Zinc-catalyzed silylation of terminal alkynes

Article abstract of DOI:10.1021/jo702557d

(Chemical Equation Presented) A rapid and high-yielding silylation of terminal alkynes employing TMSOTf and catalytic quantities of Zn(OTf) ₂ has been developed. The reaction works well for a variety of substrates including reactive esters. Fifteen examples with yields of >90% are reported.

Full text of DOI:10.1021/jo702557d

temperature in a sealed tube. To increase the practicality of this
route, Gevorgyan developed a direct silylation of terminal
alkynes using super-stoichiometric quantities of ZnCl2 and
aminosilanes, in 1,4-dioxane at 100 °C (Scheme 1).9 This
protocol demonstrated tolerance of base- and nucleophile-
sensitive functional groups but still has the drawback of
requiring stoichiometric amounts of a zinc halide and elevated
reaction temperature. A lower temperature reaction employing
Zn(OTf)2 and trialkylsilyl chlorides was reported, but this
method also requires stoichiometric amounts of zinc and was
not reported to tolerate a wide variety of functional groups.10
Herein we report the first zinc-catalyzed silylation of terminal
alkynes.11,12
Zinc-Catalyzed Silylation of Terminal Alkynes
Ronald J. Rahaim, Jr.‡ and Jared T. Shaw*,†
Broad Institute of HarVard and MIT Program in Chemical
Biology, 7 Cambridge Center, Cambridge, Massachusetts 02142
shaw@chem.ucdaVis.edu
ReceiVed NoVember 28, 2007
SCHEME 1. Protocols for the Silylation of Terminal
Alkynes with Zinc
A rapid and high-yielding silylation of terminal alkynes
employing TMSOTf and catalytic quantities of Zn(OTf)2 has
been developed. The reaction works well for a variety of
substrates including reactive esters. Fifteen examples with
yields of >90% are reported.
The increasing importance of preparing complex terminal
alkynes for applications in multistep synthesis and biological
experiments requires new methods for the preparation of
alkynylsilanes. Alkynylsilanes are versatile starting materials1
that are utilized in Hiyama couplings,2 metathesis reactions,3
Lewis acid catalyzed alkynylations,4 and as protected forms of
terminal alkynes.5 Preparation of silylalkynes is routinely done
by deprotonation of terminal alkynes with organolithium, or
Grignard reagents, followed by addition of a silyl electrophile.
The high nucleophilicity of lithium and magnesium acetylides
limits functional group compatibility of this reaction.
We reasoned the catalysis of alkyne silylation could result
from matching the counterion of the zinc catalyst with the
leaving group on silicon. Zn(OTf)2 is often the best catalysts
for generation of zinc alkynylides.13 Trapping of these inter-
mediates with a trialkylchlorosilane would liberate chloride and
ultimately generate ZnCl2, which is not sufficiently reactive to
re-enter the catalytic cycle. Use of a trialkylsilyl triflate would
ensure regeneration of Zn(OTf)2 and thus allow a process that
is catalytic in zinc (Scheme 2).
Initial investigations began with 4-ethynyltoluene as a test
substrate. A variety of solvents and bases were screened using
10 mol % of Zn(OTf)2 and 1.5 equiv of TMSOTf (Table 1).
Using Zhu’s silylation protocol10 as a reference point, dichlo-
Recent efforts to solve this problem have focused on the use
of less nucleophilic metal acetylides.6 Silylation of 1-alkynes
takes place with excess zinc powder,7 or in situ prepared
activated zinc,8 and silyl chlorides in acetonitrile at elevated
† Current address: Department of Chemistry, University of California, One
Shields Avenue, Davis, CA 05616.
‡ Current address: Department of Chemistry and Biochemistry, Scripps-
Florida, Jupiter, FL 33458.
(6) Yamaguchi, M.; Hayashi, A.; Minami, T. J. Org. Chem. 1991, 56,
4091-4092.
(7) Sugita, H.; Hatanaka, Y.; Hiyama, T. Tetrahedron Lett. 1995, 36,
2769-2772.
