Direct Electrophilic Silylation of Terminal Alkynes

Article abstract of DOI:10.1021/ol036328p

(Equation presented) A variety of alkynylsilanes were efficiently prepared via direct silylation of terminal alkynes with aminosilanes in the presence of zinc halides. Base- and nucleophile-sensitive functionalities were perfectly tolerated under the abov

Full text of DOI:10.1021/ol036328p

ORGANIC
LETTERS
2004
Vol. 6, No. 3
421-424
Direct Electrophilic Silylation of
Terminal Alkynes
,†
Aleksey A. Andreev,* Valeri V. Konshin,† Nikolai V. Komarov,† Michael Rubin,‡
,‡
Chad Brouwer,‡ and Vladimir Gevorgyan*
Kuban State UniVersity, 149 StaVropolskaya Street, Krasnodar, 350040 Russian
Federation, and UniVersity of Illinois at Chicago, 845 West Taylor Street,
Chicago, Illinois 60607
Vlad@uic.edu
Received November 28, 2003
ABSTRACT
A variety of alkynylsilanes were efficiently prepared via direct silylation of terminal alkynes with aminosilanes in the presence of zinc halides.
Base- and nucleophile-sensitive functionalities were perfectly tolerated under the above reaction conditions. Initial mechanistic studies support
the electrophilic character of this transformation.
Silylalkynes are important synthons for organic chemistry.1
They are usually synthesized in one-pot procedures involving
the deprotonation of terminal alkynes with organolithium or
Grignard reagents, followed by trapping of the resulting metal
acetylides with the appropriate silyl electrophiles: such as
halo-,2 alkoxy-,3 and acyloxysilanes,4 silyl sulfonates,5 si-
loxanes,6 or silylimidazoles.7 However, more attractive,
complementary methods not involving the use of strong bases
are not well developed. The only reported procedure for the
direct synthesis of various silylalkynes8 is not practical, as
it requires heating the terminal alkyne, silyl chloride, and
excess Zn powder in acetonotrile in a sealed tube.9 Attempts
to perform this reaction at atmospheric pressure employing
either Zn/Cu9 couple or Zn powder10 proved nonselective,
producing inseparable mixtures containing the product and
reduced alkene byproducts. Herein, we wish to report a selec-
tive zinc halide-mediated direct silylation of terminal alkynes
with aminosilanes,11 providing an efficient route to differently
substituted silylalkynes in good to very high yields.
† Kuban State University.
‡ University of Illinois at Chicago.
(1) For silyl protection of terminal alkynes, see: (a) Green, T. W.; Wuts,
P. G. M. ProtectiVe Groups in Organic Synthesis, 3rd ed.; Wiley: New
York, 1999. For directing an addition reaction to internal double or triple
bonds in the presence of silyl-protected terminal alkynes, see: (b) Palmer,
C. J.; Casida, J. E. Tetrahedron Lett. 1990, 31, 1539. (c) Schmidt, H. M.;
Arens, J. F. Recl. TraV. Chim. Pays Bas 1967, 86, 1138. (d) Holmes, A.
B.; Raphael, R. A.; Wellard, N. K. Tetrahedron Lett. 1976, 1539. For
selective electrophilic attack, see for example: (e) Shi Shun, A. L. K.;
Chernick, E. T.; Eisler, S.; Tykwinski, R. P. J. Org. Chem. 2003, 68, 1339-
1347. (f) Kawanami, Y.; Katsuki, I.; Yamaguchi, M. Tetrahedron Lett. 1983,
24, 5131. (g) Brikofer, L.; Rittir, A.; Uhlenbrauck, H. Chem. Ber. 1963,
96, 3280.
(2) See for example: (a) Jager, V.; Viehe, G. Metoden zur Herstellung
und Umwandlung von Alkine. In Houben-Weyl, Metoden der Organischen
Chemie; Thieme: Stuttgart, Germany, 1977; Vol. 2a. (b) Brandsma, L.
PreparatiVe Acetylenic Chemistry, 2nd ed.; Elsevier: Amsterdam, The
Netherlands, 1988.
(4) Renga, J. M.; Wang, P. C. Tetrahedron Lett. 1985, 26, 1175.
(5) See, for example: (a) Patel, S. T.; Percy, J. M.; Wilkes, R. D. J.
Org. Chem. 1996, 61, 166. (b) Kedar, T. E.; Miller, M. W.; Hegedus, L. S.
J. Org. Chem. 1996, 61, 6121. (c) Tobe, Y.; Nakagawa, N.; Naemura, K.;
Wakabayashi, T.; Shida, T.; Achiba, Y. J. Am. Chem. Soc. 1998, 120, 4544.
(d) Auner, N.; Grasmann, M. J. Organomet. Chem. 2001, 621, 10.
(6) (a) Mori, A.; Hishida, T.; Soga, Y.; Kawakami, Y. Chem. Lett. 1995,
107. (b) Mori, A.; Sato, H.; Mizuno, K.; Hiyama, T.; Shintani, K.;
Kawakami, Y. Chem. Lett. 1996, 517. (c) Hirabayashi, K.; Takahisa, E.;
Nishihara, Y.; Mori, A. Bull. Chem. Soc. Jpn. 1998, 71, 2409.
(7) Bourgeois, P.; Lucrece, J.; Dunogues, J. J. Heterocycl. Chem. 1978,
1543.
(8) For the moderately yielding synthesis of trimethylsilyl acetylene via
sodium-mediated silylation of ethyne with TMSCl, see: Schmidbauer, H.;
Ebenhoch, J. Z. Naturforsch. 1988, 43b, 49.
(3) (a) Shibata, T.; Yamashita, K.; Ohta, T.; Soai, K. Tetrahedron 2000,
56, 9259. (b) Medvedeva, A. S.; Novokshonov, V. V.; Demina, M. M.;
Voronkov, M. G. J. Organomet. Chem. 1998, 553, 481. (c) Hoeyer, T.;
Kjaer, A.; Lykkesfeldt, J. Collect. Czech. Chem. Commun. 1991, 56, 1042.
(9) Sugita, H.; Hatanaka, Y.; Hiyama, T. Tetrahedron Lett. 1995, 36,
2769.
(10) Maeorg, U.; Viirlaid, S.; Hagu, H.; Verkruijsse, H. D.; Brandsma,
L. J. Organomet. Chem. 2000, 601, 341.
10.1021/ol036328p CCC: $27.50 © 2004 American Chemical Society
Published on Web 01/15/2004

