Property and reactivity of fluoro(silyl)acetylenes and fluoro(stannyl) acetylenes

Article abstract of DOI:10.1021/jo1018602

Fluoro(silyl)acetylenes and fluoro(stannyl)acetylenes underwent a radical addition reaction of THF to furnish the corresponding fluorinated cyclic ethers in moderate to good yields. These intriguing addition reaction proved to proceed via a radical reaction mechanism.

Full text of DOI:10.1021/jo1018602

pubs.acs.org/joc
family and reported a synthetic method for the facile prep-
Property and Reactivity of Fluoro(silyl)acetylenes
and Fluoro(stannyl)acetylenes
aration of fluoro(triisopropylsilyl)acetylene 1a.5 As we
noticed that 1a turned out to be stable only in a hexane
solution at low temperature, its further synthetic applica-
tions remained unexplored. After we started to investigate
the properties and reactivity of fluoro(silyl)acetylenes, we
successfully isolated fluoro(triisopropylsilyl)acetylene 1a in
the pure form and measured its 13C NMR for the first time.
In addition, we serendipitously encountered the addition
reaction of THF to other analogous fluoro(silyl)acetylenes
and fluoro(stannyl)acetylenes except for 1a. In this paper, we
disclose an intriguing behavior of fluoro(silyl)acetylenes and
fluoro(stannyl)acetylenes and propose the possible reaction
mechanism of the fluorinated cyclic ethers.
Masahiro Shiosaki, Masashi Unno, and
Takeshi Hanamoto*
Department of Chemistry and Applied Chemistry,
Saga University, Honjyo-machi 1, Saga 840-8502, Japan
*hanamoto@cc.saga-u.ac.jp
Received September 20, 2010
Although we have previously established the facile prep-
aration of 1a from 1,1-difluoroethylene, the fluoroacetylene
was only stable in a hexane solution. Thus, concentration of
the hexane solution containing 1a resulted in the decomposi-
tion of 1a. However, the different perspective for this out-
come provided us a hint that hexane as a solvent might
be responsible for stabilization of 1a. On the basis of this
idea we carried out purification of 1a through distillation
from the corresponding hexadecane solution containing 1a
(we confirmed that hexadecane has a higher boiling point in
comparison with that of 1a by GC-MS in advance) using a
short path distillation apparatus. We determined that the
desired acetylene 1a was successfully distilled at 30-35 °C
(bath temperature) at 40 Pa as a colorless oil. To our delight,
the isolated compound 1a was stable enough to execute the
following measurement. We immediately attempted to mea-
sure the 13C NMR spectrum of 1a. Although 1a in CDCl3
started slowly to decompose at -10 °C, over ten accumula-
tion times we were able to perform the 13C NMR measure-
ment without any detectable decomposition of 1a. The 13C
NMR spectrum of 1a is shown in Figure 1.
Fluoro(silyl)acetylenes and fluoro(stannyl)acetylenes
underwent a radical addition reaction of THF to furnish
the corresponding fluorinated cyclic ethers in moderate
to good yields. These intriguing addition reaction proved
to proceed via a radical reaction mechanism.
Fluorinated organic molecules would be one of the most
important classes of halogenated compounds with rare
occurrence in nature.1 They often play a significant role in
the modern drug discovery process, which should make the
development of new synthetic methodologies to facilitate
their preparation worthwhile.2 Therefore, a number of
methods have been reported to synthesize a variety of
fluoroalkanes, fluoroalkenes, and fluoroarenes due to their
useful applications. In contrast to such main stream, study
on fluoroalkyne chemistry has lagged far behind.3 One of
the reasons may be attributed to the instability and explosive
nature of fluoroacetylenes in previous reports.4 We have
recently undertaken studies aimed at such a fluoroacetylene
Interestingly, one acetylene carbon signal appeared at
19.09 ppm (d, J=17.4 Hz) and the other signal appeared
at 106.91 ppm (d, J = 337.6 Hz). On the basis of the coupling
constant of carbon atom-fluorine atom, the former was
assigned to the sp-carbon attached to silicon and the latter
was assigned to the sp-carbon attached to fluorine. Although
we did not have any rational reason to explain these two
sp-carbon chemical shifts at the present stage, this is the first
13C NMR spectrum observation of sp-carbon attached
directly to fluorine. In addition, the elemental analysis of
1a was successfully conducted to give satisfactory results
(elemental analysis calcd for C11H21FSi: C 65.94, H 10.56;
found: C 66.19, H 10.82) for the first time, although exposure
of the colorless oil 1a to air resulted in coloration to the pale
yellow oil.
