Reaction of Baylis-Hillman adducts with fluorinated silanes

Article abstract of DOI:10.1002/ejoc.201001051

Reactions of acylated Baylis-Hillman adducts bearing nitrile, ester, or ketone groups with C₆F₅-substituted silicon reagents Me_nSi(C₆F₅)_4-n (n = 1-3) have been studied. The reactions are in

Full text of DOI:10.1002/ejoc.201001051

FULL PAPER
DOI: 10.1002/ejoc.201001051
Reaction of Baylis–Hillman Adducts with Fluorinated Silanes
Artem A. Zemtsov,[a] Vitalij V. Levin,[a] Alexander D. Dilman,*[a] Marina I. Struchkova,[a]
Pavel A. Belyakov,[a] Vladimir A. Tartakovsky,[a] and Jinbo Hu[b]
Keywords: Fluorine / Silanes / Michael addition / Baylis–Hillman adducts / Chemoselectivity
Reactions of acylated Baylis–Hillman adducts bearing nitrile,
ester, or ketone groups with C6F5-substituted silicon reagents
MenSi(C6F5)4–n (n = 1–3) have been studied. The reactions
are initiated by Bu4NOAc (5 mol-%) in MeCN or DMF under
mild conditions and afford products of allylic substitution of
the acetoxy group by the C6F5 carbanion in good yields. Pre-
dominant or exclusive formation of one geometrical isomer
was observed in all cases (Z for nitriles, E for esters and
ketones). For substrates containing carbonyl groups, nucleo-
philic attack of the C6F5 carbanion chemoselectively oc-
curred at the C=C bond. Reactions of acylated Baylis–Hill-
man adducts with Me3SiCF3 were found to be inefficient, as
the CF3 carbanion had the propensity to attack the C=O bond
of substrates with ester or ketone substituents.
nitrile groups[6] or Meldrum’s acid,[7] which renders such
substrates highly electrophilic.[8] Here we report the results
of studies to extend the scope of the Michael reaction by
using fluorinated silanes. We employed compounds of type
A as Michael acceptors, which can be obtained from alde-
hydes and simple electron-deficient alkenes by Baylis–Hill-
man reactions followed by acylation [Equation (2)].
Introduction
Organosilanes bearing a perfluorinated group have be-
come valuable reagents for the introduction of fluorinated
substituents into organic molecules.[1,2] Thus, in the pres-
ence of basic activators (e.g., fluoride or acetate ions) the
silicon reagents are activated to generate pentacoordinate
species, which serve as a source of fluorinated carbanion in
reactions with electrophiles [Equation (1)].
(2)
The presence of the acetoxy group in substrates A serves
two purposes. Firstly, due to its electron-withdrawing effect,
it enhances the electrophilicity of the alkene double bond.[9]
Secondly, after the nucleophilic addition at the C=C bond,
the acetoxy group is eliminated, and if acetate anion serves
as a Lewis base,[3b] the process can become catalytic in acet-
ate.[10] (Scheme 1).
(1)
Although the use of silanes for the nucleophilic addition
of fluorinated groups to C=O and C=N bonds has been
extensively investigated,[1,3,4] the addition to electron-de-
ficient alkenes is still considered a challenging problem. The
difficulties in performing such transformations are associ-
ated with low reactivity of typical Michael acceptors bear-
ing nitrile or ester substituents, whereas α,β-unsaturated
aldehydes and ketones undergo preferential attack at the
carbonyl carbon atom.[5]
Recently, we reported an approach for the nucleophilic
trifluoromethylation of alkenes bearing either two geminal
[a] N. D. Zelinsky Institute of Organic Chemistry,
119991 Moscow, Leninsky Prospect 47, Russian Federation
Fax: +7-499-135-53-28
E-mail: adil25@mail.ru
[b] Key Laboratory of Organofluorine Chemistry,
Shanghai Institute of Organic Chemistry,
Chinese Academy of Sciences,
Scheme 1. Proposed reaction mechanism.
345 Ling-Ling Road, Shanghai 200032, P. R. China
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201001051.
The overall transformation may be viewed as an allylic
SN2Ј substitution leading to products B. The trisubstituted
Eur. J. Org. Chem. 2010, 6779–6785
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
6779

A. D. Dilman et al.
FULL PAPER
double bond of products B is anticipated to be less reactive Table 1. Pentafluorophenylation of nitrile 1a.
than the terminal double bond of A. Another important
variable is the nature of the silicon reagent. Indeed, we have
previously shown that the efficiency of reactions involving
silanes is strongly influenced by the number of perfluori-
nated and heteroatom groups borne by the silicon.[11] In the
Entry
Silane[a]
Initiator (equiv.) Solvent
T
[°C]
Time
[h]
Yield
[%][b]
case of the trifluoromethyl group, the only available silane
is Me3SiCF3 (Ruppert–Prakash reagent). Synthesis of other
CF3-containing silanes is complicated.[12] At the same time,
various C6F5-substituted silanes can be readily synthesized
by using pentafluorophenylmagnesium bromide and chlo-
rosilanes.[13] Inspired by this realization, we first studied re-
actions of substrates A with C6F5-substituted silanes and
then with the Ruppert–Prakash reagent.
1
2
3
4
5
6
7
8
9
MeSi(RF)3
MeSi(RF)3
MeSi(RF)3
MeSi(RF)3
MeSi(RF)3 Et3N·HF (0.05) DMF
MeSi(RF)3 Bu4NOAc (0.02) DMF
MeSi(RF)3 Bu4NOAc (0.02) THF
MeSi(RF)3 Bu4NOAc (0.05) MeCN
NaOAc (0.1)
NaOAc (0.1)
NaOAc (0.1)
DABCO (0.05)
DMF
DMF
DMF –20
DMF –20
20
0
2
3
36
52
72
57
47
56
46
63
18
18
18
18
18
18
0
0
0
0
MeSi(RF)3 Bu4NOAc (0.05) MeCN –20
18 82[c]
10
11
12
13
14
Me2Si(RF)2 Bu4NOAc (0.05) DMF
Me2Si(RF)2 Bu4NOAc (0.05) MeCN
0
0
0
18
18
18
18
18
24
40
Results and Discussion
Me3SiRF
FSi(RF)3
Bu4NOAc (0.05) MeCN
Bu4NOAc (0.05) MeCN 20
14
[d]
–
Nitrile 1a was selected as a model substrate and its
pentafluorophenylation was carried out. Silanes were em-
ployed in ratios leading to 1.5 equivalents of C6F5 per
equivalent of substrate (Table 1). The addition of sodium
acetate (10 mol-%) to a solution of 1a and MeSi(C6F5)3 in
DMF at room temperature was exothermic, leading to com-
plete consumption of starting 1a. Disappointingly, product
2a was obtained in only 36% yield under these conditions.
The reaction led predominantly to a complex mixture
(Table 1, Entry 1). Lowering the reaction temperature to
–20 °C led to a doubling of the yield of 2a although longer
reaction times were necessary (Table 1, Entry 3). To screen
the effectiveness of different solvents, we resorted to the ex-
clusive use of tetrabutylammonium acetate as the acetate
source given its high solubility in a variety of media.[3b] It
was ultimately determined that the cleanest reaction oc-
curred in MeCN using 0.05 equivalents of acetate and fur-
nishing 2a in 82% isolated yield as a 94:6 mixture of Z/E
isomers (Table 1, Entry 9).
