Zirconium-Mediated Cross-Coupling of Terminal Alkynes and Vinyl Bromides: Selective Synthesis of Cyclobutene and 1,3-Diene Derivatives

Article abstract of DOI:10.1002/chem.200305337

A diastereoselective synthesis of 1,3-butadiene or cyclobutene derivatives by a zirconium-mediated reaction of alkenyllithium compounds and vinyl bromides is reported. The key steps involve the generation of zirconocene-alkyne complexes from haloalkenes and subsequent coupling with alkenyl bromides. Thus, formally the process supposes the cross-coupling reaction between a terminal alkyne and an alkenyl bromide. Moreover, the use of butyl vinyl ether instead of vinyl bromide as the unsaturated system allows an alternative access to different 1,3-butadiene regioisomers.

Full text of DOI:10.1002/chem.200305337

FULL PAPER
Zirconium-Mediated Cross-Coupling of Terminal Alkynes and Vinyl
Bromides: Selective Synthesis of Cyclobutene and 1,3-Diene Derivatives
Josÿ Barluenga,* Fÿlix RodrÌguez, LucÌa çlvarez-Rodrigo, and Francisco J. FaÊanµs[a]
Abstract: A diastereoselective synthesis of 1,3-butadiene or cyclobutene deriva-
tives by a zirconium-mediated reaction of alkenyllithium compounds and vinyl
bromides is reported. The key steps involve the generation of zirconocene alkyne
complexes from haloalkenes and subsequent coupling with alkenyl bromides. Thus,
formally the process supposes the cross-coupling reaction between a terminal
alkyne and an alkenyl bromide. Moreover, the use of butyl vinyl ether instead of
vinyl bromide as the unsaturated system allows an alternative access to different
1,3-butadiene regioisomers.
Keywords: dienes ¥ CÀC coupling ¥
cross-coupling
zirconium
¥
cyclobutenes
¥
Introduction
we published for the first time zirconium-mediated coupling
reactions with electron-rich olefins to obtain functionalized
1,3-butadienes (Scheme 1).[10]
Low-valent metals from the two ends of the transition series
have been widely used for the reductive coupling of unsatu-
rated molecules.[1] Usually, this process occurs through a
metallacycle intermediate which can be easily transformed
into a variety of interesting products.[2] In the last few years,
the development of new synthetic methodologies mediated
by organozirconium compounds has provided a variety of
possibilities for the efficient preparation of a multitude of
organic molecules.[3] Particularly interesting is the function-
alization of unactivated alkynes through the formation of
zirconacycles from a zirconocene alkyne complex.[4] The
Negishi system,[5] which is used for the generation of these
zirconocene alkyne complexes, has become a powerful tool
in organic synthesis. This reagent has been successfully used
in the key step in the synthesis of several natural products.[6]
However, a major restriction of this system is that substrates
containing terminal alkynes cannot be used, presumably due
to the ready oxidative addition of the electron-rich metallo-
cene to the acidic acetylene hydrogen atom.[7] An alternative
method for the formation of zirconocene alkyne complexes
involves a b-hydrogen activation process.[8] By using this ap-
proach we reported the first zirconium-mediated intramolec-
ular coupling of terminal alkynes.[9] Moreover, back in 1995
Scheme 1. Zirconium-mediated cross-coupling reaction of alkenyl bro-
mides and enol ethers or vinyl bromide. Cp=cyclopentadiene.
Herein we report a more detailed study of this reaction.
Thus, we have used different vinyl lithium derivatives as
synthetic equivalents of terminal alkynes in zirconium-medi-
ated coupling reactions with vinyl bromides and vinyl
ethers. These reactions allowed us to access different 1,3-bu-
tadiene regioisomers by just varying the nature of the olefin
used.
Results and Discussion
Zirconium-mediated cross-coupling of N-methyl-N-proparg-
yl aniline and vinyl bromides: As shown in Scheme 1, treat-
ment of N-(2-bromoallyl)-N-methylaniline (1) with tert-bu-
tyllithium at À788C followed by reaction with zirconocene
methyl chloride at temperatures ranging between À78 and
[a] Prof. Dr. J. Barluenga, Dr. F. RodrÌguez, L. çlvarez-Rodrigo,
Dr. F. J. FaÊanµs
Instituto Universitario de QuÌmica Organometµlica ™Enrique Moles∫
Unidad Asociada al CSIC, Universidad de Oviedo
Juliµn ClaverÌa 8, 33006 Oviedo (Spain)
208C affords the zirconacyclopropene 2. As reported in our
[10a]
previous communication,
complex 2 reacts with vinyl
Fax : (+34)985-103450
E-mail: barluenga@sauron.quimica.uniovi.es
bromide 4a (R=H) to form dienes 3 (57% yield) or 6 (59%
101
¹ 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2004, 10, 101 108
DOI: 10.1002/chem.200305337

FULL PAPER
yield) depending on the electrophile used in last step of
the reaction (iodine or aqueous hydrochloric acid, respec-
tively; Scheme 2). However, in a careful study of this reac-
lithium at À788C, with zirconocene methyl chloride in tetra-
hydrofuran at temperatures ranging between À78 and À608C,
followed by addition of different vinyl bromides 4 and
warming to 658C, led after reaction with the appropriate
electrophile to dienes 9 or 10 in different ratios depending
on the structure of the starting organolithium compound
and the structure of the vinyl bromide used (Scheme 3 and
Table 1).
Scheme 2. Zirconium-mediated cross-coupling reaction with alkenyl bro-
mides 4.
Scheme 3. 1,3-butadienes 9 and/or 10 from the zirconium-mediated cross-
coupling reaction of organolithium derivatives 8 and alkenyl bromides 4.
tion we have also observed the formation of dienes 5a (28%
yield) and 5b (30% yield) as minor products of the reaction.
Note that dienes 5a and 5b are regioisomers of 3 and 6,
respectively. When we tried to extend the reaction to
other vinyl bromides such as 1-bromo-1-propene (4b;
R=Me), surprisingly, only dienes 5c,d were obtained in
high yield and the expected diene regioisomers analogous
to 3 or 6 were not observed
From the analysis of the results summarized in Table 1
some trends can be inferred. The use of vinyl bromide 4a
led to mixtures of dienes 9 and 10 when the R1 group of the
alkenyllithium 8 was an alkyl chain (Table 1, entries 1,2).
However, the major products of the reactions were the
(Scheme 2).
Table 1. 1,3-butadienes 9 and/or 10 from organolithium derivatives 8 and alkenyl bromides 4.
Entry
R1
8
R
4
E+ (E)
Product
Yield [%][a]
Zirconium-mediated coupling
reactions of alkenyllithium de-
rivatives and vinyl bromides:
Taking into account the results
described above for the prop-
argyl aniline zirconocene com-
plex 2, we decided to investi-
gate the behavior of other vinyl
lithium derivatives as synthetic
equivalents of terminal alkynes
in zirconium-mediated coupling
reactions with vinyl bromides.
Thus, the reaction of organo-
lithium compounds 8, easily ob-
tained from the corresponding
vinyl bromides 7 and tert-butyl-
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
PhCH2
Ph(CH2)3
Ph
8a
8b
8c
8d
8a
8b
8a
8a
8a
8a
8e
8b
8c
8d
8f
H
H
H
H
Ph
Ph
Me
Me
Me
Me
Me
Me
Me
Me
Me
Hex
Hex
4a
4a
4a
4a
H2O (H)
H2O (H)
H2O (H)
H2O (H)
H2O (H)
H2O (H)
H2O (H)
D2O (D)
D2O (D)
D2O (D)
H2O (H)
H2O (H)
I2 (I)
9a/10a
9b/10b
9c
22/60
24/62
69
4-MeC6H4
PhCH2
Ph(CH2)3
PhCH2
PhCH2
PhCH2
PhCH2
Ph(CH2)2
Ph(CH2)3
Ph
9d
72
trans-4c
trans-4c
4b[b]
9e/10c
9f/10d
10e
10f
10f
10f
10g
10h
10i
10j
54/32
55/35
88
83
77
80
70
71
65
71
69
81
77
4b[b]
cis-4b
trans-4b
4b[b]
4b[b]
4b[b]
4-MeC6H4
tBu
PhCH2
Ph(CH2)3
4b[b]
I2 (I)
I2 (I)
H2O (H)
H2O (H)
4b[b]
10k
10l
10m
8a
8b
trans-4d
trans-4d
[a] Isolated yield based on starting alkenyl halides 7. [b] 1:1 cis/trans mixture.
dienes 10, which were easily separated from the minor prod-
ucts 9. To our surprise, when the reactions were carried out
with organolithium compounds 8c,d, where R1 is an aromat-
ic group, we obtained exclusively the−extended× dienes 9 and
the corresponding−branched× dienes 10 were not observed in
the crude mixtures of the reactions (Table 1, entries 3,4).