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8326 J. Org. Chem. 2010, 75, 8326–8329
Published on Web 11/10/2010
DOI: 10.1021/jo1018602
r
2010 American Chemical Society

Shiosaki et al.
JOCNote
SCHEME 1. Synthesis of 2b and 3b
a new major peak emerged at m/z 234 along with minor
peaks. After the usual workup, the residual oil was separated
by silica gel column chromatography to afford the corre-
sponding products. The main product showed one vinyl
proton signal at 5.07 ppm (δ, J = 34.1 Hz) in the 1H NMR
spectrum, one vinyl fluorine signal at -85.9 ppm (dd, J =
33.9, 24.2 Hz) in the 19F NMR spectrum, and two vinyl
carbon signals at 99.7 (d, J = 3.1 Hz) and 167.69 ppm (d, J =
279.6 Hz) in the 13C NMR spectrum, respectively. On the
basis of these NMR data, this molecule was assigned to be
(E)-[2-fluoro-2-(tetrahydrofuran-20-yl)vinyl]dimethylphenylsilane
2b.8 On the other hand, the minor (Z)-isomer 3b showed one
FIGURE 1. 13C NMR of 1a.
TABLE 1. 13C NMR Chemical Shifts (ppm) for sp-Carbon Atoms
δC1
δC2
exptl
HF
MP2
B3LYP
106.9
115.8
111.8
119.1
19.1
17.0
17.2
16.4
1
vinyl proton signal at 4.96 ppm (d, J = 61.7 Hz) in the H
NMR spectrum and one vinyl fluorine signal at -95.0 ppm (dd,
J = 62.0, 8.9 Hz) in the 19F NMR spectrum. The characteristic
H-F coupling constant of each stereoisomer justified the
structural assignment. The E/Z ratio of the stereoisomers
(2b/3b) was determined to be 86:14 by GC-MS analysis,
using a crude reaction mixture prior to chromatographic
purification (Scheme 1).
chemical calculations for 1a using Gaussian03.6 Geometry
optimizations were performed at the B3LYP/6-31G** level,
and the optimized structures were used for the subsequent
calculations of molecular properties. The GIAO nuclear
magnetic shielding values were calculated at all atomic
positions at the HF, MP2, and B3LYP levels of theory using
the 6-311þG(2d,p) basis set. The chemical shifts for the
carbon atoms were obtained by subtracting their chemical
shielding values from the one calculated for TMS, which
is 192.6, 192.9, or 182.8 ppm for HF, MP2, or B3LYP,
respectively. Table 1 summarizes the observed and calcu-
lated chemical shifts for the sp-carbon atoms. As shown in
the table, the present quantum chemical calculations repro-
duce the observed chemical shifts.
