Impact of silyl enol ether stability on palladium-catalyzed arylations

Article abstract of DOI:10.1021/om1000259

The effect of stability on arylation of silyl enol ethers as dictated by the presence of bulky silyl groups was elucidated through experiment and calculation. With the enhancement of stability of the silyl enol ethers, especially of acyclic ethers, the ef

Full text of DOI:10.1021/om1000259

1818 Organometallics 2010, 29, 1818–1823
DOI: 10.1021/om1000259
Impact of Silyl Enol Ether Stability on Palladium-Catalyzed Arylations
Yong Guo, Guo-Hong Tao, Alex Blumenfeld, and Jean’ne M. Shreeve*
Department of Chemistry, University of Idaho, Moscow, Idaho 83844-2343
Received January 7, 2010
The effect of stability on arylation of silyl enol ethers as dictated by the presence of bulky silyl
groups was elucidated through experiment and calculation. With the enhancement of stability of the
silyl enol ethers, especially of acyclic ethers, the efficiency of palladium-catalyzed arylation of silyl
enolates based on ketone precursors was greatly increased.
Scheme 1. Previous Results of Pd-Catalyzed Arylations of
Silyl Enol Ethers4a
Introduction
Silyl enol ethers are widely used in a variety of organic
reactions such as aldol, Michael, and [4þ2] cycloaddition
reactions, alkylations, acylations, and oxidative processes.1
Recently the reactions of silyl enol ethers have been
expanded to palladium-catalyzed arylation.2-4 In the palla-
dium-catalyzed arylation of ketones with aryl halides, the
number of successful arylations was markedly improved
when the ketones were first converted to their corresponding
silyl enol ethers. These reactions normally require use of
stoichiometric amounts of strong alkali, such as sodium tert-
butoxide.2,5 However, acyclic silyl enol ethers gave unsatis-
factory results when compared with their cyclic analogues.4a
For example, ether 1 gives a better yield than that obtained
with ether 4 using the same coupling conditions since 4 is
more sensitive to hydrolysis (Scheme 1). The majority of the
products in the case of 4 is the hydrolysis product. Steric
effects are not a sound explanation for the decrease in yield.
In order to address this issue, we examined the effect of
substituents bonded to the silicon atom. Now we report our
recent discovery that silicon reagents with bulky substituents
can increase the yield and selectivity of Pd-catalyzed aryla-
tions and reduce the loadings of palladium because of the
stabilization of silyl enol ethers.
Scheme 2. Synthesis of r-Monofluoropropiophenone
trimethylsilyl chloride, triethylsilyl chloride, or tri-n-propyl-
silyl chloride was tried in the first step. It was found that the
stability of trimethylsilyl enol ether was too low to give pure 8,
which is found to be contaminated with non-fluorinated
ketone 6 as the hydrolysis product in the second step. When
tri-n-propylsilyl chloride was used, the final product con-
tained an unknown impurity, which was difficult to separate.
However pure 8 was obtained in 88% yield when triethylsilyl
chloride was utilized in the first step as shown in Scheme 2.
After the preparation of fluorinated ketone 8, silyl enol
ethers were synthesized from 8 and other ketones. Ketone 8
was chosen for the following reasons: (1) it is an acyclic
ketone; (2) it is possible to monitor the reaction process with
19F NMR spectrometry; and (3) the current demand for
synthesis of fluorinated compounds in medicinal and agri-
cultural sciences.6 Although fluorinated silyl enol ethers and
Result and Discussion
Fluorinated ketone 8 was synthesized in a two-step
reaction: first the generation of the silyl enol ether with
subsequent fluorination using Selectfluor (Scheme 2). Initially
*Corresponding author. E-mail: jshreeve@uidaho.edu.
(1) Kobayashi, S.; Manabe, K.; Ishitani, H.; Matsuo, J.-I. Sci. Synth.
2002, 4, 317–369.
(2) (a) Bellina, F.; Rossi, R. Chem. Rev. 2010, 110, 1082-1146.
(b) Culkin, D. A.; Hartwig, J. F. Acc. Chem. Res. 2003, 36, 234–245.
(3) (a) Iwama, T.; Rawal, V. H. Org. Lett. 2006, 8, 5725–5728.
(b) Su, W.; Raders, S.; Verkade, J. G.; Liao, X.; Hartwig, J. F. Angew.
Chem., Int. Ed. 2006, 45, 5852–5855. (c) Kuwajima, I.; Urabe, H. J. Am.
Chem. Soc. 1982, 104, 6831–6833. (d) Chae, J.; Yun, J.; Buchwald, S. L.
Org. Lett. 2004, 6, 4809–4812.
(4) (a) Guo, Y.; Twamley, B.; Shreeve, J. M. Org. Biomol. Chem.
