Stereoselective preparation of E vinyl zirconium derivatives from E or Z enol ethers

Full text of DOI:10.1021/jo005561n

7218
J . Org. Chem. 2000, 65, 7218-7220
Sch em e 1
Ster eoselective P r ep a r a tion of E Vin yl
Zir con iu m Der iva tives fr om E or Z En ol
Eth er s
Annie Liard and Ilan Marek*
Department of Chemistry and Institute of Catalysis Science
and Technology, Technion-Israel Institute of Technology,
Technion City, 32000 Haifa, Israel
chilanm@tx.technion.ac.il
Received J une 28, 2000
Since the discovery of a convenient method for the
generation of low-valent zirconium species, synthetic
organic transformations using “Cp2Zr” have been exten-
sively developed.1 This reagent is easily prepared in situ
by treatment of Cp2ZrCl2 with 2 equiv of n-butyllithium
and is known as the Negishi reagent.1 It has been shown
to exist as a zirconocene-butene complex equivalent 1
(Scheme 1) and reacts with unsaturated compounds to
form the corresponding zirconacycles.2 It is also known
that due to the oxophilic nature of zirconium metal, an
easy elimination of alkoxy group in a â-position can be
induced to form the unsaturated compound.3 Accordingly,
several allylic,4 allenic,5 γ-6and γ,γ-alkoxy allylic7 zirco-
nium species were prepared.8 However, this concept of
â-elimination was only sporadically used for the prepara-
tion of vinyl zirconium derivatives. The initial report was
published by Takahashi et al. by reaction of 2-chloroalk-
ene derivatives9 with 1, and more recently, this strategy
has been successfully applied by Ichikawa and Minami10
for the synthesis of fluorinated vinyl zirconium moieties.
In both cases, a good leaving group was used (halide or
tosyloxy groups) for the â-elimination and no information
on the stereochemical outcome of this reaction was
described.11 As vinyl organometallic derivatives represent
an important class of synthons for the creation of carbon-
carbon bonds, strategies are well described and used.12
However, the latter uses, most of the time, the corre-
sponding halides as starting materials. So, a general
method for the preparation of vinyl organometallic
derivatives from unactivated enol ether is still needed.13
We have recently described that the addition of zir-
conocene or titanocene derivatives to halogeno- or thio-
phenyl alkyne moieties gives, respectively, the function-
alized alkynylmetal14 or metallometallacyclopropene de-
rivatives15 (M ) Ti or Zr), via an “addition-â-elimination”
sequence. In this paper, we report the extension of this
concept to the formation of vinyl organometallic deriva-
tives (Scheme 1). We indeed found that this reaction
occurs smoothly at room temperature in THF by the
addition of the E methoxy enol ether 216 to 1.5 equiv of
zirconocene complex 1. The vinyl zirconium derivative 4
is obtained quantitatively, as determined by gas chro-
matography analysis with internal standard. Hydrolysis
of the reaction mixture give undec-1-ene 5 in 90% yield
after purification as described in Scheme 1.
The formation of a discrete organometallic species was
checked by deuteriolysis of the reaction mixture and only
the E isomer was obtained. The postulated mechanism
for this reaction is that the in situ formed zirconocene
derivative 1 reacts with the methoxy enol ether 2E, via
a ligand exchange, to give an unstable intermediate
methoxyzirconacyclopropane derivative 3.17 Then, 3 un-
dergoes a very fast â-elimination at room temperature
to give the vinyl zirconium derivative 4. An alternative
mechanistic pathway could also be the oxidative addition
of 1 into the vinylic carbon-methoxy bond. However, it
can be ruled out since we do not observe any aromatic
organometallic derivatives by treatment of anisole with
1. Surprisingly, when the same reaction is performed on
the Z enol ether (2Z instead of 2E), the same E isomer 6
is obtained after treatment of the reaction mixture with
MeOD (Scheme 2).18
(1) For reviews: (a) Negishi, E.-I.; Takahashi, T. Bull. Chem. Soc.
J pn. 1998, 71, 755 (b) Negishi, E.-I.; Takahashi, T. Acc. Chem. Res.
1994, 27, 124 (c) Negishi, E.-I.; Kondakov, D. Y. Chem. Soc. Rev. 1996,
26, 417.
(2) Negishi, E.-I. In Comprehensive Organic Synthesis; Paquette, L.
A., Ed.; Pergamon Press: Oxford, 1991; Vol. 5, p 1163.
(3) (a) Rousset, C. J .; Swanson, D. R.; Lamaty, F.; Negishi, E.-I.