Attempts to vary the silicon reagent did not lead to fur-
ther yield improvement (Table 1, Entries 10–14). For exam-
ple, silanes Me2Si(C6F5)2 and Me3SiC6F5 reacted readily
but provided complex mixtures, whereas the use of (EtO)3-
SiC6F5 afforded lower yields. Notably, the use of fluoro-
silane FSi(C6F5)3, which has been shown to be the most
effective silane in reactions mediated by weak Lewis ac-
ids,[11] was completely unproductive.
(EtO)3SiRF Bu4NOAc (0.05) MeCN
0
73
[a] RF = C6F5, MeSi(RF)3 (0.5 equiv.); Me2Si(RF)2 (0.75 equiv.);
Me3SiRF (1.5 equiv.); FSi(RF)3 (0.5 equiv.); (EtO)3SiRF (1.5 equiv).
[b] Determined by NMR spectroscopy with internal standard, un-
less otherwise noted. [c] Isolated yield. [d] No reaction.
tion. The assignment of configuration was made on the ba-
sis of 2D NOESY data for 2a,b,d–f; the configurations of
2c and 2g were assigned by analogy to the former products.
Table 2. Pentafluorophenylation of nitriles 1.
Entry
R
Time
[h]
2
Yield
Z/E
94:6
93:7
Ͼ99:1
Ͼ99:1
91:9
of 2 [%][a]
1
2[b]
3
Ph
18
6
3
72
72
18
20
2a
2b
2c
2d
2e
2f
82
80
93
85
81
71
77
4-MeOC6H4
4-NO2C6H4
1-naphthyl
2-furyl
4
5
6[b]
7[b]
Et
96:4
86:14
cyclohexyl
2g
[a] Isolated yield of Z and E isomeric mixture. [b] Reaction per-
formed at 0 °C.
Under the optimized conditions, a series of nitriles 1 was
subjected to pentafluorophenylation using MeSi(C6F5)3
[14]
(Table 2). The rate of the reaction was found to be sensitive
to the nature of the substituent R of substrates 1. Electron-
We next evaluated the reactivity of substrates in which
rich systems or, most notably, substrates with aliphatic the double bond was activated by ester or keto groups
groups were found to react slowly (e.g., Table 2, Entries 6 (Table 3). The reaction of methyl ester 3a (R = Ph) with
and 7). Nevertheless, good yields of products could be MeSi(C6F5)3 afforded only 50% yield of desired product 4a
achieved for all substrates. The Z isomers of 2 were formed regardless of temperature, solvent, and amount of activator
predominantly in all cases. The preference for Z isomer for- (Table 3, Entries 1–4). The use of other silanes in DMF led
mation can be rationalized by the greater thermodynamic to increased yields with the optimum case being with Me3-
stability of these isomers relative to the corresponding E SiC6F5 (Table 3, Entry 9). Ester substrates 3b–f were also
isomers, which suffer from strong 1,3-allylic interactions be- subjected to the optimized pentafluorophenylation condi-
tween the R and CH2 groups during the course of the reac- tions and products 4b–f were furnished in high yield
6780
www.eurjoc.org
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2010, 6779–6785

Reaction of Baylis–Hillman Adducts with Fluorinated Silanes
Table 3. Pentafluorophenylation of substrates 3 and 5.
Entry
Z
R
Sub-
strate
Silane
(equiv.)
Solvent
T
[°C]
Time
[h]
Conv.
[%]
Product
Yield[a]
[%]
E/Z
[b]
1
2
CO2Me
Ph
3a
3a
3a
3a
3a
3a
3a
3a
3a
3b
3c
3d
3e
3f
5a
5a
5a
5a
5b
5c
MeSi(C6F5)3 (0.5)
MeSi(C6F5)3 (0.5)
MeSi(C6F5)3 (0.5)
MeSi(C6F5)3 (0.5)
Me2Si(C6F5)2 (0.75)
Me2Si(C6F5)2 (0.75)
Me2Si(C6F5)2 (0.75)
Me3SiC6F5 (1.5)
Me3SiC6F5 (1.5)
Me3SiC6F5 (1.5)
Me3SiC6F5 (1.5)
Me3SiC6F5 (1.5)
Me3SiC6F5 (1.5)
Me3SiC6F5 (1.5)
MeSi(C6F5)3 (0.5)
MeSi(C6F5)3 (0.5)
Me3SiC6F5 (1.5)
Me2Si(C6F5)2 (0.75)
Me2Si(C6F5)2 (0.75)
Me2Si(C6F5)2 (0.75)
MeCN
MeCN
THF
–20
20
–20Ǟ20
20
–20
–20
–20Ǟ0
–20Ǟ0
–20
–20
–20
–20
–20
–20
–20Ǟ0
–20
–20
–20
–20
–20
18
24
18
18
18
18
18
18
18
4
54
41
25
52
91
4a
4a
4a
4a
4a
4a
4a
4a
4a
4b
4c
4d
4e
4f
6a
6a
6a
6a
6b
6c
(27)
85:15
[b]
3[c]
4
5
6
7
8
DMF
MeCN
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
MeCN
DMF
DMF
DMF
DMF
DMF
(25)
(23)
(58)
(55)
(73)
83
85
91
70
80
89:11
92:8
76
89:11
88:12
89:11
87:13
94:6
88:12
Ͼ99:1
82:18
81:19
Ͼ99:1
Ͼ99:1
Ͼ99:1
Ͼ99:1
Ͼ99:1
Ͼ99:1
100
100
100
100
100
100
100
100
100
87
9
10
11
12
13
14
15
16
17
18
19
20
4-NO2C6H4
4-MeOC6H4
2-pyridyl
2-thienyl
Et
18
3
18
20
18
72
8
18
3
21
86
61
62
C(O)Me
Ph
100
100
100
100
(80)[d]
88
4-NO2C6H4
PhCH2CH2
80
88
[a] Isolated yield. The yields in parenthesis were determined by NMR spectroscopy with internal standard. [b] Complex mixture was
formed with yield of desired product Ͻ20%. [c] 0.2 equiv. Bu4NOAc was used. [d] Small amounts of unidentified byproducts were ob-
served.
(Table 3, Entries 10–14). In contrast to nitrile products 2, ciency of particular silane/substrate combinations depends
which bore predominantly the Z configuration, esters 4 on the reactivity of the corresponding five-coordinate sili-
were produced primarily as E isomers with a trans arrange- conate species, which serves as the nucleophile.
ment of the R substituent and the bulkier ester group. The
We next studied reactions of Baylis–Hillman adducts
assignment of configuration of 4a,f was made on the basis with the Ruppert–Prakash reagent, which would lead to
of 2D NOESY; configuration of 4b–e was established by CF3-containing products. Trifluoromethylation of sub-
analogy according to systematic chemical shift differ- strates 1a, 3a, and 5a was performed in the presence of
ences.[15]
Bu4NOAc (5 mol-%), and the results are summarized in
Reactions of ketones 5 proceed to completion even at Scheme 2.
low temperature, reflecting the enhanced reactivity of these
Trifluoromethylation of nitrile 1a gave desired product 7
Michael acceptors compared to esters 3. Brief variation of in moderate yield, and all attempts to improve the efficiency
the silane performed with substrate 5a (R = Ph) demon- of this process were unsuccessful. Ester substrate 3a gave an
strated that Me2Si(C6F5)2 is the ideal C6F5 source. The sub- inseparable mixture containing compounds 8 and 9 (both
strates with aromatic and aliphatic groups reacted cleanly existing as isomeric mixtures) in a combined yield of 30%.
to afford desired products 6a–c in excellent yields exclu- Reaction of ketone 5a with the Ruppert–Prakash reagent
sively as the E isomers (Table 3, Entries 18–20) The E con- furnished 10 as a mixture of two diastereoisomers (1.5:1dr);
figuration of 6a–c was established by 2D NOESY spectra. Michael addition products were not observed. The results
Products arising from nucleophilic addition at the C=O obtained using 3a and 5a suggest that, for reactions with
bond were not detected in crude material.