(1) (a) Dunetz, J. R.; Danheiser, R. L. J. Am. Chem Soc. 2005, 127,
5776-5777. (b) Kamijo, S.; Jin, T.; Yamamoto, Y. Tetrahedron Lett. 2003,
44, 689-691. (c) Trost, B. M.; Machacek, M.; Schnaderbeck, M. J. Org.
Lett. 2000, 2, 1761-1764. (d) Kwon, W.; Sakamoto, K.; Kabuto, C.; Kira,
M. Chem. Lett. 2000, 1416-1417. (e) Louw, J.; Baan, J. L.; Kanter, F. J.
J.; Bickelhaupt, F.; Klumpp, G. W. Tetrahedron 1992, 48, 6087-6104. (f)
Fallon, G. D.; Fitzmaurice, N. J.; Jackson, W. R.; Perlmutter, P. Chem.
Commun. 1985, 4-5. (g) Westmijze, H.; Kleijn, H.; Vermeer, P. J.
Organomet. Chem. 1984, 276, 317-323.
(2) (a) Hatanaka, Y.; Hiyama, T. J. Org. Chem. 1988, 53, 918-920. (b)
Hatanaka, Y.; Hiyama, T. Tetrahedron Lett. 1990, 31, 2719-2722. (c)
Hatanaka, Y.; Hiyama, T. Synlett 1991, 845-853.
(3) (a) Wang, J.; Gurevich, Y.; Botoshansky, M.; Eisen, M. S. J. Am.
Chem. Soc. 2006, 128, 9350-9351. (b) Kim, M.; Park, S.; Maifeld, S. V.;
Lee, D. J. Am. Chem. Soc. 2004, 126, 10242-10243. (c) Baba, T.; Kato,
A.; Takahashi, H.; Toriyama, F.; Handa, H. Ono, Y.; Sugisawa, H. J. Catal.
1998, 176, 488-494.
(8) Sugita, H.; Hatanaka, Y.; Hiyama, T. Synlett 1996, 637-639.
(9) Andreev, A. A.; Konshin, V. V.; Komarov, N. V.; Rubin, M.;
Brouwer, C.; Gevorgyan, V. Org. Lett. 2004, 6, 421-424.
(10) Jiang, H.; Zhu, S. Tetrahedron Lett. 2005, 46, 517-519.
(11) A related reaction using AgCl (0.1 equiv), TMSCl, and DBU has
been reported: Taniguchi, Y.; Inanaga, J.; Yamaguchi, M. Bull. Chem. Soc.
Jpn. 1981, 54, 3229-3230.
(12) Several examples of catalytic dehydrogenative silylation of alkynes
using a variety of metal catalysts have been reported, albeit with modest
yield and substrate tolerance. Yb: (a) Takaki, K.; Komeyama, K.; Takehira,
K. Tetrahedron Lett. 2003, 59, 10381-10395. (b) Takaki, K.; Kurioka,
M.; Kamata, T.; Takehira, K.; Makioka, Y.; Fujiwara, Y. J. Org. Chem.
1998, 63, 9265-9269. Pt: (c) Voronkov, M. G.; Ushakova, N. I.;
Tsykhanskaya, I. I.; Pukhnarevich, V. B. J. Organomet. Chem. 1984, 264,
39-48. CuCl: (d) Liu, H. Q.; Harrod, J. F. Can. J. Chem. 1990, 68, 1100-
1105. MgO: (e) Itoh, M.; Mitsuzuka, M.; Utsumi, T.; Iwata, K.; Inoue, K.
J. Organomet. Chem. 1994, 476, C30-C31. (f) Itoh, M.; Mitsuzuka, M.;
Iwata, K.; Inoue, K. Macromolecules 1994, 27, 7917-7919.
(13) Fassler, R.; Tomooka, C. S.; Frantz, D. E.; Carreira, E. M. Proc.
Natl. Acad. Sci. U.S.A. 2004, 101, 5843-5845.
