Synthesis of hindered and functionalized 1-CF3 substituted olefins via a carbolithiation-elimination-metalation cascade

Article abstract of DOI:10.1021/jo961356p

Addition of organolithium reagents to trifluoromethyl enol ethers 1a-d and thio enol ethers 2a provided stereoselectively the corresponding trisubstituted fluoroalkenes 3a-d in 70-90% yields. The products could themselves react with organolithium reagents and undergo a vinyl metalation providing, after trapping with an electrophile, tetrasubstituted olefins in excellent yields and with stereoselectivity. This method can be applied to other fluoroalkyl enol ethers (Rf = C₂F₅). The product, tetrasubstituted olefin, can be obtained directly from enol ether with 2 equiv of reagent through a carbolithiation-elimination-metalation cascade.

Full text of DOI:10.1021/jo961356p

J . Org. Chem. 1996, 61, 9111-9114
9111
Syn th esis of Hin d er ed a n d F u n ction a lized 1-CF 3 Su bstitu ted
Olefin s via a Ca r bolith ia tion -Elim in a tion -Meta la tion Ca sca d e
J ean-Pierre Be´gue´, Danie`le Bonnet-Delpon,* Denis Bouvet, and Michael H. Rock
BIOCIS CNRS-URA 1843, Centre d’Etudes Pharmaceutiques, Rue J . B. Cle´ment, Chaˆtenay-Malabry,
F-92296, France
Received J uly 17, 1996X
Addition of organolithium reagents to trifluoromethyl enol ethers 1a -d and thio enol ethers 2a
provided stereoselectively the corresponding trisubstituted fluoroalkenes 3a -d in 70-90% yields.
The products could themselves react with organolithium reagents and undergo a vinyl metalation
providing, after trapping with an electrophile, tetrasubstituted olefins in excellent yields and with
stereoselectivity. This method can be applied to other fluoroalkyl enol ethers (Rf ) C2F5). The
product, tetrasubstituted olefin, can be obtained directly from enol ether with 2 equiv of reagent
through a carbolithiation-elimination-metalation cascade.
Sch em e 1
The addition of organometallic reagents to alkenes is
of considerable interest, in particular for the construction
of stereogenic centers.1 Alkenes are activated toward
carbometalation by the presence of a π-acceptor substitu-
ent on the double bond and/or a heteroatom in the allylic
position.2
In the case of allylic alcohols, since earlier reported
papers,3 great effort has been focused on the achievement
of stereocontrol in the reaction and, more recently, on
enantioselective carbometalation.4,5 In most cases, the
addition of the organic moiety of the organometallic
reagent occurs at the olefinic carbon closest to the alcohol
to give the dimetallic species A, which can be subse-
quently trapped with an electrophile. However, depend-
ing on the substitution pattern of the olefin, and on the
structure of the organometallic agents, the addition can
take place to the Câ carbon, leading to the dimetallic
species B, which readily undergoes an elimination pro-
cess (Scheme 1).6
Sch em e 2
Terminal CF3-substituted olefins7 and thioenol ethers7a
have been shown to react with organolithium reagents
through this latter addition-elimination process provid-
ing gem-difluoroalkenes (Scheme 2). In this reaction, one
fluorine atom of the CF3-group acts as an allylic leaving
group as in the SN2′ reaction of allylic alcohols, and a
cyclic mechanism involving concerted C-C bond forming
and C-F bond breaking has been proposed.
We reported in a preliminary communication that
nonterminal CF3-substituted enol and thioenol ethers,
conjugated with unsaturation in the â-position, also
undergo addition of organolithium reagents but with the
opposite regioselectivity to that of CF3-substituted ter-
minal olefins.8 In this paper, we detail our work on the
reactivity of organolithium reagents with different types
of nonterminal CF3-substituted vinylic compounds.
X Abstract published in Advance ACS Abstracts, November 15, 1996.
