Preparation and synthetic transformation of alkenyl carbamates into vinyl zirconocene derivatives

Article abstract of DOI:10.1055/s-2005-918436

The carbocupration reaction of alkynyl carbamates leads to the stereospecific preparation of polysubstituted alkenyl carbamates. Subsequent treatment of these enol carbamates with the Negishi reagent gave the corresponding vinyl zirconocene species. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2005-918436

PAPER
3311
Preparation and Synthetic Transformation of Alkenyl Carbamates into Vinyl
Zirconocene Derivatives
T
H
ransformation of
e
Alkenyl Ca
l
rbama
e
tes into Vin
n
yl Zirconoce
a
ne Derivatives Chechik-Lankin, Ilan Marek*
The Mallat Family Laboratory in Organic Chemistry, Department of Chemistry, Institute of Catalysis Science and Technology,
The Lise Meitner-Minerva Center for Computational Quantum Chemistry, Technion-Israel Institute of Technology, Haifa 32 000, Israel
E-mail: chilanm@tx.technion.ac.il
Received 15 September 2005
Interestingly, regardless of the stereochemistry of the
Abstract: The carbocupration reaction of alkynyl carbamates leads
starting heterosubstituted olefins 1a–f, a complete isomer-
ization reaction occured to give the pure trans-vinyl zir-
to the stereospecific preparation of polysubstituted alkenyl carbam-
ates. Subsequent treatment of these enol carbamates with the
Negishi reagent gave the corresponding vinyl zirconocene species.
conocene derivatives
3
stereospecifically. This
isomerization has been rationalized as a carbometallative
ring expansion between 1 and 2, which leads to the corre-
sponding five-membered ring zirconacycle 4 in which the
Keywords: alkynyl carbamates, vinyl zirconocene derivatives, or-
ganocopper reagents
3
carbon–heteroatom bond of the sp -metallated center C1
isomerizes to produce the most stable intermediate. Such
isomerization could be due to an interaction between the
heterosubstituent and the zirconium atom, which would
We have recently reported that heterosubstituted alkenes
1
2
1
a–f such as enol ether, silyl enol ether, vinyl-, alkyl-,
and aryl sulfides, vinyl sulfoxides, and even vinyl
sulfones were excellent candidates for the stereoselective
preparation of alkenyl and conjugated dienyl organome-
tallic derivatives. Typically, reactions were complete in a
3
produce a weakening of the C –Zr bond facilitating the
1
9
4
5
isomerization (Scheme 2). Thus, whatever the stereo-
chemistry of 1, the conformation of RX–Zr is always an-
tiperiplanar to C –C before the elimination reaction.
6
2
3
few hours at room temperature by treatment of the alkene
7
with the Negishi reagent C H ZrCp 2 (prepared in situ Although this transformation leads to only one isomer, we
4
8
2
by reaction of the commercially available Cp ZrCl with were interested in developing a stereospecific transforma-
2
2
8
2
two equivalents of n-BuLi) with these alkenes tion of heterosubstituted olefins into sp -organometallic
(
Scheme 1).
derivatives (E- and Z-olefins give E- and Z-vinyl metals,
respectively). Following our hypothetical mechanism, we
thought that stereospecificity could be achieved if we sim-
ply avoid the isomerization reaction of the zirconacycle
intermediate (Z)-4 into (E)-4 as described in Scheme 3.
Oct
Oct
Oct
Oct
OMe
(
E)-1c
SPh
1d
83%
SPr
Oct
OSiMe2t-Bu
1b
1a
E/Z 65/35
9
0%
75%
85%
XR
XR
R
R
R
R
XR
Oct
Oct
7
5%
XR
Et
ZrCp2
Et
ZrCp2
E
E
6
5%
(
E)-1e SPh
ZrCp XR
SPh
Z)-1c
2
(E)-4
(Z)-4
3
(
O
Scheme 3
70%
90%
85%
Oct
Therefore, the challenging question was to find a config-
Oct
SPh
O
urationally stable geminal configuration between the sp3
Oct
SO2Ph
SO2Ph
(
Z)-1e
R = Ph, Me, Tol
(Z)-1f
carbon–zirconium bond and the X–R bond at room tem-
perature – the temperature at which our transformation
proceeds. Fortunately, Hoppe had initially shown that the
(
E)-1f
Scheme 1
n-C4H8ZrCp2
XR
1
R
R
R
R
2
2
XR
Et 3
ZrCp2
ZrCp2XR
Cp2LnZr XR
3
4
1
a–f
Carbometallative ring
expansion into
zirconacyclopentane
Elimination
E/Z ratio
Scheme 2
SYNTHESIS 2005, No. 19, pp 3311–3318
x
x.
x
x
.
2
0
0
5
Advanced online publication: 27.10.2005
DOI: 10.1055/s-2005-918436; Art ID: C08705SS
Georg Thieme Verlag Stuttgart · New York
©

3
312
H. Chechik-Lankin, I. Marek
PAPER
n-C4H8ZrCp2
2
R
ZrCp2OCON(i-Pr)2
Z
?
??
Path A
R
OCON(i-Pr)2
R
OCON(i-Pr)2
Z
E
Path B
R
Met
OCON(i-Pr)2
R
H
OCON(i-Pr)2
OCON(i-Pr)2
R
n-C4H8ZrCp2
ZrCp2OCON(i-Pr)2
2
E
?
??