(4) (a) Hayashi, M.; Inubushi, A.; Mukaiyama, T. Bull. Chem. Soc. Jpn.
1988, 61, 4037-4042. (b) Chan, T. H.; Fleming, I. Synthesis 1979, 761-
786. (c) Utimoto, K.; Tanaka, M.; Kitai, M.; Nozaki, H. Tetrahedron Lett.
1978, 19, 2301-2304.
(5) Greene, T. W.; Wuts, P. G. M. In ProtectiVe Groups in Organic
Synthesis, 3rd ed.; Wiley: New York, 1999; pp 654-659.
10.1021/jo702557d CCC: $40.75 © 2008 American Chemical Society
Published on Web 03/11/2008
2912
J. Org. Chem. 2008, 73, 2912-2915

SCHEME 2. Proposed Catalytic Cycle for Zinc Silylation of
Terminal Alkynes
romethane and triethylamine were tested first, affording the
silylated alkyne quantitatively (entry 1). Toluene (entry 2), 1,4-
dioxane (entry 4), and diethyl ether (entry 5) also afforded the
silylalkyne in high yield. Reducing the amount of TMSOTf or
Et3N to 1.1 equiv reduced the yield (entries 9 and 10).
Concomitantly lowering the TMSOTf and Et3N concentration
to 1.1 equiv lowered the yield even further to 80%. The
efficiency of the reaction was directly affected by the choice of
base (entries 1 and 11-14), with triethylamine providing the
best results. Next the catalyst concentration was varied. As little
as 2.5 mol % of Zn(OTf)2 could be employed (entry 16), but
further reduction (1 mol %) eroded the yield. When silylation
is attempted in the absence of Zn(OTf)2 (entry 18), the starting
material is recovered, substantiating the idea that the silylation
is catalyzed by zinc.
TABLE 1. Optimization of Zn(OTf)2-Catalyzed Silylation
FIGURE 1. Silylation of alkynes (1 mmol) with 5 mol % of Zn(OTf)2,
1.5 equiv of TMSOTf, and 1.5 equiv of Et3N in CH2Cl2 (4 mL) at
23 °C for 12 h. Yield given for isolated material after flash chroma-
tography: a10 mol % of Zn(OTf)2; b15 mol % of Zn(OTf)2; c3.0 equiv
mol % of
Zn(OTf)2
entry
solvent
CH2Cl2
toluene
THF
1,4-dioxane
Et2O
CH3CN
EtOAc
DMF
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
base
Et3N
Et3N
Et3N
Et3N
Et3N
Et3N
Et3N
Et3N
Et3N
Et3N
i-Pr2NEt
pyridine
2,6-lutidine
PSd
Et3N
Et3N
% yielda
d
of TMSOTf and 3.0 equiv of Et3N; prepared from the corresponding
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
10
10
10
10
10
10
10
10
10
10
10
10
10
10
5
100
87
14
100
100
46
49
40
84b
80b,c
81
4
29
0
98
99
62
0
e
diyne; prepared form 3-butyne-1-ol.
base, providing 16 and 17 each in quantitative yield. Finally,
the nucleophile-sensitive dipropargyl maleate was disilylated
in 100% yield, providing an improved yield of 18 when
compared to the method of Gevorgyan (68%).
Several reports have indicated that the source of Zn(OTf)2
can affect the reactions of the resulting zinc alkynylides. In the
case of aldehyde alkynylation,14 there are several instances in
the literature that state that the source of Zn(OTf)2 can affect
the yield of the reaction.15 We found that Zn(OTf)2 purchased
from Aldrich and Strem showed the same reactivity for
substrates that afforded >90% yield with 5 mol % catalyst.
Some variability was observed for the more problematic
substrates. For example, subjection of 5-chloro-1-pentyne to the
reaction conditions with 15 mol % of Zn(OTf)2 from Aldrich
increased the yield of silylalkyne to 85%, whereas the use of
15 mol % of Zn(OTf)2 from Strem lowered the yield to 38%.