Me3SiCF3, the increase in C=C bond electrophilicity in
It is clear that for pentafluorophenylation reactions all changing from an ester to a ketone substituent is over-
substrates (nitriles, esters, and ketones) can be effectively whelmed by the increased reactivity of the ketone carbonyl
converted in good yields although different silicon reagents group. This observation contrasts the results obtained with
MenSi(C6F5)4–n (n = 1–3) have to be employed for each type reactions of 3a and 5a with C6F5-substituted silanes in
of substrate. Although the underlying reason for this phe- which the only products observed result from nucleophilic
nomenon is not clear at present, we propose that the effi- attack at the C=C bond.
Eur. J. Org. Chem. 2010, 6779–6785
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
6781

A. D. Dilman et al.
FULL PAPER
General Procedure for Pentafluorophenylation of Esters 3: Tetrabut-
ylammonium acetate (15 mg, 0.05 mmol) was added to a mixture
of 3 (1.0 mmol) and C6F5SiMe3 (360 mg, 1.5 mmol) in DMF
(2 mL) at –20 °C. The reaction mixture was kept at this temperature
for the time given in Table 3 and worked up as described in pro-
cedure A.
General Procedure for Pentafluorophenylation of Enones 5: Tetra-
butylammonium acetate (15 mg, 0.05 mmol) was added to a mix-
ture of 5 (1.0 mmol) and (C6F5)2SiMe2 (294 mg, 0.75 mmol) in
DMF (2 mL) at –20 °C. The reaction mixture was kept at this tem-
perature for the time given in Table 3 and worked up as described
in procedure A.
2-[(Pentafluorophenyl)methyl]-3-phenylacrylonitrile (2a): Yield:
254 mg (82%), E/Z = 6:94. M.p. 68–70 °C. Rf = 0.21 (hexane/
1
EtOAc, 8:1). H NMR (300 MHz, CDCl3, Z isomer): δ = 3.82 (s,
2 H, CH2), 7.11 (s, 1 H, CH), 7.38–7.51 (m, 3 H, CHAr), 7.69–7.81
1
(m, 2 H, CHAr) ppm. H NMR (300 MHz, CDCl3, E isomer): δ =
Scheme 2. Trifluoromethylation reactions.
3.91 (s, 2 H, CH2) ppm. 13C NMR (75 MHz, CDCl3, Z isomer): δ
= 28.6 (m), 106.3, 110.1 (tm, J = 17.9 Hz), 117.5, 128.8, 128.9,
130.7, 132.6, 137.7 (dm, J = 247.6 Hz), 140.9 (dm, J = 247.6 Hz),
145.4 (dm, J = 248.8 Hz), 145.5 ppm. 13C NMR (75 MHz, CDCl3,
E isomer): δ = 22.7, 129.8, 133.2, 146.2 ppm. 19F (282 MHz,
CDCl3, Z isomer): δ = –164.6 (ddd, J = 21.2, 21.2, 8.5 Hz, 2 F,
meta), –157.6 (t, J = 21.2 Hz, F, para), –145.5 (dd, J = 21.2, 8.5 Hz,
ortho) ppm. 19F (282 MHz, CDCl3, E isomer): δ = –164.8 (m, 2F,
meta), –145.1 (dd, J = 21.2, 8.5 Hz, 1 F, ortho) ppm. C16H8F5N
(309.23): calcd. C 62.14, H 2.61, N 4.53; found C 62.07, H 2.65, N
4.35.
Conclusions
The reactions of acylated Baylis–Hillman adducts with
C6F5-substituted silicon reagents proceed under mild condi-
tions by using catalytic amounts of tetrabutylammonium
acetate and furnish the corresponding products in good
yields. However, the optimized conditions require different
silicon reagents MenSi(C6F5)4–n (n = 1–3) for different sub-
strate types. The products are formed either as predomi-
nantly Z isomers in the case of nitrile substrates, or as pre-
dominantly E isomers in case of ester or ketone substrates.
Of special note is that ketone substrates underwent exclus-
ive nucleophilic attack by the C6F5 carbanion at the C=C
bond in preference to the carbonyl group. The reactions of
Baylis–Hillman adducts with Me3SiCF3 are inefficient with
nucleophilic attack at the carbonyl group being a serious
undesirable pathway.
3-(4-Methoxyphenyl)-2-[(pentafluorophenyl)methyl]acrylonitrile
(2b): Yield: 271 mg (80%), E/Z = 7:93. M.p. 50–52 °C. Rf = 0.21
1
(hexane/EtOAc, 5:1). H NMR (300 MHz, CDCl3, Z isomer): δ =
3.78 (s, 2 H, CH2), 3.85 (s, 3 H, OMe), 6.93 (d, J = 8.8 Hz, 2 H,
CHAr), 7.02 (s, 1 H, =CH), 7.72 (d, J = 8.8 Hz, 2 H, CHAr) ppm.
1H NMR (300 MHz, CDCl3, E isomer): δ = 3.87 (s, 3 H, OMe),
3.91 (s, 2 H, =CH), 7.31 (s, 1 H, =CH), 7.36 (d, J = 8.8 Hz, 2 H,
CHAr) ppm. 13C NMR (75 MHz, CDCl3, Z isomer): δ = 28.5, 55.4,
103.1, 110.5 (tm, J = 18.1 Hz), 114.3, 118.1, 125.6, 138.7, 137.7
(dm, J = 247.6 Hz), 140.8 (dm, J = 248.2 Hz), 145.1, 145.4 (dm, J
= 248.2 Hz), 161.5 ppm. 13C NMR (75 MHz, CDCl3, E isomer): δ
= 114.4, 131.2, 145.7 ppm. 19F (282 MHz, CDCl3, Z isomer): δ =
–164.7 (ddd, J = 21.2, 21.2, 6.4 Hz, 2 F, meta), –157.9 (t, J =
21.2 Hz, 1 F, para), –145.6 (dd, J = 21.2, 6.4 Hz, 2 F, ortho) ppm.
19F (282 MHz, CDCl3, E isomer): –164.8 (m, 2 F, meta), –157.7 (t,
J = 21.2 Hz, 1 F, para), –145.2 (dd, J = 21.2, 6.4 Hz, 2 F, or-
tho) ppm. C17H10F5NO (339.26): calcd. C 60.18, H 2.97, N 4.13;
found C 60.11, H 3.03, N 4.07.
Experimental Section
General Remarks: All reactions were performed under an argon
atmosphere. DMF was distilled under vacuum from P2O5 and
stored over 4 Å MS. MeCN was successively distilled from P2O5
and CaH2 and stored over 4 Å MS. Column chromatography was
carried out on Merck silica gel (Kieselgel 60, 230–400 mesh). Silica
gel plates coated with F-254 indicator were used for thin-layer ana-
lytical chromatography and compounds were visualized with UV
and/or acidic aq. KMnO4 solution. NMR spectra were recorded
with a Bruker AM-300 instrument. For minor isomers characteris-
tic signals are given. Microanalyses were performed with a Karlo
Erba 1106 instrument. For the synthesis of Baylis–Hillman acet-
ates, see the Supporting Information.