Tetrahedron Lett. 1989, 30, 5105. (b) Hoveyda, A. H.; Morken, J . P. J .
Org. Chem. 1993, 58, 4237. (c) Houri, A. F.; Didiuk, M. T.; Xu, Z.;
Horan, N. R.; Hoveyda, A. H. J . Am. Chem. Soc. 1993, 115, 6614. (d)
Takahashi, T.; Suzuki, N.; Kageyama, M.; Kondakov, D. Y.; Hara, R.
Tetrahedron Lett. 1993, 34, 4811.
(4) (a) Ito, H.; Taguchi, T.; Hanzawa, Y. Tetrahedron Lett. 1992, 33.
1295. (b) Hanzawa, Y.; Kiyono, H.; Tanaka, N.; Taguchi, T. Tetrahedron
Lett. 1997, 38, 4615.
(5) Ito, H.; Nakamura, T.; Taguchi, T.; Hanzawa, Y. Tetrahedron
Lett. 1992, 33, 3769.
(6) Ito, H.; Taguchi, T.; Hanzawa, Y. Tetrahedron Lett. 1992, 33,
7873.
(7) (a) Ito, H.; Taguchi, T. Tetrahedron Lett. 1997, 38, 5829. (b) Sato,
A.; Ito, H.; Taguchi, T. J . Org. Chem. 2000, 65, 918.
(8) (a) Hanzawa, Y.; Ito, H.; Taguchi, T. Synlett 1995, 299 (b) Ito,
H.; Nakamura, T.; Taguchi, T.; Hanzawa, Y. Tetrahedron 1995, 51,
4507.
(12) Larock, R. C. Comprehensive Organic Transformations; VCH:
New York, 1989.
(9) Takahashi, T.; Kotora, M.; Fischer, R.; Nishihara, Y.; Nakajima,
K. J . Am. Chem. Soc. 1995, 117, 11039.
(13) C-O bond cleavage of vinyl ethers with Cp2*Sm(thf)2 was
reported: Takaki, K.; Maruo, M.; Kamata, T.; Makioka, Y.; Fujiwara,
Y. J . Org. Chem. 1996, 61, 8332.
(14) Morlender-Vais, N.; Kaftanov, J .; Marek, I. Synthesis 2000, 917.
(15) Averbuj, C.; Kaftanov, J .; Marek, I. Synlett 1999, 11, 1939.
(16) Alexakis, A.; Normant, J . F. Isr. J . Chem. 1984, 24, 113.
(17) All our attempts to isolate the hydrolyzed product of 3 failed.
(18) The reaction of vinyl zirconium derivatives with electrophiles
occurs with retention of the stereochemistry.
(10) (a) Ichikawa, J .; Fujiwara, M.; Nawata, H.; Okauchi, T.;
Minami, T. Tetrahedron Lett. 1996, 37, 8799 (b) Fujiwara, M.;
Ichikawa, J .; Okauchi, T.; Minami, T. Tetrahedron Lett. 1999, 40, 7261.
(11) The only available information was described in ref 9, footnote
20. A J value of 19 Hz was obtained (trans configuration) for a vinyl
zirconium without a description of the stereochemistry of the starting
material.
10.1021/jo005561n CCC: $19.00 © 2000 American Chemical Society
Published on Web 09/28/2000

Notes
J . Org. Chem., Vol. 65, No. 21, 2000 7219
Ta ble 1. Rea ction of 1 w ith En ol Eth er s a n d Tr a p p in g w ith Electr op h iles
starting
materials
entries
R1
R2
OR
OMe
OMe
OMe
E/Z ratio
electrophile
product
yielda (%)
1
2
3
4
5
6
7
8
9
C9H19
C9H19
C9H19
C9H19
C9H19
C9H19
Ph
Ph
Ph
Ph
H
H
H
H
H
H
H
H
H
H
Ph
2
2
2
2
9
10
11
11
11
11
16
75/25
75/25
75/25
75/25
80/20
65/35
70/30
70/30
70/30
70/30
H3O+
MeOD
I2
PhI, CuCl 5% Pd(PPh3)4
MeOD
5
6
7
8
6
90
70
89
75
40
75
70
75
70
60
70
OMe
OtBu
OSitBuMe2
OMe
OMe
OMe
I2
7
H3O+
12
13
14
15
17
MeOD
I2
allylCl 10% CuCl/2LiCl
MeOD
10
11
OMe
OMe
H
a
Yield of isolated products after purification by column chromatography.