The steric constraints of the silyl triflate had a dramatic effect
on the efficiency of the reaction (Table 2). 5-Phenyl-1-pentyne
was readily silylated in excellent yield under the standard
reaction conditions. Replacement of TMSOTf with triethylsilyl
triflate (TESOTf) provided a modest yield of the expected
product (entry 2). The yield was significantly increased when
2.5
1
0
Et3N
Et3N
a Determined by GC/MS with biphenyl as an internal standard. b With
1.1 equiv of TMSOTf. c With 1.1 equiv of Et3N. d PS ) proton sponge
(1,8-bis(dimethylamino)naphthalene).
A variety of substrates were examined using the optimized
conditions (Figure 1). Wide substrate tolerance was observed.
Silylation of a series of substituted phenyl acetylenes revealed
that introduction of a modestly electron-withdrawing group
(CF3) or an electron-donating group (CH3O) reduced the yield.
An increase in catalyst loading to 10 or 15 mol % increased
the yield in these cases. High yields of products containing
phenyl (12%), cinnamoyl (13%), and p-nitrobenzoyl (14%)
esters were observed. Disilylation of 1,8-nonadiyne and 3-butene-
1-ol were possible by doubling the quantity of TMSOTf and
(14) Frantz, D. E.; Fassler, R.; Tomooka, C. S.; Carreira, E. M. Acc.
Chem. Res. 2000, 33, 373-381.
(15) Kirkham, J. E. D.; Courtney, T. D. L.; Lee, V.; Baldwin, J. E.
Tetrahedron 2005, 61, 7219-7232 and references cited therein.
J. Org. Chem, Vol. 73, No. 7, 2008 2913

TABLE 2. Screening of Silyl Triflates
ethynyl)trimethylsilane as a light yellow solid. The crude material
was analytically pure by H NMR, so flash chromatography was
1
not performed: 1H NMR (300 MHz, CDCl3) δ 7.43 (d, J ) 8.29
Hz, 2H), 7.31 (d, J ) 8.36 Hz, 2H), 0.24 (s, 9H); 13C NMR (75
MHz, CDCl3) δ 133.3, 131.4, 122.7, 122.1, 103.8, 95.5, -0.1.
Physical and spectral data were consistent with an authentic
commercial sample.
9-(3-(Trimethylsilyl)prop-2-ynyl)-9H-carbazole (10): Subjec-
tion of 9-(prop-2-ynyl)-9H-carbazole (1 mmol, 0.205 g) to the
general silylation procedure afforded 0.2773 g (100%) of 9-(3-
(trimethylsilyl)prop-2-ynyl)-9H-carbazole as a white solid after flash
chromatography (hexanes/EtOAc: 95/5): mp 128-129 °C; 1H
NMR (300 MHz, CDCl3) δ 7.98 (d, J ) 7.72 Hz, 2H), 7.38 (m,
4H), 7.15 (m, 2H), 4.92 (s, 2H), 0.00 (s, 9H); 13C NMR (75 MHz,
CDCl3) δ 139.9, 125.7, 123.1, 120.3, 119.3, 108.9, 99.2, 89.2, 33.4,
-0.2; IR (neat) 2205, 1330, 837, 747 cm-1; LRMS (EI, 70 eV)
277 (100), 204 (22), 180 (14), 166 (34), 152 (7), 73 (13); HRMS
(EI) m/z calcd for C18H20NSi (M + Na)+ 278.1365, found:
278.1354.
entry
R3SiOTf
TMSOTf
TESOTf
TESOTf
Et3SiH + TfOH
TBSOTf
TBSOTf
solvent
temp
% yielda
1
2
3
4
5
6
7
8
CH2Cl2
CH2Cl2
toluene
toluene
CH2Cl2
toluene
toluene
CH2Cl2
23 °C
23 °C
80 °C
80 °C
23 °C
80 °C
80 °C
23 °C
100
50
100
94
20
45
0
TIPSOTf
Me2SiHOTfb
86
a Isolated yields after flash chromatography. b Prepared from Ph(Me)2SiH
and TfOH; see ref 16.
dichloromethane was replaced with toluene and the reaction
mixture was heated to 80 °C (entry 3). Use of tert-butyldim-
ethylsilyl triflate (TBSOTf) afforded the TBS alkyne in only
45% yield with the modified protocol (entry 6), whereas
triisopropylsilyl triflate (TIPSOTf) failed (entry 7). It was also
determined that TESOTf could be prepared in situ16 (entry 4).
