Generation and reactions of trifluoromethylethenyl titanium(II) species

Article abstract of DOI:10.1021/jo901392n

(Chemical Equation Presented) The reaction of (trifluoromethyl) dimethylphenylsilylacetylene and (η²-propene)Ti(O ⁱPr)₂ generated in situ smoothly proceeded giving the corresponding (η²-1-dimethylphenylsilyl-2-t

Full text of DOI:10.1021/jo901392n

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TABLE 1. Preparation of 1 under Various Conditionsa
Generation and Reactions of Trifluoromethylethenyl
Titanium(II) Species
Takeshi Hanamoto* and Kenji Yamada
entry
solvent
amine
additiveb
yieldc (%)
Department of Chemistry and Applied Chemistry, Saga
University, Honjyo-machi 1, Saga 840-8502, Japan
1
2
3
4
5
THF
Ether
THF
THF
THF
DIA
none
none
none
HMPA
HMPA
52
0
0
69
85
DEA
DEA
DIA
hanamoto@cc.saga-u.ac.jp
Received July 1, 2009
HMDS
aAll reactions were conducted using BuLi (2.4 equiv) and amine
(2.4 equiv) at -78 °C. bHMPA (15 mol %) was used. cIsolated yield after
distilltion.
sulfanyl group as a scaffold on the olefin, that of R-trifluoro-
methylvinyl anion species remains as an important problem due
to easy elimination of fluorine.5 If we could transform triflu-
oromethyl-containing alkynes into the corresponding alky-
ne-titanium complex, we may have a chance to perform the R-
trifuoromethylvinylation reaction without loss of fluorine.
Here we wish to report the first generation and reaction of
(η2-trifluoromethylated dimethylphenylsilylalkyne)Ti(OiPr)2
to afford the corresponding functionalized allylic alcohols
with high regioselectivity.
We planned our study by investigating the reactivity of
(trifluoromethyl)dimethylphenylsilylacetylene 1 toward the
alkyne-titanium complex (η2-alkyne)Ti(OiPr)2. According
to a procedure reported by Yamazaki and co-workers, 1 was
prepared by using LDA and 2-bromo-3,3,3-trifluoropro-
pene at -78 °C followed by addition of chloro(dimethyl-
phenyl)silane in 52% isolated yield.6 However, we soon
encountered difficulty in reproducing similar results. There-
fore, prior to investigation of our study, a practical proce-
dure for the preparation of 1 was required. After many
slightly modified experiments, we noticed the following
two problems: (i) The incomplete conversion to 1 was
confirmed on the basis of the GC calibration curve method.
(ii) The workup procedure often resulted in partial decom-
position of 1, decreasing the yield. The former was settled by
the addition of HMPA to the reaction mixture to enhance the
reactivity of the corresponding lithium acetylide toward
chloro(dimethylphenyl)silane. The latter was solved by the
addition of a large amount of hexane to the reaction mixture
prior to quench. Thus, we established the synthetic proce-
dure of 1 in 85% isolated yield shown in Table 1.
The reaction of (trifluoromethyl)dimethylphenylsilylace-
tylene and (η2-propene)Ti(OiPr)2 generated in situ smoothly
proceeded giving the corresponding (η2-1-dimethylphenyl-
silyl-2-trifluoromethylalkyne)Ti(OiPr)2, which reacted with
aldehydes and ketones to afford the corresponding addition
products in good yields with good to excellent regioselec-
tivity.
Transition metal-alkyne complexes are very useful syn-
thetic intermediates for the preparation of functionalized
olefins.1 They are well-accepted to behave as 1,2-dianionic
species. Among them, an alkyne-titanium complex, (η2-
alkyne)Ti(OiPr)2, developed by Sato and co-workers is a
versatile synthetic intermediate and has been employed in a
wide variety of reactions.1a,2 On the other hand, we have
been working on the development of versatile fluorine-
containing building blocks prepared from easily available
fluorinated molecules.3 Very recently, we reported the synthesis
and reactions of β-trifluoromethylvinyl sulfides as a poten-
tial synthetic intermediate.4 Although the smooth generation
of β-trifluoromethylvinyl anion species achieved by using
*To whom correspondence should be addressed. Fax: 81-952-28-8548.