Scheme 4
deprotonation of O-alkyl carbamate with s-BuLi leads to tion reaction,19 we were interested in using the carbocu-
a configurationally stable organolithium derivative and pration reaction since organocopper derivatives are
later on, Beak extended the application of this method to known for their high regio-, stereo-, and chemoselectivi-
1
0
20
N-Boc-pyrrolidines. Consequently, we decided to study ty, which enables them to add smoothly to the triple
2
1
the stereospecificity of a new unknown transformation, bond of various alkynes even in the presence of other
namely the conversion of E- and Z-vinyl carbamate into functionalities.22 However, when organocopper deriva-
2
the corresponding sp -organozirconocene derivatives tives are added to heterosubstituted alkynes, different pos-
(
Scheme 4). The preparation of Z-vinyl (N,N-diisopro- sible regioisomers may be obtained; the directing effect of
1
0a
pyl)carbamate was well known (Scheme 4, path A) and oxygen and nitrogen leads to the branched product (cop-
its transformation into functionalized derivatives such as per at the b-position relative to the heteroatom) whereas
1
1
12
13
14
15
lactol, acetylene, aldehyde, Z-alkene, enyne, Z-si- those of sulfur and phosphorus lead to the linear product
1
6
17
lyl enol ether, and Z-vinyl triflate derivatives have (geminal relationship between copper and the heteroatom,
found many applications. All of these methods were ad- Scheme 5).23
vantageously used in many total syntheses where the
Although alkynyl carbamate is an oxy-substituted alkyne
preparation of enantiomerically enriched anti-homoallyl-
and therefore should lead to the branched isomer, we
1
0a
ic alcohols was necessary, but surprisingly, no transfor-
mation of the same Z-vinyl (N,N-diisopropyl)carbamate
into organometallic was described.
thought that the electron-withdrawing effect of the car-
bamoyl group combined with its strong ability to coordi-
nate organometallic derivatives should reverse the
Moreover, the stereoselective preparation of pure E-vinyl regiochemistry of the carbometallation reaction across the
N,N-diisopropyl)carbamate has not been described in the alkyne. Indeed, when ethynyl carbamate 5, easily pre-
(
1
8
24
literature. As stated earlier, we required an easy and pared from 2,2,2-tribromoethyl carbamate, was treated
straightforward access to either the E- or Z-isomer of vi- with an organocopper reagent [RMgBr (1 equiv), CuBr (1
nyl (N,N-diisopropyl)carbamate, thus, we initially decid- equiv), Et O, –30 °C, 30 min], the corresponding carbo-
2
ed to develop a new stereoselective preparation of the E- metallated product is obtained as described in Scheme 6.
isomer. Retrosynthetic analysis for the exclusive forma-
The reaction is extremely fast since the carbometallated
tion of the E-isomer shows that it should be easily pre-
product 6 is formed after 90 minutes at –78 °C. Primary
pared by a regiospecific syn addition of substituents R and
(
(
R = Bu) as well as secondary alkyl groups
R = cyclohexyl) add cleanly to the alkyne furnishing
H across the alkyne. Obviously, the proton addition can be
derived from the hydrolysis of a carbon–metal bond
only the pure E-isomers 7 and 8, respectively, in good iso-
lated yields. Even the phenyl and methyl groups, which
(
Scheme 4, path B).
According to the retrosynthetic analysis described in are known to be very sluggish towards the carbocupration
20
Scheme 4, path B, a regio- and stereospecific carbometal- reaction, lead to the expected addition product in good
lation reaction of ethynyl carbamate should be the key re- to moderate yields (9 and 10, respectively). The presence
action for the preparation of the E-enol carbamate. of a discrete organometallic was checked by the reaction
Among all the possible candidates for the carbometalla- of 6 (R = Bu) with either iodine or by reaction with allyl-
Cu
Cu
H
R
RCu, MgBr2
RCu, MgBr2
R
H
H
XR
XR
XR
XR = OR, NR2
Branched isomer
XR = SR, S(O)R, SO2R
Linear isomer
??
??
H
OCON(i-Pr)2
Scheme 5
Synthesis 2005, No. 19, 3311–3318 © Thieme Stuttgart · New York

PAPER
Transformation of Alkenyl Carbamates into Vinyl Zirconocene Derivatives
3313
H
OCON(Pr-i)2
5
RCu, MgBr2
Et2O
H
R = Bu H9C4
H9C4
H
R = Bu
OCON(i-Pr)2 then H+
then allyBr
H
OCON(i-Pr)2
7
12
78%
Cu O
O
R
8
1%
N
H
H
R = Et
OCON(i-Pr)2 then H+
H9C4
I
c-C6H11
H
R = Bu
6
then I2
OCON(i-Pr)2
H
8
11
72%
7
2%
R = Ph
then H+
H
R = Me H C
H
H5C6
H
3
then H+
OCON(i-Pr)2
OCON(i-Pr)2
H
1
5
0
9
0%
8
6%
Scheme 6
bromide to give 11 and 12 in 72% and 78% yields, respec- Substituted alkynyl carbamate such as propynyl carbam-
2
5
tively. Thus, a carbamoyl moiety attached to an ethynyl ate 16 also reacts easily with organocopper to afford ste-
residue indeed reverses the regiochemistry of the carbocu- reospecifically the trisubstituted enol carbamates 17–19
pration reaction (compare the regiochemistry for the as a single geometrical isomer (Scheme 8).25
alkoxy alkyne on Scheme 5 and ethynyl carbamate on
Finally, to extend the scope of this reaction, we were also
Scheme 6) but the reaction has to be performed in a non-
interested in developing the copper-catalyzed carbomag-
polar solvent such as diethyl ether. When more polar sol-
nesiation reaction. Therefore, ethynyl carbamate 5 was re-
acted with a stoichiometric amount of alkylmagnesium
vents such as THF are used, the classical regioisomer
from the carbocupration of alkoxy-alkyne is obtained (the
halide in diethyl ether in the presence of copper iodide (10
branched product is obtained in a 4:1 ratio as described in
mol%). The carbometallation reaction proceeds smoothly
Scheme 7).