When the phenyl-substituted vinyl bromide trans-4c was
used in the reaction with alkyl-substituted organolithium de-
rivatives 8a,b, the reaction also afforded mixtures of the
dienes 9 and 10, with the former being the major regioisom-
er (Table 1, entries 5,6). Interestingly, all experiments car-
ried out with alkyl-substituted vinyl bromides 4b,d led, in-
dependently of the structure of the starting organolithium
Abstract in Spanish: Se describe una sÌntesis diastereoselecti-
ve de 1,3-butadienos o ciclobutenos a travÿs de una reacciÛn
entre compuestos alquenillitio y bromuros de alquenilo pro-
movida por complejos de zirconio. Los pasos claves de este
proceso son la generaciÛn de un complejo alquino-zirconoce-
no a partir de un haloalqueno y la posterior reacciÛn de aco-
plamiento con bromuros de alquenilo. AsÌ, formalmente el
proceso supone el acoplamiento entre un alquino terminal y
un bromuro de alquenilo. Ademµs, el uso de vinilÿteres como
sistema insaturado en lugar de bromuro de vinilo permite ac-
ceder alternativamente a los 1,3-butadienos regioisÛmeros.
102
¹ 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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Chem. Eur. J. 2004, 10, 101 108

Zirconium-Mediated Cross-Coupling
101 108
compound 8, to the exclusive isolation of the corresponding
branched dienes 10e m, while extended dienes 9 were not
observed in the crude mixtures of any of these reactions
(Table 1, entries 7 17). Highly remarkable are the results
from the zirconium-promoted coupling reaction of 8a and 1-
bromo-1-propene (4b; cis, trans, or a mixture of both stereo-
isomers), in which, independently of the stereochemistry of
4b, the same stereoisomer of diene 10f is formed when deu-
terium oxide was used as the electrophile (Table 1, en-
tries 8 10).
11c,d depending only on the electrophile used in last step of
the reaction (Table 2, entries 3,4). However, when the reac-
tion was warmed to 408C for 2 h, a mixture of diene 10f
and cyclobutene 11d was obtained (Table 2, entry 5). At this
point it should be remembered that the reaction at 658C led
exclusively to diene 10f (see Scheme 3 and Table 1, entry 8).
Moreover, when this reaction was slowly warmed from 25 to
658C and followed by thin-layer chromatography (TLC),
formation of cyclobutene 11 could be observed at first and
then the spot corresponding to this product slowly vanished
and a new spot corresponding to diene 10 appeared; finally,
after 1 h at 658C only the spot corresponding to the latter
compound was observed. Even more surprising results were
obtained when the reaction was carried out with cis-4b,
trans-4b, or the mixture of both stereoisomers (Table 2, en-
tries 4,6,7). All these experiments led to the same diaster-
eoisomer of the cyclobutene 11d, as unequivocally deter-
mined by NMR spectroscopy experiments.
Preparation of cyclobutene derivatives: To gain some insight
into the mechanism of the reaction we performed a set of
experiments with several organolithium compounds 8 and
vinyl bromides 4 while varying the temperature of the reac-
tion. Also, with these experiments we wanted to study the
influence of the temperature on the ratio of dienes 9/10 in
those cases where mixtures of both were obtained. The reac-
tions were carried out as described above but the tempera-
ture was maintained at 258C for 18 h. Under these condi-
tions formation of the expected dienes 10 was not observed
and instead cyclobutenes 11 were isolated (Scheme 4 and
Table 2). The structure of cyclobutenes 11 was determined
by NMR spectroscopy experiments.
Zirconium-mediated coupling reactions of alkenyllithium
derivatives and butyl vinyl ether: As shown in Scheme 3 and
Table 1 (entries 1,2), the reaction of zirconocene alkyne
complexes derived from an alkyl-substituted organolithium
compound 8a,b with vinyl bromide 4a led to separable mix-
tures of dienes 9 and 10, with the branched diene 10 being
the major product of the reaction. Intrigued by the possibili-
ty of obtaining diene 9 as the main product of the reaction
and taking into account our previously reported results on
the reaction of zirconocene alkyne complexes with vinyl
ethers,[10a] we decided to carry out a set of experiments with
different organolithium compounds 8 and butyl vinyl ether
(Scheme 5 and Table 3). If this succeeded, we would be able
to obtain either diene 9 or 10 only by choosing between
vinyl bromide or butyl vinyl ether as the counterpart in the
zirconium-mediated coupling reaction of organolithium de-
rivatives 8.
Scheme 4. Cyclobutene derivatives 11 from the zirconium-mediated
cross-coupling reaction of organolithium derivatives 8 and alkenyl bro-
mides 4.
Analysis of Table 2 showed us several interesting features.
For example, when vinyl bromide 4a was used, variable
amounts of dienes 9 were obtained together with major
products 11 (Table 2, entries 1,2). It should be noted that in
these cases the amount of 9 is similar to that obtained when
the reaction was carried out at 658C (see Scheme 3 and
Table 1, entries 1,2). More interesting results were obtained
from several experiments performed with organolithium
compound 8a and 1-bromo-1-propene (4b). As mentioned
before, at 258C the reaction gave exclusively cyclobutenes
Scheme 5. 1,3-butadienes 9 from the zirconium-mediated cross-coupling
reaction of organolithium derivatives 8 and butyl vinyl ether.
The reaction was performed
following a procedure similar to
the one before described. Thus,
after addition of the butyl vinyl
ether at À608C the solution
was allowed to warm first to
room temperature and then to
658C for one hour. After addi-
tion of the corresponding elec-
trophile the reaction was
worked up to obtain extended
Table 2. Cyclobutenes 11 from organolithium derivatives 8 and alkenyl bromides 4.
Entry
R1
8
R
4
T [oC]
E+ (E)
Product
Yield [%][a]
1
2
3
4
5
6
7
8
9
PhCH2
Ph(CH2)2
PhCH2
PhCH2
PhCH2
PhCH2
PhCH2
Ph(CH2)2
Ph(CH2)3
8a
8e
8a
8a
8a
8a
8a
8e
8b
H
H
4a
4a
25
25
25
25
40
25
25
25
25
H2O (H)
H2O (H)
H2O (H)
D2O (D)
D2O (D)
D2O (D)
D2O (D)
H2O (H)
H2O (H)
11a[b]
11b[c]
11c
11d
10f/11d
11d
11d
11e
11f
56
61
72
75
35/44
68
72
70
66
Me
Me
Me
Me
Me
Me
Me
4b[d]
4b[d]
4b[d]
cis-4b
trans-4b
4b[d]
4b[d]
[a] Isolated yield based on starting alkenyl halides 7. [b] 24% of 9a was also isolated. [c] 21% of 9b was also
isolated. [d] 1:1 cis/trans mixture.
dienes
9
(Scheme 5
and
103
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J. Barluenga et al.
FULL PAPER
Table 3. 1,3-butadienes 9 from organolithium derivatives 8 and butyl
vinyl ether.
phile (path a in Scheme 6). Reaction with butyl vinyl ether
also follows this mechanism to give diene 9 in all cases. On
the other hand, formation of diene 10 and cyclobutene 11
can be understood from intermediate 14B through an intra-
molecular migratory insertion process to afford cyclobu-
tene zirconocene complex 16.[11] Quenching of this inter-
mediate with the electrophile leads to cyclobutene deriva-
tive 11. Moreover, thermal cleavage of cyclobutene complex
16 affords the new diene zirconocene complex 17, which
gives diene 10 after reaction with the electrophile. Forma-
tion of diene 10 and cyclobutene 11 from the same inter-
mediate 16 seems undoubted from analysis of the results
summarized in Tables 1 and 2 (compare entries 4 and 5 of
Table 2 with entry 8 of Table 1). Thus, the experiments car-
ried out at room temperature led to cyclobutene 11, whereas
at higher temperatures the ring-opening process is favored
to give 17 and finally diene 10.