We turned our attention to substrate scope and chose
fluoro(dimethylphenylsilyl)acetylene 1b as an analogous
molecule of 1a. We attempted to prepare 1b in the similar
manner. After complete addition of the components at -78 °C,
the reaction mixture was allowed to stand at room tempera-
ture overnight under exclusion of light.7 At this time we
encountered the following unexpected finding. When we
checked the reaction progress by GC-MS analysis prior
to quench, the original peak corresponding to 1b [m/z 163
(Mþ - Me), M = 178 (C10H11FSi)] almost disappeared and
These unexpected results prompted us to examine sub-
strate scope. Various chlorosilanes and chlorostannanes
were subjected to investigation. Although the addition reac-
tions proceeded giving the corresponding adducts 2c-h, the
yields were generally modest under similar conditions [Table 2,
Method A (left column)]. Interestingly, sterically demanding
chlorotriphenylsilane scarcely underwent the first substitu-
tion reaction of lithium fluoroacetylide with the result that a
trace amount of the corresponding adduct was detected by
GC-MS (entry 6). These unsatisfactory results led us to
reexamine the reaction conditions for the preparation of
2b. After many attempts,9 we eventually found that the key
factor contributing to higher yield probably depended on the
reaction concentration. Thus, after the complete generation
of 1b at -78 °C was confirmed, the reaction mixture was
gradually warmed to -40 °C. At this temperature, an
excessive amount of THF was carefully added to the mixture.
This diluted reaction mixture was gradually warmed to room
temperature while being stirred, which resulted in acceptable
yield (up to 78%). Once the optimum reaction conditions
had been identified, the remaining substrates were again
subjected to examination. All of the reactions proceeded
well with moderate to high yields [Table 2, Method B (right
column)]. Although the yields were improved in this way in
almost every case, the problem of stereoselectivity still
remains unsolved. To gain the reaction progress in detail
we monitored the reaction of 1b with the reaction temperature
by GC-MS analysis. The first appearance of the peak 2b
(6) Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.; Robb,
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Bearpark, M.; Heyd, J. J.; Brothers, E.; Kudin, K. N.; Staroverov, V. N.;
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Stratmann, R. E.; Yazyev, O.; Austin, A. J.; Cammi, R.; Pomelli, C.;
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G. A.; Salvador, P.; Dannenberg, J. J.; Dapprich, S.; Daniels, A. D.; Farkas,
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O.; Foresman, J. B.; Ortiz, J. V.; Cioslowski, J.; Fox, D. J. Gaussian 09,
(8) Muramatsu, H.; Inukai, K.; Iwata, Y.; Murakami, S. Bull. Chem. Soc.
Jpn. 1967, 40, 1284.
(9) Use of THF as a solvent is essential to successful preparation of
fluoro(silyl)acetylene.
Revision A.2; Gaussian, Inc., Wallingford CT, 2009.
(7) The same reaction in the light caused formation of unidentified
byproduct and decreased the yield of 2b.
J. Org. Chem. Vol. 75, No. 23, 2010 8327

Shiosaki et al.
JOCNote
TABLE 2. Reaction of Fluoro(silyl)acetylene and Fluoro(stannyl)acetylene
SCHEME 2. Plausible Reaction Mechanism
stage no formation of 2b and 3b was detected in the complex
mixtures by GC-MS.
Furthermore, EPR studies of the reaction were briefly
attempted to confirm its radical mechanism. We monitored
the EPR spectra of the reaction solution containing 1b and
5,5-dimethyl-1-pyroline N-oxide (DMPO) as a radical trap
reagent with the reaction temperature. We observed the
multiplet line with a g value of 2.0066, which corresponded
to 5,5-dimethyl-2-substituted-1-pyrrolidine N-oxide radical.
These peaks corresponded to the triplet hyperfine structure
by an N nuclei (l = 1) and the doublet hyperfine structure by
one adjacent H nuclei (l = 1/2). The former hyperfine cou-
pling constant (AN) was 1.38 mT and the latter one (AH) was
1.72 mT. However, no further information about the sub-
stituent at the 2-position on the pyrrolidine ring was
obtained under our experimental conditions.