We used this protocol to prepare dimethylsilyltriflate, prepared
from the corresponding silane,17 which yielded the alkynylsilane
product in high yield. Gevorgyan’s9 reaction shows a similar
trend in the reactivity of sterically demanding silylating agents.
In conclusion, we have demonstrated the first catalytic
conditions for silylation of terminal alkynes. The reaction is
extremely efficient for introduction of several synthetically
useful trialkylsilyl groups and avoids the use of stoichiometric
quantities of strong bases and metal mediators.
5-(Trimethylsilyl)pent-4-ynyl acetate (11): Subjection of pent-
4-ynyl acetate (1 mmol, 0.132 mL) to the general silylation
procedure afforded 0.1586 g (80%) of 5-(trimethylsilyl)pent-4-ynyl
acetate as a clear oil after flash chromatography (hexanes/Et2O:
95/5): 1H NMR (500 MHz, CDCl3) δ 4.14 (t, J ) 6.31 Hz, 2H),
2.31 (t, J ) 7.04 Hz, 2H), 2.04 (s, 3H), 1.83 (q, J ) 6.67 Hz, 2H),
0.14 (s, 9H); 13C NMR (125 MHz, CDCl3) δ 170.8, 105.7, 85.3,
63.1, 27.7, 20.8, 16.6, 0.1; IR (neat) 2959, 2175, 1741, 1234, 837,
758 cm-1; LRMS (EI, 70 eV) 198 (1), 197 (9), 139 (18), 138 (100),
125 (32), 73 (100), 66 (30), 59 (18); HRMS (EI) m/z calcd for
C10H18O2SiNa (M + Na)+ 221.0974, found 221.0971.
Phenyl 7-(trimethylsilyl)hept-6-ynoate (12): Subjection of
phenyl hept-6-ynoate (1 mmol, 0.195 mL) to the general silylation
procedure afforded 0.2741 g (100%) of phenyl 7-(trimethylsilyl)-
hept-6-ynoate as a clear oil after flash chromatography (hexanes/
Et2O: 90/10): 1H NMR (300 MHz, CDCl3) δ 7.37 (t, J ) 7.65
Hz, 2H), 7.23 (t, J ) 7.40 Hz, 2H), 7.08 (d, J ) 7.89 Hz, 2H),
2.60 (t, J ) 7.39 Hz, 2H), 2.31 (t, J ) 7.02 Hz, 2H), 1.87 (quint,
Experimental Section
J ) 7.54 Hz, 2H), 1.65 (quint, J ) 7.36 Hz, 2H), 0.16 (s, 9H); 13
C
General Procedure for the Silylation of Terminal Alkynes:
A round-bottom flask was charged with zinc triflate (0.05 mmol,
0.018 g) and sealed with a septum under an atmosphere of argon.
An argon inlet was attached followed by the sequential addition of
dry CH2Cl2 (4.2 mL), dry triethylamine (1.5 mmol, 0.209 mL), the
alkyne (1 mmol), and TMSOTf (1.5 mmol, 0.271 mL). The reaction
was stirred until complete as judged by TLC (approximately 12 h)
then quenched with saturated NH4Cl. The mixture was extracted
with ether; the aqueous layer was back extracted with ether, and
the combined organics were dried, filtered, and concentrated. The
crude material was then subjected to flash chromatography.