(1) Wardell. J . L. Inorganic Reactions and methods VCH: New York,
1988; Vol 11, p 129-142. Knochel P. In Comprehensive Organic
Synthesis; Trost, B., Fleming, I., Eds.; Pergamon: Oxford, 1991; Vol.
4, Chapter 44, p 865.
(2) Richey, H. G., J r.; Erickson, W. F.; Heyn, A. S. Tetrahedron Lett.
1971, 2187-2190. Klein, S.; Marek, I.; Normant, J . F. J . Org. Chem.
1994, 59, 2925-2926.
Resu lts a n d Discu ssion
(3) Crandall, J . K.; Clark, A. C. Tetrahedron Lett. 1969, 325-328.
Crandall, J . K.; Clark, A. C. J . Org. Chem. 1972, 37, 4236-4242.
Felkin, H.; Swierczwski, G.; Tambute, A. Tetrahedron Lett. 1969, 707-
710.
(4) Kocienski, P.; Love, C.; Roberts, D. A. Tetrahedron Lett. 1989,
30, 6753-6756. Kato, T.; Marumoto, S.; Sato, T.; Kuwajima, I. Synlett
1990, 671-672. Marumoto, S.; Kuwajima, I. J . Am. Chem. Soc. 1993,
115, 9021-9024. Houri, A. F.; Didiuk, M. T.; Xu, Z.; Horan, N. R.;
Hoveyda, A. H. J . Am. Chem. Soc. 1993, 115, 6614-6624.
(5) Klein, S.; Marek, I.; Poisson J . F.; Normant, J . F. J . Am. Chem.
Soc. 1995, 117, 8853-8854.
(6) Dimmel, D. R.; Huang, S. J . Org. Chem. 1973, 38, 2756-2759.
(7) (a) Feiring, A. E. J . Org. Chem. 1980, 45, 1962-1964. (b)
Fontanelli R.; Sianesi, D. Ann. Chim. (Roma) 1965, 55, 862-871. (c)
Fuchigami, T.; Shibata, Y.; Suzuki, Y. Tetrahedron Lett 1986, 3173-
3176. (d) Be´gue´, J -P.; Bonnet-Delpon, D.; Rock, M. H. Tetrahedron Lett.
1995, 36, 5003-5006. (e) Hiyama, T.; Obayashi, M.; Sawahata, M.
Tetrahedron lett. 1983, 24, 4113-4116. (f) Kendrick, D. A.; Kolb, M.
J . Fluorine Chem. 1989, 45, 265-272. (g) Be´gue´, J -P.; Bonnet-Delpon,
D.; Rock, M. H. Synlett, 1995, 659-660. (h) Be´gue´, J -P.; Bonnet-Delpon,
D.; Rock, M. H. J . Chem. Soc. Perkin Trans. 1 1996, 1609-1613.
En ol a n d Th ioen ol Eth er s 1 a n d 2. The treatment
of enol ethers (Z)-1a -c and the thioenol ether (Z)-2a ,9
with 1.1 equiv of tert-butyllithium reagent at -78 °C in
diethyl ether or tetrahydrofuran and warming up to 0
°C, resulted in the stereoselective formation of trifluo-
romethyl alkenes (E)-3a -c, and (E)-3a , respectively, in
excellent yields (Scheme 3, Table 1). The E configuration
of alkenes 3 was demonstrated by NOE experiments. For
example, after complete assignment of protons by COSY,
(8) Be´gue´, J -P.; Bonnet-Delpon, D.; Rock, M. H. Tetrahedron lett.
1996, 37, 171-174.
(9) Be´gue´, J -P.; Bonnet-Delpon, D.; Mesureur, D.; Ne´e, G.; Wu S.
W. J . Org. Chem. 1992, 57, 3807-3814. Be´gue´, J -P.; Bonnet-Delpon,
D.; Kornilov, A. Org. Syn., in press. Be´gue´, J . P.; Bonnet-Delpon, D.;
M’Bida, A. Tetrahedron Lett. 1993, 34, 7753-7754.
S0022-3263(96)01356-4 CCC: $12.00 © 1996 American Chemical Society

9112 J . Org. Chem., Vol. 61, No. 26, 1996
Begue et al.