under these conditions (only the pure E-isomer was ob-
Internal delivery of the organometallic reagent via com- tained) but at a slightly higher temperature (–40 °C in-
plex 15 is the suggested explanation for the anomalous re- stead of –78 °C), which may be attributed to a slow
gioselectivity observed for the carbocupration of 5.26 transmetallation step between the chelated sp organocop-
Thus, the branched isomer 13 resulted from the ‘normal’ per to the corresponding organomagnesium derivative.
regioselective addition, whereas the linear isomer 6 was Moreover, as described in Scheme 9, the reactivity of the
2
2
7
2
the product of a directed reaction. The carbamate–orga- newly formed sp organometallic is completely different
nocopper complex 15 is proposed to be the intermediate in from the reactivity of the organocopper since 6MgBr also
the latter case.
reacts with aldehyde to give 20 in good isolated yield.
Bu
OCON(i-Pr)2
BuCu, MgBr2
BuCu, MgBr2
Et2O
Cu
OCON(i-Pr)2
Cu
H
Bu
H
H
H
OCON(i-Pr)2
THF
5
1
3
6
H+
H+
R
Cu
O
Bu
Bu
O
N
OCON(i-Pr)2
OCON(i-Pr)2
5%
7
1
5
81%
1
4/7 = 80/20
5
Scheme 7
Bu
BuCu, MgBr2
PhCu, MgBr2
Ph
H3C
H3C
OCON(i-Pr)2
OCON(i-Pr)2
Et2O
then H+
Et2O
OCON(i-Pr)2
H3C
1
7
16
+
18
60%
then H
80%
c-C6H11Cu, MgBr2
Et2O
+
then H
c-H11C6
H3C
OCON(i-Pr)2
1
9
7
1%
Scheme 8
Synthesis 2005, No. 19, 3311–3318 © Thieme Stuttgart · New York

3
314
H. Chechik-Lankin, I. Marek
PAPER
BuMgBr
0 mol% CuI
Et2O
1
MgBr
H+
Bu
Bu
H
H
OCON(i-Pr)2
OCON(i-Pr)2
MgBr
OCON(i-Pr)2
5
–40 °C
7
6
PhMgBr
0 mol% CuI
Et2O
7
0%
1
Ph
Bu
OH
PhCHO
–40 °C
Ph
then H+
OCON(i-Pr)2
OCON(i-Pr)2
9
20
8
6%
69%
Scheme 9
With two simple methods in hand for the stereoselective 2 is not a catalyst for the isomerization of enol carbamate.
2
5
10
preparation of the E- and Z-isomers of diversely sub- Thus, following our working hypothesis, this isomeriza-
stituted enol carbamates, we came back to our initial pre- tion may be also derived from a slow equilibration of the
occupation, namely, the stereospecific transformation of Z-zirconacyclopentane intermediate into its E-isomer
vinyl carbamate into vinyl zirconocene derivatives. Orig- (Scheme 11). When a more polar solvent such as THF is
inally, when the pure E-isomer 7 was treated with zir- used in the reaction, the percentage of isomerization in-
conocene reagent 2 in diethyl ether for 1.5 hours at 20 °C, creased (Z/E, 65:35), which may be explained by the
the corresponding vinyl zirconocene 21 was easily ob- weaker intramolecular chelation of the zirconocene moi-
tained as determined by gas chromatography analysis of ety by the carbamate in the zirconacyclopentane interme-
hydrolyzed aliquots. After addition of iodine, the corre- diate. On the other hand, when less polar solvents were
sponding E-vinyl iodide 22 was obtained in 78% isolated used such as toluene, no improvement in the stereochem-
yield and as a single geometrical isomer (Scheme 10).
istry was detected. Diethyl ether was found to be the opti-
mum solvent for the reaction. We were pleased to see that
this transformation was very fast and complete in less than
We, then, decided to study the behavior of the Z-vinyl car-
bamate 7 under the same experimental conditions. There-
fore, when (Z)-7 was subjected to our classical
3
0 minutes, the starting material completely disappeared
resulting in the final product. Under these conditions, the
Z/E ratio slightly increases to 85:15, which indicates that
additional isomerization may occur as a result of a pro-
longed reaction time. To prove this hypothesis, the fol-
lowing experiment was carried out. The Z-vinyl
carbamate 7 was treated with zirconocene reagent 2 in di-
ethyl ether, after 30 minutes a complete transformation
into the corresponding vinyl zirconocene 21 resulted.
Then, half of the reaction was removed and treated with
iodine. The crude NMR of this removed portion shows
that the vinyl iodide has a Z/E ratio of 85:15. The remain-
ing part of the reaction mixture was stirred for a further
four hours at room temperature and finally quenched with
iodine. In this portion, the Z/E ratio of the vinyl iodide 22
experimental conditions (1 h in Et O at r.t.) followed by
2
iodinolysis, the corresponding Z-vinyl iodide 22 was ob-
tained in 75% yield but with a Z/E ratio of 80:20 as de-
scribed in Scheme 11.