2009, 1716–1722. (b) Guo, Y.; Shreeve, J. M. Chem. Commun. 2007, 3583–
3585.
(5) Fox, J. M.; Huang, X.; Chieffi, A.; Buchwald, S. L. J. Am. Chem.
Soc. 2000, 122, 1360–1370.
(6) (a) Kirsch, P. Modern Fluoroorganic Chemistry: Synthesis,
Reactivity, Applications; Wiley-VCH Verlag GmbH & Co. KGaA:
Weinheim, 2004. (b) Hiyama, T. Organofluorine Compounds: Chemistry
and Applications; Springer: New York, 2000. (c) Uneyama, K. Organo-
fluorine Chemistry; Blackwell: New Delhi, 2006. (d) Ma, J.-A.; Cahard, D.
Chem. Rev. 2004, 104, 6119–6146. Chem. Rev. 2008, 108, PR1-PR43. (e)
Prakash, G. K. S.; Beier, P. Angew. Chem., Int. Ed. 2006, 45, 2172–2174. (f)
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O'Hagan, D. Angew. Chem., Int. Ed. 2008, 47, 1179–1182.
r
pubs.acs.org/Organometallics
Published on Web 03/16/2010
2010 American Chemical Society

Article
Organometallics, Vol. 29, No. 7, 2010 1819
Scheme 3. Synthesis of Silyl Enol Ethers
Table 1. Screening of Silyl Enol Ethers in Pd-Catalyzed
Arylationa
enamines could be synthesized by a C-F activation method
and it was applied in amino acid and dipeptide synthesis,7 the
method employed here is straightforward, giving a mono-
fluoroenol silyl ether from a R-monofluoro ketone by using
base (Scheme 3).8 Using this methodology, the same or a
slightly lesser equivalent of silyl chloride than ketone could
be used. The generated silyl enol ethers with low polarities
could be quickly separated from unreacted ketones by using
column chromatography on silica gel. The use of excessive
silyl chlorides should be avoided because of the purification
problem arising from the presence of unreacted high-boiling
silyl chlorides that are difficult to remove. By using this
method we synthesized monofluorinated silyl enol ethers
9-13 and non-fluorinated silyl enol ethers 15-17. The
structures of 9 and 17 were confirmed by NOESY and
NOE effects, respectively (see Supporting Information).
In Table 1, the results obtained using various silyl groups
are compared. Silyl enol ethers were reacted with 2 equiv of
4-methylphenyl bromide 2 in toluene at 95 °C in the presence
a Reaction conditions: 0.2 mmol of silyl enol ether, 2.0 equiv of aryl
halide, 1.2 equiv of TBAT, 3 mol % Pd(dba)2, 6 mol % t-Bu3P, 0.4 mL
of toluene, 95 °C. b Determined by 19F NMR. c Reference 4a. d Not
determined.
of 3% Pd(dba)2 [bis(dibenzylideneacetone)palladium], 6%
t-Bu3P, and 1.2 equiv of tetrabutylammonium tripheny1-
silyldifluorosilicate (TBAT).9 In our previous work, the
arylation of silyl enol ether 4 gave a 25% yield of the coupling
product 5 (entry 1, Table 1), with the remainder being the
hydrolysis product. Here the yields were improved when
bulky silyl enol ethers 9-13 were used (entries 2 to 6 in
Table 2). Among these reactions, the best yield of the
coupling product 5 and the best selectivity were obtained
when dimethylphenylsilyl enol ether 9 was used. The ratio of
coupling ketone 5 to hydrolysis ketone 8 is 7.2:1 (entry 2,
Table 1). In general, bulky silyl groups stabilize the silyl enol
ether, depress the hydrolysis of silyl enol ether, and finally
increase the yield of the arylation. The order of the yields and
selectivities that is observed with different substituents is
PhMe2Si > n-BuMe2Si > n-Pr3Si > n-Bu3Si ≈ i-Bu3Si >
Et3Si. Bulkiness alone cannot account for the difference in
reactivities and selectivities.
(7) (a) Amii, H.; Uneyama, K. Chem. Rev. 2009, 109, 2119–2183. (b)
Uneyama, K.; Amii, H. J. Fluorine Chem. 2002, 114, 127–131. (c) Amii, H.;
Uneyama, K. Fluorine-Containing Synthons; ACS Symposium Series 911;
2005; pp 455-495. (d) Guo, Y.; Fujiwara, K.; Amii, H.; Uneyama, K. J. Org.
Chem. 2007, 72, 8523–8526. (e) Uneyama, K.; Guo, Y.; Fujiwara, K.; Komatsu,
Y. Current Fluoroorganic Chemistry; ACS Symposium Series 949; 2007; pp
462-476. (f) Guo, Y.; Fujiwara, K.; Uneyama, K. Org. Lett. 2006, 8, 827–829.