(2Z)-3-(4-Nitrophenyl)-2-[(pentafluorophenyl)methyl]acrylonitrile
(2c): Yield: 329 mg (93%), E/Z = Ͻ1:99. M.p. 80–82 °C. Rf = 0.22
1
(hexane/EtOAc, 4:1). H NMR (300 MHz, CDCl3): δ = 3.88 (s, 2
H, CH2), 7.18 (s, 1 H, =CH), 7.89 (d, J = 8.8 Hz, 2 H, CHAr), 8.28
(d, J = 8.8 Hz, 2 H, CHAr) ppm. 13C NMR (75 MHz, CDCl3): δ =
28.7, 109.3 (tm, J = 18.1 Hz), 111.2, 116.6, 124.1, 129.6, 137.7 (dm,
J = 247.6 Hz), 138.7, 141.0 (dm, J = 247.1 Hz), 142.6, 145.4 (dm,
J = 248.0 Hz), 148.5 ppm. 19F (282 MHz, CDCl3): δ = –164.0 (ddd,
J = 21.2, 21.2, 8.5 Hz, 2 F, meta),–156.7 (t, J = 21.2 Hz, 1 F, para),
–145.3 (dd, J = 21.2, 8.5 Hz, 2 F, ortho) ppm. C16H7F5N2O2
(354.23): calcd. C 54.25, H 1.99, N 7.91; found C 54.27, H 1.98, N
7.74.
General Procedure for Pentafluorophenylation of Nitriles 1 (Pro-
cedure A): Tetrabutylammonium acetate (15 mg, 0.05 mmol) was
added to a mixture of 1 (1.0 mmol) and (C6F5)3SiMe (272 mg,
0.5 mmol) in MeCN (2 mL) at –20 °C, and the resulting suspension
was stirred under conditions described in Table 2. For workup, the
mixture was quenched with 0.5 m HCl (12 mL), and the aqueous
phase was extracted with Et2O (3ϫ5 mL). The combined organic
layer was filtered through Na2SO4 and concentrated, and the resi-
due was purified by column chromatography.
(2Z)-3-(Naphthalen-1-yl)-2-[(pentafluorophenyl)methyl]acrylonitrile
(2d): Yield: 305 mg (85%). M.p. 126–128 °C. Rf = 0.30 (hexane/
EtOAc, 6:1). 1H NMR (300 MHz, CDCl3): δ = 3.93 (s, 2 H, CH2),
7.48–7.65 (m, 3 H, CHAr), 7.80–7.98 (m, 5 H, 4 CHAr, =CH), 7.90
6782
www.eurjoc.org
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2010, 6779–6785

Reaction of Baylis–Hillman Adducts with Fluorinated Silanes
1
(s, 1 H, CH) ppm. 13C NMR (75 MHz, CDCl3): δ = 28.3 (m), 110.1
(tm, J = 18.1 Hz), 110.2, 117.1, 122.9, 125.3, 126.4, 126.7, 127.0,
128.8, 130.1, 130.7, 131.0, 133.3, 137.7 (dm, J = 247.6 Hz), 140.9
(dm, J = 247.8 Hz), 144.0, 145.3 (dm, J = 248.2 Hz) ppm. 19F
NMR (282 MHz, CDCl3): δ = –161.9 (ddd, J = 21.2, 21.2, 8.5 Hz,
2 F, meta), –154.9 (t, J = 21.2 Hz, 1 F, para), –143.1 (dd, J = 21.2,
8.5 Hz, 2 F, ortho) ppm. C20H10F5NO (359.29): calcd. C 66.86, H
2.81, N 3.90; found C 66.75, H 2.84, N 3.75.
=CH) ppm. H NMR (300 MHz, CDCl3, Z isomer): δ = 3.63 (s, 3
H, OMe), 3.82 (s, 2 H, CH2), 6.72 (s, 1 H, =CH) ppm. 13C NMR
(75 MHz, CDCl3, E isomer): δ = 21.5 (m), 52.1, 112.4 (tm, J =
16.5 Hz), 128.2, 128.5, 128.7, 135.1, 137.3 (dm, J = 251.4 Hz), 139.6
(dm, J = 250.8 Hz), 141.9, 145.4 (dm, J = 250.8 Hz), 167.3 ppm.
19F (282 MHz, CDCl3, E isomer): δ =–164.1 (ddd, J = 21.2, 21.2,
8.5 Hz, 2 F, meta), –158.3 (t, J = 21.2 Hz, 1 F, para), –142.7 (dd, J
= 21.2, 8.5 Hz, ortho) ppm. C17H11F5O2 (342.26): calcd. C 59.66,
H 3.24; found C 59.71, H 3.31.
3-(2-Furyl)-2-[(pentafluorophenyl)methyl]acrylonitrile (2e): Yield:
242 mg (81 %), E/Z = 9:91. M.p. 74–75 °C. Rf = 0.31 (hexane/ Methyl 3-(4-Nitrophenyl)-2-[(pentafluorophenyl)methyl]acrylate
1
EtOAc, 6:1). H NMR (300 MHz, CDCl3, Z isomer): δ = 3.75 (s,
2 H, CH2), 6.52 (dd, J = 3.7, 1.8 Hz, 1 H, OCH=CH), 6.88 (s, 1 (hexane/EtOAc, 6:1). H NMR (300 MHz, CDCl3, E isomer): δ =
H, NC–C=CH), 7.00 (d, J = 3.7 Hz, 1 H, C=CH), 7.55 (d, J = 3.79 (s, 3 H, OMe), 3.88 (s, 2 H, CH2), 7.52 (d, J = 8.8 Hz, 2 H,
1.8 Hz, 1 H, OCH) ppm. H NMR (300 MHz, CDCl3, E isomer): CHAr), 7.91 (s, 1 H, =CH), 8.28 (d, J = 8.8 Hz, 2 H, CHAr) ppm.
4.16 (s, 2 H, CH2), 6.58 (dd, J = 3.7, 1.8 Hz, 1 H, OCH=CH), 6.72
1H NMR (300 MHz, CDCl3, Z isomer): δ = 3.65 (s, 3 H, OMe),
(4b): Yield: 329 mg (85%), E/Z = 94:6. M.p. 104–106 °C. Rf = 0.23
1
1
(d, J = 3.7 Hz, 1 H, C=CH), 6.96 (s, 1 H, NC-C=CH), 7.63 (d, J 6.78 (s, 1 H, =CH), 7.39 (d, J = 8.8 Hz, 2 H, CHAr), 8.17 (d, J =
= 1.8 Hz, 1 H, OCH) ppm. 13C NMR (75 MHz, CDCl3, Z isomer): 8.8 Hz, 2 H, CHAr) ppm. 13C NMR (75 MHz, CDCl3, E isomer):
δ = 27.6, 102.5, 110.1 (tm, J = 18.1 Hz), 112.5, 115.1, 117.5, 132.1, δ = 21.4, 52.4, 111.9–112.1 (m), 123.4, 123.8, 129.0, 129.5, 131.1,
137.6 (dm, J = 247.6 Hz), 140.9 (dm, J = 247.6 Hz), 145.0, 145.4
(dm, J = 247.6 Hz), 149.0 ppm. 19F (282 MHz, CDCl3, Z isomer):
δ = –161.8 (ddd, J = 21.2, 21.2, 8.5 Hz, 2 F, meta), –155.1 (t, J =
21.2 Hz, 1 F, para), –143.1 (dd, J = 21.2, 8.5 Hz, 2 F, ortho) ppm.
19F (282 MHz, CDCl3, E isomer): –162.5 (m, 2 F, meta), –155.6
(t, J = 21.2 Hz, para), –142.5 (dd, J = 21.2, 8.5 Hz, ortho) ppm.
