Lewis acid-controlled reactions of zirconacyclopentadienes with isocyanates and isothiocyanates. One-pot three- or four-component synthesis of multiply substituted iminocyclopentadienes and butadiene-tethered 1,6-bisamides and electrophilic cyclization

Article abstract of DOI:10.1016/j.tet.2007.02.015

Multiply substituted zirconacyclopentadienes including bicyclic zirconacyclopentadienes and zirconaindenes reacted with isocyanates and isothiocyanates in the presence of Lewis acids to afford iminocyclopentadienes and conjugated 1,6-bisamides, depending on the nature of Lewis acids, isocyanates, and isothiocyanates used. Only in the presence of BF₃ could iminocyclopentadienes be obtained in high isolated yields when zirconacyclopentadienes were treated with isocyanates. On the contrary, BF₃ could not mediate the reaction of zirconacyclopentadienes with isothiocyanates. For the reactions of zirconacyclopentadienes with isothiocyanates, EtAlCl₂ was found effective to generate iminocyclopentadienes as the products. Interestingly, however, for the reactions of zirconacyclopentadienes with isocyanates, EtAlCl₂ was found to work very differently from BF₃. Instead of iminocyclopentadienes, conjugated 1,6-bisamides and conjugated mono-amides were obtained as products in high isolated yields from the reactions of zirconacyclopentadienes with isocyanates, depending on the substituents of isocyanates. The reaction path and products could be controlled by Lewis acids. As a demonstration of the usefulness of thus obtained unsaturated bisamides, electrophilic cyclization using acids, NBS, and I₂ was carried out. Electrophilic cyclization of multisubstituted conjugated 1,6-bisamide derivatives afforded cyclic iminoethers in excellent yields with perfect selectivity. Only one of the amide groups took part in the electrophilic cyclization.

Full text of DOI:10.1016/j.tet.2007.02.015

Tetrahedron 63 (2007) 6614–6624
Lewis acid-controlled reactions of zirconacyclopentadienes
with isocyanates and isothiocyanates. One-pot three- or
four-component synthesis of multiply substituted
iminocyclopentadienes and butadiene-tethered
1,6-bisamides and electrophilic cyclization
Qiaoshu Hu,a Jiang Lu,a Congyang Wang,a Chao Wanga and Zhenfeng Xia,b,
*
aBeijing National Laboratory for Molecular Sciences (BNLMS), Key Laboratory of Bioorganic Chemistry and Molecular Engineering
of Ministry of Education, College of Chemistry, Peking University, Beijing 100871, China
bState Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry,
Chinese Academy of Sciences, Shanghai 200032, China
Received 10 December 2006; revised 2 February 2007; accepted 5 February 2007
Available online 9 February 2007
Abstract—Multiply substituted zirconacyclopentadienes including bicyclic zirconacyclopentadienes and zirconaindenes reacted with isocy-
anates and isothiocyanates in the presence of Lewis acids to afford iminocyclopentadienes and conjugated 1,6-bisamides, depending on the
nature of Lewis acids, isocyanates, and isothiocyanates used. Only in the presence of BF3 could iminocyclopentadienes be obtained in high
isolated yields when zirconacyclopentadienes were treated with isocyanates. On the contrary, BF3 could not mediate the reaction of zircona-
cyclopentadienes with isothiocyanates. For the reactions of zirconacyclopentadienes with isothiocyanates, EtAlCl2 was found effective to
generate iminocyclopentadienes as the products. Interestingly, however, for the reactions of zirconacyclopentadienes with isocyanates,
EtAlCl2 was found to work very differently from BF3. Instead of iminocyclopentadienes, conjugated 1,6-bisamides and conjugated mono-
amides were obtained as products in high isolated yields from the reactions of zirconacyclopentadienes with isocyanates, depending on
the substituents of isocyanates. The reaction path and products could be controlled by Lewis acids. As a demonstration of the usefulness
of thus obtained unsaturated bisamides, electrophilic cyclization using acids, NBS, and I2 was carried out. Electrophilic cyclization of multi-
substituted conjugated 1,6-bisamide derivatives afforded cyclic iminoethers in excellent yields with perfect selectivity. Only one of the amide
groups took part in the electrophilic cyclization.
