5. Bu4NF, THF, rt, quant.16
6. Bu4NF, 0.4 eq., THF, MeOH, ⫺20⬚C to ⫺10⬚C, 98% yield.17
 10.1002/9780470053485.ch8, Downloaded from https://onlinelibrary.wiley.com/doi/10.1002/9780470053485.ch8 by Tokyo University Of Science, Wiley Online Library on [06/01/2025]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
PROTECTION FOR THE ALKYNE ⫺CH 929

TMS H

O O
H TBAF H
MeO N TMS MeO N TMS
O O

7. K2CO3, MeOH16 or KOH, MeOH, 76%, 99% yield.18–20 Under basic condi-
tions such as these, the more electron-deficient silylalkyne will be cleaved
faster.21
OMOM OMOM
TMS H
O NaOH, MeOH O
TES TES
MOMO 25°C, 99% MOMO
OTIPS OTIPS

Very electron-deficient TMS acetylenes such as eynones are unstable and

lose the TMS group upon stirring in MeOH.22
8. KF, 18-crown-6, aq. THF, 88% yield.23
TMS TMS H
KF
CuBr, THF 18-crown-6

MeOH aq. THF

90% 88%
H GeMe3 GeMe3

In a similar example, a trimethylsilyl group was cleaved with NaOH, MeOH,

H2O in the presence of a triethylgermyl group.24 The triethylgermyl group
can also be cleaved with methanolic HClO4; the rate increases with increas-
ing electron density.25
9. Na(MeO)3BH, THF, H2O, ⫺20⬚C, 2.5 h, 60% yield ⫹ 20% starting material
(SM).8
TMS H
Na(MeO)3BH
HO THF, H 2O, –20°C, 2.5 h HO

60% yield
20% SM
TMS TMS

10. MeLi/LiBr.26
11. Amberlyst basic resin, MeOH, 80–98% yield.27 These conditions remove the
TMS group in the presence of a secondary TES and TBS.28
12. LiOH, THF, H2O, 1 h, 98% yield. A TIPS alkyne is stable to these
conditions.29
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930 PROTECTION FOR THE ALKYNE ⫺CH

[(3-Cyanopropyl)dimethylsilyl]-alkyne (CPDMS-alkyne)
This derivative was prepared as a polar analog of the TMS group to facilitate chro-
matographic purification. It is cleaved using conditions that cleave the TMS group.30

Triethylsilylalkyne (TES-alkyne)
The relative rates of cleavage in aqueous, methanolic alkali at 29.4⬚C for the follow-
ing silanes are: PhC⬅CSiMe3 / PhC⬅CSiEtMe2 /PhC⬅CSiEt2Me/ PhC⬅CSiEt3/
PhC⬅CSiPh3, 277: 49: 7.4: 1: 11.8.31 A TES group can be cleaved selectively in the
presence of a TBDMS group (t-BuOK, MeOH, 40⬚C, 65%).10 A bis TES derivative
can be selectively cleaved.32

NaBH(OMe)3 (n-Bu)4NPh3SnF2

THF, H 2O (CH2O)n, THF

H TES 82% TES TES 73% HO H

t-Butyldimethylsilylalkyne and Thexyldimethylsilylalkyne

(TBDMS- and TDS-alkyne)

Formation
1. For the TBDMS group, KHMDS, THF, TBDMSOTf, ⫺78⬚C, 98% yield.10
The TDS group behaves similarly, except that it is slightly more hindered.
LHMDS can also be used as a base.33
2. TBDMSH, Ir4 (CO)12, Ph3P, 120⬚C, 40 h, 95% yield. This method works for
the introduction of other common silyl ethers such as the TES derivative. The
problem with the method is that in some cases, hydrosilylation occurs to form
vinylsilanes.34

Cleavage
1. Bu4NF, THF, ⫺23⬚C, 75% yield.35,36
2. Bu4NF, 2-nitrophenol, THF, 0–23⬚C, 87% yield. The 2-nitrophenol was added
as a weak acid (pKa ⫽ 7.22) to prevent the elimination of a vinyl bromide.33
N N
Cl Cl

O O
H O O H O O
HO TBAF, THF HO
OTBS OH
Br Br
NO2
TBS H
OH
TBS H
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PROTECTION FOR THE ALKYNE ⫺CH 931

Benzyldimethylsilylalkyne (BDMS⫺alkyne): C6H5CH2Si(CH3)2-alkyne

Benzyldimethylsilylacetylene was prepared by the reaction of HC⬅CMgBr with the
silyl chloride as part of a Fostriecin synthesis.37

Dimethyl[1,1-dimethyl-3-(tetrahydro-2H-pyran-2-yloxy)propylsilylalkyne)],
(DOPS-alkyne)

Cleavage
THF, 0.1 eq. BuLi, ⫺78⬚C, 2.5 h; ⫺20⬚C, 2 h.16
1. H+ EtOH or MeOH
2. THF, 0.1 eq. BuLI
TMS (CH2)12 Si OTHP TMS (CH2)12 H
–78°C, 2.5 h; 20°C, 2 h

Protection of the OH with an alcohol protective group gives this approach con-
siderable versatility.

Biphenylyldimethylsilylalkyne (BDMS-alkyne)

Formation
BuLi, BDMSCl, THF, 75–98% yield. The advantage of this group is that many of
the derivatives tend to be crystalline and thus provide a safe alternative for purifica-
tion. Some smaller silylalkynes have been reported to explode upon distillation.38

Cleavage
K2CO3, MeOH, 72–98% yield. Cleavage occurs selectively in the presence of biphe-
nyldiisopropylalkyne.38

Triisopropylsilylalkyne (TIPS-alkyne)

Cleavage
TBAF, THF, H2O, 20⬚C, 99% yield.39,40

Biphenyldiisopropylsilylalkyne (BDIPS-alkyne)

Formation
BuLi, BDIPSCl, THF, 81% yield.38

Cleavage
The cleavage of this group is reported to be similar to the triisopropylsilyl analog.38
 10.1002/9780470053485.ch8, Downloaded from https://onlinelibrary.wiley.com/doi/10.1002/9780470053485.ch8 by Tokyo University Of Science, Wiley Online Library on [06/01/2025]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
932 PROTECTION FOR THE ALKYNE ⫺CH

2-(2-Hydroxypropyl)alkyne: alkyne-CMe2OH
Hydroxymethylalkyne: alkyne-CH2OH

Formation
In this case the low-cost 2-methyl-2-hydroxy-3-butyne is used as a convenient
source of acetylene.

Cleavage
1. NaOH, benzene, reflux, ⬎96% yield.41–43

H3C
OH
H
CH3
aq NaOH, PhH

OTBDMS reflux, >96% OTBDMS

Ref. 41

2. For the hydroxylmethyl derivative: MnO2, KOH, Et2O, rt, 88% yield.44

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