Sch em e 3
F igu r e 1.
of halides, which take place only with electron-deficient
olefins, where a good leaving group is â to an electron-
withdrawing substituent.16 Since in reactions of ethyl-
enic compounds with organolithium reagents, metalation
of the double bond can compete with carbometalation,
the formation of alkenes 3 could be envisaged through
the formation of a vinyl anion followed by elimination of
lithium ethoxide, leading to the corresponding alkynes,
and a further stereoselective carbolithiation. Such a
process which requires 2 equiv of organolithium reagent
has been ruled out.
Formation of 3-5 and 7 can therefore be explained by
the addition of the organolithium reagent to the double
bond to form the intermediate C, followed by elimination
of lithium ethoxide (Figure 1). Compared with terminal
olefins, the displacement of the ethoxy group instead of
the fluorine atom is determined by the regioselectivity
of the initial addition of the reagent to the double bond,
which seems to be directed by the stabilizing â-substitu-
ent. Assuming that this elimination is likely anti, the
carbolithiation of enol and thioenol ethers is cis, leading
to the syn intermediate C, which eliminates into the (E)-
olefins 3-5 and 7.
All our attempts to trap the postulated lithiated
intermediate C by performing the reaction in the pres-
ence of trimethylsilyl chloride and by adding a chelating
agent such as N,N,N′,N′-tetramethylethylene diamine
(TMEDA) failed, indicating that the elimination of lithium
ethoxide is instantaneous, even at -78 °C.
Olefin s 3. We envisaged that CF3-substituted olefins
3 could themselves undergo a further carbolithiation
which, in the case of the same regioselectivity as for
terminal CF3-substituted olefins, would provide gem-
difluoroalkenes or, in the case of the opposite regioselec-
tivity as from enol ethers, would lead to a lithiated
intermediate D (Figure 1). In the absence of leaving
group, D could be trapped by an electrophile.
The olefin 3a was first treated in THF with 1 equiv of
n-butyllithium or tert-butyllithium, from -78 to 0 °C, and
the solution was quenched with one equiv of propanal.
A mixture of the allylic alcohol 8a and starting material
(10/90) was obtained, indicating that a vinylic metalation
occurred from 3a instead of the expected addition (Scheme
4). Neither difluoroalkene nor product resulting from the
lithiated species D could be detected. This lack of
reactivity indicates that the stabilization of the lithium
species by a conjugated group is not the only condition
for the carbolithiation to occur. The presence of a good
leaving group â to the metalated carbon is also a driving
force. The reaction was then performed in hexane at
room temperature in the presence of 1 equiv of TMEDA
and 1 equiv of tert-butyllithium, and the resulting orange-
Ta ble 1. Rea ction of Vin yl Eth er s w ith Or ga n olith iu m
Rea gen ts
vinyl ether
R′Lia
product (% yield)
1a
t-BuLi
n-BuLi
PhLi
t-BuLi
t-BuLi
t-BuLi
t-BuLi
t-BuLi
3a (92)
4a (96)
5a (92)
3b (80)
3c (70)
3d (0)b
3a (80)
7a (82)
1b
1c
1d
2a
6a
a
b
1.1 equiv of R′Li from -78 to 0 °C. Starting material
recovered even with an excess of t-BuLi and in the presence of
TMEDA.
heteronuclear multiple-quantum coherence (hmqc), and
heteronuclear multiple bond coherence (hmbc) experi-
ments, irradiation of the tert-butyl group resulted in a
8% enhancement of ortho aromatic protons. The reaction
was also successful when the phenyl group was replaced
by another conjugated substituent, such as a styryl group
(1b), but failed in the case of an alkyl substituent (1d ).