Tin acetylenes can be conveniently synthesized through
the direct stannation of terminal alkynes with amino-12 or
alkoxystannanes.13 Although an analogous noncatalyzed
reaction with silicon analogues is unfeasible, we found that
this transformation is achievable in the presence of zinc
halides. Thus, heating phenylacetylene (1a) with N-TMS-
diethylamine (TMSDEA) (2a) in the presence of 1.2 equiv14
of zinc chloride in dichloromethane15 afforded silylalkyne
3a in 70% yield (Table 1, entry 1). Solvent optimization
13) whereas N-TMS-piperidine (2g) and N-TMS-morpholine
(2h) exhibited silylating efficiency comparable to that for
N-TMS-diethylamine (entries 14 and 15). Next, the optimized
conditions (Table 1, entries 5 and 6)16 were applied to the
direct silylation of different alkynes 3a-l (Table 2). It was
Table 2. ZnCl2-Mediated Silylation of Terminal Alkynes
Table 1. Optimization of the Lewis Acid-Mediated Silylation
of Alkynes
Lewis
acid
yield,
a
entry
aminosilane 2
solvent
CH2Cl2
DMF
toluene
THF
%
1
2
3
4
5
6
7
8
9
N-TMS-diethylamine (2a )
ZnCl2
70b
27b
88b
2a
2a
2a
2a
ZnCl2
ZnCl2
ZnCl2
ZnCl2
>99b
1,4-dioxane
1,4-dioxane
94b
N-TMS-dimethylamine (2b) ZnCl2
92c
2a
2a
2a
ZnBr2
ZnI2
Zn(OTf)2 1,4-dioxane
ZnCl2
ZnCl2
ZnCl2
ZnCl2
ZnCl2
ZnCl2
1,4-dioxane >99b
1,4-dioxane >99b
49b
0c
0c
0c
54c
90c
86c
10 N-TMS-imidazole (2c)
11 N-TMS-acetamide (2d )
12 HMDS (2e)
13 N-TMS-benzylamine (2f)
14 N-TMS-piperidine (2g)
15 N-TMS-morpholine (2h )
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
a Isolated yield. b Method A: reactions were performed in 1.0-mmol
scale. c Method B: reactions were performed in 100-mmol scale.
indicated that this reaction proceeded most readily in THF
and 1,4-dioxane (entries 4 and 5). A 100-mmol-scale silyla-
tion at ambient pressure proceeded smoothly to give 3a in
equally high yield (entry 6). Other zinc halides tested pro-
vided virtually quantitative yields of the product (entries 7
and 8). Substitution of zinc halides with zinc triflate caused
the reaction to proceed sluggishly and resulted in a moderate
yield of 3a (entry 9). Interestingly, other commonly used
N-based silylating agents, such as N-TMS-imidazole (2c),
N-TMS-acetamide (2d), and HMDS (2e), appeared to be
completely ineffective in this reaction (entries 10-12).
N-TMS-benzylamine (2f) was moderately effective (entry
a Isolated yield. b Method A. c Method B. d ZnBr2 was used. e Yield of
bis-silylated product.
found that various aryl alkynes underwent smooth silylation
with TMSDEA to give silylalkynes 3a-f in very high yield
(entries 1-6). Silylation of 1-octyne (1g), benzyl propargyl
ether (1h), and various propargyl esters (1i-l) proceeded
uneventfully as well (entries 7-12). Remarkably, silylation
under these conditions proceeded equally well in both small
(1 mmol) and multigram (100 mmol) scale. Furthermore, a
variety of functional groups were tolerated and no traces of
reduced products were detected (Table 2).
Further experiments demonstrated that other aminosilanes
4, possessing nonsterically demanding silyl groups, can also
serve as silylating agents in this reaction. Thus, phenylacety-
lene, under the standard reaction conditions, readily under-
went silylation with diethylaminoarylsilanes 4a,b to give the
corresponding silylalkynes 5a,b in excellent yields (Scheme
(11) A wide variety of aminosilanes are commercially available and
reasonably inexpensive.
(12) (a) Logue, M. W.; Teng, K. J. Org. Chem. 1982, 47, 2549. (b)
Djeghaba, Z.; Jousseaume, B.; Ratier, M.; Dunoudin, J. G. J. Organomet.
Chem. 1986, 304, 115.
(13) (a) Wrackmeyer, B.; Bihlmayer, C. J. Organomet. Chem. 1984, 266,
33. (b) Stille, J. K.; Simpson, J. H. J. Am. Chem. Soc. 1987, 109, 2138. (c)
Williamson, B. L.; Stang, P. J. Synlett 1992, 199. (d) Godt, A. J. Org.
Chem. 1997, 62, 7471.
(14) Attempts to employ catalytic amounts of zinc halides caused a
dramatic decrease of yields of the silylated products.
(15) Initial experiments were performed in Wheaton minivials equipped
with Mininert valves.
(16) Although employment of ZnBr2 and ZnI2 provided slightly higher
yields, cheaper and more easily handled ZnCl2 was chosen for use in further
experiments.
422
Org. Lett., Vol. 6, No. 3, 2004