The different outcome of the reaction leading to dienes 9
or 10 when vinyl bromides 4a d are used can be explained
by a combination of electronic and steric effects. As repre-
sented in Scheme 6 formation of one or the other diene
only depends on the orientation of the vinyl bromide in the
insertion process to afford 14A or 14B. The electronic ef-
fects favor the orientation depicted in Scheme 7 to give re-
Entry
R1
8
E+ (E)
Product
Yield [%][a]
1
2
3
4
5
PhCH2
8a
8e
8b
8c
8d
I2 (I)
9g
9h
9b
9c
9d
82
85
86
78
80
Ph(CH2)2
Ph(CH2)3
Ph
H2O (H)
H2O (H)
H2O (H)
H2O (H)
4-MeC6H4
[a] Isolated yield based on starting alkenyl halides 7.
Table 3). No traces of regioisomer dienes 10 were observed
in any case in the crude mixtures of the reactions. Maybe,
the most interesting results were obtained from the reaction
with alkyl-substituted organolithium compounds 8a,b,e
(Table 3, entries 1 3). These results can be considered com-
plementary to those obtained from the reaction with vinyl
bromide 4a (see Scheme 3 and Table 1, entries 1,2). On the
other hand, the reactions with aromatic-substituted organo-
lithium derivatives 8c,d led to extended dienes 9c,d with
either vinyl bromide (Table 1, entries 3,4) or butyl vinyl
ether (Table 3, entries 4,5).
Mechanisms of the reactions: A plausible mechanism that
explains the formation of dienes 9 or 10 and cyclobutene 11
is outlined in Scheme 6. First, addition of organolithium
Scheme 7. Orientation of alkenyl bromides and enol ethers during the in-
sertion process. Electronic and steric effects.
gioisomer 14B and finally diene 10.[12] However, steric hin-
drance between the Cp ligands of the zirconocene moiety
and the bromide or the R group also has to be taken into
account. Thus, when vinyl bromide 4a (R=H) is used, the
electronic effects favor formation of 14B but the steric fac-
tors favor the regioisomer 14A. These two opposite effects
would explain the formation of mixtures of dienes 9 and 10
in certain cases. When the vinyl bromide has an alkyl sub-
stituent (4b or 4d) there is a comparative hindrance be-
tween the Cp ligands and the bromine atom or R group. In
these cases the electronic effects dominate and formation of
14B and finally diene 10 is preferred. The formation of mix-
tures of dienes 9 and 10 when b-bromostyrene (4c) is used
could presumably be attributed to the comparative steric
and electronic effects between the bromine and the phenyl
group. Thus, both orientations are possible in the insertion
reaction of 4c into 13 and mixtures of 9 and 10 are obtained.
Finally, in the insertion reaction of vinyl ethers, both the
electronic and steric effects favor the formation of diene 9
from an intermediate analogous to 14A, as depicted in
Scheme 7 (see also Scheme 6).[12]
Scheme 6. Proposed mechanism for the formation of dienes 9 and 10 and
cyclobutenes 11.
compound 8 to zirconocene methyl chloride gives the meth-
yl(vinyl)zirconocene complex 12. A cyclometalation reaction
and subsequent elimination of methane leads to zircono-
cene alkyne derivative 13. The insertion of the double bond
of the vinyl bromide takes place regioselectively at the less
hindered zirconium carbon bond of 13. However, depending
on the orientation of the vinyl bromide during the insertion
step, two different zirconacyclopentene derivatives, 14A or
14B, can be obtained. Intermediate 14A can undergo b
elimination of bromine to give butadiene zirconocene deriv-
ative 15, which gives diene 9 after reaction with an electro-
Probably, the most surprising and intriguing results descri-
bed in this work are those that refer to the formation of the
same diastereoisomer of cyclobutadiene 11d independently
104
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Chem. Eur. J. 2004, 10, 101 108

Zirconium-Mediated Cross-Coupling
101 108
Tetrahydrofuran (THF), hexane, and Et2O were distilled over sodium
benzophenone ketyl under N2 immediately prior to use, and CH2Cl2 was
distilled over P2O5. The solvents used in column chromatography, hexane
and EtOAc, were distilled before use. TLC was performed on aluminum-
backed plates coated with silica gel 60 with F254 indicator (Scharlau).
Flash column chromatography was carried out on silica gel 60, 230 240
mesh. 1H NMR (200, 300, 400 MHz) and 13C NMR (50.5, 75.5, 100 MHz)
spectra were measured at room temperature on Bruker AC-200, AC-300,
and AMX-400 instruments, respectively, with tetramethylsilane (d=
0.0 ppm, 1H NMR) or CDCl3 (d=77.00 ppm, 13C NMR) as the internal
standard. Carbon multiplicities were assigned by DEPT techniques.
High-resolution mass spectra (HRMS) were determined on a Finnigan
MAT 95 spectrometer. Elemental analyses were carried out on a Perkin
Elmer 2400 microanalyzer.
General procedure for the preparation of dienes 3, 5, 6, 9, and 10: tert-
Butyllithium (2 mmol) was added to a stirred solution of the required al-
kenyl bromide (or iodide) 1 or 7 (1 mmol) in dry THF (10 mL) at À78
8C. After being stirred at this temperature for 30 min, the solution was
added dropwise through a cannula to a stirred solution of bis(cyclopenta-
dienyl)zirconium methyl chloride (1.2 mmol) in dry THF (10 mL) at À78
8C. After 30 min at this temperature, an excess of the appropriate alkenyl
bromide 4 (3 10 mmol; 10 mmol of butyl vinyl ether can also be used,
see Table 3) was added. The mixture was allowed to warm to room tem-
perature and then heated to reflux for 3 h. The reaction was cooled to
room temperature and the required electrophile was added (an excess of
water, deuterium oxide, or iodine (2 mmol)). After 1 hour, the reaction
was worked up by addition of water (20 mL) or a saturated solution of
sodium thiosulphate (20 mL, when iodine was used as electrophile) and
extracted with diethyl ether (3î10 mL). The combined organic layers
were dried over anhydrous sodium sulphate and concentrated, and the
residue was purified by column chromatography to give compounds 3, 5,
6, 9, or 10.
Scheme 8. Proposed mechanism for the formation of the same diaster-
eiosomer of 10 or 11 from trans-4b or cis-4b.
of the cis or trans geometry of the vinyl bromide 4b. Al-
though more detailed studies must be done, we tentatively
propose the mechanism depicted in Scheme 8 to explain
these facts. Thus, we think that the insertion of vinyl bro-
mide 4b into the zirconium carbon bond is a nonsynchro-
nous process, which formally generates intermediates I or II
from trans-4b or cis-4b, respectively.[13] Rotation around the
s bond would allow the conversion of one intermediate into
the other. Formation of compounds 10 and 11 could be ex-
plained both from trans-14B and from cis-14B. From trans-
14B, a migratory insertion reaction with retention of config-
uration would lead to 16. Alternatively, a migratory inser-
tion reaction with inversion of configuration on cis-14B
would also lead to compound 16. Finally, a conrotatory
cleavage of intermediate 16 affords diene 17 (precursor of
diene 10), or reaction of 16 with the corresponding electro-
phile gives cyclobutene 11 where the Me and E groups are
in a cis arrangement.