Ó 2007 Elsevier Ltd. All rights reserved.
1. Introduction
cooperation between Lewis acids and zirconacycles is very
effective and leads to a variety of unprecedented reac-
tions.12–14 For example, Lewis acid-mediated reaction of
zirconacyclopentadienes with aldehydes afforded cyclopen-
tadiene derivatives via cleavage of the C]O double bond of
aldehydes.12 Recently, we applied this strategy in the reac-
tions of zirconacyclopentadienes with isocyanates;15 imino-
cyclopentadiene derivatives were formed in one-pot reaction
via selective cleavage of the C]O double bond of
RN]C]O.15 During our further investigation into this
synthetically useful reaction, we found that, in addition to
promoting the reactivity, Lewis acids could also control the
reaction direction. Thus, different products could be obtained
from the same reagents only by applying different Lewis
acids. It was also found that isocyanates and isothiocyanates
behaved remarkably different from each other when treated
with zirconacyclopentadienes in the presence of Lewis acids.
Transition metal mediated C–C bond forming reactions are
frequently used in organic synthesis. On the other hand, clas-
sical Lewis acids, including AlCl3, BF3, TiCl4, and SnCl4,
are well known to promote or catalyze a variety of organic
transformations.1 Combination of these two powerful proto-
cols would result in synthetically useful and conceptually
new methodologies.2–11 Indeed, Lewis acids play a very im-
portant role in many transition metal mediated C–C bond
forming reactions, including promotion of reactivity and
increase of selectivity.3–11
We started our research project on the cooperation of Lewis
acids with zirconocene-mediated C–C bond forming reac-
tions in 1998. Our results have demonstrated that the
In this full paper, we would like to report: (1) formation of
iminocyclopentadiene derivativesandindeniminederivatives
* Corresponding author. Tel./fax: +86 10 6275 9728; e-mail: zfxi@pku.
edu.cn
0040–4020/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2007.02.015

Q. Hu et al. / Tetrahedron 63 (2007) 6614–6624
6615
2) 2 equiv. ArNCO
from zirconacyclopentadiene/RNCO/BF3$Et2O and zircona-
cyclopentadiene/RNCS/EtAlCl2, (2) formation of conju-
gated 1,6-bisamides from zirconacyclopentadiene/RNCO/
EtAlCl2, (3) electrophilic cyclization of multisubstituted
conjugated 1,6-bisamides, and (4) mechanistic aspects.
4 equiv. BF3 Et2O
0 °C to 80 °C, 3h
[M=O]n
R
R
R
R
R
R
1) Cp2Zr(II)
+
ZrCp2
NAr
R'
R'
R'
R'
2
R'
R'
1
2') 1.3 equiv. ArNCS
4 equiv. EtAlCl2
r.t., 1h
2. Results and discussion
[M=S]n
2.1. Formation of iminocyclopentadiene derivatives and
indenimine derivatives from zirconacyclopentadiene/
RNCO/BF3$Et2O and zirconacyclopentadiene/RNCS/
EtAlCl2
Pr
Pr
Pr
Pr
Pr
Pr
Pr
Pr
Pr
Pr
Pr
N
N
Cl
Cl
N
Pr
Cl
Zirconacyclopentadienes can be readily generated from al-
kynes, diynes, and benzynes with low-valent zirconocene
species.16–19 No reaction proceeded when a zirconacyclo-
pentadiene was treated with an isocyanate or an isothiocya-
nate, which are important and useful hetero-cumulenes.
Since isocyanates and isothiocyanates can form adducts
with Lewis acids and hence activated, we tried a variety of
Lewis acids as additives to the mixture of zirconacyclopen-
tadienes with isocyanates or isothiocyanates.