137.3 (dm, J = 252.0 Hz), 139.7 (dm, J = 250.1 Hz), 145.2 (m, J =
250.1 Hz), 147.6, 166.5 ppm. 19F (282 MHz, CDCl3, E isomer): δ
= –163.4 (ddd, J = 21.2, 21.2, 8.5 Hz, 2 F, meta),–157.2 (t, J =
21.2 Hz, 1 F, para), –142.7 (dd, J = 21.2, 8.5 Hz, 2 F, ortho) ppm.
Z isomer: δ = –162.6 (ddd, J = 21.2, 21.2, 8.5 Hz, 2 F, meta),
–156.0 (t, J = 21.2 Hz, 1 F, para), –143.2 (dd, J = 21.2, 8.5 Hz, 2
F, ortho) ppm. C17H10F5NO4 (387.26): calcd. C 52.73, H 2.60, N
3.62; found C 52.69, H 2.54, N 3.61.
C
14H6F5NO (299.20): calcd. C 56.20, H 2.02, N 4.68; found C
56.25, H 2.02, N 4.68.
2-[(Pentafluorophenyl)methyl]pent-2-enenitrile (2f): Yield: 185 mg Methyl 3-(4-Methoxyphenyl)-2-[(pentafluorophenyl)methyl]acrylate
(71%), E/Z = 4:96. Oil. Rf = 0.26 (hexane/EtOAc, 10:1). 1H NMR
(300 MHz, CDCl3, Z isomer): δ = 1.08 (t, J = 7.5 Hz, 3 H, CH3),
(4c): Yield: 339 mg (91%), E/Z = 88:12. Oil. Rf = 0.26 (hexane/
EtOAc, 8:1). H NMR (300 MHz, CDCl3, E isomer): δ = 3.76 (s,
1
2.39 (qd, J = 7.5, 7.4 Hz, 2 H, CH2CH), 3.61 (s, 2 H, CH2), 6.32 3 H, OMe), 3.83 (s, 3 H, CO2Me), 3.97 (s, 2 H, CH2), 6.93 (d, J =
(t, J = 7.4, = Hz, 1 HCH) ppm. 1H NMR (300 MHz, CDCl3, E
isomer): δ = 1.11 (t, J = 7.2 Hz, 3 H, CH3), 6.47 (t, J = 7.7 Hz, 1
H, CH) ppm. 13C NMR (75 MHz, CDCl3, Z isomer): δ = 12.7,
8.8 Hz, 2 H, CHAr), 7.33 (d, J = 8.8 Hz, 2 H, CHAr), 7.84 (s, 1 H,
=CH) ppm. H NMR (300 MHz, CDCl3, Z isomer): δ = 3.67 (s, 3
H, OCH3), 3.78 (s, 2 H, CH2), 3.79 (s, 3 H, CO2Me), 6.67 (s, 1 H,
1
25.0, 26.8 (m), 109.6, 110.2 (tm, J = 18.0 Hz), 116.2, 137.7 (dm, J =CH), 6.82 (d, J = 8.8 Hz, 2 H, CHAr), 7.21 (d, J = 8.8 Hz, 2 H,
= 247.6 Hz), 140.9 (dm, J = 247.2 Hz), 145.3 (dm, J = 248.2 Hz),
151.7 ppm. 19F (282 MHz, CDCl3, Z isomer): δ = –165.0 (ddd, J
= 21.2, 21.2, 8.5 Hz, 2 F, meta), –158.2 (t, J = 21.2 Hz, F, para),
CHAr) ppm. 13C NMR (75 MHz, CDCl3, E isomer): δ = 21.5 (m),
51.9, 55.2, 113.1 (tm, J = 18.2 Hz), 114.0, 126.0, 127.3, 130.7, 137.3
(dm, J = 250.5 Hz), 139.7 (dm, J = 250.9 Hz), 141.5, 145.4 (dm, J
–146.0 (dd, J = 21.2, 8.5 Hz, 2 F, ortho) ppm. 19F (282 MHz, = 250.9 Hz), 160.1, 167.6 ppm. 19F (282 MHz, CDCl3, E isomer):
CDCl3, E isomer: –145.6 (dd, J = 21.2, 8.5 Hz, 2 F, ortho) ppm. δ = –164.2 (ddd, J = 21.2, 21.2, 8.5 Hz, 2 F, meta), –158.6 (t, J =
C12H8F5N (261.19): calcd. C 55.18, H 3.09, N 5.36; found C 55.07,
H 3.17, N 5.37.
21.2 Hz, 1 F, para), –142.9 (dd, J = 21.2, 8.5 Hz, 2 F, ortho) ppm.
C18H13F5O3 (372.29): calcd. C 58.07, H 3.52; found C 58.20, H
3.53.
3-Cyclohexyl-2-[(pentafluorophenyl)methyl]acrylonitrile (2g): Yield:
243 mg (77%), E/Z = 14:86. Oil. Rf = 0.28 (hexane/EtOAc, 12:1). Methyl (2E)-2-[(Pentafluorophenyl)methyl]-3-(pyridin-2-yl)acrylate
1H NMR (300 MHz, CDCl3, Z isomer): δ = 1.06–1.43 (m, 5 H,
5CHCy), 1.63–1.81 (m, 5 H, 5 CHCy), 2.53 (dtt, J = 10.5, 10.5,
3.3 Hz, 1 H, CHCy), 3.59 (s, 2 H, C6F5-CH2), 6.16 (d, J = 9.9 Hz,
(4d): Yield: 240 mg (70 %). M.p. 61–63 °C. Rf = 0.24 (hexane/
EtOAc, 5:1). 1H NMR (300 MHz, CDCl3): δ = 3.80 (s, 3 H, OMe),
4.66 (s, 2 H, CH2), 7.23 (ddd, J = 7.7, 4.7, 1.2 Hz, 1 H, N–
1 H, C=CH) ppm. 1H NMR (300 MHz, CDCl3, E isomer): 3.65 (s, CH=CH), 7.37 (ddd, J = 7.7, 1.2, 1.0 Hz, 1 H, N–C=CH), 7.68–
2 H, CH2), 6.31 (dt, J = 10.3, 1.5 Hz, 1 H, C=CH) ppm. 13C NMR
(75 MHz, CDCl3, Z isomer): δ = 25.1, 25.5, 27.0 (m), 31.5, 31.8,
40.8, 109.9–110.7 (m), 137.4 (dm, J = 247.5 Hz), 140.9 (dm, J =
247.5 Hz), 145.2, (dm, J = 247.5 Hz), 155.4 ppm. 13C NMR
(75 MHz, CDCl3, E isomer): δ = 25.2, 26.2, 31.5, 38.2, 155.2 ppm.