This reaction can be applied to other fluoroalkyl com-
pounds: under the same conditions, enol ether 6a (Rf )
C2F5) led to the olefin 7a in a 82% yield. Other organo-
lithium reagents such as n-butyllithium, and the less
reactive phenyllithium, also provided the corresponding
trisubstituted alkenes 4a and 5a from 1a . However,
thioenol ether 2a was found to be unreactive toward
phenyllithium. The stereochemistry of 4a was assigned
by analogy of NMR data with those of 3a (δ19F and
3J CF).10 The particular steric strain in 5a did not allow
such an analogy. This E configuration was unambigu-
ously assigned by the observation of a hetero NOE
{19F},1H effect (9%) between CF3 and the ethylenic
proton, which are exceptionally close (2 Å), as shown by
already described X-ray data.11
The reaction is formally a substitution of an ethoxy or
ethylthio group by an alkyl group. Such pseudosubsti-
tutions are unusual for an alkoxy group12,13 but are well
documented for the reactions of organolithium reagents
with gem-difluoroalkenes14 and perfluoroalkenes,15 in
which a fluorine atom is the leaving group. These
reactions are in sharp contrast to vinylic substitutions
(10) Be´gue´, J -P.; Bonnet-Delpon, D.; Mesureur, D.; Oure´vitch, M.
Magn. Reson. Chem. 1991, 29, 675-678.
(11) Ruban, G., Zobel, D., Kossmehl, G., Nuck, R. Chem. Ber. 1980,
113, 3384-3388.
(12) One example of such a “substitution” has been described from
propargyl ethers13a and one from a dienyl ether.13b
(13) (a) Kooyman, J . G. A.; Hendricks, H. P. G.; Montijn, P. P.;
Brandsma, L.; Arens, J . F. Rec. Trav. Chim. 1968, 87, 69-72. (b)
Gaonac’h, O.; Maddaluno, J .; Chauvin, J .; Duhamel, L. J . Org. Chem.
1991, 56, 4045-4048.
(14) Lee, J .; Tsukazaki, M.; Snieckus, V. Tetrahedron Lett. 1993,
34, 415-418. Ishikawa, N.; Nakai, T.; Hayashi, S. Chem Lett. 1980,
935.
(15) Qian, C-P.; Nakai, T. A.C.S. Symp. Ser. 1991, 456, 82-90 and
references cited therein. Hout, J -F.; Muzard, M.; Portella, C. Synlett,
1995, 247-248.
(16) Rappoport. Z. Acc. Chem. Res. 1981, 14, 7-15. Rappoport. Z.
Acc. Chem. Res. 1992, 25, 474-479.

Synthesis of Hindered and Functionalized Olefins
J . Org. Chem., Vol. 61, No. 26, 1996 9113
Sch em e 4
cally hindered (fluoroalkyl)alkenes, the access to which
through a Wittig reaction is limited by the preparation
of hindered fluoroalkyl ketones.18 From these trisubsti-
tuted fluoroolefins, a further treatment with organo-
lithium reagent leads either to a vinyl anion, which can
be trapped, or to a second addition, depending on the
â-substituent.
Exp er im en ta l Section
The compounds 1a , 1c, 1d , and 6a were described in ref 9.
Rea ction of Or ga n olith iu m Rea gen t w ith En ol a n d
Th ioen ol Eth er : Gen er a l P r oced u r e. To a solution of the
enol ethers 1 and 6 or the thioenol ether 2 (1 mmol) in diethyl
ether (10 mL) at -78 °C was added RLi (1 mol equiv). The
solution was stirred for a further 15 min at -78 °C and then
allowed to warm to 0 °C over 1 h. The resulting brown reaction
mixture was then poured into a saturated ammonium chloride
solution (10 mL) and extracted with diether ether (3 × 25 mL).
The combined organic extracts were dried (MgSO4) and
evaporated to give a brown oil which was purified by chroma-
tography on silica gel (eluent: pentane/Et2O 95/5) to the pure
compounds 3-5 and 7.