N-[(Z)-2-Iodo-2,4-pentadienyl]-N-methylaniline (3) and N-{2-[(E)-2-io-
domethylene]-3-butenyl}-N-methylaniline (5a): Alkenyl bromide
1
(0.23 g, 1 mmol) was treated with tBuLi (1.2 mL, 2 mmol) and
[Cp2Zr(Me)Cl] (0.34 g, 1.2 mmol). This was followed by addition of vinyl
bromide 4a (0.35 mL, 5 mmol). After addition of iodine (0.52 g, 2 mmol)
and the extractive work-up, the resulting crude product was purified by
silica gel column chromatography (hexane/CH2Cl2 (4:1)). 3: 1H NMR
(300 MHz, CDCl3): d=7.31 7.21, 6.82 6.71 (2îm, 5H; ArH), 6.90 (dt,
J=16.6, 9.8 Hz, 1H; CH=CH2), 6.72 (d, J=9.8 Hz, 1H; CI=CH), 5.81
5.63 (m, 2H; CH=CH2), 4.60 (s, 2H; NCH2), 3.42 (s, 3H; NCH3) ppm;
13C NMR (100 MHz, CDCl3): d=148.4, 138.0, 132.2, 129.1, 121.0, 117.0,
111.9, 107.2, 65.2, 38.3 ppm; HRMS (EI): calcd for C12H14IN: 299.0170;
found: 299.0164; elemental analysis: calcd (%) for C12H14IN: C 48.18, H
4.72, N 4.68; found: C 48.35, H 4.63, N 4.51. 5a: 1H NMR (300 MHz,
CDCl3): d=7.41 7.28, 6.92 6.72 (2îm, 6H; ArH and CH2d=CH), 6.39 (s,
1H; CHI), 5.53 (d, J=17.8 Hz, 1H; CHH=CH), 5.46 (d, J=11.4 Hz, 1H;
CHH=CH), 4.20 (s, 2H; NCH2), 3.05 (s, 3H; NCH3) ppm; 13C NMR
(100 MHz, CDCl3): d=148.9, 139.9, 136.8, 129.0, 117,4, 116.6, 111.8, 81.9,
56.0, 38.3 ppm; HRMS (EI): calcd for C12H14IN: 299.0170; found:
299.0166; elemental analysis: calcd (%) for C12H14IN: C 48.18, H 4.72, N
4.68; found: C 48.28, H 4.63, N 4.56.
Conclusion
We have reported a diastereoselective synthesis of 1,3-buta-
diene or cyclobutene derivatives by a zirconium-mediated
reaction of alkenyllithium compounds and vinyl bromides.
The reaction is proposed to proceed through the formation
of an alkyne zirconocene intermediate and thus, formally,
this process supposes the cross-coupling reaction between a
terminal alkyne and an alkenyl bromide. Remarkably, the
insertion reaction occurs with complete regioselectivity with
respect to the zirconium complex and also with respect to
the alkenyl bromide in those cases where this is alkyl-substi-
tuted. Moreover, the use of butyl vinyl ether instead of vinyl
bromide as the unsaturated system allowed an alternative
access to different 1,3-butadiene regioisomers.
N-[(E)-2,4-Pentadienyl]-N-methylaniline (6) and N-methyl-N-(2-methyl-
ene-3-butenyl)aniline (5b): Alkenyl bromide
1 (0.23 g, 1 mmol) was
treated with tBuLi (1.2 mL, 2 mmol) and [Cp2Zr(Me)Cl] (0.34 g,
1.2 mmol). This was followed by addition of vinyl bromide 4a (0.35 mL,
5 mmol). After the extractive work-up, the resulting crude product was
purified by silica gel column chromatography (hexane/CH2Cl2 (4:1)). 6:
1H NMR (300 MHz, CDCl3): d=7.31 7.22, 6.81 6.71 (2îm, 5H; ArH),
6.50 6.10 (m, 2H; CH=CH=CH2), 5.75 (dt, J=14.7, 5.5 Hz, 1H;
NCH2CH=CH), 5.20 5.00 (m, 2H; CH=CH2), 4.0 (d, J=5.5 Hz, 2H;
NCH2), 3.00 (s, 3H; NCH3) ppm; 13C NMR (100 MHz, CDCl3): d=140.4,
136.3, 132.0, 129.8, 129.0, 116.5, 116.4, 112.4, 54.2, 37.9 ppm; HRMS (EI):
calcd for C12H15N: 173.1204; found: 173.1204; elemental analysis: calcd
(%) for C12H15N: C 83.19, H 8.73, N 8.08; found: C 83.30, H 8.58, N 8.11.
5b: 1H NMR (300 MHz, CDCl3): d=7.31 7.21, 6.78 6.67 (2îm, 5H;
ArH), 6.53 (dd, J=17.9, 11.2 Hz, 1H; CH2=CH), 5.27 (d, J=17.9 Hz, 1
H; CHH=CH), 5.17 (s, 1H; C=CHH), 5.16 (d, J=11.2 Hz, 1H; CHH=
CH), 5.06 (s, 1H; C=CHH), 4.12 (s, 2H; NCH2), 3.05 (s, 3H;
NCH3) ppm; 13C NMR (100 MHz, CDCl3): d=149.4, 140.5, 137.4, 129.0,
Experimental Section
General: All reactions involving organometallic species were carried out
under an atmosphere of dry N2 with oven-dried glassware and syringes.
105
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¹ 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

J. Barluenga et al.
FULL PAPER
116.0, 115.6, 113.4, 111.7, 53.7, 38.3 ppm; HRMS (EI): calcd for C12H15N:
173.1204; found: 173.1205; elemental analysis: calcd (%) for C12H15N: C
83.19, H 8.73, N 8.08; found: C 83.29, H 8.64, N 8.01.
gel column chromatography (hexane). Spectral data for 9e[18] were in
complete accordance with literature values. 10c: 1H NMR (300 MHz,
CDCl3): d=7.50 7.12 (m, 10H; ArH), 6.90 (d, J=16.4 Hz, 1H; PhCH=
CH), 6.62 (d, J=16.4 Hz, 1H; PhCH=CH), 5.33 (s, 1H; C=CHH), 5.01
(s, 1H; C=CHH), 3.71 (s, 2H; PhCH2) ppm; 13C NMR (100 MHz,
CDCl3): d=144.8, 139.2, 137.1, 130.5, 128.9, 128.7, 128.4, 128.2, 127.4,
126.3, 126.0, 118.6, 38.5 ppm; elemental analysis: calcd (%) for C17H16: C
92.68, H 7.32; found: C 92.79, H 7.19.
N-{2-[(E)-Iodomethylene]-3-pentenyl}-N-methylaniline (5c): Alkenyl
bromide 1 (0.23 g, 1 mmol) was treated with tBuLi (1.2 mL, 2 mmol) and
[Cp2Zr(Me)Cl] (0.34 g, 1.2 mmol). This was followed by addition of al-
kenyl bromide 4b (0.86 mL, 10 mmol). After addition of iodine (0.52 g,
2 mmol) and the extractive work-up, the resulting crude product was pu-
rified by silica gel column chromatography (hexane/CH2Cl2 (4:1)). 5c:
1H NMR (300 MHz, CDCl3): d=7.40 7.10, 6.85 6.60 (2îm, 5H; ArH),
6.50 (d, J=16.1 Hz, 1H; CH3CH=CH), 6.18 5.85 (m, 2H; CH3CH and
CHI), 4.10 (s, 2H; NCH2), 2.98 (s, 3H; NCH3), 1.89 (d, J=6.7 Hz, 3H;
CH3CH) ppm; 13C NMR (100 MHz, CDCl3): d=140.3, 134.3, 131.5, 129.6,
129.0, 116.6, 112.4, 111.8, 78.5, 56.5, 38.3, 18.8 ppm; HRMS (EI): calcd
for C13H16IN: 313.0327; found: 313.0324; elemental analysis: calcd (%)
for C13H16IN: C 49.86, H 5.15, N 4.47; found: C 49.94, H 5.06, N 4.33.