ꢀ
ꢀ
(8) Belanger, E; Cantin, K.; Messe, O.; Tremblay, M.; Paquin, J.-F.
J. Am. Chem. Soc. 2007, 129, 1034–1035.
(9) (a) Handy, C. J.; Lam, Y.-F.; DeShong, P. J. Org. Chem. 2000, 65,
3542–3543. (b) Pilcher, A. S.; Ammon, H. L.; DeShong, P. J. Am. Chem.
Soc. 1995, 117, 5166–5167.

1820 Organometallics, Vol. 29, No. 7, 2010
Table 2. Scope of Pd-Catalyzed Arylation of Silyl Enol Ethersa
Guo et al.
a Reaction conditions: 0.2 mmol of silyl enol ether, 2.0 of equiv aryl halide, 1.2 equiv of TBAT, 3 mol % Pd(dba)2, 6 mol % t-Bu3P, 0.4 mL of toluene,
95 °C. b Selectivity = the ratio of arylation/hydrolysis.
The relative rate of cleavage of R1OSiR2 in acidic clea-
giving 48-74% product yields with moderate selectivities
(entries 8 to 10, Table 2).
3
vage conditions and basic cleavage conditions is different.10
The order is R1OTMS > R1OTES > R1OTBDMS >
R1OTIPS > R1OTBDPS in acidic cleavage conditions and
R1OTIPS > R1OTBDMS = R1OTBDPS > R1OTES >
R1OTMS basic cleavage conditions. Somehow, R1OTBDPS,
which is the most robust in acidic cleavage conditions, is not the
most unstable in basic cleavage conditions. Bulkiness is not the
only reason for the hydrolytic stabilities of the silyl ethers.
The scope of Pd-catalyzed arylation of silyl enol ethers is
shown in Table 2. The dimethylphenylsilyl enol ether 9
reacted with monobromobenzene, 4-bromotoluene, 4-iodo-
toluene, 1-bromo-4-tert-butylbenzene, 4-bromobenzotri-
fluoride, and methyl 3-bromobenzonate to give yields of
74-88% of the arylated ketones 18, 5, 19, 20, and 21 with
good selectivities (entries 1 to 7 in Table 2). The silyl enol
ether 15, derived from a cyclic ketone, reacted with mono-
bromobenzene, 4-bromotoluene, and 40-bromoacetophenone,
It is worth noting the behavior of cyclic silyl enol ethers.
The 74% yield for the reaction of cyclic tri-n-propylsilyl enol
ether 15 with 4-bromotoluene was higher than that obtained
using acyclic tri-n-propylsilyl enol ether 11 (58% yield)
comparing entry 9 (Table 2) with entry 4 (Table 1). This fact
suggests that cyclic silyl enol ethers are more stable than their
acyclic analogues. Another important feature of this reaction
is the loading of the catalyst that was reduced with the
increased stability of the silyl enol ether. For example, the
quantity of Pd(dba)2 required in the arylation of tri-n-
propylsilyl enol ether 15 (3 mol %, entry 9, Table 2) was
significantly lower than that required when triethylsilyl enol
ether 1 was used (15 mol %, Scheme 1).
The reaction was also extended to non-fluorinated silyl
enol ethers (entries 11 to 14, Table 2). The reaction of tri-n-
propylsilyl enol ether 16 and 4-bromotoluene gave the
coupled product in 46% yield, and the ratio of arylation/
hydrolysis was 3.6:1 (entry 11, Table 2). The reaction depic-
ted in entry 13 of Table 2, in which dimethylphenylsilyl enol
(10) (a) Moloney, M. G.; Yaqoob, M. Sci. Synth. 2008, 36, 1031–
1106. (b) R€ucker, C. Chem. Rev. 1995, 95, 1009–1064.

Article
Organometallics, Vol. 29, No. 7, 2010 1821
ether, 17, was used rather than tri-n-propylsilyl enol ether,
16, but otherwise identical to the ones described in entry 11 of
Table 2, gave a 77% yield of arylated product, and the ratio
of 24/6 was 6.8:1. The fact that PhMe2Si substituent is more
effective than n-Pr3Si is the same result obtained with its
fluorinated analogue. While the coupling of monobromo-
benzene and dimethylphenylsilyl enol ether 17 in entry 12
(Table 2) gave a 70% yield of the desired product, the
reaction of methyl 3-bromobenzonate (entry 14, Table 2)
under similar conditions produced the coupled product in a
yield of 40%. The selectivity for the arylated product instead
of hydrolysis product was reduced to 1.0:1. It should be
noted that the selectivity in the reaction of the fluorinated
silyl enol ether was 8.6:1, but these selectivities vary. No
decrease in yield was found for the fluorinated analogue
when the meta-substituent on the phenyl group of the aryl
halide is an electron-withdrawing ester function (entry 7,
Table 2).