On the basis of these results and previous findings in
another group,10 our proposed radical mechanism is shown
in Scheme 2. Initially, a trace amount of inevitable and/or
adventitious oxygen generated the corresponding THF
radical 4. The radical 4 almost regioselectively attacked at
the β-carbon of 1b to yield the corresponding fluorovinyl
radical 5. The radical 5 abstracted the R-hydrogen of THF to
afford the products (2b and 3b) and to regenerate the THF
radical 4. As the result, the complete radical cycle mechanism
should be successfully accomplished. In summary, we have
demonstrated fluoro(triisopropylsilyl)acetylene 1a and the
first successful 13C NMR measurement of the radical reac-
tion of fluoro(silyl)acetylenes (1b-f) and fluoro(stannyl)-
acetylenes (1h and 1i) with THF. We also have verified the
stability of these fluoro(silyl)acetylenes and fluoro(stannyl)-
acetylenes in THF in the absence of oxygen. Although their
final decomposition mechanism is not clear at the present
stage, these findings would contribute a new aspect of fluoro-
acetylene chemistry.
aIsolated yield. bDetermined by GC-MS analysis in the crude reaction
mixture otherwise noted. Under the preliminary reaction conditions.
c
dReaction concentration (0.17 M). eUnder the optimized reaction con-
ditions. fReaction concentration (0.10 M). gReaction concentration
i
(0.07 M). hDetermined by NMR after column chromatography. The
corresponding fluoro(triphenylsilyl)acetylene was scarcely detected by
GC-MS analysis.
along with 1b was observed at around -20 °C. Thus, 1b
remained intact in THF at least below ca. -30 °C, and was
subjected to the addition reaction of THF at ca. -20 °C,
giving 2b and 2c.
Our next task is to clarify whether this reaction proceeded
via an ionic or a radical process. We conducted the following
two reactions under different conditions. Thus, after prepar-
ing 1b at -78 °C again, first we slowly added an excessive
amount of THF (5 mL) and water (10 equiv to 1b) to this
solution at -40 °C. The mixture was gradually warmed to
room temperature after the complete addition. In this case,
the addition reaction smoothly proceeded to afford the
corresponding products 2b and 3b in essentially the same
manner [82%, 2b:3b = 81:19, compare to entry 1 (Method B)
in Table 1 (78%, 2b:3b = 82:18)]. On the other hand, after
preparing 1b at -78 °C, the addition of 2,2,6,6-tetramethyl-
piperidine-1-oxyl (TEMPO, 1.1 equiv to 1b) instead of water
at the same time completely retarded the addition reaction to
afford no THF adducts at -20 °C. Moreover, even at room
temperature, the peak of 1b was observed essentially intact
by GC-MS in the reaction mixture for a short time. TEMPO
gradually decomposed at this temperature under these con-
ditions, which may cause decomposition of 1b, finally giving
the complex reaction mixtures. Surprisingly, even at the final
Experimental Section
[2-Fluoro-2-(tetrahydrofuran-20-yl)vinyl]dimethylphenylsilane
(2b and 3b). A 25-mL two-necked flask equipped with a mag-
netic stir bar, a stopcock, and a three-way stopcock was charged
with 2.5 mL of THF under argon. To this solution was added
sBuLi (1.04 M in cyclohexane-hexane solution, 1.4 mL, 1.46 mmol,
2.2 equiv) dropwise via syringe at -78 °C. After being stirred for
(10) Bergstrom, D. E.; Ng, M. W.; Wong, J. J. Chem. Soc., Perkin Trans. 1
1983, 741.
8328 J. Org. Chem. Vol. 75, No. 23, 2010

Shiosaki et al.
JOCNote
an additional 5 min, the solution was cooled to -120 °C via
liquid N2/ethanol bath. At this temperature, argon was replaced
with 1,1-difluoroethylene (balloon). The mixture was gradually
warmed to -85 °C. HMPA (6.0 μL, 5 mol %) at -85 °C and
chlorodimethylphenylsilane (110 μL, 0.67 mmol) at -78 °C were
successively added to the solution via syringe. After the mixture
was stirred for 10 min, the reaction flask was covered with
aluminum foil. The mixture was slowly warmed to -40 °C while
an excess amount of 1,1-difluoroethylene was gradually let
out through the drying glass tube filled with calcium chloride.