Br
2a: 75%
2b: 64%
Pr
2c: 81%
Pr
Pr
N
Pr
Pr
Pr
Pr
Pr
Pr
N
Cl
Cl
N
Pr
Pr
Pr
Cl
Me
2d: 61%
2e: 76% from ArNCS
2f: 45% from ArNCO
85% from ArNCS
Pr
N
Et
Et
Pr
Pr
Et
Et
Reaction of zirconacyclopentadienes with isocyanates in the
presence of BF3$Et2O proceeded smoothly, affording imino-
cyclopentadiene derivatives as the sole products in high
isolated yields (Fig. 1). It should be pointed out that only
aromatic isocyanates can be used. Aliphatic isocyanates
lead to messy mixture of products even at lower temperatures
(ꢀ78 ꢁC), probably due to their relatively higher reactivity.
Both products 2f and 2g were formed in lower yields from
their corresponding ArNCO. The electron-donating substit-
uents of the phenyl isocyanates are considered responsible
for the lower yields of products, probably because these iso-
cyanates have relatively higher reactivity, which would lead
to more byproducts. Other Lewis acids did not lead to good
results: AlCl3 and FeCl3 led to inseparable messy mixture of
products even at lower temperature (ꢀ78 ꢁC); TiCl4, InCl3,
CoCl2, VCl3, and Sc(CF3SO3)3 did not promote the reaction
and the zirconacyclopentadienes remained even at higher
temperature (80 ꢁC). When EtAlCl2 was used, totally differ-
ent products were obtained. The result will be discussed
later. Thus, among those Lewis acids investigated, only
BF3 could mediate formation of iminocyclopentadienes
from zirconacyclopentadienes and isocyanates.
Et
Et
N
Cl
N
Cl
Cl
Pr
Et
Et
OMe
Cl
Cl
2g: 35%
2h: 75%
2i: 75% from ArNCS
Ph
N
Ph
N
Ph
Ph
Bu
Ph
Ph
Bu
2j: 91%
2k: 64%
Figure 1. Formation of iminocyclopentadienes from zirconacyclopenta-
diene/ArNCO/BF3$Et2O or zirconacyclopentadiene/ArNCS/EtAlCl2. If
not specified, products were obtained from ArNCO.
R
R
2) 1.3 equiv. ArNCS
4 equiv. EtAlCl2
R
R
1)
R
R
ZrCp2
NAr
80 °C, 1h
Cp2ZrPh2
100 °C, 9h
or 2') 2 equiv. ArNCO
4 equiv. BF3 Et2O
80 °C, 1h
3
4
However, when we treated isothiocyanates with zirconacyclo-
pentadienes in the presence of BF3, we found BF3 could not
mediate the reaction of zirconacyclopentadienes with isothio-
cyanates. Surprisingly, after a survey of various Lewis acids,
EtAlCl2 was found to be effective for promoting the reaction
of zirconacyclopentadienes with isothiocyanates, leading to
iminocyclopentadienes (Fig. 1), the same type of products
were obtained from zirconacyclopentadiene/RNCO/
BF3$Et2O. Although the reason is not clear yet, the electron-
donating substituents of the isothiocyanates did not show re-
markable influences on the yield of products, for example,
product 2fwas obtained fromTolylNCS in85%isolated yield.
Pr
Pr
Pr
Pr
Pr
Pr
N
N
Cl
N
Cl
Me
Cl
4a: 63%
4b: 48% from ArNCO 4c: 65% from ArNCS
69% from ArNCS
Pr
N
Bu
Bu
Pr
Bu
Bu
N
N
Cl
OMe
Me
4d: 28%
4e: 51%
4f: 59%
Similarly, as shown in Figure 2, indenimines were success-
fully obtained from zirconaindene/RNCO/BF3$Et2O or
from zirconaindene/RNCS/EtAlCl2.17 In these reactions,
Figure 2. One-pot synthesis of indenimine derivatives from one benzyne,
one normal alkyne, and one isocyanate or isothiocyanate.

6616
Q. Hu et al. / Tetrahedron 63 (2007) 6614–6624
Table 1. Four-component one-pot synthesis of conjugated 1,6-bisamides
from two alkynes and two isocyanates or from one diyne and two iso-
cyanates
similarly, low yields of products were obtained when
ArNCO having electron-donating substituents were used
(for example, 4b and 4d).