Scheme 4. Comparison of Reactivities of Silyl Enol Ethers (17
and 9) in Pd-Catalyzed Arylation
Scheme 5. NBO Charges at Silicon Atoms at B3LYP/6-31Gþþ
In order to confirm the difference in the use of a fluori-
nated silyl enol ether compared with a non-fluorinated ether,
both dimethylphenylsilyl enol ethers 9 and 17 in 0.1 mmol
amounts, respectively, were placed into the same reaction
mixture with 0.4 mmol of methyl 3-bromobenzonate, 3%
mol % Pd(dba)2, 6 mol % t-Bu3P, 1.2 equiv of TBAT, and
0.4 mL of toluene at 95 °C (Scheme 4). The ratio of 26:6 from
the non-fluorinated silyl enol ether 17 remained at 1:1, which
was lower than that of 21:8 (6.0:1). Fluorine at the terminal
site of the vinyl group of the silyl enol ether 9 seems to
stabilize the silyl enol ether compared with the non-fluori-
nated one, but the difference became obvious only when
methyl 3-bromobenzonate was used as the arylating reac-
tant.
2.5% higher than that in dimethylphenylsilyl enol ether 17 or
dimethylphenylsilyl enol ether 9. Although the reason can-
not be fully explained, NBO calculations show a positive
enhancement of the hydrolytic lability of PhMe2Si-substi-
tuted silyl enol ether.
The natural bond orbital (NBO) approach11 was used to
explain the electrophilicities of the silicon atoms in the silyl
enol ethers 4, 17, and 9 (Scheme 5). Charges were obtained
from NBO analysis implemented with the Gaussian 03
(Revision D.01) suite of programs.12 The geometric optimi-
zation of the structures, frequency analyses, and NBO
analyses were carried out using the B3LYP functional with
the 6-31þGþþ basis set. All of the optimized structures were
characterized to be true local energy minima on the potential
energy surface without imaginary frequencies. The NBO
charges describe qualitatively the variations of the reactivity
of silyl enol ethers toward the nucleophilic attack by the
oxygen atom in water or the fluorine atom in TBAT. The
NBO charge at the silicon atom in triethylsilyl enol ether 4 is
Conclusion
The stabilities of silyl enol ethers play an important role in
Pd-catalyzed arylation. With the increase of stabilities, the
selectivities and yields of arylations were greatly improved,
especially for the acyclic silyl enol ethers. The loadings of the
catalysts were reduced significantly. NBO charges at the
silicon atoms provide an additional description of the experi-
mentally established reactivities of the compounds from the
series studied.
Experimental Section
(11) (a) Reed, A. E.; Weinstock, R. B.; Wienhold, F. J. Chem. Phys.
1985, 83, 735–746. (b) Reed, A. E.; Wienhold, F.; Curtiss, L. A. Chem. Rev.
1988, 88, 899–926.
General Methods. A 1 M toluene solution of P(t-Bu)3 (Aldrich
Chemical Co.) was used as received or was made by diluting pure
tri-tert-butylphosphine (Alfa Aesar) with dry toluene. Toluene
was distilled under nitrogen over sodium prior to use. All other
(12) Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.;
Robb, M. A.; Cheeseman, J. R.; Montgomery, J. A., Jr.; Vreven, T.;
Kudin, K. N.; Burant, J. C.; Millam, J. M.; Iyengar, S. S.; Tomasi, J.;
Barone, V.; Mennucci, B.; Cossi, M.; Scalmani, G.; Rega, N.; Petersson,
G. A.; Nakatsuji, H.; Hada, M.; Ehara, M.; Toyota, K.; Fukuda, R.;
Hasegawa, J.; Ishida, M.; Nakajima, T.; Honda, Y.; Kitao, O.; Nakai,
H.; Klene, M.; Li, X.; Knox, J. E.; Hratchian, H. P.; Cross, J. B.; Bakken,
V.; Adamo, C.; Jaramillo, J.; Gomperts, R.; Stratmann, R. E.; Yazyev,
O.; Austin, A. J.; Cammi, R.; Pomelli, C.; Ochterski, J. W.; Ayala, P. Y.;
Morokuma, K.; Voth, G. A.; Salvador, P.; Dannenberg, J. J.;
Zakrzewski, V. G.; Dapprich, S.; Daniels, A. D.; Strain, M. C.; Farkas,
O.; Malick, D. K.; Rabuck, A. D.; Raghavachari, K.; Foresman, J. B.;
Ortiz, J. V.; Cui, Q.; Baboul, A. G.; Clifford, S.; Cioslowski, J.; Stefanov,
B. B.; Liu, G.; Liashenko, A.; Piskorz, P.; Komaromi, I.; Martin, R. L.;
Fox, D. J.; Keith, T.; Al-Laham, M. A.; Peng, C. Y.; Nanayakkara, A.;
Challacombe, M.; Gill, P. M. W.; Johnson, B.; Chen, W.; Wong, M. W.;
Gonzalez, C.; Pople, J. A. Gaussian 03, revision D.01; Gaussian, Inc.:
Wallingford, CT, 2004.