Sch em e 5
1-((E)-3,3-Dim eth yl-2-(tr iflu or om eth yl)-1-bu ten yl)ben -
zen e (3a ). Enol ether 1a (0.216 g, 1 mmol) in Et2O (10 mL),
treated with tert-butyllithium (0.8 mL of a 1.5 M solution in
hexanes), afforded, after work up and purification, 3a (0.210
1
g, 92%): IR (neat) 1645 cm-1
;
19F NMR δ -60.3; H NMR δ
1.1 (s, 9 H), 7.15 (m, 2H, ortho), 7.3 (m, 4 H, CdCH and Ph);
13C NMR δ 31.3, 35.0, 125.1 (q, J CF ) 277 Hz), 127.0 (para);
1
3
127.5 (ortho), 127.9, 133.5 (q, J CF ) 8.3 Hz), 137.3, 138.2 (q,
red solution was again quenched with one equiv of
propanal. It is possible to perform this reaction in a one-
pot process from 1a . The allylic alcohol 8a was thus
obtained in a 75% yield in the first case and 53% in the
second case. This last yield has not been optimized.
Surprisingly, when performed with 3b, this reaction in
THF or in hexane using TMEDA did not result in a vinyl
metalation but again in an addition, which, after the
subsequent fluoride elimination, provided a gem-difluo-
roalkene (Scheme 5). 13C NMR spectrum exhibits C-F
coupling constants for all of the four ethylenic carbons,
indicating that the double bonds are conjugated. The
structure of 9b was confirmed by C-H (hmbc) and H-F
correlations. In particular, a correlation is observed
between the aromatic protons and a saturated carbon.
The organic moiety of the reagent was therefore intro-
duced on the Cδ carbon. Thus the addition to the
nonhindered R,â-disubstituted double bond of the styryl
substituent of 3b is more favored than metalation of the
trisubstituted double bond.
2J CF ) 24.2 Hz). Anal. Calcd for C13H15F3: C, 68.4; H, 6.6.
Found: C, 68.2; H, 6.75.
The same reaction performed between thioenol ether 2a
(0.232 g, 1 mmol) in Et2O (10 mL) and tert-butyllithium (0.8
mL of a 1.5 M solution in hexanes) afforded, after work up
and purification, 3a (0.183 g, 80%).
1-((Z)-2-(Eth ylsu lfa n yl)-3,3,3-tr iflu or o-l-p r op en yl)ben -
zen e (2a ): IR (neat) 1616 cm-1 19F NMR δ -64.8; 1H NMR δ
;
1.1 (t, 3J ) 7.4 Hz, 3H), 2.7 (q, 3J ) 7.4 Hz, 2H), 7.25-7.7 (1H
1
vinyl and Ph); 13C NMR δ 14.4, 28.5, 123.5 (q, J CF ) 273.7
Hz), 123.6 (q, 2J CF ) 31.3 Hz), 128.4, 129.6, 130.5, 139.4. Anal.
Calcd for C11H11SF3: C, 56.9; H, 4.7. Found: C, 56.6; H, 4.9.
1-((E)-2-(Tr iflu or om eth yl)-1-h exen yl)ben zen e (4a). Enol
ether 1a (0.216 g, 1 mmol) in Et2O (10 mL), treated with
n-butyllithium (0.48 mL of a 2.5 M solution in hexanes),
afforded, after work up and purification, 4a (0.220 g, 96%):
1
IR (neat) 1640 cm-1
;
19F NMR δ -66.9; H NMR δ 0.9 (t, J )
7 Hz, 3 H), 1.3-1.44 (m, 2 H), 1.54-1.70 (m, 2 H), 2.44 (m, 2
H), 7.1 (1 H, CdCH), 7.4 (m, 5 H, C6H5); 13C NMR δ 13.7, 22.7,
26.1, 30.7, 124.9 (q, 1J CF ) 274 Hz), 127.1, 128.4, 128.8, 130.8,
131.5 (q, 2J CF ) 35.9 Hz), 131.9, (q, 3J CF ) 6.4 Hz), 134.8. Anal.
Calcd for C13H15F3: C, 68.4; H, 6.6. Found: C, 68.6; H, 6.8.