R
O
R
2) ArNCO
EtAlCl2
R
R
R
R
R
R
R
R
A number of useful preparation methods for iminocyclo-
pentadiene derivatives have been developed.20,21 Our
method represents an alternative route to highly substituted
iminocyclopentadiene, via a one-pot three-component pro-
cess combining zirconacene-mediated C–C bond forming
reactions with Lewis acid-mediated organic transformation
(Eq. 1). It should be pointed out that these reactions are
highly site-selective; only the C]O double bond in
ArN]C]O or the C]S double bond in ArN]C]S is
cleaved to form the cyclopentadienyl imines.
1) Cp2Zr (II)
1) Cp2Zr (II)
HN Ar
O
ZrCp2
+
3) H2O
R
R
HN Ar
5
1
R
O
R
2) ArNCO
EtAlCl2
R
HN Ar
O
ZrCp2
3) H2O
R
R
R
HN Ar
5
7
Entry
1
Alkyne
Isocyanate
Isolated yield
of 5 (%)
R
R
R
R
+
+
Cp2Zr(II)/LA
R'
R'
C
NAr
ð1Þ
Pr
Pr
5a (65)
5b (80)
NCO
R'
[M=X]n
X = O, S
ArN=C=X
R'
Cl
Pr
Pr
Pr
Pr
2
3
NCO
Cl
2.2. One-pot synthesis of butadiene-tethered
1,6-bisamide derivatives
5c (89)
Cl
NCO
As mentioned above, Lewis acid EtAlCl2 behaved for the
reaction of zirconacyclopentadienes with isothiocyanates
similarly as BF3 did for the reaction of zirconacyclopenta-
dienes with isocyanates. Both of the reaction systems of
zirconacyclopentadiene/RNCO/BF3$Et2O and zirconacyclo-
pentadiene/RNCS/EtAlCl2 afforded iminocyclopentadiene
derivatives. However, when EtAlCl2 was added to the
mixture of zirconacyclopentadienes 1 with isocyanates, a
reaction did take place, generating conjugated bisamide 5
and mono-amide 6 derivatives, rather than those iminocyclo-
pentadiene derivatives 2. In fact, totally no formation of
iminocyclopentadiene derivatives 2 was observed from the
reaction system of zirconacyclopentadiene/RNCO/EtAlCl2.
Furthermore, it was found that this EtAlCl2-mediated
reaction of zirconacyclopentadienes with isocyanates was
substrate-dependent, affording either mono-amide and/or
bisamide derivatives depending on the substituents of
ArNCO (Eq. 2). Both the mono-amide and the bisamide
derivatives are very useful compounds, since the functional
groups (amides) and the butadienyl skeletons can be further
applied for the synthesis of diversified structures.22–24
Cl
Cl
4
5
Et
Et
Pr
5d (71)
5e (59)
NCO
NCO
Pr
Ph
Cl
6
5f (62)
NCO
Ph
amides 6 were obtained as a mixture (Table 2). Interestingly,
when 4-bromophenyl isocyanate was used, the reaction gave
only the mono-amide 6a (entry 4, Table 2) as the product.
No bisamide was obtained in this case. Deuterolysis of the
reaction mixture afforded a D-incorporated product 6eD
(entry 5, Table 2), which indicated that the intermediate
could be further used. As an example of application, we
added a different isocyanate to the proposed reaction inter-
mediate 8 (Scheme 1). In this way, mixed bisamide deriva-
tives 9a and 9b could be prepared in one-pot from two
alkynes and two different isocyanates. When the reaction
mixture was treated with I2, the butadienyl iodide product
6I was obtained in 68% isolated yield.