Sch em e 2
So, whatever be the stereochemistry of the initial
methoxy-enol ether, the reaction is >99% stereoselective
but nonstereospecific, producing the E vinyl zirconium
in good overall yields.
F igu r e 1.
These transmetalations reactions increase the scope
of this reaction since several electrophiles, classical of the
palladium or copper chemistry, can be introduced for the
alkylation step. However, when tri-and tetrasubstituted
enol ethers were treated with 1, no reaction was ob-
served.
The scope of this reaction is relatively broad since
methoxy enol ethers 2 and 11 derived respectively from
aliphatic (entries 1 to 4, Table 1)16 and aromatic alde-
hydes (entries 7-10, Table 1)19 as well as methoxy enol
ether 16 derived from ketone (entry 11, Table 1) undergo
this formal “methoxyzirconium exchange”. In all cases,
only the E isomer was detected on the crude NMR. To
check if the steric hindrance of the leaving group has an
effect on the stereochemical outcome of this process, the
reaction was also performed on the terbutoxy enol ether
9 (entry 5, Table 1).20 Here again, only the E isomer was
obtained after deuteriolysis albeit in lower yield [only
40% of 6 was obtained after 4 h at room temperature,
the balance being the starting material (with the same
E/Z ratio of 80/20)]. However, when the silyl enol ether
10 (entry 6, Table 1) was treated with 1, the reaction
occurred smoothly to give the corresponding vinyl zirco-
nium derivative, which was trapped by iodine into 7 in
75% yield.21 Moreover, alkenyl zirconocenes participate
in a wide range of ligand transfer reactions after trans-
metalation.22 These can be transmetalated into palladium
species23 and coupled with aromatic iodide (entry 4, Table
1)24 or transmetalated into vinyl copper by addition of a
catalytic amount of copper salt and reacted with classical
electrophiles of copper chemistry as with allyl chloride
(entry 10, Table 1).25
Although the “addition-â-elimination” sequences de-
scribed in Scheme 1 seem to be reasonable, more com-
plicated intermediates are probably involved during the
complexation between the methoxy enol ether and the
zirconocene 1. Our hypothesis is that the initial step
proceeds most likely via a dipolar zirconate species
represented by 18 (Figure 1),26 and then isomerization
should occur to give the trans methoxy zirconacyclopro-
pane 3 before â-elimination. These types of nonconcerted
paths for reactions of alkene with zirconocene complexes
were already discussed in the literature by Negishi and
Takahashi.27 Moreover, no stereoisomerization of 2Z was
observed by using 10 mol % of nBu2ZrCp2, which indicates
that zirconocene 1 is not a catalyst for the isomerization
of methoxy enol ether 2Z into 2E (and no other products
were detected).
To probe further the interaction between the enol
ethers and 1 via 18, we thought that by reducing the
potentiality to form the oxonium of the vinylic oxygen it
would decrease the percentage of isomerization. For this
purpose, we have prepared the vinylic carbamate 19. We
were pleased to find that the treatment of the geometrical
mixture of the vinylic carbamate 19 (E/Z 57:43) with
zirconocene 1, gives, after iodinolysis the corresponding
vinyl iodide 7 in a 60/40 E/Z ratio (Scheme 3). So, indeed
only a slight isomerization was observed.28
(19) Tzalis, D.; Koradin, C.; Knochel, P. Tetrahedron Lett. 1999, 40,
6193.
(20) tert-Butoxy enol ether is easily prepared by carbocupration of
the corresponding alkoxyallene derivative; see ref 16.
(21) Surprisingly, the behavior of the silane, (1,1-dimethylethyl)
dimethyl[[1E/Z)-3-phenyl-1-propenyl]oxy] is totally different and a
kinetic resolution occur; only the E-isomer reacts. These results will
be reported in due course.
(22) Wipf, P.; J ahn, H. Tetrahedron 1996, 52, 12853.
(23) (a) Negishi, E. I.; Van Horn, D. E. J . Am. Chem. Soc. 1977, 99,
3168 (b) Okukado, N.; Van Horn, D. E.; Klima, W. L. Negishi, E. I.
Tetrahedron Lett. 1978, 1027 (c) Negishi, E.; Okukado, N.; King, A.
O.; Van Horn, D. E.; Spiegel, B. J . Am. Chem. Soc. 1978, 100, 2254.
(24) Hazin, P. N.; Bruno, J . W. Organometallics 1987, 6, 918.
(25) Takahashi, T.; Kotora, M.; Kasai, K.; Suzuki, N. Tetrahedron
Lett. 1994, 35, 5685.