19F (282 MHz, CDCl3, Z isomer): δ = –162.3 (ddd, J = 21.2, 21.2,
8.5 Hz, 2 F, meta),–155.5 (t, J = 21.2 Hz, 1 F, para), –143.4 (dd, J
7.76 (m, 2 H, =CH, N–C=CH–CH), 8.65 (ddd, J = 4.7, 1.8, 1.0 Hz,
1 H, N–CH) ppm. 13C NMR (75 MHz, CDCl3): δ = 21.1 (m), 52.3,
113.9 (tm, J = 16.5 Hz), 123.2, 126.9, 131.2, 136.5, 137.3 (dm, J =
250.6 Hz), 138.2, 139.5 (dm, J = 250.6 Hz), 145.6 (dm, J =
248.5 Hz), 149.3, 154.0, 167.8 ppm. 19F (282 MHz, CDCl3), δ =
–164.8 (ddd, J = 21.2, 21.2, 8.5 Hz, 2 F, meta), –159.4 (t, J =
21.2 Hz, 1 F, para), –142.7 (dd, J = 21.2, 8.5 Hz, 2 F, ortho) ppm.
= 21.2, 8.5 Hz, 2 F, ortho) ppm. 19F (282 MHz, CDCl3, E isomer): C16H10F5NO2 (343.25): calcd. C 55.99, H 2.94, N 4.08; found C
δ = –155.4 (m, 1 F, para), –143.0 (dd, J = 21.2, 8.5 Hz, 2 F, or-
tho) ppm. C16H14F5N (315.28): calcd. C 60.95, H 4.48, N 4.44;
found C 61.04, H 4.54, N 4.45.
55.94, H 2.91, N 4.05.
Methyl 2-[(Pentafluorophenyl)methyl]-3-(2-thienyl)acrylate (4e):
Yield: 279 mg (80%), E/Z = 82:18. M.p. 46–48 °C. Rf = 0.37 (hex-
1
Methyl 2-[(Pentafluorophenyl)methyl]-3-phenylacrylate (4a): Yield:
ane/EtOAc, 8:1). H NMR (300 MHz, CDCl3, E isomer): δ = 3.77
284 mg (83%), E/Z = 87:13. Oil. Rf = 0.24 (hexane/EtOAc, 10:1). (s, 3 H, OMe), 4.12 (s, 2 H, CH2), 7.13 (dd, J = 5.1, 3.7 Hz, 1 H,
1H NMR (300 MHz, CDCl3, E isomer): δ = 3.78 (s, 3 H, OMe),
3.95 (s, 2 H, CH2), 7.31–7.47 (m, 5 H, CHAr), 7.92 (s, 1 H,
S–CH=CH), 7.34 (d, J = 4.7 Hz, 1 H, S–C=CH), 7.52 (d, J =
5.1 Hz, 1 H, S–CH), 8.00 (s, 1 H, =CH) ppm. 1H NMR (300 MHz,
Eur. J. Org. Chem. 2010, 6779–6785
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
6783

A. D. Dilman et al.
FULL PAPER
CDCl3, Z isomer): δ = 3.82 (s, 3 H, OMe), 7.00 (s, 1 H, =CH),
7.03 (dd, J = 5.1, 3.7 Hz, 1 H, S–CH=CH), 7.26 (d, J = 3.7 Hz, 1
H, C=CH), 7.44 (d, J = 5.1 Hz, 1 H, S–CH) ppm. 13C NMR
(75 MHz, CDCl3, E isomer): δ = 22.3 (m), 52.1, 112.5 (tm, J =
16.2 Hz), 123.6, 127.4, 129.7, 133.3, 133.9, 137.4 (dm, J =
250.3 Hz), 137.5, 139.8 (dm, J = 250.3 Hz), 145.6 (dm, J =
250.3 Hz), 175.2 ppm. 19F (282 MHz, CDCl3, E isomer): δ =–164.0
(ddd, J = 21.2, 21.2, 8.5 Hz, 2 F, meta), –158.2 (t, J = 21.2 Hz, 1 F,
para), –142.5 (dd, J = 21.2, 8.5 Hz, 2 F, ortho) ppm. 19F (282 MHz,
CDCl3, Z isomer): δ = –163.3 (ddd, J = 21.2, 21.2, 8.5 Hz, 2 F,
meta), –157.2 (t, J = 21.2 Hz, 1 F, para), –143.2 (dd, J = 21.2,
8.5 Hz, 2 F, ortho) ppm. C15H9F5O2S (348.29): calcd. C 51.73, H
2.60; found C 51.67, H 2.61.
–142.9 (dd, J = 21.2, 8.5 Hz, 2 F, ortho) ppm. C19H15F5O (354.31):
calcd. C 64.41, H 4.27; found C 64.46, H 4.28.
(2Z)-3-Phenyl-2-(2,2,2-trifluoroethyl)acrylonitrile (7) (Procedure B):
Tetrabutylammonium acetate (15 mg, 0.05 mmol) was added to a
mixture of nitrile 1a (201 mg, 1.0 mmol) and CF3SiMe3 (221 μL,
1.5 mmol) in MeCN (2 mL) at –20 °C, and the resulting suspension
was stirred at 0 °C for 18 h. For workup, the mixture was quenched
by the addition of 0.5 m HCl (4 mL) and water (8 mL). The aque-
ous phase was extracted with Et2O (3ϫ5 mL), and the combined
organic layer was filtered through Na2SO4 and concentrated. The
residue was purified by column chromatography (hexane/EtOAc,
5:1) to give the product (187 mg) containing ca. 7% of an unidenti-
fied impurity (based on 19F NMR), thereby corresponding to ca.
40 % yield of compound 7. Subsequent recrystallization from a
large amount of hexane/EtOAc (6:1) afforded analytically pure ma-
terial. M.p. 62–66 °C Rf = 0.27 (hexane/EtOAc, 5:1). 1H NMR
(300 MHz, CDCl3): δ = 3.18 (q, J = 9.6 Hz, 2 H, CH2), 7.17 (s, 1
H, =CH), 7.44–7.52 (m, 3 H, CHAr), 7.76–7.85 (m, 2 H,
CHAr) ppm. 13C NMR (75 MHz, CDCl3): δ = 40.1 (q, J =
31.3 Hz), 99.4, 117.5, 124.6 (q, J = 277.8 Hz), 129.0, 129.1, 131.3,
132.5, 150.2 ppm. 19F (282 MHz, CDCl3): δ = –66.7 (t, J = 9.6 Hz,
3 F, CF3) ppm. C11H8F3N (211.18): calcd. C 62.56, H 3.82, N 6.63;
found C 62.61, H 3.72, N 6.54. The Z configuration was established
by 2D NOESY experiments.
Methyl 2-[(Pentafluorophenyl)methyl]pent-2-enoate (4f): Yield:
253 mg (86%), E/Z = 81:19. Oil. Rf = 0.27 (hexane/EtOAc, 25:1).
1H NMR (300 MHz, CDCl3, E isomer): δ = 1.10 (t, J = 7.5 Hz, 3
H, CH2CH3), 2.34 (qd, J = 7.5, 7.4 Hz, 2 H, CH2CH3), 3.70 (s, 3
H, OMe), 6.92 (t, J = 7.4, 1 HCH) ppm. 1H NMR (300 MHz,
CDCl3, Z isomer): δ = 1.01 (t, J = 7.5, 3 H, CH2CH3), 2.48 (qd, J
= 7.5, 7.4 Hz, 2 H, CH2CH3), 3.72 (s, 3 H, OMe), 5.93 (t, J =
7.5 Hz, 1 H, =CH) ppm. 13C NMR (75 MHz, CDCl3, E isomer): δ
= 12.9, 20.3 (m), 22.2 (t, J = 1.4 Hz), 51.8, 113.2 (tm, J = 18.5 Hz),
126.7, 137.4 (dm, J = 251.4 Hz), 139.8 (dm, J = 251.4 Hz), 145.5
(dm, J = 251.4 Hz), 147.4, 167.2 ppm. 19F (282 MHz, CDCl3, E
isomer): δ =–164.1 (ddd, J = 21.2, 21.2, 8.5 Hz, 2 F, meta),–158.4
(t, J = 21.2 Hz, 1 F, para), –143.1 (dd, J = 21.2, 8.5 Hz, ortho) ppm.