The same reaction performed between thioenol ether 2a
(0.232 g, 1 mmol) in Et2O (10 mL) and n-butyllithium (0.48
mL of a 2.5 M solution in hexanes) at -78 °C afforded, after
work up and purification, 4a (0.182g, 80%).
Con clu sion
We have demonstrated that the course of the reaction
of nonterminal CF3-substituted vinylic compounds with
organolithium reagents is strongly dependent on the
substitution pattern. From enol and thioenol ethers,
providing a conjugated substituent is present in the
â-position, a stereoselective carbolithiation occurs. An
instantaneous stereoselective elimination of lithium ethox-
ide/thioethoxide provided E-trisubstituted fluoroolefins
in high yields, with the introduction of the organic moiety
of the reagent on the carbon initially bearing the ethoxy/
thioethoxy group. This reaction offers an alternative
route to the Wittig reaction between a trifluoromethyl
ketone and an ylide which generally provides the opposite
stereoisomer.17 Furthermore, it allows a route to steri-
(E)-3,3,3-Tr iflu or o-1,2-d ip h en yl-1-p r op en e (5a ). Enol
ether 1a (0.216 g, 1 mmol) in Et2O (10 mL), treated with
phenyllithium (0.6 mL of a 2 M solution in Et2O) afforded, after
work up and purification, 5a (0.220 g, 92%): mp 62 °C (lit.11
recrystallization from MeOH, mp 61.5-62 °C); IR (neat) 1649
1
cm-1
;
19F NMR δ -66.0; H NMR δ 7.0-7.6 (m, 11H, CdCH
and Ph); 13C NMR δ 122.0 (q, J CF ) 274 Hz), 127.3, 127.4,
128.4, 128.7, 128.8, 128.9, 129.0, 129.1, 129.6, 130.0, 130.2,
130.5 (q, 2J CF ) 28.6 Hz), 132.7 (q, 3J CF ) 6.8 Hz), 141.4. Anal.
Calcd for C15H11F3: C, 72.6; H, 4.4. Found: C, 73.8; H, 4.8.
1-((1E,3Z,E)-4-Eth oxy-5,5,5-tr iflu or o-1,3-p en ta d ien yl)-
ben zen e (1b). A 5 g portion of enol ether 1b was prepared
according to ref 9 and was obtained from 17.9 g of (E)-3-
phenylprop-2-enephosphonium salt, 1.1 g of NaH and 4.7 g of
1
(17) Camps, F.; Sanchez, F-J , Messeguer, A. Synthesis 1988, 823-
826.
(18) Be´gue´, J -P.; Bonnet-Delpon, D. Tetrahedron 1991, 47, 3207-
3258.

9114 J . Org. Chem., Vol. 61, No. 26, 1996
Begue et al.
ethyl trifluoroacetate in a 60% yield of a Z/E mixture (90/10):
oil which was purified by chromatography on silica gel (elu-
ent: pentane/Et2O 90:10) to the pure compound 8a (0.213 g,
75%).
IR (neat) 1650, 1619 cm-1
;
19F NMR δ -65.3 (E), -68.9 (Z);
3
1H NMR δ 1.3/1.31 (Z) (t, 3 H, J ) 7 Hz), 3.8/3.9 (Z) (q, 2 H,
3
J ) 7 Hz), 5.75/6.25 (Z) (d, J ) 10.9 Hz, dCH), 6.4/6.6 (Z) (d,
On e-P ot P r ocess. A solution of 1a (0.216 g, 1 mmol) and
N,N,N′,N′-tetramethylethylenediamine (0.234 g, 1 mmol) in
hexane (10 mL) was treated with 2 equiv of tert-butyllithium
(1.2 mL of a 1.5 M solution in hexanes) at room temperature.