(E,E)-1,7-Diphenyl-1,3-heptadiene (9f) and (E)-1-phenyl-3-(3-phenyl-
propyl)-1,3-butadiene (10d): Alkenyl iodide 7b (0.27 g, 1 mmol) was
treated with tBuLi (1.2 mL, 2 mmol) and [Cp2Zr(Me)Cl] (0.34 g,
1.2 mmol). This was followed by addition of alkenyl bromide trans-4c
(0.40 mL, 3 mmol). After the extractive work-up, the resulting crude
product was purified by silica gel column chromatography (hexane). 9f:
1H NMR (300 MHz, CDCl3): d=7.52 7.14 (m, 10H; ArH), 6.85 (dd, J=
15.6, 10.4 Hz, 1H; PhCH=CH), 6.51 (d, J=15.6 Hz, 1H; PhCH=CH),
6.29 (dd, J=15.0, 10.4 Hz, 1H; PhCH=CH=CH), 5.91 (dt, J=15.0,
7.0 Hz, 1H; C=CHCH2), 2.73 (t, J=7.5 Hz, 2H; PhCH2), 2.26 (td, J=7.5,
7.0 Hz, 2H; Ph(CH2)2CH2), 1.84 (quintuplet, J=7.5 Hz, 2H;
PhCH2CH2) ppm; 13C NMR (100 MHz, CDCl3): d=142.2, 137.5, 135.1,
130.8, 130.0, 129.2, 128.4, 128.2, 127.0, 126.0, 125.6, 35.2, 32.2, 30.8 ppm;
elemental analysis: calcd (%) for C19H20: C 91.88, H 8.12; found: C 91.85,
H 8.10. 10d: 1H NMR (300 MHz, CDCl3): d=7.48 7.18 (m, 10H; ArH),
6.85 (d, J=16.4 Hz, 1H; PhCH=CH), 6.53 (d, J=16.4 Hz, 1H; PhCH=
CH), 5.20 (s, 1H; C=CHH), 5.12 (s, 1H; C=CHH), 2.74 (t, J=7.6 Hz, 2
H, PhCH2), 2.41 (t, J=7.7 Hz, 2H; Ph(CH2)2CH2), 1.98 1.87 (m, 2H;
PhCH2CH2) ppm; 13C NMR (100 MHz, CDCl3): d=145.7, 142.2, 137.2,
130.8, 128.4, 128.2, 127.9, 127.3, 126.3, 125.7, 116.3, 35.6, 31.4, 29.9 ppm;
elemental analysis: calcd (%) for C19H20: C 91.88, H 8.12; found: C 92.04,
H 7.93.
N-Methyl-N-(2-methylene-3-pentenyl)aniline (5d): Alkenyl bromide
1
(0.23 g, 1 mmol) was treated with tBuLi (1.2 mL, 2 mmol) and
[Cp2Zr(Me)Cl] (0.34 g, 1.2 mmol). This was followed by addition of al-
kenyl bromide 4b (0.86 mL, 10 mmol). After the extractive work-up, the
resulting crude product was purified by silica gel column chromatography
(hexane/CH2Cl2 (4:1)). 5d: 1H NMR (300 MHz, CDCl3): d=7.29 7.15,
6.80 6.60 (2îm, 5H; ArH), 6.21 (d, J=16.1 Hz, 1H; CH3CH=CH), 6.76
(dq, J=16.1, 6.7 Hz, 1H; CH3CH), 5.06 (s, 1H; C=CHH), 4.88 (s, 1H;
C=CHH), 4.06 (s, 2H; NCH2), 2.98 (s, 3H; NCH3), 1.83 (d, J=6.7 Hz, 3
H; CH3CH) ppm; 13C NMR (100 MHz, CDCl3): d=149.4, 140.3, 131.7,
128.9, 124.9, 115.9, 112.8, 111.6, 54.2, 38.2, 18.5 ppm; HRMS (EI): calcd
for C13H17N: 187.1361; found: 187.1360; elemental analysis: calcd (%) for
C12H15N: C 83.37, H 9.15, N 7.48; found: C 83.45, H 9.13, N 7.37.
(E)-5-Phenyl-1,3-pentadiene (9a) and 2-benzyl-1,3-butadiene (10a): Al-
kenyl iodide 7a (0.24 g, 1 mmol) was treated with tBuLi (1.2 mL,
2 mmol) and [Cp2Zr(Me)Cl] (0.34 g, 1.2 mmol). This was followed by ad-
dition of vinyl bromide 4a (0.35 mL, 5 mmol). After the extractive work-
up, the resulting crude product was purified by silica gel column chroma-
(E)-2-Benzyl-1,3-pentadiene (10e): Alkenyl iodide 7a (0.24 g, 1 mmol)
was treated with tBuLi (1.2 mL, 2 mmol) and [Cp2Zr(Me)Cl] (0.34 g,
1.2 mmol). This was followed by addition of alkenyl bromide 4b
(0.86 mL, 10 mmol). After the extractive work-up, the resulting crude
product was purified by silica gel column chromatography (hexane). 10e:
1H NMR (400 MHz, CDCl3): d=7.42 7.19 (m, 5H; ArH), 6.17 (dq, J=
15.7, 1.5 Hz, 1H; CH3CH=CH), 5.77 (dq, J=15.7, 6.7 Hz, 1H; CH3CH),
5.07 (s, 1H; (Z)C=CHH), 4.80 (s, 1H; (E)C=CHH), 3.56 (s, 2H; PhCH2),
1.77 (dd, J=6.7, 1.5 Hz, 3H; CH3) ppm; 13C NMR (100 MHz, CDCl3):
d=145.0, 139.7, 132.8, 128.7, 128.1, 125.9, 125.8, 115.4, 38.7, 18.2 ppm; el-
emental analysis: calcd (%) for C12H14: C 91.08, H 8.92; found: C 91.17,
H 8.82.
[15]
tography (hexane). Spectral data for 9a[14] and 10a were in complete
accordance with literature values.
(E)-7-Phenyl-1,3-heptadiene (9b) and 2-(3-phenylpropyl)-1,3-butadiene
(10b): Alkenyl iodide 7b (0.27 g, 1 mmol) was treated with tBuLi
(1.2 mL, 2 mmol) and [Cp2Zr(Me)Cl] (0.34 g, 1.2 mmol). This was fol-
lowed by addition of vinyl bromide 4a (0.35 mL, 5 mmol) or butyl vinyl
ether (1.29 mL, 10 mmol). After the extractive work-up, the resulting
crude product was purified by silica gel column chromatography
(hexane). Spectral data for 9b[16] were in complete accordance with liter-
ature values. 10b: 1H NMR (300 MHz, CDCl3): d=7.38 7.20 (m, 5H;
ArH), 6.41 (dd, J=17.7, 10.7 Hz, 1H; CH=CH2), 5.32 (s, 1H; C=CHH),
5.23 (d, J=17.7 Hz, 1H; CH=CHH), 5.09 (d, J=10.7 Hz, 1H; CH=
CHH), 5.07 (s, 1H; C=CHH), 2.70 (t, J=7.5 Hz, 2H; PhCH2), 2.30 (t,
J=7.5 Hz, 2H; Ph(CH2)2CH2), 1.95 1.70 (m, 2H; PhCH2CH2) ppm;
13C NMR (100 MHz, CDCl3): d=146.0, 142.3, 138.8, 128.3, 128.2, 125.6,
115.7, 113.1, 35.6, 30.8, 29.7 ppm; elemental analysis: calcd (%) for
C13H16: C 90.64, H 9.36; found: C 90.73, H 9.26.
(1Z,3E)-2-Benzyl-1-deuterio-1,3-pentadiene (10f): Alkenyl iodide 7a
(0.24 g, 1 mmol) was treated with tBuLi (1.2 mL, 2 mmol) and
[Cp2Zr(Me)Cl] (0.34 g, 1.2 mmol). This was followed by addition of al-
kenyl bromide 4b (or cis-4b or trans-4b; 0.86 mL, 10 mmol). After addi-
tion of D2O (1 mL) and the extractive work-up, the resulting crude prod-
uct was purified by silica gel column chromatography (hexane). 10f:
1H NMR (300 MHz, CDCl3): d=7.40 7.17 (m, 5H; ArH), 6.17 (dq, J=
15.7, 1.5 Hz, 1H; CH3CH=CH), 5.77 (dq, J=15.7, 6.7 Hz, 1H; CH3CH),
4.79 (s, 1H; C=CHD), 3.56 (s, 2H; PhCH2), 1.77 (dd, J=6.7, 1.5 Hz, 3H;
CH3) ppm; 13C NMR (100 MHz, CDCl3): d=144.8, 139.7, 132.8, 128.7,
128.2, 125.9, 125.8, 115.1 (t, J=14 Hz), 38.7, 18.2 ppm.