When the reaction mixture reached -40 °C, the additional THF
(5.0 mL) was carefully added to the solution. After removal of
the cooling bath at -30 °C, the reaction mixture was allowed to
stand overnight. To the resulting solution was carefully added
hexane and water, successively. After the resultant mixture was
extracted with hexane, additional extraction was repeated twice.
The combined solution was dried over sodium sulfate. The
solution was concentrated in vacuo and the residual oil was
quickly purified by chromatography on a short silica gel column
covered with aluminum foil (hexane:ethyl acetate:triethylamine =
200:4:1 as an eluent) to give a mixture of 2b and 3b [78% (130.7 mg),
E/Z = 82:18]. The pure sample 2b was obtained even at the
expense of the yield from partial fractions by the second
chromatography on longer silica gel column of the mixture of
2b and 3b under the same separation conditions. 2b: Rf 0.49;
hexane:ethyl acetate:triethylamine = 200:4:1; elemental anal-
ysis calcd for C14H19FOSi: C 67.16, H 7.65; found: C 67.19, H
7.69; δH = 0.40 (3H, s), 0.42 (3H, s), 1.70-2.00 (4H, m),
3.65-3.90 (2H, m), 4.43 (1H, dt, JHF = 25.0 Hz, JHH = 7.3 Hz),
5.07 (1H, d, JHF = 34.1 Hz), 7.30-7.50 (5H, m) ppm; δF
-85.9 (dd, JFH = 34.1, 25.0 Hz) ppm; δC = -0.86 (d, JCF
=
=
1.9 Hz), -0.69 (d, JCF = 1.9 Hz), 26.3 (s), 29.2 (s), 69.2 (s), 76.1
(d, JCF = 32.4 Hz), 99.7 (d, JCF = 3.1 Hz), 127.9 (s), 129.2 (s),
133.6 (s), 138.5 (d, JCF = 1.9 Hz), 167.7 (d, JCF = 279.6 Hz)
ppm; ν = 3069, 2956, 2873, 1652, 1429, 1112, 1059, 791,
700 cm-1; GC-MS (m/z) 235 [Mþ - 15 (Me), 47], 193 (46),
155 (8), 129 (76), 105 (23), 77 (100), 53 (16). 3b: Rf 0.30; hexane:
ethyl acetate:triethylamine = 200:4:1; δH = 0.40 (3H, s), 0.41
(3H, s), 1.85-2.16 (4H, m), 3.80-4.00 (2H, m), 4.39 (1H, dt,
JHF = 8.3 Hz, JHH = 4.8 Hz), 4.96 (1H, d, JHF = 61.7 Hz),
7.30-7.50 (5H, m) ppm; δF = -95.0 (dd, JFH = 61.7, 8.3 Hz)
ppm; ν = 3071, 2957, 1662, 1428, 1249, 1114, 1078, 1060, 834,
731, 699 cm-1; GC-MS (m/z) 235 [Mþ - 15 (Me), 0.9], 173 (4),
139 (100), 129 (60), 91 (65), 79 (42), 77 (84).
Acknowledgment. We greatly thank both Tosoh F-Tech,
Inc. for a gift of 1,1-difluoroethylene and Chisso Corp. for a
gift of chlorolsilanes. We thank Prof. Junji Inanaga, Prof.
Hiroshi Furuno, and Prof. Satoru Karasawa at Kyushu
University and Prof. Masayuki Koikawa at Saga University
for their valuable discussions and experimental support.
Supporting Information Available: Characterization of new
compounds 2c-i, and NMR spectral for all new compounds.
This material is available free of charge via the Internet at http://
pubs.acs.org.
J. Org. Chem. Vol. 75, No. 23, 2010 8329