4-((Trimethylsilyl)ethynyl)benzonitrile (1): Subjection of 4-ethy-
nylbenzonitrile (1 mmol, 0.127 g) to the general silylation procedure
afforded 0.1947 g (98%) of 4-((trimethylsilyl)ethynyl)benzonitrile
as a light yellow solid after flash chromatography (hexanes/Et2O:
90/10): 1H NMR (500 MHz, CDCl3) δ 7.58 (d, J ) 8.52 Hz, 2H),
7.52 (d, J ) 8.52 Hz, 2H), 0.25 (s, 9H); 13C NMR (125 MHz,
CDCl3) δ 132.3, 131.8, 127.9, 118.3, 111.7, 102.9, 99.5, -0.3.
Physical and spectral data were consistent with literature prece-
dent.18
NMR (75 MHz, CDCl3) δ 171.8, 150.7, 129.3, 125.7, 121.5, 106.6,
85.0, 33.8, 27.9, 24.0, 19.5, 0.1; IR (neat) 2172, 1758, 1192, 1125,
837, 757 cm-1; LRMS (EI, 70 eV) 273 (4), 181 (100), 109 (38),
93 (47), 77 (20), 73 (77); HRMS (EI) m/z calcd for C16H22O2SiNa
(M + Na)+ 297.1287, found 297.1295.
3-(Trimethylsilyl)prop-2-ynyl cinnamate (13): Subjection of
prop-2-ynyl cinnamate (1 mmol, 0.186 g) to the general silylation
procedure afforded 0.2501 g (97%) of 3-(trimethylsilyl)prop-2-ynyl
cinnamate as a clear oil after flash chromatography (hexanes/
EtOAc: 95/5): 1H NMR (500 MHz, CDCl3) δ 7.53 (d, J ) 16.03
Hz, 1H), 7.31 (m, 2H), 7.18 (m, 3H), 6.26 (d, J ) 16.02 Hz, 1H),
4.63 (s, 2H), 0.01 (s, 9H); 13C NMR (125 MHz, CDCl3) δ 165.9,
145.6, 134.1, 130.4, 128.8, 128.0, 117.1, 99.0, 92.0, 52.7, -0.3;
IR (neat) 1715, 1635, 1151, 838, 760 cm-1; LRMS (EI, 70 eV)
258 (7), 257 (23), 185(5), 145 (14), 131 (100), 103 (51), 77 (31),
73 (84); HRMS (EI) m/z calcd for C15H19O2Si (M + H)+ 259.1882,
found 259.1879.
4-(Trimethylsilyl)but-3-ynyl 4-nitrobenzoate (14): Subjection
of but-3-ynyl 4-nitrobenzoate (1 mmol, 0.219 g) to the general
silylation procedure afforded 0.2716 g (93%) of 4-(trimethylsilyl)-
but-3-ynyl 4-nitrobenzoate as a light tan solid after flash chroma-
tography (hexanes/EtOAc: 95/5): mp 132-133 °C; 1H NMR (300
MHz, CDCl3) δ 8.31 (d, J ) 8.82 Hz, 2H), 8.23 (d, J ) 8.86 Hz,
2H), 4.47 (t, J ) 6.82 Hz, 2H), 2.73 (t, J ) 6.82 Hz, 2H), 0.14 (s,
9H); 13C NMR (75 MHz, CDCl3) δ 164.3, 150.6, 135.4, 130.7,
123.5, 101.6, 87.0, 63.4, 20.4, -0.06; IR (neat) 2211, 1716, 1522,
1244, 1103, 847, 715 cm-1; LRMS (EI, 70 eV) 276 (87), 224 (100),
178 (14), 134 (9), 104 (54), 76 (39), 73 (19); HRMS (EI) m/z calcd
for C14H18NO4Si (M + H)+ 292.1005, found 292.1007.
((4-Bromophenyl)ethynyl)trimethylsilane (5): Subjection of
1-bromo-4-ethynylbenzene (1 mmol, 0.181 g) to the general
silylation procedure afforded 0.2531 g (100%) of ((4-bromophenyl)-
(16) TESOTf was prepared by adding triethylsilane to a 1 M solution of
TfOH in CH2Cl2 at 0 °C. The resultant solution was then added to a mixture
of Zn(OTf)2,5-phenyl-1-pentyne, Et3N, and toluene.