A loss in stereospecificity is therefore observed. We ini-
tially checked that our starting material, namely the Z-vi-
nyl carbamate 7, does not undergo an isomerization
reaction into the E-vinyl carbamate, before its transforma-
tion into vinyl zirconocene derivative 21. Indeed, when
the reaction described in Scheme 11 was trapped with io-
dine prior to completion, three products were observed;
the E- and Z-isomers of the vinyl iodide 22 and the Z-vinyl
carbamate 7; no trace of the E-isomer of 7 was observed.
From this we can conclude that the zirconocene complex
n-C4H8ZrCp2
H9C4
H9C4
I2
H9C4
2
Et2O
r.t.
OCON(i-Pr)2
ZrCp2OCON(i-Pr)2
I
7
21
22
E-isomer
8%
E-isomer
7
Scheme 10
n-C4H8ZrCp2
H9C4
OCON(i-Pr)2
H9C4
ZrCp2OCON(i-Pr)2 I2
H9C4
I
2
Solvent
r.t.
7
21Z
22
75%
Z-isomer
Solvent
Et2O
THF
Z/E ratio
80:20
6
8
5:35
0:20
N
O
N
R
R
O
Toluene
O
O
Et
ZrCp2
Et
ZrCp2
Scheme 11
Synthesis 2005, No. 19, 3311–3318 © Thieme Stuttgart · New York

PAPER
Transformation of Alkenyl Carbamates into Vinyl Zirconocene Derivatives
3315
4
h, r.t.
n-C4H8ZrCp2
H9C4
OCON(i-Pr)2
H9C4
ZrCp2OCON(i-Pr)2 then I2
H9C4
I
2
Et2O
0 min, r.t.
21
I2
22
Z/E = 57/43
7
3
Z-isomer
H9C4
I
2
2
Z/E = 85/15
Scheme 12
was found to be only 57:43, which shows that the Z-vinyl
zirconocene 21 was indeed isomerized in situ positive pressure of argon. All glassware was oven dried at 150 °C
Experiments involving organometallics were carried out under a
(
Scheme 12).
overnight and assembled quickly while hot under a stream of argon.
Liquid N was used as a cryogenic and all indicated temperatures
2
To rationalize the isomerization of the Z-vinyl zir-
conocene 21, we assumed that a catalytic amount of free
zirconocene reagent 2 reacts with 21 to give either the
are internal. Unless otherwise stated, a three-necked round-bottom
flask equipped with an internal thermometer, a septum cap, and an
argon inlet was used with a magnetic stirrer. Et O and THF were
2
biszirconated species 23 or 24, in which the carbon–zirco- distilled from Na/benzophenone ketyl. Organolithium and organo-
nium bond has no reason to be configurationally stable magnesium reagents were titrated with i-BuOH (1 M, toluene)
using 1,10-phenanthroline or 2,2¢-biquinolyl as indicators, respec-
and therefore undergoes partial isomerization
tively. TLC was performed on silica gel coated plates, visualized ei-
(
Scheme 13).
ther under a UV lamp or by using a 10% phosphomolybdic acid soln
in EtOH followed by heating or sometimes with I vapor.
2
R
ZrCp2OCON(i-Pr)2
Z)-21
R
NMR spectra have been recorded on either a Bruker AC 200,
ZrCp2OCON(i-Pr)2
(
(E)-21
AC300, or AC 500 spectrometers in CDCl as a solvent. Chemical
3
shifts are reported in ppm relative to TMS as internal standard
n-C4H8ZrCp2
1
13
(
0.1%) for H NMR spectra and CDCl for C NMR spectra.
3
2
R
ZrCp2OCON(i-Pr)2
ZrCp2
Stoichiometric Carbocupration; General Procedure (GP1)
To a soln of CuI (2.2 equiv) in anhyd solvent (10 mL) at – 60 °C was
added alkyl magnesium bromide (2.2 equiv). The reaction mixture
was warmed to the indicated temperature and stirred for 30 min.
Then, the reaction mixture was cooled to –78 °C and alkynyl car-
bamate 5 (1 equiv) in anhyd solvent was added dropwise. The reac-
tion was warmed to the indicated temperature and stirred for an
additional 90 min. After 90 min, the reaction was quenched by the
R
ZrCp2OCON(i-Pr)2
Zr
Cp
Cp
2
3
24
Scheme 13
The existence of a biszirconated species has already been addition of a sat. soln of NH Cl and a sat. soln of NH OH (30%)
4
4
(
1:2, 30 mL) and warmed to r.t. The phases were separated and the
shown when alkynyl zirconocene 25 was treated with an
aqueous phase was extracted with Et O (3 × 50 mL). The combined
organic layers were washed with a sat. soln of NH
of NH OH (30%) (1:2, 50 mL) and dried over anhyd MgSO .
excess of 2 to give the corresponding tris-metallated al-
2
kene 26 as shown after deuteriolysis (Scheme 14).28
Cl and a sat. soln
4
4
4
n-C4H8ZrCp2
Copper-Catalyzed Carbomagnesiation; General Procedure
(GP2)
R
ZrCp2Cl
D3O+
R
D
D
D
2
R
ZrCp2Cl
Zr
To a soln of CuI (0.1 equiv) in anhyd solvent (10 mL) at –60 °C was
added alkyl magnesium bromide (2.2 equiv). The reaction mixture
was warmed to –20 °C and stirred for 30 min. Then, the reaction
mixture was cooled to –78 °C and alkynyl carbamate 5 (1 equiv) in
anhyd solvent (10 mL) was added dropwise. The reaction soln was
warmed to the indicated temperature and stirred for an additional 5
h. After 4 h, the reaction was quenched by the addition of a sat. soln
of NH Cl and a sat. soln of NH OH (30%) (1:2, 30 mL) and warmed
25
Cp
Cp
9
0%
26
Scheme 14
In conclusion, we have initially described a new prepara-
tion for the stereospecific preparation of polysubstituted
vinyl carbamate, as a single geometrical isomer, from
alkynyl carbamates and organocopper reagents. We have
been able to use these derivatives for the synthetically
useful transformation of enol carbamate into sp -organo- (1:2, 50 mL) and dried over anhyd MgSO4.