C13H11F5O2 (294.22): calcd. C 53.07, H 3.77; found C 52.89, H
3.65.
Trifluoromethylation of Ester 3a: Production of 3a was performed
in a fashion similar to procedure B, but using DMF as solvent and
stirring at –20 °C for 18 h. The crude material contained equimolar
amounts of compounds 8 and 9 as well as unidentified impurities.
Column chromatography (hexane/EtOAc, 20:1) afforded an insepa-
rable mixture of compounds 8 and 9, which was analyzed by 19F
NMR spectroscopy with PhCF3 as an internal standard.
(3E)-3-[(Pentafluorophenyl)methyl]-4-phenylbut-3-en-2-one (6a):
Yield: 287 mg (88 %). Oil. Rf = 0.22 (hexane/EtOAc, 10:1). 1H
NMR (300 MHz, CDCl3): δ = 2.46 (s, 3 H, CH3), 3.89 (s, 2 H,
CH2), 7.29–7.46 (m, 5 H, CHAr), 7.74 (s, 1 H, =CH) ppm. 13C
NMR (75 MHz, CDCl3): δ = 20.6 (m), 25.7, 113.3 (tm, J =
16.5 Hz), 128.61, 128.63, 128.9, 135.0, 137.2 (dm, J = 250.8 Hz),
137.9, 139.4 (dm, J = 250.8 Hz), 142.1 (dm, J = 250.8 Hz), 142.2,
198.7 ppm. 19F (282 MHz, CDCl3): δ = –164.3 (ddd, J = 21.2, 21.2,
8.5 Hz, 2 F, meta), –158.9 (t, J = 21.2 Hz, 1 F, para), –143.0 (dd, J
= 21.2, 8.5 Hz, 2 F, ortho) ppm. C17H11F5O (326.26): calcd. C
62.58, H 3.40; found C 62.62, H 3.48.
Methyl 3-Phenyl-2-(2,2,2-trifluoroethyl)acrylate (8): Mixture of iso-
mers, 4:1. Oil. Rf = 0.24 (hexane/EtOAc, 20:1). 1H NMR
(300 MHz, CDCl3, major isomer): δ = 3.46 (q, J = 10.2 Hz, 2 H,
CH2CF3), 3.88 (s, 3 H, OMe), 8.01 (s, 1 H, =CH), 7.23–7.50 (m, 5
1
H, Ph) ppm. H NMR (300 MHz, CDCl3, minor isomer): δ = 3.68
(s, 3 H, OMe), 7.00 (s, 1 H, =CH) ppm. 13C NMR (75 MHz,
CDCl3, major isomer): δ = 32.2 (q, J = 30.7 Hz), 52.5, 125.6 (q, J
= 278.1 Hz), 167.6 ppm. 13C NMR (75 MHz, CDCl3, minor iso-
mer): δ = 39.3 (q, J = 30.4 Hz), 52.0, 168.0 ppm. 19F (282 MHz,
CDCl3, major isomer): δ = –64.1 (t, J = 9.5 Hz, 3 F, CF3) ppm.
19F (282 MHz, CDCl3, minor isomer): δ = –66.7 (t, J = 10.6 Hz, 3
F, CF3) ppm.
(3E)-4-(4-Nitrophenyl)-3-[(pentafluorophenyl)methyl]but-3-en-2-one
(6b): Yield: 297 mg (80%). M.p. 108–109 °C. Rf = 0.21 (hexane/
EtOAc, 4:1). 1H NMR (300 MHz, CDCl3): δ = 2.47 (s, 3 H, CH3),
3.82 (s, 2 H, CH2), 7.52 (d, J = 8.6 Hz, 2 H, CHAr), 7.73 (s, 1 H,
=CH), 8.28 (d, J = 8.6 Hz, 2 H, CHAr) ppm. 13C NMR (75 MHz,
CDCl3): δ = 20.6, 25.7, 112.4 (tm, J = 17.3 Hz), 123.9, 129.5, 137.2
(dm, J = 250.2 Hz), 139.2, 139.7 (dm, J = 251.4 Hz), 140.3, 141.6,
145.0 (dm, J = 250.2 Hz), 147.7, 198.0 ppm. 19F (282 MHz,
CDCl3): δ = –163.6 (ddd, J = 21.2, 21.2, 8.5 Hz, 2 F, meta), –157.8
(t, J = 21.2 Hz, 1 F, para), –142.9 (dd, J = 21.2, 8.5 Hz, 2 F, or-
tho) ppm. C17H10F5NO3 (371.26): calcd. C 55.00, H 2.71, N 3.77;
found C 55.14, H 2.71, N 3.64.
1-Phenyl-2-{2,2,2-trifluoro-1-methoxy-1-[(trimethylsilyl)oxy]-
ethyl}prop-2-en-1-yl Acetate (9): Mixture of isomers, 1:1; character-
1
istic signals are given. H NMR (300 MHz, CDCl3): δ = 0.09 and
0.22 (s, 9 H, 2SiMe3), 2.07 and 2.12 (s, 3 H, 2 CH3COO), 3.14 and
3.29 (s, 3 H, 2OMe), 5.54–5.80 (m, 2 H, 2H2C=), 6.50 and 6.51 (s,
1 H, 2 CH-OAc) ppm. 13C NMR (75 MHz, CDCl3): δ = 0.9 (m)
and 1.0 (m), 50.0 and 50.2, 122.2 (q, J = 289.3 Hz) ppm. 19F
(282 MHz, CDCl3): δ = –82.6 and –82.0 (s, 3 F, CF3) ppm.
1-Phenyl-2-{2,2,2-trifluoro-1-methyl-1-[(trimethylsilyl)oxy]-
ethyl}prop-2-en-1-yl Acetate (10): Trifluoromethylation of ketone
5a was performed according to procedure B, but with stirring at
–20 °C for 18 h. The residue was purified by column chromatog-
(3E)-3-[(Pentafluorophenyl)methyl]-6-phenylhex-3-en-2-one (6c):
Yield: 312 mg (88%). Oil. Rf = 0.24 (hexane/EtOAc, 6:1). 1H NMR
(300 MHz, CDCl3): δ = 2.29 (t, J = 7.5 Hz, 3 H, CH3), 2.68 (dt, J
= 7.2, 7.2 Hz, 2 H, PhCH2CH2), 2.82 (t, 2 H, PhCH2), 3.62 (s, 2 raphy (hexane/EtOAc, 20:1). Yield: 173 mg (48%). Mixture of iso-
H, C6F5CH2), 6.79 (t, J = 7.2 Hz, 1 H, CH), 7.15–7.35 (m, 5 H,
mers, 1.5:1. Oil. Rf = 0.28 (hexane/EtOAc, 20:1). 1H NMR
(300 MHz, CDCl3, major isomer): δ = –0.02 (s, 9 H, SiMe3), 1.62
CHAr) ppm. 13C NMR (75 MHz, CDCl3): δ = 19.1, 25.4, 31.0, 34.6,
113.3 (tm, J = 17.8 Hz), 126.4, 128.3, 128.6, 137.2 (dm, J = (s, 3 H, C-CH3), 2.07 (s, 3 H, CH3CO2), 5.58 (s, 1 H, =CHAHB),
251.0 Hz), 138.0, 139.6 (dm, J = 251.1 Hz), 145.0, 145.2 (dm, J = 5.63 (s, 1 H, =CHAHB), 6.65 (CH-OAc), 7.27–7.41 (m, 5 H,
1
251.1 Hz), 198.0 ppm. 19F (282 MHz, CDCl3): δ = –164.0 (ddd, J CHAr) ppm. H NMR (300 MHz, CDCl3, minor isomer): δ = 0.17
= 21.2, 21.2, 8.5 Hz, 2 F, meta), –158.7 (t, J = 21.2 Hz, 1 F, para),
(s, 9 H, SiMe3), 1.60 (s, 3 H, C-CH3), 2.10 (s, 3 H, CH3CO2), 5.48
6784
www.eurjoc.org
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2010, 6779–6785

Reaction of Baylis–Hillman Adducts with Fluorinated Silanes
Tartakovsky, Tetrahedron Lett. 2008, 49, 3108–3111; d) G. K. S.