(17) For the preparation of silyl triflates, and a general order of ligand
displacement with triflic acid, see: Uhlig, W. Chem. Ber. 1996, 129, 733-
739 and references cited therein.
(18) Dirk, S. M.; Tour, J. M. Tetrahedron 2003, 59, 287-293.
2914 J. Org. Chem., Vol. 73, No. 7, 2008

2-(5-(Trimethylsilyl)pent-4-ynyl)isoindoline-1,3-dione (15):
Subjection of 2-(pent-4-ynyl)isoindoline-1,3-dione (1 mmol, 0.213
g) to the general silylation procedure afforded 0.2854 g (100%) of
2-(5-(trimethylsilyl)pent-4-ynyl)isoindoline-1,3-dione as a pale yel-
low solid after flash chromatography (hexanes/EtOAc: 80/20): mp
78-81 °C; 1H NMR (500 MHz, CDCl3) δ 7.82 (dd, J ) 1.35 and
3.08 Hz, 2H), 7.69 (dd, J ) 0.97 and 3.08 Hz, 2H), 3.75 (t, J )
7.06 Hz, 2H), 2.29 (t, J ) 7.09 Hz, 2H), 1.91 (quint, J ) 7.09 Hz,
2H), 0.06 (s, 9H); 13C NMR (125 MHz, CDCl3) δ 168.2, 133.8,
132.1, 123.1, 105.6, 85.2, 37.2, 27.4, 17.6, -0.05; IR (neat) 2200,
1704, 1392, 841, 726 cm-1; LRMS (EI, 70 eV) 285 (5), 270 (100),
153 (2), 146 (2), 130 (30), 73 (37); HRMS (EI) m/z calcd for C16H19-
NO2SiNa (M + Na)+ 308.1083, found 308.1086.
Trimethyl(4-(trimethylsilyl)but-3-ynyloxy)silane (17): Subjec-
tion of 3-butyn-1-ol (1 mmol, 0.076 mL) to the general silylation
procedure with 3 equiv of TMSOTf (3 mmol, 0.542 mL) and 3
equiv of triethylamine (3 mmol, 0.418 mL) afforded 0.2139 g
(100%) of trimethyl(4-(trimethylsilyl)but-3-ynyloxy)silane as a clear
oil after flash chromatography (hexanes/Et2O: 80/20): 1H NMR
(300 MHz, CDCl3) δ 3.56 (t, J ) 7.19 Hz, 2H), 2.32 (t, J ) 7.19
Hz, 2H), 0.02 (s, 9H), 0.00 (s, 9H); 13C NMR (75 MHz, CDCl3) δ
103.9, 85.7, 61.2, 24.1, 0.1, -0.4. Physical and spectral data were
consistent with literature precedent.19
following flash chromatography (hexanes/Et2O: 99/1): 1H NMR
(500 MHz, CDCl3) δ 7.2 (m, 5H), 2.75 (t, J ) 7.61 Hz, 2H), 2.27
(t, J ) 6.95 Hz, 2H), 1.85 (quint, J ) 7.28 Hz, 2H), 1.02 (t, J )
7.86 Hz, 9H), 0.60 (q, J ) 7.90 Hz, 6H); 13C NMR (125 MHz,
CDCl3) δ 141.6, 128.5, 128.3, 125.8, 108.1, 82.1, 34.6, 30.4, 19.3,
7.5, 4.5; IR (neat) 2951, 2171, 1455, 1016, 696 cm-1; LRMS (EI,
70 eV) 258 (1), 229 (100), 202 (13), 201 (62), 119 (3), 115 (20),
91 (45); HRMS (EI) m/z calcd for C17H26SiNa (M + Na)+
281.0974, found 281.0972.