1
chemicals were used as received from commercial sources. H
and 19F NMR spectra were obtained on a 300 or 500 MHz
spectrometer, and chemical shifts were recorded relative to
tetramethylsilane and CFCl3, respectively. The solvent was
CDCl3 unless otherwise stated. The purity of products was
determined by C, H, and N elemental analyses.
2-Fluoro-1-phenyl-1-propanone (8). 4a To a -78 °C solution of
ketone 6 (2.68 g, 20.0 mmol) in THF (140 mL) was added
LiHMDS (24 mL, 24 mmol, ca. 1.0 M in THF). A solution of
Et3SiCl (3.01 g, 20.0 mmol) in THF (20 mL) was added dropwise
to the resulting enolate solution. The reaction mixture was
allowed to warm to room temperature overnight. Saturated
NH4Cl (ca. 50 mL) and water (ca. 500 mL) were added to the

1822 Organometallics, Vol. 29, No. 7, 2010
Guo et al.
reaction mixture. The resulting mixture was extracted with
hexane (3 ꢀ 150 mL). The combined organic layers were washed
with brine and dried over anhydrous Na2SO4, and the solvent
was evaporated to give the crude silyl enol ether 7. The latter was
dissolved in CH3CN (20 mL), and the solution was cooled to
0 °C. Selectfluor (7.08 g, 20.0 mmol) was added in several
portions to the solution. After the addition of Selectfluor, the
cold bath was removed and the reaction mixture was allowed to
warm to room temperature over several hours. After the com-
pletion of the fluorination, the solvent was evaporated. Water
(20 mL) was added to the residue, and the product was extracted
with ethyl ether (3 ꢀ 20 mL). The combined organic layers were
washed with brine and dried over anhydrous Na2SO4, and the
solvent was evaporated. The pure product 8 (2.68 g, 17.6 mmol,
88%) was isolated as a colorless liquid by flash chromatography
using 2% EtOAc/hexane. 1H NMR: δ 1.67 (dd, J=24.2, 6.8 Hz,
3H), 5.70 (dq, J = 48.6, 6.8 Hz, 1H), 7.44-7.54 (m, 2H),
7.57-7.65 (m, 1H), 7.99 (d, J = 7.4 Hz, 2H). 19F NMR: δ
-180.5 (dq, J=48.6, 24.2 Hz).
Tri-n-butyl[[2-fluoro-(1E)-1-phenyl-1-propenyl]oxy]silane (12).
Following the general procedure, the pure product (526 mg,
75%) was isolated as a colorless oil by flash chromatography
using 1% EtOAc/hexane. Rf [10% EtOAc in hexane]=0.70. IR
(film): 2957, 2924, 2866, 1691, 1458, 1306, 1217, 1153, 829, 699
cm-1. 1H NMR: δ 0.56-0.61 (m, 6H), 0.85 (t, J=6.9 Hz, 9H),
1.23-1.28 (m, 12H), 2.03 (d, J=18 Hz, 3H), 7.27-7.38 (m, 5H).
19F NMR: δ -119.5 (q, J=18 Hz, E-isomer, 97%), -133.7 (q,
J=17 Hz, Z-isomer, 3%). EI-MS (m/z, relative intensity): 350
(Mþ, 28), 303 (8), 265 (23), 237 (69), 181 (100), 117 (21), 115 (20),
105 (90), 91 (9), 77 (67). Anal. Calcd for C21H35FOSi (fw 350.6):
C, 71.94; H, 10.06. Found: C, 72.05; H, 10.18.
Tri-isobutyl[[2-fluoro-(1E)-1-phenyl-1-propenyl]oxy]silane (13).
Following the general procedure, the pure product (414 mg,
59%) was isolated as a colorless oil by flash chromatography
using 1% Et2O/hexane. Rf [10% EtOAc in hexane]=0.74. IR
(film): 2953, 2868, 1691, 1364, 1307, 1219, 1154, 837, 699 cm-1
.
1H NMR: δ 0.64 (dm, J=6.8 Hz, 6H), 0.91 (d, J=6.6 Hz, 18H),
1.77-1.87 (m, 3H), 2.01 (d, J=18 Hz, 3H), 7.27-7.37 (m, 5H).