(1) (a) Sato, F.; Urabe, H.; Okamoto, S. Chem. Rev. 2000, 100, 2835. (b)
Kulinkovich, O. G.; Meijere, A. de. Chem. Rev. 2000, 100, 2789. (c) Negishi,
E.; Takahashi, T. Acc. Chem. Res. 1994, 27, 124. (d) Buchwald, S. L.; Nielsen,
R. B. Chem. Rev. 1988, 88, 1047. (e) Kataoka, Y.; Miyai, J.; Oshima, K.;
Takai, K.; Utimoto, K. J. Org. Chem. 1992, 57, 1973.
(2) Harada, K.; Urabe, H.; Sato, F. Tetrahedron Lett. 1995, 36, 3203.
(3) (a) Hanamoto, T.; Hashimoto, E.; Miura, M.; Furuno, H.; Inanaga, J.
J. Org. Chem. 2008, 73, 4736. (b) Hanamoto, T.; Suetake, T.; Koga, Y.;
Kawanami, T.; Furuno, H.; Inanaga, J. Tetrahedron 2007, 63, 5062. (c)
Hanamoto, T.; Egashira, M.; Ishizuka, K.; Furuno, H.; Inanaga, J. Tetra-
hedron 2006, 62, 6332. (d) Hanamoto, T.; Koga, Y.; Kido, E.; Kawanami, T.;
Furuno, H.; Inanaga, J. Chem. Commun. 2005, 2041. (e) Hanamoto, T.;
Koga, Y.; Kawanami, T.; Furuno, H.; Inanaga, J. Angew. Chem., Int. Ed.
2004, 43, 3582. (f) Hanamoto, T.; Hakoshima, Y.; Egashira, M. Tetrahedron
Lett. 2004, 45, 7573.
According to a reported procedure for the preparation
of (η2-alkyne)Ti(OiPr)2 from [Ti(OiPr)4/iPrMgCl/acetylene=
1.2:2.4:1], we attempted to generate the corresponding trifluoro-
methylsilylacetylene complex 1a (Scheme 1). To our delight,
the formation of trifluoromethylsilylacetylene complex 1a was
(5) (a) Uneyama, K.; Katagiri, T.; Amii, H. Acc. Chem. Res. 2008, 41, 817.
(b) Nadano, R.; Ichikawa, J. Synthesis 2006, 128. (c) Peng, S.; Qing, F. L.
J. Chem. Soc., Perkin Trans. 1 1999, 3345. (d) Hong, F.; Tang, X.; Hu, C.
J. Chem. Soc., Chem. Commun. 1994, 289. (e) Hanzawa, Y.; Kawagoe, K.;
Kimura, N.; Kobayashi, Y. Chem. Pharm. Bull. 1986, 34, 3953. (f) Drakesmith,
F. G.; Stewart, O. J.; Tarrant, P. J. Org. Chem. 1967, 33, 280.
(6) Yamazaki, T.; Mizutani, K.; Kitazume, T. J. Org. Chem. 1995, 60,
6046.
(4) (a) Hanamoto, T.; Anno, R.; Yamada, K.; Ryu, K.; Maeda, R.; Aoi,
K.; Furuno, H. Tetrahedron 2009, 65, 2757. (b) Hanamoto, T.; Anno, R.;
Yamada, K.; Ryu, K. Tetrahedron Lett. 2007, 48, 3727.
DOI: 10.1021/jo901392n
r
Published on Web 08/28/2009
J. Org. Chem. 2009, 74, 7559–7561 7559
2009 American Chemical Society

Hanamoto and Yamada
JOCNote
SCHEME 1. Generation and Protonation of the Ti(II) Complex
1a
SCHEME 2. Transformation of 4a
the corresponding cis-allylic alcohols in good yields (entries 5
and 6). Interestingly, ketones regardless of whether they were
acyclic, cyclic, or aromatic reacted with 1a to provide a single
regioisomer in each case, albeit in moderate yields (entries
7-9). The regiochemistry of the cis-allylic alcohols was
mainly assigned on the basis of their 19F NMR spectra. As
we expected, the major regioisomer 4 showed a single peak,
indicating that a trifluoromethyl group is attached to a
vinylic carbon having no hydrogen. On the other hand, the
minor regioisomer 5 showed a doublet peak. In addition to
the carbonyl compounds, other electrophiles such as iodine,
iodomethane, chlorotributylstannane, and benzoyl chloride
were examined under the same reaction conditions; however,
no addition products were obtained, and 2 was mostly
obtained after aqueous workup.