(E)-1-Phenyl-1,3-butadiene (9c): Alkenyl bromide 7c (0.13 mL, 1 mmol)
was treated with tBuLi (1.2 mL, 2 mmol) and [Cp2Zr(Me)Cl] (0.34 g,
1.2 mmol). This was followed by addition of vinyl bromide 4a (0.35 mL,
5 mmol) or butyl vinyl ether (1.29 mL, 10 mmol). After the extractive
work-up, the resulting crude product was purified by silica gel column
chromatography (hexane). Spectral data for 9c[14] were in complete ac-
cordance with literature values.
(E)-2-(2-Phenylethyl)-1,3-pentadiene (10g): Alkenyl iodide 7e (0.26 g,
1 mmol) was treated with tBuLi (1.2 mL, 2 mmol) and [Cp2Zr(Me)Cl]
(0.34 g, 1.2 mmol). This was followed by addition of alkenyl bromide 4b
(0.86 mL, 10 mmol). After the extractive work-up, the resulting crude
product was purified by silica gel column chromatography (hexane). 10g:
1H NMR (300 MHz, CDCl3): d=7.41 7.10 (m, 5H; ArH), 6.15 (d, J=
15.9 Hz, 1H; CH3CH=CH), 5.73 (dq, J=15.9, 6.7 Hz, 1H; CH3CH), 4.94
(s, 1H; C=CHH), 4.90 (s, 1H; C=CHH), 2.84 (t, J=7.8 Hz, 2H; PhCH2),
2.49 (t, J=7.8 Hz, 2H; PhCH2CH2), 1.83 (d, J=6.7 Hz, 3H, CH3) ppm;
13C NMR (100 MHz, CDCl3): d=145.4, 141.6, 133.1, 128.3, 128.1, 125.6,
124.6, 113.1, 34.6, 34.0, 18.1 ppm; elemental analysis: calcd (%) for
C13H16: C 90.64, H 9.36; found: C 90.73, H 9.25.
(E)-1-(4-Tolyl)-1,3-butadiene (9d): Alkenyl iodide 7d (0.24 g, 1 mmol)
was treated with tBuLi (1.2 mL, 2 mmol) and [Cp2Zr(Me)Cl] (0.34 g,
1.2 mmol). This was followed by addition of vinyl bromide 4a (0.35 mL,
5 mmol) or butyl vinyl ether (1.29 mL, 10 mmol). After the extractive
work-up, the resulting crude product was purified by silica gel column
chromatography (hexane). Spectral data for 9d[17] were in complete ac-
cordance with literature values.
(E)-2-(3-Phenylpropyl)-1,3-pentadiene (10h): Alkenyl iodide 7b (0.27 g,
1 mmol) was treated with tBuLi (1.2 mL, 2 mmol) and [Cp2Zr(Me)Cl]
(0.34 g, 1.2 mmol). This was followed by addition of alkenyl bromide 4b
(0.86 mL, 10 mmol). After the extractive work-up, the resulting crude
product was purified by silica gel column chromatography (hexane). 10h:
(E)-1,5-Diphenyl-1,3-pentadiene (9e) and (E)-3-benzyl-1-phenyl-1,3-bu-
tadiene (10c): Alkenyl iodide 7a (0.24 g, 1 mmol) was treated with tBuLi
(1.2 mL, 2 mmol) and [Cp2Zr(Me)Cl] (0.34 g, 1.2 mmol). This was fol-
lowed by addition of alkenyl bromide trans-4c (0.40 mL, 3 mmol). After
the extractive work-up, the resulting crude product was purified by silica
106
¹ 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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Zirconium-Mediated Cross-Coupling
101 108
1H NMR (300 MHz, CDCl3): d=7.41 7.18 (m, 5H; ArH), 6.13 (d, J=
15.8 Hz, 1H; CH3CH=CH), 5.73 (dq, J=15.8, 6.7 Hz, 1H; CH3CH), 4.95
(s, 1H; C=CHH), 4.91 (s, 1H; C=CHH), 2.70 (t, J=7.8 Hz, 2H; PhCH2),
2.29 (t, J=7.9 Hz, 2H; Ph(CH2)2CH2), 1.95 1.80 (m with d, J=6.7 Hz, 5
H; PhCH2CH2 and CH3) ppm; 13C NMR (100 MHz, CDCl3): d=145.8,
142.3, 133.2, 128.3, 128.1, 125.6, 124.6, 112.9, 35.6, 31.7, 29.8, 18.1 ppm; el-
emental analysis: calcd (%) for C14H18: C 90.26, H 9.74; found: C 90.38,
H 9.61.
(Z)-4-Iodo-5-phenyl-1,3-pentadiene (9g): Alkenyl iodide 7a (0.24 g,
1 mmol) was treated with tBuLi (1.2 mL, 2 mmol) and [Cp2Zr(Me)Cl]
(0.34 g, 1.2 mmol). This was followed by addition of butyl vinyl ether
(1.29 mL, 10 mmol). After addition of iodine (0.52 g, 2 mmol) and the ex-
tractive work-up, the resulting crude product was purified by silica gel
column chromatography (hexane). 9g: 1H NMR (300 MHz, CDCl3): d=
7.41 7.12 (m, 5H; ArH), 6.49 (dt, J=16.9, 9.7 Hz, 1H; CH2=CH), 6.25
(d, J=9.7 Hz, CI=CH), 5.44 (d, J=16.9 Hz, 1H; CH=CHH), 5.33 (d, J=
9.7 Hz, 1H; CH=CHH), 3.94 (s, 2H; PhCH2) ppm; 13C NMR (100 MHz,
CDCl3): d=138.8, 138.1, 135.1, 129.0, 128.4, 126.8, 120.5, 108.4, 51.7 ppm;
elemental analysis: calcd (%) for C11H11I: C 48.91, H 4.10; found: C
45.05, H 4.02.
(E,E)-1-Iodo-2-phenyl-1,3-pentadiene (10i): Alkenyl bromide 7c
(0.13 mL, 1 mmol) was treated with tBuLi (1.2 mL, 2 mmol) and
[Cp2Zr(Me)Cl] (0.34 g, 1.2 mmol). This was followed by addition of al-
kenyl bromide 4b (0.86 mL, 10 mmol). After addition of iodine (0.52 g,
2 mmol) and the extractive work-up, the resulting crude product was pu-
rified by silica gel column chromatography (hexane). 10i: 1H NMR
(200 MHz, CDCl3): d=7.39 7.18 (m, 5H; ArH), 6.61 (d, J=15.4 Hz, 1H;
CH3CH=CH), 6.17 (s, 1H; CHI), 5.71 (dq, J=15.4, 6.7 Hz, 1H; CH3CH),
1.85 (d, J=6.7 Hz, 3H; CH3) ppm; 13C NMR (75 MHz, CDCl3): d=149.2,
140.3, 134.8, 132.9, 128.6, 128.0, 127.6, 78.3, 18.5 ppm; elemental analysis:
calcd (%) for C11H11I: C 48.91, H 4.10; found: C 48.80, H 4.01.
(E)-6-Phenyl-1,3-hexadiene (9h): Alkenyl iodide 7c (0.26 g, 1 mmol) was
treated with tBuLi (1.2 mL, 2 mmol) and [Cp2Zr(Me)Cl] (0.34 g,
1.2 mmol). This was followed by addition of butyl vinyl ether (1.29 mL,
10 mmol). After the extractive work-up, the resulting crude product was
purified by silica gel column chromatography (hexane). Spectral data for
9h[19] were in complete accordance with literature values.
General procedure for the preparation of cyclobutenes 11: tert-Butyllithi-
um (2 mmol) was added to a stirred solution of the appropriate alkenyl
bromide (or iodide) 1 or 7 (1 mmol) in dry THF (10 mL) at À788C.
After stirring at this temperature for 30 min, the solution was added
dropwise through a cannula to a stirred solution of bis(cyclopentadienyl)-
zirconium methyl chloride (1.2 mmol) in dry THF (10 mL) at À788C.