Dimethyl(5-phenylpent-1-ynyl)silane (Table 2, entry 8): A
round-bottom flask was charged with zinc triflate (0.1 mmol, 0.036
g) and sealed with a septum under an atmosphere of argon. An
argon inlet was attached followed by the sequential addition of dry
CH2Cl2 (3 mL), dry triethylamine (2.0 mmol, 0.279 mL), 5-phenyl-
1-pentyne (1 mmol, 0.156 mL), and a 0.91 M solution of
dimethylsilyl triflate (1.5 mmol, 1.65 mL). The 0.91 M solution of
dimethylsilyl triflate was prepared by the dropwise addition of
phenyldimethylsilane (3 mmol, 0.46 mL) to triflic acid (1 M in
CH2Cl2, 3.3 mmol, 3.3 mL) at 0 °C. After complete addition of
phenyldimethylsilane, the reaction was warmed to room temperature
and used directly. Following the general workup procedure, 0.1738
g (86%) of dimethyl(5-phenylpent-1-ynyl)silane was afforded as a
1
clear oil after flash chromatography (hexanes/Et2O: 95/5): H NMR
(500 MHz, CDCl3) δ 7.30 (m, 5H), 4.20 (s, 1H), 2.78 (t, J ) 7.56
Hz, 2H), 2.30 (t, J ) 7.05 Hz, 2H), 1.90 (quint, J ) 7.31 Hz, 2H),
0.3 (s, 6H); 13C NMR (125 MHz, CDCl3) δ 141.5, 128.5, 128.3,
125.9, 108.6, 82.0, 34.7, 30.0, 19.3, -2.7; IR (neat) 2954, 2175,
2133, 1249, 878 cm-1; LRMS (EI, 70 eV) 202 (9), 187 (22), 186
(3), 185 (15), 143 (33), 119 (1), 105 (17), 104 (100), 91 (40), 59
(22); HRMS (EI) m/z calcd for C13H19Si (M + H)+ 203.1256, found
203.1263.
Bis(3-(trimethylsilyl)prop-2-ynyl) maleate (18): Subjection of
diprop-2-ynyl maleate (1 mmol, 0.192 g) to the general silylation
procedure with 3 equiv of TMSOTf (3 mmol, 0.542 mL) and 3
equiv of Et3N (3 mmol, 0.418 mL) afforded 0.3365 g (100%) of
bis(3-(trimethylsilyl)prop-2-ynyl) maleate as a light yellow solid
after flash chromatography (hexanes/Et2O: 50/50): 1H NMR (300
MHz, CDCl3) δ 6.92 (s, 2H), 4.79 (s, 4H), 0.17 (s, 18H); 13C NMR
(75 MHz, CDCl3) δ 163.8, 133.5, 98.0, 92.8, 53.5, -0.4. Physical
and spectral data were consistent with literature precedent.9
Triethyl(5-phenylpent-1-ynyl)silane (Table 2, entry 3): A
round-bottom flask was charged with zinc triflate (0.1 mmol, 0.036
g) and sealed with a septum under an atmosphere of argon. An
argon inlet was attached followed by the sequential addition of dry
toluene (4 mL), dry triethylamine (1.5 mmol, 0.209 mL), 5-phenyl-
1-pentyne (1 mmol, 0.156 mL), and TESOTf (1.5 mmol, 0.339
mL). The round-bottom flask was placed in an oil bath at 80 °C
and stirred for 12 h. After the general workup, 0.2583 g (100%) of
triethyl(5-phenylpent-1-ynyl)silane was afforded as a clear oil
Acknowledgment. This research was funded by the Broad
Institute Scientific Planning and Allocation of Resources
Committee (SPARC). Dr. John Greaves (University of Cali-
fornia, Irvine) is acknowledged for obtaining mass spectral data,
and Dr. Yuchen Tang (University of California, Davis) is
acknowledged for assistance in preparing this manuscript.
Supporting Information Available: Experimental details,
1
product characterization data, and H and 13C NMR spectra for
compounds 1-18, and Table 2 entries 3 and 8. This material is
available free of charge via the Internet at http://pubs.acs.org.
(19) Marko´, I. E.; Bayston, D. J. Tetrahedron 1994, 50, 7141-7156.
JO702557D
J. Org. Chem, Vol. 73, No. 7, 2008 2915