After 5 min, a red color appeared, propanaldehyde (58 mg, 1
mmol) was added, the solution was stirred for 30 min. Workup
afforded a mixture (80/20) of 8a and 1a . After purification,
pure 8a was obtained (0.151 g, 53%). The yield has not been
3J ) 15.8 Hz, dCH), 6.85 (dd, 3J ) 10.9 Hz, 3J ) 15.8 Hz,
dCHCHdCH), 7.2 (5H); 13C NMR δ 14.4/15.5 (Z), 64.9 (Z)/
3
70.6 , 108.5, 118.7, 119.0 (q, J CF ) 4.2 Hz), 120.2, 122.0 (q,
1J CF ) 275 Hz), 126.5, 127.0, 128.6, 129.6, 136.6, 142.5 (Z)/
2
143.2 (q, J CF ) 29.3). Anal. Calcd for C13H13OF3: C, 64.46;
H, 5.37. Found: C, 64.57; H, 5.44.
1-((1E,3E)-5,5-Dim eth yl-4-(tr iflu or om eth yl)-1,3-h exa d i-
en yl)ben zen e (3b). Enol ether 1b (0.242 g, 1 mmol) in Et2O
(10 mL), treated with tert-butyllithium (0.8 mL of a 1.5 M
solution in hexanes) at -78 °C, afforded, after work up and
optimized: IR (CCl4) 3640 cm-1, 1635 cm-1
;
19F NMR δ -48.9
(s); 1H NMR δ 0.8 (t, J ) 6 Hz, CH3), 0.9 (s, 9 H,), 1.5 (m, 2 H,
CH2), 4.6 (1H, CHOH), 6.9-7.2 (m, 5 H, Ph); 13C NMR δ 10.2,
purification, 3b (0.203 g, 80%): IR (neat) 1631, 1606 cm-1 19F
;
4
1
28.9, 31.5, 37.2, 73.1 (q, J CF ) 4.6 Hz, CHOH), 125.5 (q, J CF
NMR δ -60.3, -54.0 (1E,3Z, 5%); 1H NMR δ 1.48 (s, 9 H),
2
) 282 Hz), 126.9, 127.0, 127.1, 129.7, 130.6, 135.2 (q, J CF
)
6.80 (m, 2 H), 7.6 (m, 6 H, CdCH and Ph); 13C NMR δ 31.5,
3
23.5 Hz) 136.6, 149.2 (q, J CF ) 2.9 Hz). Anal. Calcd for
1
3
34.3, 125.4 (q, J CF ) 274 Hz), 127.1, 128.9, 132.1 (q, J CF ) 8
C16H21F3O: C, 67.13; H, 7.34. Found: C, 67.30; H, 7.35.
2
Hz), 135.7 (q, J CF ) 29.8 Hz), 136.6, 139.4. Anal. Calcd for
1-((2E)-1,4-Di-ter t-bu tyl-5,5-d iflu or o-2,4-p en ta d ien yl)-
ben zen e (9b). A solution of 3b (0.254 g, 1mmol) in THF (10
mL) was treated with tert-butyllithium (0.66 mL of a 1.5 M
solution in hexanes) at -78 °C. The solution was stirred for
15 min at -78 °C and then warmed to room temperature. The
mixture was quenched with ammonium chloride and extracted
with dichloromethane (3 × 25 mL). The combined organic
extracts were dried (MgSO4) and evaporated to give a yellow
oil which was purified by chromatography on silica gel (pen-
tane) to give the pure compound 9b (0.175g, 60%): IR (neat)
C15H17F3: C, 70.9; H, 6.7. Found: C, 70.7; H, 6.9.
1-((E)-3,3-Dim et h yl-2-(t r iflu or om et h yl)-1-b u t en yl)-4-
m eth oxy)ben zen e (3c). Enol ether 1c (0.246 g, 1 mmol) in
Et2O (10 mL), treated with tert-butyllithium (0.8 mL of a 1.5
M solution in hexanes) at -78 °C, afforded, after work up and
purification, 3c (0.210 g, 70%): IR (neat) 1640 cm-1
;
19F NMR
1
δ -60.0; H NMR δ 1.0 (s, 9 H), 3.8 (s, 3H), 6.7-7.3 (m, 5 H,
CdCH and Ph); 13C NMR δ 31.4, 35.0, 55.3, 110.1, 125.2 (q,
3
1J CF ) 278 Hz), 126.7, 127.4, 132.0, 133.4 (q, J CF ) 8 Hz),
138.6 (q, 2J CF ) 23 Hz). Anal. Calcd for C14H17OF3: C, 65.11;
H, 6.59. Found: C, 64.92; H, 6.6.