19F NMR: δ -119.3 (q, J=18 Hz, E-isomer, 97%), -134.1 (q,
J=17.5 Hz, Z-isomer, 3%). EI-MS (m/z, relative intensity): 350
(Mþ, 6), 265 (23), 237 (39), 209 (21), 181 (100), 117 (16), 115 (16),
105 (25), 91 (5), 77 (48). Anal. Calcd for C21H35FOSi (fw 350.6):
C, 71.94; H, 10.06. Found: C, 71.31; H, 10.33. HRMS-EI: calcd
for C21H35FOSi 350.2441, found 350.2399.
General Procedure for the Silyl Enol Ether Preparation.
Dimethylphenyl[[2-fluoro-(1E)-1-phenyl-1-propenyl]oxy]silane
(9). To a solution of ketone 8 (304 mg, 2 mmol) at -78 °C was
added LiHMDS (2.4 mL, 2.4 mmol, ca. 1.0 M in THF) in THF
(10 mL). A solution of PhMe2SiCl (341 mg, 2 mmol), in order to
separate the final silyl enol ether products easily (excess chloro-
silanes were not used in all examples), in THF (6 mL) was
added dropwise to the resulting enolate solution. The reaction
mixture was allowed to warm to room temperature overnight.
Saturated NH4Cl (ca. 10 mL) and water (ca. 50 mL) were added
to the reaction mixture. The resulting mixture was extracted
with hexane. The combined organic layers were washed with
brine and dried over anhydrous Na2SO4, and the solvent was
evaporated to give the crude product. The pure product (509 mg,
89%) was isolated as a colorless oil by flash chromatography
using 2% Et2O/hexane. Rf [5% ether in hexane]=0.60. IR (film):
1693, 1428, 1385, 1306, 1253, 1218, 1151, 1119, 923, 858, 833,
Tri-n-propyl(2-fluoro-3,4-dihydronaphthalen-1-yloxy)silane (15).
Following the general procedure on a 5 mmol scale, the pure
product (1.47 mg, 92%) was isolated as a pale yellow oil by
flash chromatography using 5% Et2O/hexane. Rf [5% Et2O in
hexane]=0.82. IR (film): 2956, 2928, 2869, 1691, 1454, 1325,
1
1207, 1087, 1064, 996, 950, 899, 814, 760 cm-1. H NMR: δ
0.73-0.80 (m, 6H), 0.98 (t, J=7.2 Hz, 9H), 1.37-1.52 (m, 6H),
2.68-2.66 (m, 2H), 2.94 (td, J=8.3, 2.0 Hz, 2H), 7.04-7.14 (m,
2H), 7.20 (d, J=7.2 Hz, 1H), 7.39 (d, J=7.3 Hz, 1H). 19F NMR:
δ -127.6 (s). EI-MS (m/z, relative intensity): 320 (Mþ, 37), 277
(22), 235 (61), 208 (51), 129 (98), 115 (28), 105 (28), 91 (46), 63
(100). Anal. Calcd for C19H29FOSi (fw 320.5): C, 71.20; H, 9.12.
Found: C, 71.06; H, 9.30.
1
789, 698 cm-1. H NMR: δ 0.38 (d, J=1.1 Hz, 6H), 2.01 (d,
J=18.1 Hz, 3H), 7.27-7.39 (m, 8H), 7.55 (dd, J=7.6, 1.7 Hz,
2H). 19F NMR: δ -118.2 (q, J = 18.1 Hz, E-isomer, 96%),
-132.2 (q, J=17.4 Hz, Z-isomer, 4%). EI-MS (m/z, relative
intensity): 286 (Mþ, 45), 271 (14), 256 (8), 207 (9), 192 (15), 191
(23), 139 (56), 135 (100), 104 (43), 91 (33), 77 (42). Anal. Calcd
for C17H19FOSi (fw 286.4): C, 71.29; H, 6.69. Found: C, 70.91;
H, 6.85.
n-Butyldimethyl[[2-fluoro-(1E)-1-phenyl-1-propenyl]oxy]silane
(10). Following the general procedure, the pure product (380
mg, 70%) was isolated as a colorless oil by flash chromatogra-
phy using 2% Et2O/hexane. Rf [5% ether in hexane]=0.58. IR
(film): 2958, 2924, 1691, 1383, 1306, 1252, 1217, 1153, 923, 846,
788, 699 cm-1. 1H NMR: δ 0.09 (s, J=1.0 Hz, 6H), 0.60 (t, J=8.0
Hz, 2H), 0.85 (t, J=6.6 Hz, 3H), 1.24-1.29 (m, 4H), 2.05 (d,
J=18.1 Hz, 3H), 7.26-7.37 (m, 5H). 19F NMR: δ -119.1 (q,
J=18.1 Hz, E-isomer, 97%), -132.9 (q, J=17.3 Hz, Z-isomer,
3%). EI-MS (m/z, relative intensity): 266 (Mþ, 7), 209 (11), 131
(27), 115 (10), 104 (12), 77 (100), 59 (30). Anal. Calcd for
C15H23FOSi (fw 266.4): C, 67.62; H, 8.70. Found: C, 67.27; H,
8.85.