4
4
to r.t. The phases were separated and the aqueous phase was extract-
ed with Et O (3 × 50 mL). The combined organic layers were
2
washed with a sat. soln of NH Cl and a sat. soln of NH OH (30%)
4
4
2
metallic derivatives by reaction with the Negishi reagent
Diisopropylcarbamic Acid Hex-1-enyl Ester (7)
C H ZrCp . Under optimum experimental conditions, the
4
8
2
A soln of butylcopper (1.9 mmol) in Et O was prepared at –25 °C
2
E-isomer leads only to the E-vinyl zirconocene, whereas
the Z-isomer gives a 85:15 mixture of Z/E-vinyl zir-
conocene. Further applications of these new methods will
be reported in due course.
according to GP1. The carbocupration reaction of alkynyl carbam-
ate 5 (0.145 g, 0.86 mmol) was performed at –65 °C. Purification by
silica gel chromatography (EtOAc–hexane, 1:50) gave 7 in 81%
yield (0.158 g).
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H. Chechik-Lankin, I. Marek
PAPER
1
1
H NMR (300 MHz, CDCl ): d = 6.96 (d, J = 17.25 Hz, 1 H), 5.25
H NMR (300 MHz, CDCl ): d = 5.69 (m, 1 H) 5.07 (t, J = 7.5 Hz,
3
3
(
m, 1 H), 3.98 (m, 2 H), 1.96 (m, 2 H), 1.20 (m, 16 H), 0.85 (t,
1 H), 4.95 (m, 2 H), 3.9–3.6 (m, 2 H), 2.96 (d, J = 6.6 Hz, 2 H), 1.96
J = 7.02 Hz, 3 H).
(m, 2 H), 1.27–1.1 (m, 16 H), 0.79 (t, J = 6.9 Hz, 3 H).
1
3
13
C NMR (75 MHz, CDCl ): d = 152.1, 134.0, 111.0, 44.9 (2 C),
C NMR (75 MHz, CDCl ): d = 153, 145.6, 133.5, 117.0, 115.9,
3
3
3
3.9, 26.0, 19.4 (4 C), 12.9.
46.9 (2 C), 33.1, 31.5, 25.2, 21.6, 19.6 (4 C), 13.1.
Diisopropylcarbamic Acid 2-Cyclohexylvinyl Ester (8)
Diisopropylcarbamic Acid 2-Methylhex-1-enyl Ester (17)
A soln of cyclohexylcopper (1.43 mmol) in Et O was prepared at
A soln of butylcopper (1.46 mmol) in Et O was prepared at –15 °C
2
2
–
10 °C according to GP1. The carbocupration reaction of alkynyl
according to GP1. The carbocupration reaction of alkynyl carbam-
ate 16 (0.133 g, 0.73 mmol) was performed at –78 °C. Purification
by silica gel chromatography (EtOAc–hexane, 1:30) gave 17 in
80% yield (0.14 g).
carbamate 5 (0.11 g, 0.65 mmol) was performed at –78 °C. Purifi-
cation by silica gel chromatography (EtOAc–hexane, 1:50) gave 8
in 72% yield (0.118 g).
1
1
H NMR (300 MHz, CDCl ): d = 6.99 (d, J = 12.55 Hz, 1 H), 5.18
H NMR (300 MHz, CDCl ): d = 6.85 (s, 1 H), 4.06–3.7 (m, 2 H),
3
3
(
m, 1 H), 3.83 (m, 2 H), 1.3–1.04 (m, 23 H).
1.9 (t, J = 7.5 Hz, 2 H), 1.6 (s, 3 H), 1.4–1.23 (m, 16 H), 0.87 (t, J =
7
.2 Hz, 3 H).
Diisopropylcarbamic Acid Styryl Ester (9)
13
C NMR (75 MHz, CDCl ): d = 153.6, 131.3 (2 C), 118.8, 39.0 (2
3
A soln of phenylcopper (2.8 mmol) in Et O was prepared at –25 °C
2
C), 33.9, 30.2, 22.6, 21.6–20.8 (4 C), 14.3, 14.2.
according to GP1. The carbocupration reaction of alkynyl carbam-
ate 5 (0.214 g, 1.27 mmol) was performed at –78 °C. Purification by
silica gel chromatography (EtOAc–hexane, 1:50) gave 9 in 86%
yield (0.27 g).
Diisopropylcarbamic Acid 2-Phenylpropenyl Ester (18)
A soln of phenylcopper (1.6 mmol) in Et O was prepared at –20 °C
2
according to GP1. The carbocupration reaction of alkynyl carbam-
ate 16 (0.153 g, 0.84 mmol) was performed at –65 °C. Purification
by silica gel chromatography (EtOAc–hexane, 1:50) gave 18 in
60% yield (0.131 g).