O
O
1) ArNCO
EtAlCl2
HN Ar
O
HN Ar
H (D)
ZrCp2
and/or
ð2Þ
2) H2O
HN Ar
5
1
6
As shown in Table 1, phenyl isocyanate, 2-chlorophenyl
isocyanate, and 2,4-dichlorophenyl isocyanate reacted with
zirconacyclopentadienes including bicyclic zirconacyclo-
pentadienes 7 resulting in the formation of conjugated 1,6-
bisamide derivatives 5 as the sole products. Mono-amides
6 were not formed in these cases.
2.3. Electrophilic cyclization of multisubstituted
butadiene-tethered 1,6-bisamides
Electrophilic cyclization of unsaturated amides is a very use-
ful direct way to construct various functionalized lactones,
lactams, and oxazolines.22,23 We have recently reported
that electrophilic cyclization of dienamides 6 (butadienyl
amides), generated from 1-lithio-1,3-diene derivatives with
RNCO, affords substituted cyclic iminoethers in excellent
yields with perfect selectivity (Scheme 2).24 As
When aryl isocyanates such as 4-chlorophenyl, 4-fluoro-
phenyl, and 4-methylphenyl isocyanates were used for the
above mentioned reactions, both bisamides 5 and mono-

Q. Hu et al. / Tetrahedron 63 (2007) 6614–6624
6617
Table 2. EtAlCl2-mediated substituent-dependent formation of bisamides
and/or mono-amides from zirconacyclopentadienes and ArNCO
R
O
R
X
Ar
O
R
N
N
Pr
O
Pr
O
R
O
Pr
ZrCp2
Ar
X = H, Br, I
12N HCl or NBS
THF/H2O (1:1)
r.t., 3 h
1) ArNCO
EtAlCl2
X
Pr
Pr
Pr
Pr
Pr
Pr
R
10
R
R
HN Ar
O
HN Ar
H (D or l)
HN Ar
O
and/or
2) aq. NaHCO3
or D2O
or 2.2 I2, in CH2Cl2
R
Pr
R
Pr HN Ar
5
Pr
Ar
R
HN Ar
1
6
N
R
H
5
R
O
O
N
Ar
Entry
ArNCO
Isolated yield
of 5 (%)
Isolated yield
of 6 (%)
X
11
Cl
1
2
3
4
5g (34)
5h (26)
5i (23)
5j (0)
6a (21)
6b (40)
6c (30)
6d (54)
Me
F
NCO
NCO
NCO
NCO
Pr
O
Et
O
Pr
Pr
Et
N
Cl
Cl
N
N
Cl
Cl
Et
H
N
Cl
Cl
Pr
H
N
Et
Br
Br
O
O
Cl
Br
Cl
: 89%
11b: 98%
11a
Et
O
Et
Et
Et
Et
N
Cl
Et
O
Cl
5a
5k (0)
6eD (48)
H
N
H
N
Et
Et
Br
NCO
H
I
O
O
a
Quenched with D2O.
11c: 75% (1:1)
11d: 60% (5:1)
Figure 3. Electrophilic cyclization of butadiene-bridged 1,6-bisamides 5.
R
N Ph-p-Br
OM
R
R
R
R
1) p-Br-PhNCO
As expected, butadiene-tethered 1,6-bisamides 5 did un-
dergo electrophilic cyclization smoothly when treated with
strong acids, NBS, or I2, affording, however, not the ex-
pected fused-ring products 10, but monocyclic iminoethers
11, analogous to the electrophilic cyclization products of 6
(Fig. 3). These multisubstituted butadiene-tethered 1,6-bis-
amides 5 behaved similarly with 6 in the electrophilic cycli-
zation reaction. Only O-attack pathway was involved and
exo cyclization product was obtained as the sole products.
ZrCp2
EtAlCl2
- 35 °C, 1 h
R
M'
R
R
1
8
M, M': Zr, Al
2) ArNCO
R
R
HN Ph-p-Br
EtAlCl2
r.t.
2) I2
3) aq.
NaHCO3
O
NHAr
3) aq.
NaHCO3
R
Et HN Ph-p-Br
O
R
2.4. Aspects of reaction mechanisms
9
Et
Et
O
9a: R = Pr,
In our previous work,12,15 we proposed that Lewis acids
played a very important role in promoting reactivity of
zirconacyclopentadienes with aldehydes and isocyanates,
probably via transmetalation or coordination. In this work,
analogous functions of Lewis acids are assumed to operate.