1649, 1602 cm-1 19F NMR δ -88.2 (dd, 2J FF ) 49.6 Hz, 4J FH
; )
2 5 1
7.6 Hz, 1F), -89.9 (dd, J FF ) 49.6 Hz, J FH ) 2.2Hz, 1F); H
1-((E)-2-ter t-Bu tyl-3,3,4,4,4-p en ta flu or o-1-bu ten yl)ben -
zen e (7a ). Enol ether 6a (0.266 g, 1 mmol) in Et2O (10 mL),
treated with tert-butyllithium (0.8 mL of a 1.5 M solution in
hexanes), afforded, after work up and purification, 7a (0.228
5
NMR δ 0.87 (s, 9H, 3 × CH3), 1.06 (d, J HF ) 2 Hz, 9H, 3 ×
3
3
CH3), 3.03 (d, J ) 9.9 Hz, 1H, CHPh), 5.6 (dd, J ) 15.4 Hz,
4J HF ) 7.6 Hz, 1H, CHdCHCHPh), 6.11 (ddd, 3J ) 15.4 Hz,
3J ) 9.9Hz, J HF ) 2.2 Hz, 1H, CHdCHCHPh), 7.2 (m, 5H);
5
g, 82%): IR (neat) 1645 cm-1 19F NMR δ -82.0 (CF3), -104.1
;
13C NMR δ 28.0, 29.6 (dd, J CF ) 4.3 Hz, J CF ) 1.9 Hz, 3 ×
4
4
(CF2); 1H NMR δ 1.0 (s, 9 H), 7.1-7.4 (m, 6H, CdCH and Ph);
2
2
CH3), 32.0, 34.2, 60.5, 98.4 (dd, J CF ) 14.9 Hz, J CF ) 11.2
13C NMR δ 31.6, 37.0, 126.9, 127.3, 127.8, 136.5 (qt, 3J CF ) 10
3
3
Hz), 122.3 (dd, J CF ) 5.2 Hz, J CF ) 1.7 Hz), 125.9, 127.6,
4
2
Hz, J CF ) 2 Hz), 138.9 (t, J CF ) 20 Hz), CF2 and CF3 not
observed. Anal. Calcd for C14H15F5: C, 60.4; H, 5.4. Found:
C, 60.5; H, 5.7.
4
4
129.1, 135.8 (dd, J CF ) 5.8 Hz, J CF ) 2.5 Hz), 142.6, 153.2
1
1
(dd, J CF ) 285.7 Hz, J CF ) 286.3 Hz). Anal. Calcd for
C19H26F2: C, 78.1; H, 8.9. Found: C, 78.2; H, 8.96.
(Z)-1-Eth yl-4,4-d im eth yl-2-p h en yl-3-(tr iflu or om eth yl)-
2-p en ten yl Alcoh ol (8a ). A solution of 3a (0.228 g, 1mmol)
and N,N,N′,N′-tetramethylethylenediamine (0.234 g, 1 mmol)
in hexane (10 mL) was treated with tert-butyllithium (0.6 mL
of a 1.5 M solution in hexanes) at room temperature. After 5
min, a red color appeared, propanaldehyde (58 mg, 1 mmol)
was added, and the solution was stirred for 30 min. The
mixture was quenched by ammonium chloride and extracted
with dichloromethane (3 × 25 mL). The combined organic
extracts were dried (MgSO4) and evaporated to give a yellow
Ack n ow led gm en t. This work was supported by
CNRS and European Community Network on Synthesis
and Molecular Recognition of Selectively Fluorinated
Bioactive Molecules (ERBCHRXCT930279). We thank
Miche`le Oure´vitch for her invaluable high-field NMR
experiments.
J O961356P