1
H NMR (300 MHz, CDCl ): d = 7.84 (d, J = 12.83 Hz, 1 H), 7.31–
3
7
.16 (m, 5 H), 6.25 (d, J = 12.84 Hz, 1 H), 3.88 (m, 2 H), 1.24 (m,
J = 6.7 Hz, 12 H).
1
3
1
C NMR (75 MHz, CDCl ): d = 151.7, 136.7, 134.0, 127.6 (2 C)
H NMR (300 MHz, CDCl ): d = 7.50 (s, 1 H), 7.37–7.2 (m, 5 H),
3
3
1
25.7, 124.9 (2 C), 111.5, 45.0 (2 C), 19.4 (4 C).
4.08–3.8 (m, 2 H), 2.09 (s, 3 H), 1.27 (d, J = 11.1 Hz, 12 H).
1
3
C NMR (75 MHz, CDCl ): d = 152.9, 137.7, 130.9, 128.8 (2 C),
3
Diisopropylcarbamic Acid Propenyl Ester (10)
1
26.7, 125.9 (2 C), 118.3, 46.8, 45.9, 20.9 (4 C), 14.0.
A soln of methylcopper (1.57 mmol) in Et O was prepared at
2
–
20 °C according to GP1. The carbocupration reaction of alkynyl
Diisopropylcarbamic Acid 2-Cyclohexylpropenyl Ester (19)
carbamate 5 (0.133 g, 0.786 mmol) was performed at –78 °C. Puri-
fication by silica gel chromatography (EtOAc–hexane, 1:50) gave
1
A soln of cyclohexylcopper (1.2 mmol) in Et O was prepared at
2
–
10 °C according to GP1. The carbocupration reaction of alkynyl
0 as a liquid in 50% yield (0.722 g).
carbamate 1b (0.109 g, 0.6 mmol) was performed at –78 °C. Purifi-
cation by silica gel chromatography (EtOAc–hexane, 1:50) gave 19
as an oil in 71% yield (0.16 g).
1
H NMR (500 MHz, CDCl ): d = 6.99 (d, J = 12.6 Hz, 1 H), 5.3 (m,
3
1
H), 4.04–3.77 (m, 2 H), 1.6 (d, J = 8.7 Hz, 3 H), 1.2 (d, 12 H, J =
1
0.5 Hz).
1
H NMR (300 MHz, CDCl ): d = 6.84 (s, 1 H) 4.0–3.8 (m, 2 H), 1.95
3
1
3
C (125.7 MHz, CDCl ): d = 155.0, 138.7, 108.6, 47.4 (2 C), 23.2
(m, H), 1.65 (s, 3 H), 1.40–1.23 (m, 22 H).
13
3
(
4 C), 14.1.
C NMR (75 MHz, CDCl ): d = 152.8, 130.2, 123.0, 45.4 (2 C),
3
4
2.1, 33.0, 26.1, 25.5, 20.9 (4 C), 11.8.
Diisopropylcarbamic Acid 1-Iodohex-1-enyl Ester (11)
A soln of butylcopper (1.82 mmol) in Et O was prepared at –25 °C
according to GP1. The carbocupration reaction of alkynyl carbam-
2
Diisopropylcarbamic Acid 1-Butylvinyl Ester (14)
A soln of butylcopper (2.07 mmol) in THF was prepared at –20 °C
according to GP1. The carbocupration reaction of alkynyl carbam-
ate 5 (0.176 g, 1.03 mmol) was performed at –78 °C. Purification by
silica gel chromatography (EtOAc–hexane, 1:50) gave 14 as an oil
in 55% yield (0.234 g).
ate 5 (0.143 g, 0.85 mmol) was performed at –65 °C. I (3 equiv,
2
0
.629 g, 2.48 mmol) in anhyd THF (5 mL) was added at –65 °C, the
reaction mixture was warmed to r.t., stirred for 15 min, and
quenched as described in GP1. After classical work up, an addition-
al washing of the organic layers was performed with a sat. aq soln
of Na S O (30 mL). Purification by silica gel chromatography
1
H NMR (500 MHz, CDCl ): d = 4.68 (s, 1 H), 4.64 (s, 1 H), 4.08–
3
2
2
3
3
.78 (m, 2 H), 2.28 (t, J = 8 Hz, 2 H), 1.47–1.34 (m, 4 H), 1.23 (d,
(
EtOAc–hexane, 1:100) gave 11 in 72% yield (0.216 g).
J = 11 Hz, 12 H), 0.92 (t, J = 7 Hz, 3 H).
1
H NMR (300 MHz, CDCl ): d = 5.37 (t, J = 7.2 Hz, 1 H), 3.91–3.71
3
1
3
C NMR (125.7 MHz, CDCl ): d = 158.7, 118.9, 101.6, 48.1 (2 C),
(
m, 2 H), 2.00 (m, 2 H), 1.36 (m, 4 H), 1.154 (d, J = 6.6 Hz, 12 H),
3
3
5.2, 30.5, 24.0, 22.5 (4 C), 15.8.
0
.82 (t, J = 6.9 Hz, 3 H).
1
3
C NMR (75 MHz, CDCl ): d = 152.4, 129.0, 102.3, 47.5–46.6 (2
3
Diisopropylcarbamic Acid Hex-1-enyl Ester (7)
C), 32.4, 30.9, 22.6, 22.0–20.8 (2 C), 14.5.