After 30 min at this temperature, an excess of the required alkenyl bro-
mide 4 (3 10 mmol) was added. The mixture was allowed to warm to
room temperature and the stirring continued for 18 h. An excess of water
or deuterium oxide was added and then the mixture was extracted with
diethyl ether (3î10 mL). The combined organic layers were dried over
anhydrous sodium sulphate and concentrated, and the residue was puri-
fied by column chromatography to give compounds 11.
(E,E)-1-Iodo-2-(4-tolyl)-1,3-pentadiene (10j): Alkenyl iodide 7d (0.24 g,
1 mmol) was treated with tBuLi (1.2 mL, 2 mmol) and [Cp2Zr(Me)Cl]
(0.34 g, 1.2 mmol). This was followed by addition of alkenyl bromide 4b
(0.86 mL, 10 mmol). After addition of iodine (0.52 g, 2 mmol) and the ex-
tractive work-up, the resulting crude product was purified by silica gel
column chromatography (hexane). 10j: 1H NMR (300 MHz, CDCl3): d=
7.16, 7.11 (2îd, J=8.2 Hz, 4H; ArH), 6.60 (d, J=15.4 Hz, 1H; CH3CH=
CH), 6.14 (s, 1H; CHI), 5.72 (dq, J=15.4, 6.8 Hz, 1H; CH3CH), 2.37 (s,
3H, CH3C6H4), 1.84 (d, J=6.8 Hz, 3H; CH3CH) ppm; 13C NMR
(100 MHz, CDCl3): d=149.0, 137.5, 137.4, 134.6, 133.0, 128.7, 128.4, 78.0,
21.1, 18.4 ppm; elemental analysis: calcd (%) for C12H13I: C 50.73, H
4.61; found: C 50.77, H 4.53.
(E,E)-2-tert-Butyl-1-Iodo-1,3-pentadiene (10k): Alkenyl iodide 7f
(0.21 g, 1 mmol) was treated with tBuLi (1.2 mL, 2 mmol) and
[Cp2Zr(Me)Cl] (0.34 g, 1.2 mmol). This was followed by addition of al-
kenyl bromide 4b (0.86 mL, 10 mmol). After addition of iodine (0.52 g,
2 mmol) and the extractive work-up, the resulting crude product was pu-
rified by silica gel column chromatography (hexane). 10k: 1H NMR
(300 MHz, CDCl3): d=6.16 (s, 1H; CHI), 5.86 (d, J=15.9 Hz, 1H;
CH3CH=CH), 5.74 (dq, J=15.9, 5.1 Hz, 1H; CH3CH), 1.85 (d, J=5.1 Hz,
3H; CH3CH), 1.08 (s, 9H; 3îCCH3) ppm; 13C NMR (100 MHz, CDCl3):
d=157.5, 132.0, 129.9, 74.6, 38.7, 29.3, 18.3 ppm; elemental analysis:
calcd (%) for C9H15I: C 43.22, H 6.04; found: C 43.30, H 5.94.
1-Benzylcyclobutene (11a): Alkenyl iodide 7a (0.24 g, 1 mmol) was treat-
ed with tBuLi (1.2 mL, 2 mmol) and [Cp2Zr(Me)Cl] (0.34 g, 1.2 mmol).
This was followed by addition of vinyl bromide 4a (0.35 mL, 5 mmol).
After the extractive work-up, the resulting crude product was purified by
silica gel column chromatography (hexane). 11a: 1H NMR (300 MHz,
CDCl3): d=7.39 7.20 (m, 5H; ArH), 5.69 5.68 (m, 1H; C=CH), 3.37 (s,
2H; PhCH2), 2.48 2.43 and 2.38 2.36 (2îm, 4H; 2îCH2) ppm;
13C NMR (100 MHz, CDCl3): 148.5, 138.8, 128.7, 128.5, 128.2, 125.9, 38.1,
31.0, 26.5 ppm; elemental analysis: calcd (%) for C11H12: C 91.61, H 8.39;
found: C 91.70, H 8.28.
1-(2-Phenylethyl)cyclobutene (11b): Alkenyl iodide 7e (0.26 g, 1 mmol)
was treated with tBuLi (1.2 mL, 2 mmol) and [Cp2Zr(Me)Cl] (0.34 g,
1.2 mmol). This was followed by addition of vinyl bromide 4a (0.35 mL,
5 mmol). After the extractive work-up, the resulting crude product was
purified by silica gel column chromatography (hexane). 11b: 1H NMR
(300 MHz, CDCl3): d=7.42 7.21 (m, 5H; ArH), 5.79 5.68 (m, 1H; C=
CH), 2.80 (t, J=7.5 Hz, 2H; PhCH2), 2.60 2.30 (m, 6H; 3îCH2) ppm;
13C NMR (100 MHz, CDCl3): d=149.8, 142.1, 128.2, 127.2, 125.6, 33.0,
32.8, 31.1, 26.5 ppm; elemental analysis: calcd (%) for C12H14: C 91.08, H
8.92; found: C 91.16, H 8.82.
(E)-2-Benzyl-1,3-decadiene (10l): Alkenyl iodide 7a (0.24 g, 1 mmol) was
treated with tBuLi (1.2 mL, 2 mmol) and [Cp2Zr(Me)Cl] (0.34 g,
1.2 mmol). This was followed by addition of alkenyl bromide trans-4d
(0.57 g, 3 mmol). After the extractive work-up, the resulting crude prod-
uct was purified by silica gel column chromatography (hexane). 10l:
1H NMR (300 MHz, CDCl3): d=7.38 7.15 (m, 5H; ArH), 6.19 (d, J=
15.9 Hz, 1H; CH2CH=CH), 5.80 (dq, J=15.9, 6.9 Hz, 1H; CH2CH=CH),
5.12 (s, 1H; C=CHH), 4.85 (s, 1H; C=CHH), 3.61 (s, 2H; PhCH2), 2.18
2.02 (m, 2H; CH2CH=CH), 1.45 1.20 (m, 8H; CH3(CH2)4), 0.92 (t, J=
7.0 Hz, 3H; CH3) ppm; 13C NMR (100 MHz, CDCl3): d=145.0, 139.7,
131.5, 131.4, 128.7, 128.1, 125.8, 115.4, 38.8, 32.7, 31.6, 29.2, 28.7, 22.5,
14.0 ppm; elemental analysis: calcd (%) for C17H24: C 89.41, H 10.59;
found: C 89.52, H 10.45.
1-Benzyl-3-methylcyclobutene (11c): Alkenyl iodide 7a (0.24 g, 1 mmol)
was treated with tBuLi (1.2 mL, 2 mmol) and [Cp2Zr(Me)Cl] (0.34 g,
1.2 mmol). This was followed by addition of vinyl bromide 4b (0.86 mL,
10 mmol). After the extractive work-up, the resulting crude product was
purified by silica gel column chromatography (hexane). 11c: 1H NMR
(400 MHz, CDCl3): d=7.37 7.23 (m, 5H; ArH), 5.77 (s, 1H; C=CH),
3.38 (s, 2H; PhCH2), 2.76 2.73 (m, 1H; CH3CH), 2.62 (dd, J=12.9,
4.1 Hz, 1H; CHCHH), 1.93 (d, J=12.9 Hz, 1H; CHCHH), 1.15 (d, J=
6.8 Hz, 3H; CH3) ppm; 13C NMR (100 MHz, CDCl3): d=146.3, 138.7,
134.0, 128.7, 128.2, 125.8, 38.5, 37.9, 34.0, 19.8 ppm; elemental analysis:
calcd (%) for C12H14: C 91.08, H 8.92; found: C 91.19, H 8.79.