(26) An R-elimination and formation of carbene can also be opera-
tive. However, there is no special reason in this case to have only the
E isomer of 4.
(27) Negishi, E.-I.; Choueiry, D.; Nguyen, T. B.; Swanson, D. R.;
Suzuki, N.; Takahashi, T. J . Am. Chem. Soc. 1994, 116, 9751.

7220 J . Org. Chem., Vol. 65, No. 21, 2000
Notes
1
identical with an authentic sample commercially available: H
Sch em e 3
NMR (200 MHz, CDCl3) δ (ppm) 0.87 (t, 3H, J ) 7 Hz), 1.25 (m,
14 H), 2.04 (bq, 2H), 4.97 (m, 2H), 5.77 (m, 1H).
(E)-1-Deu ter iou n d ecen e 6. Purification by chromatography
on silica gel (eluent: hexane) gave a colorless liquid in 70%
yield: 1H NMR (200 MHz, CDCl3) δ (ppm) 0,87 (t, 3H, J ) 7
Hz), 1.25 (m, 14 H), 2.04 (d, 1H, J ) 15.2 Hz), 4.97 (d, 1H, J )
15.2 Hz), 5.77 (m, 1H).
(E)-1-iod ou n d ecen e 7. Purification by chromatography on
silica gel (eluent: hexane) gave a yellow liquid in 89% yield,
spectrally identical with an authentic sample:30 1H NMR (200
MHz, CDCl3) δ (ppm) 0.86 (t, 3H, J ) 7 Hz), 1.24 (m, 14H), 2.03
(bq, 2H, J ) 6.8 Hz), 5.93 (d, 1H, J ) 14.2 Hz), 6.48 (dt, 1H, J
) 6.8, 14.2 Hz).
Sch em e 4
(E)-1-P h en yl-1-u n d ecen e 8. The general procedure was
used as described above. When the formation of the vinyl
zirconium was complete (checked by GC), 0.26 mL of phenyl
iodide (481 mg, 2.36 mmol, 1 equiv), copper chloride (303 mg,
3.06 mmol, 1.3 equiv), and 5% of Pd(PPh3)4 (0.11 mmol, 136 mg)
were added at room temperature. The solution was heated for 3
h at 50 °C. After usual treatment, the residue was purified by
chromatography on silica gel (eluent: hexane) to give a colorless
liquid in 75% yield, spectrally identical with an authentic
sample:31 1H NMR (200 MHz, CDCl3) δ (ppm) 0.86 (t, 3H, J ) 7
Hz), 1.26 (m, 14H), 2.03 (m, 2H), 5.48-5.62 (m, 1H), 5.91-6.02
(m, 1H), 7.05 (m, 5H).
Styr en e 12. Purification by chromatography on silica gel
(eluent: hexane) gave a colorless liquid, yield 70%, spectrally
identical with a commercially available sample: 1H NMR (400
MHz, CDCl3) δ (ppm) 5.29 (d, 1H, J ) 17.5 Hz), 5.8 (d, 1H, J )
17.5 Hz), 6.74-6.81 (dd, 1H, J ) 10.8, 17.5 Hz), 7.24-7.47 (m,
5H).
(E)-â-Deu ter iostyr en e 13. Purification by chromatography
on silica gel (eluent: hexane) gave a colorless liquid, yield 75%,
spectrally identical with an authentic sample:32 1H NMR (200
MHz, CDCl3) δ (ppm) 5.7 (d, 1H, J ) 17.5 Hz), 6.7 (d, 1H, J )
17.5 Hz), 7.11-7.37 (m, 5H).
(E)-â-iod ostyr en e 14. Purification by chromatography on
silica gel (eluent: hexane) gave a yellow liquid, yield 70%,
spectrally identical with an authentic sample:33 1H NMR (400
MHz, CDCl3) δ (ppm) 6.82 (d, 1H, J ) 15.5 Hz), 7.2-7.33 (m,
5H), 7.42 (d, 1H, J ) 15.5 Hz).
Moreover, to confirm that the isomerization occurs
effectively via a dipolar zirconate 18, we have repeated
the same experiment on the commercially available
â-bromo styrene 20 with an E/Z ratio of 88/12. When the
latter is treated first with the zirconocene equivalent 1
at room temperature for 3 h, and then with iodine, the
expected â-iodo styrene 14 is obtained in 77% yield, as a
mixture of two isomers in the same ratio that of the
starting material (E/Z 88/12) (Scheme 4).29 Clearly, when
no oxonium is formed, we do not observe any isomeriza-
tion.