Prakash, R. Mogi, G. A. Olah, Org. Lett. 2006, 8, 3589–3592;
e) N. V. Kirij, L. A. Babadzhanova, V. N. Movchun, Y. L. Yag-
upolskii, W. Tyrra, D. Naumann, H. T. M. Fischer, H. Scherer,
J. Fluorine Chem. 2008, 129, 14–21; f) for an enantioselective
reaction, see: H. Kawai, A. Kusuda, S. Nakamura, M. Shiro,
N. Shibata, Angew. Chem. Int. Ed. 2009, 48, 6324–6327.
[5] a) R. P. Singh, R. L. Kirchmeier, J. M. Shreeve, Org. Lett. 1999,
1, 1047–1049; b) for attempted Michael addition by complex-
ing the carbonyl group with bulky Lewis acids, see: D. V. Seven-
ard, V. Y. Sosnovskikh, A. A. Kolomeitsev, M. H. Königs-
mann, G.-V. Röschenthaler, Tetrahedron Lett. 2003, 44, 7623–
7627.
[6] A. D. Dilman, V. V. Levin, P. A. Belyakov, M. I. Struchkova,
V. A. Tartakovsky, Tetrahedron Lett. 2008, 49, 4352–4354.
[7] A. A. Zemtsov, V. V. Levin, A. D. Dilman, M. I. Struchkova,
P. A. Belyakov, V. A. Tartakovsky, Tetrahedron Lett. 2009, 50,
2998–3000.
[8] a) T. Lemek, H. Mayr, J. Org. Chem. 2003, 68, 6880–6886; b)
O. Kaumanns, H. Mayr, J. Org. Chem. 2008, 73, 2738–2745.
[9] Compounds A readily react with many nucleophiles, see: a) V.
Singh, S. Batra, Tetrahedron 2008, 64, 4511–4574; b) D. Basa-
vaiah, A. J. Rao, T. Satyanarayana, Chem. Rev. 2003, 103, 811–
892; c) J. N. Kim, K. Y. Lee, Curr. Org. Chem. 2002, 6, 627–
645.
(s, 1 H, =CHAHB), 5.64 (s, 1 H, =CHAHB), 6.59 (CH-OAc), 7.27–
7.41 (m, 5 H, CHAr) ppm. 13C NMR (75 MHz, CDCl3, major iso-
mer): δ = 1.8, 21.2, 22.6 (q, J = 1.4 Hz), 73.5 (q, J = 1.4 Hz), 77.6
(q, J = 29.2 Hz), 118.8 (q, J = 1.4 Hz), 125.20 (q, J = 287.6 Hz),
127.9, 128.1, 128.4, 139.4, 147.0, 169.4 ppm. 13C NMR (75 MHz,
CDCl3, minor isomer): δ = 2.0, 21.3, 23.1 (q, J = 1.4 Hz), 73.2 (q,
J = 1.4 Hz), 77.4 (q, J = 29.0 Hz), 119.0 (q, J = 1.6 Hz), 125.22 (q,
J = 287.6 Hz), 127.5, 128.0, 128.3, 139.1, 147.4, 169.5 ppm. 19F
(282 MHz, CDCl3, major isomer): δ = –81.6 (s, 3 F, CF3) ppm. 19
F
(282 MHz, CDCl3, minor isomer): δ = –80.9 (s, 3 F, CF3).
C17H23F3O3Si (360.44): calcd. C 56.65, H 6.43; found C 56.45, H
6.27.
Supporting Information (see footnote on the first page of this arti-
cle): Synthesis and characterization of starting compounds.
Acknowledgments
This work was supported by the Russian Foundation for Basic Re-
search (project 10–03–91159), the Russian Academy of Sciences
(program #7), and the Federal program “Scientific and Educa-
tional Personnel of Innovative Russia” (project 02.740.11.0258).
[10] Notably, Lewis base mediated reactions of substrates A with
organosilicon reagents have not been described. The only re-
ported process is the palladium-catalyzed coupling with tri-
ethoxysilanes ArSi(OEt)3, which was performed by using
2 equiv. of the fluoride ion, see: G. W. Kabalka, G. Dong, B.
Venkataiah, C. Chen, J. Org. Chem. 2005, 70, 9207–9210.
[11] A. D. Dilman, V. V. Levin, M. Karni, Y. Apeloig, J. Org. Chem.
2006, 71, 7214–7223.
[1] a) G. K. S. Prakash, A. K. Yudin, Chem. Rev. 1997, 97, 757–
786; b) G. K. S. Prakash, M. Mandal, J. Fluorine Chem. 2001,
112, 123–131; c) R. P. Singh, J. M. Shreeve, Tetrahedron 2000,
56, 7613–7632.
[2] K. Uneyama, J. Fluorine Chem. 2008, 129, 550–576.
[3] For detailed studies of trifluoromethylation of the C=O bond,
see: a) G. K. S. Prakash, C. Panja, H. Vaghoo, V. Surampudi,
R. Kultyshev, M. Mandal, G. Rasul, T. Mathew, G. A. Olah, [12] I. Ruppert, K. Schlich, W. Volbach, Tetrahedron Lett. 1984, 25,
J. Org. Chem. 2006, 71, 6806–6813; b) Y. Kawano, N. Kaneko,
T. Mukaiyama, Bull. Chem. Soc. Jpn. 2006, 79, 1133–1145; c)
For enantioselective reaction, see: S. Mizuta, N. Shibata, S. Ak-
iti, H. Fujimoto, S. Nakamura, T. Toru, Org. Lett. 2007, 9,
3707–3710.
2195–2198.
[13] A. D. Dilman, D. E. Arkhipov, A. A. Korlyukov, V. P. Anani-
kov, V. M. Danilenko, V. A. Tartakovsky, J. Organomet. Chem.
2005, 690, 3680–3689.
[14] The use of MeSi(C6F5)3 is quite convenient, as this compound
is tolerant of air and moisture and can be readily prepared
from the cheap reagents C6F5Br and MeSiCl3; see ref.[13]
[15] In the 1H NMR spectra of compounds 4a–f, the chemical shift
of CH= of the E isomer appears ca. 1 ppm downfield relative
to that of the Z isomer.
[4] For recent examples of trifluoromethylation of the C=N bond,
see: a) V. V. Levin, A. D. Dilman, P. A. Belyakov, M. I. Struch-
kova, V. A. Tartakovsky, Eur. J. Org. Chem. 2008, 5226–5230;
b) A. D. Dilman, D. E. Arkhipov, V. V. Levin, P. A. Belyakov,
A. A. Korlyukov, M. I. Struchkova, V. A. Tartakovsky, J. Org.
Chem. 2008, 73, 5643–5646; c) V. V. Levin, M. A. Kozlov, Y.-
H. Song, A. D. Dilman, P. A. Belyakov, M. I. Struchkova, V. A.
Received: July 26, 2010
Published Online: October 27, 2010
Eur. J. Org. Chem. 2010, 6779–6785
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
6785