A soln of BuMgBr and CuI in Et O was prepared at –20 °C accord-
2
ing to GP2. The Cu-catalyzed carbomagnesiation reaction of alky-
nyl carbamate 5 (0.148 g, 0.88 mmol) was performed at –40 °C.
Purification by silica gel chromatography (EtOAc–hexane, 1:50)
gave 7 in 70% yield (0.14 g). See physical data reported for the
stoichiometric procedure.
Diisopropylcarbamic Acid 1-Allylhex-1-enyl Ester (12)
A soln of butylcopper (1.9 mmol) in Et O was prepared at –25 °C
2
according to GP1. The carbocupration reaction of alkynyl carbam-
ate 5 (0.150 g, 0.89 mmol) was performed at –65 °C. Allyl bromide
(3.3 equiv, 0.358 g, 2.96 mmol) was added at –65 °C, the reaction
mixture was warmed to –30 °C, and stirred for 30 min. The reaction
was quenched and work up carried out as described in GP1. Purifi-
cation by silica gel chromatography (EtOAc–hexane, 1:100) gave
Diisopropylcarbamic Acid 1-(Hydroxyphenylmethyl)hex-1-
enyl Ester (20)
A soln of BuMgBr and CuI in Et O was prepared at –20 °C accord-
2
1
2 in 78% yield (185.6 g).
ing to GP2. The carbocupration reaction of alkynyl carbamate 5
Synthesis 2005, No. 19, 3311–3318 © Thieme Stuttgart · New York

PAPER
Transformation of Alkenyl Carbamates into Vinyl Zirconocene Derivatives
3317
(
0.159 g, 0.94 mmol) was performed at –40 °C. Benzaldehyde (2
(7) For reviews, see (a) Negishi, E.; Takahashi, T. Bull. Chem.
Soc. Jpn. 1988, 71, 755. (b) Negishi, E.; Takahashi, T. Acc.
Chem. Res. 1994, 27, 124. (c) Negishi, E.; Kondakov, D. Y.
Chem. Soc. Rev. 1996, 26, 417.
(8) Titanium and Zirconium in Organic Synthesis; Marek, I.,
Ed.; Wiley-VCH: Weinheim, 2002.
equiv, 0.200 g, 1.89 mmol) was added at –70 °C, the reaction mix-
ture was warmed to –60 °C, and stirred for 1 h. The reaction was
quenched and work up carried out as described in GP2. Purification
by silica gel chromatography (EtOAc–hexane, 1:10) gave 20 in
6
9% yield (0.216 g).
1
(9) Ward, A. S.; Mintz, E. A.; Kramer, M. P. Organometallics
H NMR (300 MHz, CDCl ): d = 7.45 (d, J = 8.7 Hz, 1 H), 7.09–6.9
3
1988, 7, 8.
(
(
(
1
m, 5 H), 5.78 (d, J = 6.9 Hz, 1 H), 5.68 (d, J = 7.8 Hz, 1 H), 5.23
t, J = 7.8 Hz, 1 H), 3.47 (m, 1 H), 3.22 (m, 1 H), 2.02 (m, 2 H), 1.12
m, 4 H), 0.88 (m, 12 H), 0.68 (t, J = 6.9 Hz, 3 H).
3
(
10) (a) Hense, T.; Hoppe, D. Angew. Chem. Int. Ed. 1997, 36,
2282. (b) Kerrick, S. T.; Beak, P. J. Am. Chem. Soc. 1991,
113, 9708.
C NMR (75 MHz, CDCl ): d = 155.3, 148.3, 140.8, 127.5 (2 C),
3
(11) (a) Hoppe, D.; Hanko, R.; Bronneke, A.; Lichtenberg, F.;
van Hulsen, E. Chem. Ber. 1985, 118, 2822. (b) Berque, I.;
Le Menez, P.; Razon, P.; Anies, C.; Pancrazi, A.; Ardisson,
J.; Neuman, A.; Prange, T.; Brion, J. D. Synlett 1988, 1135.
1
1
26.4, 125.4 (2 C), 122.0, 69.0, 46.1, 45.7, 31.4, 25.7, 21.9, 20.3–
9.6 (4 C), 13.5.
Diisopropylcarbamic Acid Styryl Ester (9)
A soln of PhMgBr and CuI in Et O was prepared at –20 °C accord-
(
12) (a) Pimm, A.; Kocienski, P.; Street, S. D. A. Synlett 1992,
2
886. (b) Ferezou, J. P.; Julia, M.; Li, Y.; Liu, L. W.;
ing to GP2. The Cu-catalyzed carbomagnesiation reaction of alky-
nyl carbamate 5 (0.148 g, 0.88 mmol) was performed at –40 °C.
Purification by silica gel chromatography (EtOAc–hexane, 1:50)
gave 9 in 86% yield (0.175 g). See physical data reported for the
stoichiometric procedure.
Pancrazi, A. Bull. Soc. Chim. Fr. 1995, 132, 428. (c)Smith,
N. D.; Kocienski, P. J.; Street, S. D. A. Synthesis 1996, 652.
13) (a) Hoppe, D. Angew. Chem., Int. Ed. Engl. 1984, 23, 932.
(
(b) Hoppe, D.; Zschage, O. Angew. Chem., Int. Ed. Engl.
1
4
1
1
989, 28, 69. (c) Zschage, O.; Hoppe, D. Tetrahedron 1992,
8, 8389. (d) Hoppe, D.; Hense, T. Angew. Chem. Int. Ed.