(E)-2-(3-Phenylpropyl)-1,3-decadiene (10m): Alkenyl iodide 7b (0.27 g,
1 mmol) was treated with tBuLi (1.2 mL, 2 mmol) and [Cp2Zr(Me)Cl]
(0.34 g, 1.2 mmol). This was followed by addition of alkenyl bromide
trans-4d (0.57 g, 3 mmol). After the extractive work-up, the resulting
crude product was purified by silica gel column chromatography
(hexane). 10m: 1H NMR (300 MHz, CDCl3): d=7.35 7.14 (m, 5H;
ArH), 6.05 (d, J=15.6 Hz, 1H; CH2CH=CH), 5.63 (dq, J=15.6, 6.7 Hz,
1H; CH2CH=CH), 4.90 (s, 1H; C=CHH), 4.86 (s, 1H; C=CHH), 2.64 (t,
J=7.7 Hz, 2H; PhCH2), 2.24 (t, J=7.8 Hz, 2H; Ph(CH2)2CH2), 2.10 1.92,
1.90 1.70, 1.42 1.20 (3îm, 12H; CH3(CH2)5 and PhCH2CH2), 0.89 (t, J=
7.0 Hz, 3H; CH3) ppm; 13C NMR (100 MHz, CDCl3): d=145.9, 142.4,
131.7, 130.3, 128.3, 128.1, 125.6, 113.0, 35.6, 32.7, 31.6, 29.9, 29.3, 28.8,
22.5, 14.0 ppm; elemental analysis: calcd (%) for C19H28: C 88.99, H
11.01; found: C 89.08, H 10.89.
cis-1-Benzyl-4-deuterio-3-methylcyclobutene (11d): Alkenyl iodide 7a
(0.24 g, 1 mmol) was treated with tBuLi (1.2 mL, 2 mmol) and
[Cp2Zr(Me)Cl] (0.34 g, 1.2 mmol). This was followed by addition of al-
kenyl bromide 4b (or cis-4b or trans-4b; 0.86 mL, 10 mmol). After addi-
tion of D2O (1 mL) and the extractive work-up, the resulting crude prod-
uct was purified by silica gel column chromatography (hexane). 11d:
1H NMR (400 MHz, CDCl3): d=7.37 7.20 (m, 5H; ArH), 5.77 (s, 1H;
C=CH), 3.38 (s, 2H; PhCH2), 2.76 2.70 (m, 1H; CH3CH), 2.60 (s, 1H;
107
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¹ 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

J. Barluenga et al.
FULL PAPER
CHCHD), 1.93 (d, J=12.9 Hz, 1H; CHCHH), 1.13 (d, J=6.8 Hz, 3H;
CH3) ppm; 13C NMR (100 MHz, CDCl3): d=146.3, 138.8, 134.1, 128.7,
128.2, 125.8, 38.5, 37.9 (t, J=20 Hz), 33.9, 19.8 ppm.
Ura, K. Nakajima, J. Am. Chem. Soc. 2000, 122, 3228, and referen-
ces therein. For zirconocene-stabilized aryne complexes, see, for ex-
ample: f) M. Frid, D. Pÿrez, A. J. Peat, S. L. Buchwald, J. Am.
Chem. Soc. 1999, 121, 9469, and references therein.
3-Methyl-1-(2-phenylethyl)cyclobutene (11e): Alkenyl iodide 7e (0.26 g,
1 mmol) was treated with tBuLi (1.2 mL, 2 mmol) and [Cp2Zr(Me)Cl]
(0.34 g, 1.2 mmol). This was followed by addition of alkenyl bromide 4b
(0.86 mL, 10 mmol). After the extractive work-up, the resulting crude
product was purified by silica gel column chromatography (hexane). 11e:
1H NMR (300 MHz, CDCl3): d=7.39 7.20 (m, 5H; ArH), 5.84 (s, 1H;
C=CH), 2.85 2.75 (m, 3H; PhCH2 and CH3CH), 2.65 (dd, J=12.8,
4.2 Hz, 1H; CHCHH), 2.38 (t, J=7.6 Hz, 2H; PhCH2CH2) 1.96 (dd, J=
12.8, 1.2 Hz, 1H; CHCHH), 1.18 (d, J=6.8 Hz, 3H; CH3) ppm; 13C NMR
(100 MHz, CDCl3): d=147.5, 142.1, 132.9, 128.3, 128.2, 125.6, 38.6, 34.1,
33.1, 32.7, 19.8 ppm; elemental analysis: calcd (%) for C13H16: C 90.64, H
9.36; found: C 90.72, H 9.25.
[5] E. Negishi, F. E. Cederbraum, T. Takahashi, Tetrahedron Lett. 1986,
27, 2829.
[6] a) C. Meyer, I. Marek, J. F. Normant, Tetrahedron Lett. 1996, 37,
857; b) P. A. Wender, F. E. McDonald, Tetrahedron Lett. 1990, 31,
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1992, 33, 1543; d) G. Agnel, E. Negishi, J. Am. Chem. Soc. 1991,
113, 7424; e) E. Negishi, D. R. Swanson, F. E. Cederbraum, T. Taka-
hashi, Tetrahedron Lett. 1986, 27, 2829.
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g) J. H. Tidwell, S. L. Buchwald, J. Am. Chem. Soc. 1994, 116, 11797,
and references therein.
[9] J. Barluenga, R. Sanz, F. J. FaÊanµs, Chem. Eur. J. 1997, 3, 1324.
[10] a) J. Barluenga, R. Sanz, F. J. FaÊanµs, Z. Naturforsch. 1995, B50,
312. After this paper appeared, other authors published the same
process with internal alkynes: b) T. Takahashi, Z. Xi, R. Fischer, S.
Huo, C. Xi, K. Nakajima, J. Am. Chem. Soc. 1997, 119, 4561; c) T.
Takahashi, D. Y. Kondakov, Z. Xi, N. Suzuki, J. Am. Chem. Soc.
1995, 117, 5871.
3-Methyl-1-(3-phenylpropyl)cyclobutene (11f): Alkenyl iodide 7b (0.27 g,
1 mmol) was treated with tBuLi (1.2 mL, 2 mmol) and [Cp2Zr(Me)Cl]
(0.34 g, 1.2 mmol). This was followed by addition of alkenyl bromide 4b
(0.86 mL, 10 mmol). After the extractive work-up, the resulting crude
product was purified by silica gel column chromatography (hexane). 11f:
1H NMR (300 MHz, CDCl3): d=7.31 7.21 (m, 5H; ArH), 5.77 (s, 1H;
C=CH), 2.75 2.60 (m, 3H; PhCH2 and CH3CH), 2.57 (dd, J=12.9,
4.1 Hz, 1H; CHCHH), 2.03 (t, J=7.3 Hz, 2H; Ph(CH2)2CH2) 1.96 (d, J=
12.9 Hz, 1H; CHCHH), 1.76 (quintuplet, J=7.6 Hz, 2H; PhCH2CH2),
1.18 (d, J=6.7 Hz, 3H; CH3) ppm; 13C NMR (100 MHz, CDCl3): d=
147.9, 142.4, 132.7, 128.4, 128.1, 125.5, 38.5, 35.5, 34.0, 30.4, 28.5,
20.0 ppm; elemental analysis: calcd (%) for C14H18: C 90.26, H 9.74;
found: C 90.37, H 9.61.
[11] Migratory insertion processes involving related metal carbenoids
have been reported: a) G. J. Gordon, T. Luker, M. W. Tuckett, R. J.
Whitby, Tetrahedron 2000, 56, 2113; b) A. Kasatkin, R. J. Whitby, J.
Am. Chem. Soc. 1999, 121, 7039; c) M. W. Tuckett, W. J. Watkins,
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Gordon, T. Luker, R. J. Whitby, Pure Appl. Chem. 1997, 69, 633;
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[12] The same electronic effects have been invoked to explain the results
of the hydroboration reaction of vinyl halides and enol ethers: E.
Negishi, in Organometallics in Organic Synthesis, John Wiley &
Sons, New York, 1980, p. 297.
[13] Nonconcerted pathways for the insertion reactions of alkenes with
zirconocene complexes have been reported: E. Negishi, D. Chouei-
ry, T. B. Nguyen, D. R. Swanson, N. Suzuki, T. Takahashi, J. Am.
Chem. Soc. 1994, 116, 9751.
Acknowledgements
Financial support for this work was provided by the DirecciÛn General
de InvestigaciÛn CientÌfica y Tÿcnica (DGICYT) of Spain (BQU-2001
3853) and the Ministerio de EducaciÛn y Cultura of Spain (grant to L.A.-
R.). F.R. thanks the MCYT (Programa RamÛn y Cajal) for funding.
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Received: July 15, 2003
Revised: September 3, 2003 [F5337]
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¹ 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
Chem. Eur. J. 2004, 10, 101 108