TABLE 2. Reaction of 1a with Various Carbonyl Compounds
entry
carbonyl compound
yielda (%)
ratio (4:5)b
1
2
3
4
5
6
7
8
9
benzaldehyde (3a)
4-methylbenzaldehyde (3b)
4-chlorobenzaldehyde (3c)
2-naphthaldehyde (3d)
decanal (3e)
2-ethylbutanal (3f)
acetone (3g)
cyclohexanone (3h)
acetophenone (3i)
77
76
73
43
69
68
58
46
47
86:14
75:25c
89:11
93:7
73:27
88:12
100:0
100:0
100:0
Finally, the transformation of the silyl group in the final
product 4a was briefly examined. The fluoride ion-assisted
desilylation-protonation proceeded giving the correspond-
ing allylic alcohol 6a in 61% yield,5f which means that further
functionalization of the final product should be possible
(Scheme 2).
In summary, we have developed a new protocol for
efficient preparation of trifluomethylated cis-allylic alcohols
in good yields. The reaction proceeds under mild conditions
with a wide range of aldehydes and ketones with high
regioselectivity. This methodology should aid in fluoroor-
ganic synthesis.
aIsolated yield. bDetermined by GC-MS except for entry 2.
cDetermined by 19F NMR.
indirectly supported by hydrolysis of the reaction mixture
exclusively giving the cis-vinylsilane 2 along with a small
amount of 1. When we employed double-fold of reagents to 1
[Ti(OiPr)4/iPrMgCl/acetylene = 2.4:4.8:1], the reaction com-
pletely proceeded giving 2 in 89% yield.7 The stereochemistry of
2 was determined in comparison with the 1H NMR data of the
corresponding trans-vinylsilane.8 Under the same reaction con-
ditions, the reaction with deuterium oxide (D2O) also proceeded
giving cis-bis-deuterated olefin in 75% yield as well as high D
incorporation (96:4).9 With regard to reducing reagent, the use
of BuLi instead of iPrMgCl was not effective for this reaction,
giving almost no desired products.10
With the optimized reaction conditions established, the
scope and limitation of this reaction were continuously
studied. The reaction of 1a with a variety of carbonyl
compounds (3a-i) proceeded efficiently to afford the corre-
sponding cis-allylic alcohols with good regioselectivity. The
regioselectivity was determined by GC-MS analysis using a
crude reaction mixture prior to chromatographic purifica-
tion except for entry 2. The IR spectrum of these alcohols
showed typical hydroxyl group absorption at around 3400
cm-1. The results are summarized in Table 2. A wide range of
aromatic aldehydes were suitable for this transformation in
good yields regardless of electronic and steric effects (entries
1-4). In the same manner, linear and branched aliphatic
aldehydes successfully underwent addition reaction to give
Experimental Section
3,3,3-Trifluoro-1-(dimethylphenylsilyl)propyne6 (1). A 100 mL
two-neck flask equipped with a magnetic stir bar, a stopcock,
and a three-way stopcock was charged with 10 mL of THF
under argon. To this solution were added HMDS (1.76 mL, 8.43
mmol), HMPA (90 μL, 0.517 mmol), and BuLi (2.64 M in
hexane solution, 3.20 mL, 8.45 mmol) dropwise in this order via
syringe at 0 °C. Another 25 mL two-neck flask equipped with a
magnetic stir bar, a stopcock, and a three-way stopcock was
charged with 3 mL of THF under argon. To this solution was
added 2-bromo-3,3,3-trifluoropropene (0.40 mL, 3.87 mmol)
dropwise via syringe at 0 °C. Both solutions were cooled to
-78 °C, and then the second solution was transferred to the first
solution via cannula at this temperature. After the solution was
stirred for 30 min, chlorodimethylphenylsilane (0.58 mL, 3.51
mmol) was added via syringe. After the mixture was stirred for
30 min, hexane (70 mL) was added to the mixture prior to
warming to room temperature. To the resulting solution was
carefully added saturated NH4Cl aqueous solution (15 mL).