997, 36, 2282. (e) Paulsen, H.; Hoppe, D. Tetrahedron
992, 48, 5667. (f) Berque, I.; Le Menez, P.; Razon, P.;
2
Transformation of Vinylic Carbamate into sp -Organo-
zirconocene Derivatives; General Procedure
A soln of n-BuLi (3 equiv) in hexane was added slowly to a soln of
Mahuteau, J.; Ferezou, J. P.; Pancrazi, A.; Ardisson, J.;
Brion, J. D. J. Org. Chem. 1999, 64, 373.
ZrCp Cl (1.5 equiv) in anhyd solvent (10 mL) at –78 °C. Then, the
2
2
reaction mixture was warmed to 0 °C, stirred for 5 min, and cooled
again to –78 °C. To this soln, vinyl carbamate (1 equiv) was added
dropwise in anhyd solvent (3 mL). The reaction mixture was al-
lowed to warm to r.t. and stirred for the indicated time. The forma-
tion of the adduct was checked by gas chromatography. Then, the
(
14) (a) Kocienski, P.; Dixon, N. J. Synlett 1989, 52.
(
b) Wadman, S.; Whitby, R.; Yeates, C.; Kocienski, P.;
Cooper, K. J. Chem. Soc., Chem. Commun. 1987, 241.
c) Poree, F. H.; Clavel, A.; Betzer, J. F.; Pancrazi, A.;
Ardisson, J. Tetrahedron Lett. 2003, 44, 7553.
(15) Madec, D.; Pujol, S.; Henryon, V.; Ferezou, J. P. Synlett
995, 435.
16) Madec, D.; Henryon, V.; Ferezou, J. P. Tetrahedron Lett.
999, 40, 8103.
(
reaction mixture was cooled to 0 °C and solid I (2 equiv) was add-
2
ed. The mixture was warmed to r.t., stirred for 1 h, then cooled to
1
0
°C, and quenched with a 1 M aq soln of HCl (30 mL). The reaction
was warmed to r.t. and the phases were separated. The aqueous
phase was extracted with Et O (3 × 50 mL) and the combined or-
(
1
2
(17) Poree, F. H.; Barbion, J.; Dhulut, S.; Betzer, J. F.; Pancrazi,
ganic layers were washed with a sat. soln of Na S O (50 mL), and
2
2
3
A.; Ardisson, J. Synthesis 2004, 3017.
dried over anhydrous MgSO . The solvents were evaporated under
4
(18) For mixture of isomers, see: (a) Olofson, R. A.; Wooden, G.
P.; Marks, J. T. Eur. Pat. 104984, 1984; Chem. Abstr. 1984,
reduced pressure. All the physical data correlate with those of au-
thentic samples.2
9,30
101, 190657u. (b) Franco-Filipasic, B. R.; Patarcity, R.
Chem. Ind. 1969, 8, 166. (c) Shimizu, M.; Tanaka, E.;
Yoshioka, H. J. Chem. Soc., Chem. Commun. 1987, 136.
Acknowledgment
(
d) Olofson, R. A.; Schnur, R. C.; Bunes, L.; Pepe, J. P.
Tetrahedron Lett. 1977, 1567. (e) Lee, L. H. J. Org. Chem.
965, 30, 3943. (f) Olofson, R. A.; Bauman, B. A.;
This research was supported by the Israel Science Foundation admi-
nistrated by the Israel Academy of Sciences and Humanities (459/
1
Vancowicz, D. J. J. Org. Chem. 1978, 43, 752. (g) Mahe,
R.; Dixneuf, P. H.; Lecolier, S. Tetrahedron Lett. 1986, 27,
0
4) and by the Fund for the Promotion of Research at the Technion.
I.M. is holder of the Sir Michael and Lady Sobell Academic Chair.
6333. (h) Mahe, R.; Sasaki, Y.; Bruneau, C.; Dixneuf, P. H.
J. Org. Chem. 1989, 54, 1518. (i) Hofer, J.; Doucet, H.;
Bruneau, C.; Dixneuf, P. H. Acc. Chem. Res. 1999, 32, 311.
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(
(
1) Liard, A.; Marek, I. J. Org. Chem. 2000, 65, 7218.
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(
5
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(
(
3) Farhat, S.; Marek, I. Angew. Chem. Int. Ed. 2001, 624, 1410.
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(
1329. (b) Chinkov, N.; Chechik, H.; Majumdar, S.; Liard,
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A.; Marek, I. Synthesis 2002, 2473.
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(
(
(
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Zirconocene Complexes, In Topics in Organometallic
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(
Synthesis 2005, No. 19, 3311–3318 © Thieme Stuttgart · New York

3
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H. Chechik-Lankin, I. Marek
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(
(
20) Normant, J. F.; Alexakis, A. Synthesis 1981, 841.
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(
b) Mori, S.; Nakamura, E. J. Mol. Struct. 1999, 5, 1534.
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(
(
7
23) (a) Normant, J. F.; Alexakis, A.; Commercon, A.; Cahiez,
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(30) (a) Brown, H. C.; Somayaji, V.; Richard, B. Synthesis 1984,
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16644-98-7.
G.; Villieras, J. C. R. Seances Acad. Sci., Ser. C 1974, 279,
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(
d) Alexakis, A.; Cahiez, G.; Normant, J.; Villieras, J. Bull.
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(
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1987, 28, 789.
Synthesis 2005, No. 19, 3311–3318 © Thieme Stuttgart · New York