In summary, we have demonstrated the first transfor-
mation of enol ethers into the corresponding vinyl
zirconium derivatives. This reaction occurs stereoselec-
tively, irrespective of the stereochemistry of the starting
material. Moreover, due to the potential transmetalation
step, a large variety of electrophiles can be added.
However, when the vinylic carbamate or the â-bromo
styrene are treated with the zirconocene complex 1, the
isomerization do not take place which can be attributed
to a dipolar zirconate intermediate.
(E)-1-P h en yl-1,4-p en ta d ien e 15. The general procedure was
used as described above. When the formation of the vinyl
zirconium was complete (checked by GC), 0.25 mL of allyl
chloride (3.24 mmol, 1.5 equiv), copper chloride (0.22 mmol, 21
mg, 0.1 equiv), and lithium chloride (4.32 mmol, 183 mg, 2 equiv)
were added at 0 °C. Then, the solution was stirred at 50 °C for
5 h. After usual treatment, the residue was purified by chro-
matography on silica gel (eluent: hexane) to give a colorless
liquid, yield 60%, spectrally identical with an authentic sample:
Further applications of the present reactions will be
reported in due course.
Exp er im en ta l Section
Gen er a l P r oced u r e. A solution of n-butyllitium in hexanes
(1.6 M, 3.3 equiv) was added slowly to a solution of bis-
(cyclopentadienyl)zirconium dichloride (1.5 equiv) in dry THF
at -78 °C. After the solution was stirred for 1 h at -78 °C, the
enol ether was added (1 equiv) at -78 °C. The reaction mixture
was allowed to warm to room temperature and stirred for 2.5-5
h. The quantitative formation of the adduct was checked by GC.
Then, the solution was cooled to -20 °C, and the electrophile
was added. The reaction was warmed to room temperature, and
the mixture was diluted with ether and HCl 1 N. The aqueous
phase was then extracted three times with ether. The combined
organic phase was then washed successively with a solution of
saturated aqueous sodium hydrogen carbonate, brine, and water
(in case of addition of iodine, aqueous Na2S2O3 was also used),
dried over MgSO4, and evaporated under reduced pressure. The
residue obtained was finally purified by column chromatography
on silica gel.
34
1H NMR (400 MHz, CDCl3) δ (ppm) 3.01 (m, 2H), 5.11-5.22
(m, 2H), 5.93-6.03 (m, 1H), 6.26-6.33 (dt, 1H, J ) 6.3, 15.7
Hz), 6.49 (d, 1H, J ) 15.7 Hz), 7.25-7.49 (m, 5H).
r-Deu ter iostyr en e 17. Purification by chromatography on
silica gel (eluent: hexane) gave a colorless liquid, yield 70%,
spectrally identical with an authentic sample:31 1H NMR (200
MHz, CDCl3) δ (ppm) 5.22 (s, 1H), 5.8 (s, 1H), 7.24-7.47 (m,
5H).
Ack n ow led gm en t. This research was supported in
part by The Israel Science Foundation founded by The
Academy of Sciences and Humanities (No. 060-471) and
by the fund for the promotion of research at the
Technion.
J O005561N
1-Un d ecen e 5. Purification by chromatography on silica gel
(eluent: hexane) gave a colorless liquid, yield 90%, spectrally
(30) Ichiro, T.; Hidehiko, I.; J un, O.; Yoshihiko, H.; Takao, F.;
Akihiko, H. Biosci. Biotechnol. Biochem. 1994, 58, 1158.
(31) Hazin, P. N.; Bruno, J . W. Organometallics 1987, 6, 918.
(32) Murahashi, S. I.; Yamamura, M.; Mita, N. J . Org. Chem. 1977,
42, 2870. Yoshino, T.; Manabe, Y.; Kikushi, Y. J . Am. Chem. Soc. 1964,
86, 4670.
(28) The same reaction was also performed on acetoxy enol ether,
but in this case, 1 reacts faster with the ester than with the double
bond.
(29) As suggested by a reviewer, two different mechanisms might
also operate for activation of enol ethers versus alkenyl halides.
Although our mechanism is still speculative, the dipolar species such
an 18 explain nicely our results.
(33) Suzuki, H.; Aihara, M.; Yamamoto, H.; Takamoto, Y.; Ogawa,
T. Synthesis, 1988, 236.
(34) Underiner, T. L.; Paisley, S. D.; Schmitter, J .; Lesheski, L.;
Goering, H. L. J . Org. Chem. 1989, 54, 2369.