After the organic layer was separated, additional extraction with
hexane 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 short-path distilla-
tion to give the desired product 1 as colorless oil (679.6 mg,
85%): bp 30 °C/1 mmHg (bath temperature). Anal. Calcd for
C11H11F3Si: C, 57.87; H, 4.86. Found: C, 58.16; H, 5.15.
(7) (a) Brisdon, A. K.; Crossley, I. R.; Pritchard, R. G.; Sadiq, G.;
Warren, J. E. Organometallics 2003, 22, 5534. (b) Chae, J.; Konno, T.;
Kanda, M.; Ishihara, T.; Yamanaka, H. J. Fluorine Chem. 2003, 120, 185. (c)
Ojima, I.; Fuchikami, T.; Yatabe, M. J. Organomet. Chem. 1984, 260, 335. (d)
Haszeldine, R. N.; Pool, C. R.; Tipping, A. E. J. Chem. Soc., Perkin Trans. 1
1974, 20, 2293.
€
(8) Altnau, G.; Rocsch, L.; Bohlmann, F.; Lonitz, M. Tetrahedron Lett.
1980, 21, 4069.
(9) Urabe, H.; Suzuki, D.; Sato, F. Org. Synth. 2003, 80, 120.
(10) (a) Obora, Y.; Moriya, H.; Tokunaga, M.; Tsuji, Y. Chem. Commun.
2003, 2820. (b) Eisch, J. J.; Gitua, J. N. Organometallics 2003, 22, 24.
(Z)-3,3,3-Trifluoro-1-(dimethylphenylsilyl)propene (2). A 25
mL two-neck flask equipped with a magnetic stir bar, a stop-
cock, and a three-way stopcock was charged with 1 (90.3 mg,
7560 J. Org. Chem. Vol. 74, No. 19, 2009

Hanamoto and Yamada
JOCNote
0.396 mmol) and [Ti(OiPr)4] (0.30 mL, 0.963 mmol) in ether
(7 mL) under argon. To this solution was added iPrMgCl (2.0 M
in ether, 0.95 mL, 1.90 mmol) at -78 °C, and then the solution
was warmed to -50 °C over 30 min, during which time it turned
dark red. After the mixture had been stirred at -50 °C for an
additional 2 h, water (50 μL, 2.8 mmol) was added. After the
mixture was stirred for 1 h, the reaction was quenched with 1 M
HCl. After the organic layer was separated, additional extrac-
tion with hexane/ether=3/1 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 silica gel chromatography (hexane/ether=10/1) to give the
desired product 2 as a colorless oil (80.9 mg, 89%): IR (neat)
3073, 2961, 1626, 1376, 1288, 1199, 1120, 849, 817, 786 cm-1; 1H
NMR (CDCl3, 300 MHz) δ 0.46 (6H, q, J=0.9 Hz), 6.32 - 6.47
(2H, m), 7.35-7.41 (3H, m), 7.48-7.54 (2H, m); 13C NMR
(CDCl3, 75 MHz) δ -2.0 (q, J=2.5 Hz), 122.9 (d, J=271.5 Hz),
127.9, 129.3, 133.5, 133.6 (d, J = 34.9 Hz), 137.6, 141.3 (d,
J=5.6 Hz); 19F NMR (CDCl3, 283 MHz) δ -62.7 (d, J=6.8 Hz);
GC-MS m/z 215 [Mþ - 15 (Me), 0.2], 171 (7), 153 (2), 133 (42),
115 (77), 91 (17), 77 (100). Anal. Calcd for C11H13F3Si: C, 57.37;
H, 5.69. Found: C, 57.75; H, 5.77.
Acknowledgment. We greatly thank F-Tech Co., Ltd. for
a gift of 2-bromo-3,3,3-trifluoropropene.
Supporting Information Available: Characterization of new
compounds 4a-i. The material is available free of charge via the
Internet at http://pubs.acs.org.
J. Org. Chem. Vol. 74, No. 19, 2009 7561