Tri-n-propyl[[2-fluoro-(1E)-1-phenyl-1-propenyl]oxy]silane (11).
Following the general procedure, the pure product (530 mg,
86%) was isolated as a colorless oil by flash chromatography
using 5% Et2O/hexane. Rf [10% EtOAc in hexane]=0.67. IR
(film): 2956, 2926, 2869, 1691, 1306, 1217, 1153, 1067, 1004, 923,
837, 699 cm-1. 1H NMR: δ 0.56-0.61 (m, 6H), 0.90 (t, J=7.2
Hz, 9H), 1.28-1.37 (m, 6H), 2.03 (d, J=18 Hz, 3H), 7.27-7.37
(m, 5H). 19F NMR: δ -119.6 (q, J=18 Hz, E-isomer, 97%),
-133.6 (q, J = 17 Hz, Z-isomer, 3%). EI-MS (m/z, relative
intensity): 308 (Mþ, 23), 261 (4), 237 (17), 223 (45), 181 (100),
117 (28), 115 (27), 105 (78), 91 (32) 63 (69). Anal. Calcd for
C18H29FOSi (fw 308.5): C, 70.08; H, 9.47. Found: C, 70.04; H,
9.67.
Tri-n-propyl[(1Z)-1-phenyl-1-propenyl]oxy]silane (16). Follo-
wing the general procedure on a 20 mmol scale, the pure product
(5.4 g, 93%) was isolated as a colorless oil by flash chromato-
graphy using hexane. Rf [10% EtOAc in hexane] = 0.67. IR
1
(film): 2956, 2926, 2869, 1653, 1322, 1059, 856, 760 cm-1. H
NMR: δ 0.56-0.62 (m, 6H), 0.91 (t, J=7.2 Hz, 9H), 1.27-1.41
(m, 6H), 1.74 (dd, J=6.9, 1.0 Hz, 3H), 5.19 (qd, J=5.9, 1.0 Hz,
1H), 7.22-7.31 (m, 3H), 7.41-7.45 (m, 2H). EI-MS (m/z,
relative intensity): 290 (Mþ, 5), 261 (52), 247 (100), 219 (19),
205 (62), 177 (14), 163 (26), 117 (31), 115 (37), 89 (87), 61 (48), 45
(49). Anal. Calcd for C18H30OSi (fw 290.5): C, 74.42; H, 10.41.
Found: C, 74.62; H, 10.64.
Dimethylphenyl[[(1Z)-1-phenyl-1-propenyl]oxy]silane (17).
Following the general procedure on a 5 mmol scale, the pure
product (795 mg, 60%) was isolated as a colorless oil by flash
chromatography using 2% Et2O/hexane. Rf [10% EtOAc in
hexane]=0.55. IR (film): 3071, 3054, 3026, 2915, 2859, 1652,
1492, 1444, 1428, 1322, 1284, 1119, 1060, 869, 832, 788, 696
cm-1. 1H NMR: δ 0.37 (s, 6H), 1.64 (d, J=6.9 Hz, 3H), 5.29 (q,
J = 6.9 Hz, 1H), 7.19-7.28 (m, 3H), 7.32-7.44 (m, 5H),
7.57-7.62 (m, 2H). EI-MS (m/z, relative intensity): 268 (Mþ,
84), 253 (15), 239 (31), 190 (24), 175 (28), 163 (19), 137 (62), 135
(100). Anal. Calcd for C17H20OSi (fw 268.4): C, 76.07; H, 7.51.
Found: C, 75.56; H, 7.51.
General Procedure for the Arylation of Silyl Enol Ether.