above proposal, we performed comparative kinetic studies21
of silylation of differently para-substituted phenylalkynes 1
with 2a in the presence of 2 equiv of ZnCl2 (Scheme 3).
The results revealed an apparent electronic effect opposite
to that expected for the nucleophilic path A: electron-
releasing groups (Me, OMe) facilitated the reaction, whereas
electron-withdrawing substituents (CF3, NO2) suppressed it
(Scheme 3). Furthermore, our test experiments revealed that
zinc acetylide 7, prepared by an independent method,22 did
not react with 2, providing further evidence against the po-
tential involvement of 7 in our silylation reaction. It is
believed that the obtained kinetic data (Scheme 3) strongly
support the electrophilic character of this transformation. We
suggest two possible pathways for this silylation reaction.
According to the first path (B), electrophilic attack of ZnX2
at the alkyne produces zwitterionic species 9, which, upon
transmetalation, transforms into vinyl cation 10.23
Alternatively, direct addition of the silylium species24
across the triple bond would form 10 directly (path C). Fin-
ally, aminozincate-assisted deprotonation of 10 would give
alkynylsilane 3. The basicity of amide in the aminozincate
is probably crucial for this deprotonation step, as supported
by the failure of silylation with less basic aminosilanes 2c-e
(Table 1, entries 10-12). It should be mentioned that in the
case of acetylenes possessing R-hydrogen atoms, 3g-l, the
regiochemistry of deprotonation could have become an issue,
potentially leading to isomeric allenylsilanes. However,
formation of the latter was never observed,25 most likely due
to thermodynamic reasons.27
Scheme 1
1). Installation of the larger triethylsilyl group with this
method was reasonably successful (74%), whereas attempts
to silylate 1a with the bulkier TBS group failed.
Naturally, we were interested in elucidating the mechanism
of this novel Lewis acid-mediated silylation of alkynes.
Despite some apparent differences,17 we thought that Car-
reira’s direct zinc triflate-catalyzed nucleophilic addition of
terminal alkynes to carbonyl compounds18 could serve as a
prototype for our silylation reaction. According to the nu-
cleophilic pathway (path A, Scheme 2), aminosilane-assisted
deprotonation of alkyne 6, activated by the Lewis acid, would
produce zinc acetylide 7 which, upon quenching with silyl
electrophile 2, would give product 3. In light of the following
observations, however, the nucleophilic mechanism (path A)
involving zinc acetylide species 719 seems very unlikely.
Presuming that deprotonation of 1 occurs at the rate-limiting
step, electron-withdrawing substituents at the para position
of arylalkyne 1 (R) should facilitate the reaction, whereas
electron-releasing groups should suppress it.20 To test the
In summary, we have developed a novel selective one-
step method for the synthesis of silylalkynes, which proceeds
via zinc halide-mediated silylation of terminal alkynes with
Scheme 2
Org. Lett., Vol. 6, No. 3, 2004
423