2-Fluoro-2-(4-methylphenyl)-1-phenyl-1-propanone (5).4a To a
mixture of Pd(dba)2 (3.5 mg, 3 mol %), tetrabutylammonium
(triphenylsilyl)difluorosilicate (TBAT, 126 mg, 0.24 mmol, 1.2
equiv), and 4-bromotoluene (69 mg, 0.4 mmol, 2 equiv) were
added freshly dried toluene (0.4 mL) and t-Bu3P (12 μL of a 1 M
toluene solution, 6 mol %) at 95 °C under a nitrogen atmo-
sphere. Silyl enol ether 9 (57 mg, 0.2 mmol) was added via

Article
Organometallics, Vol. 29, No. 7, 2010 1823
syringe with stirring. After 20 min, the mixture was cooled and
passed through a short pad of silica gel. The precipitate was
washed with ethyl acetate. The solvent was removed under
reduced pressure. The desired product 5 (41 mg, 84%) was
isolated by flash chromatography using 1% Et2O/hexane. (In
some cases, the product contained a small amount of PhMe2SiF,
which was removed by reaction with tetrabutylammonium
fluoride in THF solvent.)
276 (0.05), 105 (100), 77 (55), 51 (16). Anal. Calcd for C16H12F4O
(fw 269.3): C, 64.87; H, 4.08. Found: C, 65.07; H, 4.37.
Methyl 3-(1-Fluoro-1-methyl-2-oxo-2-phenylethyl)benzonate
(21). IR (film): 1727, 1687, 1289, 1221 694 cm-1; 1H NMR: δ:
1.95 (d, J=23.1 Hz, 3H), 3.93 (s, 3H), 7.36 (m, 2H), 7.49 (m, 2H),
7.67 (d, J=7.7 Hz, 1H), 7.90 (d, J=8.1 Hz, 2H), 8.01 (d, J=7.8
Hz, 1H), 8.20 (s, 1H). 19F NMR: δ -150.1 (q, J=23.1 Hz, 1F).
EI-MS (m/z, relative intensity): 286 (Mþ, 0.08), 105 (100), 77
(34). Anal. Calcd for C17H15FO3 (fw 286.3): C, 71.32; H, 5.28.
Found: C, 71.34; H, 5.39.
2-Fluoro-1,2-diphenyl-1-propanone (18).4a IR (film): 1686,
1
1597, 1267, 1151, 702 cm-1. H NMR: δ 1.93 (d, J=23 Hz,
3H), 7.32-7.51 (m, 8H), 7.90 (dt, J=8.5, 1.5 Hz, 2H). 19F NMR:
δ -150.9 (q, J=23 Hz). EI-MS (m/z, relative intensity): 228
(Mþ, 0.3), 208 (1), 105 (100), 77 (44). Anal. Calcd for C15H13FO
(fw 228.3): C, 78.93; H, 5.74. Found: C, 78.54; H, 5.75.
Methyl 3-(1-Methyl-2-oxo-2-phenylethyl)benzonate (26). IR
(film): 1724, 1684, 1595, 1448, 1287, 1217, 1111, 971, 750
1
cm-1. H NMR: δ 1.56 (d, J=6.9 Hz, 3H), 3.90 (s, 3H), 4.76
(q, J=6.9 Hz, 1H), 7.33-7.49 (m, 5H), 7.87-8.00 (m, 4H). EI-
MS (m/z, relative intensity): 268 (Mþ, 0.98), 237 (7.4), 105 (100),
77 (64). Anal. Calcd for C17H16O3 (fw 268.3): C, 76.01; H, 6.01.
Found: C, 76.21; H, 6.09.
2-Fluoro-2-(4-tert-butylphenyl)-1-phenyl-1-propanone (19).
1
IR (film): 2962, 1686, 1267, 1107, 702 cm-1. H NMR: δ 1.32
(s, 9H), 1.93 (d, J=23 Hz, 3H), 7.24-7.52 (m, 7H), 7.92 (d,
J=6.7 Hz, 2H). 19F NMR: δ -149.3 (q, J=23 Hz). EI-MS (m/z,
relative intensity): 285 (Mþ þ 1, 3.3), 264 (3.3), 249 (7.3), 179
(100), 164 (24), 105 (92). Anal. Calcd for C19H21FO (fw 284.4):
C, 80.25; H, 7.44. Found: C, 79.85; H, 7.50.
2-Fluoro-2-(4-trifluoromethylphenyl)-1-phenyl-1-propanone (20).
IR (film): 1691, 1327, 1128, 705 cm-1; 1H NMR: δ: 1.94 (d, J=23.1
Hz, 3H), 7.35-7.41 (m, 2H), 7.48-7.55 (m, 1H), 7.60-7.69 (m,
4H), 7.87-7.92 (m, 2H). 19F NMR: δ -61.9 (s, 3F), -151.0 (q,
J=23.1 Hz, 1F). EI-MS (m/z, relative intensity): 269 (Mþ, 0.01),
Acknowledgment. The authors gratefully acknowledge
the support of HDTRA1-07-1-0024, NSF (CHE-0315275),
and ONR (N00014-06-1-1032).
Supporting Information Available: Spectroscopic data and
NBO calculations. This material is available free of charge via
the Internet at http://pubs.acs.org.