tionalities are tolerated under these direct silylation condi-
tions. Further studies to establish the scope and to elucidate
a precise mechanism for this novel silylation are underway
in our laboratories.
Scheme 3
Acknowledgment. Financial support for this project was
provided by NSF Grant CHE-0096889 (V.G.).
Supporting Information Available: Detailed experi-
mental procedures and spectral data. This material is available
free of charge via the Internet at http://pubs.acs.org.
OL036328P
(21) See the Supporting Information for details.
(22) See, for example: (a) Ramos Tombo, G. M.; Didier, E.; Loubinoux,
B. Synlett 1990, 547. (b) Ruitenberg, K.; Kleijn, H.; Westmijze, H.; Meijer,
J.; Vermeer, P. Recl. J. R. Neth. Chem. Soc. 1982, 101, 405. (c) Bumagin,
N. A.; Ponomarev, A. B.; Beletskaya, I. P. Zh. Org. Khim. 1987, 23, 1345.
(23) Sudo, T.; Asao, N.; Gevorgyan, V.; Yamamoto, Y. J. Org. Chem.
1999, 64, 2494.
(24) (a) Lambert, J. B.; Zhao, Y.; Wu, H. J. Org. Chem. 1999, 64, 2729.
(b) Rubin, M.; Schwier, T.; Gevorgyan, V. J. Org. Chem. 2002, 67, 1936.
(c) Imamura, K.; Yoshikawa, E.; Gevorgyan, V.; Sudo, T.; Asao, N.;
Yamamoto, Y. Can. J. Chem. 2001, 79, 1624.
(25) Likewise, formation of isomeric allenes has never been observed
in earlier reported electrophilic hydrosilylation24c and hydrostannation26 of
alkynes, proceeding via intermediates analogous to 10.
(26) Gevorgyan, V.; Liu, J.-X.; Yamamoto, Y. J. Chem. Soc., Chem.
Commun. 1998, 37.
(27) Our ab initio calculations (6-31G*) indicated that 1-trimethylsilyl-
1-butyne is ca. 9 kcal/mol more stable than its allenic isomer 1-trimethylsilyl-
1,2-butadiene. Thus, even if allenylsilane, a potential kinetic product of
the deprotonation of 10, is initially formed, it should undergo complete
isomerization to its thermodynamically more stable alkynyl counterpart
under the reaction conditions.
aminosilanes. The procedure is very straightforward and the
reaction is high yielding and easily scaled up. We believe
this method has high potential in synthesis, complementing
the existing nucleophilic methods for the synthesis of
silylalkynes, as a wide range of nucleophile-sensitive func-
(17) As mentioned above (Table 1, entry 9), in our reactions zinc triflate
was the less efficient Lewis acid among the other zinc salts tested.
Furthermore, attempts to apply Carreira’s standard conditions for the
silylation of alkynes with TMSCl in the presence of Et3N resulted in
negligible yields of the products. See the Supporting Information for details.
(18) See, for example: Frantz, D. E.; Fassler, R.; Carreira, E. M. J. Am.
Chem. Soc. 2000, 122, 1806.
(19) For involvement of zinc acetylide species in the zinc triflate-
catalyzed addition of alkynes to aldehydes, see: Frantz, D. E.; Fassler, R.;
Carreira, E. M. J. Am. Chem. Soc. 1999, 121, 11245.
(20) Terekhova, M. I.; Petrov, E. S.; Vasilevskii, S. F.; Ivanov, V. F.;
Shvartsberg, M. S. IzV. Akad. Nauk SSSR, Ser. Khim. 1984, 923.
424
Org. Lett., Vol. 6, No. 3, 2004