Ar = 2,4-dichlorophenyl
39% isolated yield
9b: R = Et,
I
Et
6I
Ar = 2-chlorophenyl
51% isolated yield
68% isolated yield
Scheme 1. Formation of mixed bisamide derivatives in one-pot from two
alkynes and two different isocyanates or butadienyl iodide.
Scheme 3 shows a proposed reaction mechanism for the
formation of iminocyclopentadienes from reactions of
a demonstration of the usefulness of the butadiene-tethered
1,6-bisamides, we carried out electrophilic cyclization
reactions of butadiene-tethered 1,6-bisamides 5, expecting
formation of structurally interesting heterocycles.
LA
Ar-N=C=X
ZrCp2
ZrCp2
LA
X
X = O, S
insertion
Ar
N
1
12
R
R
R
R
R
R
NBS
or I2
H+
C
NR'
C NR'
C O
NHR'
O
O
R
R
R
R
LA
X
R
R
Br (I)
6
metathesis
NAr
ZrCp2
R
R
N
Ar
E
[Cp2Zr=X]n
LA
E = H+, I+, or Br+
C O
NHR'
R
R
2
13
6'
Scheme 3. A proposed reaction mechanism for the formation of iminocyclo-
pentadienes. When X¼O, LA¼BF3, while X¼S, LA¼EtAlCl2.
Scheme 2. Electrophilic cyclization of butadienyl amides.

6618
Q. Hu et al. / Tetrahedron 63 (2007) 6614–6624
zirconacyclopentadienes with isocyanates and isothiocya-
nates promoted by Lewis acids. An adduct between an iso-
cyanate or an isothiocyanate is firstly generated in situ in
the reaction mixture. Upon activation through this form of
adduct interaction, insertion of the C]X moiety of
ArN]C]X (X¼O or S) into the Zr–C bond of zircona-
cyclopentadienes took place to afford seven-membered zir-
conacycles 12, which underwent intramolecular nucleophilic
attack to form intermediates 13. Isolation of 13 has been
so far failed. However, metathesis of 13 is proposed to
play an essential role for the final formation of iminocyclo-
pentadienes 2.25 Indeed, hydrolysis of the reaction mixtures
gave an unstable compound, which transformed into cyclo-
pentadienone derivatives in CHCl3 after 3 days. In addition,
NMR spectra showed that iminocyclopentadienes 2 were al-
ready formed in situ before hydrolysis. It should be pointed
out that specific combination of substrates with Lewis acids,
e.g., zirconacyclopentadiene/RNCO/BF3$Et2O and zircona-
cyclopentadiene/RNCS/EtAlCl2, is very important for the
formation of iminocyclopentadiene derivatives and inden-
imine derivatives.
Alternatively, zirconacyclopentadienes 1 might undergo
double insertion by the above mentioned adduct. Thus, as
shown in Scheme 4, the first insertion gave seven-membered
ring intermediate 12, the remaining Zr–C bond of which
was inserted by a second molecule of the adduct to generate
intermediate 14. Hydrolysis of 14 afforded the butadiene-
tethered bisamides 5. In this type of reaction, only the
combination of zirconacyclopentadiene/ArNCO/EtAlCl2
worked.
For the combination of zirconacyclopentadiene/ArNCO/
EtAlCl2 to afford bisamides, transmetalation of Zr–C
bond to Al–C bond might also be involved. As given
in Scheme 5, transmetalation of 1 might give intermedi-
ates 15 and 16. Both of the intermediates 15 and 16
then react with two molecules of ArNCO via double
insertion to generate acyclic intermediate 17 and cyclic
intermediate 18.
3. Conclusion
Lewis acid-controlled reactions of zirconacyclopentadienes
with isocyanates and isothiocyanates have been developed.
Thus, a one-pot three-component procedure for the con-
struction of highly substituted iminocyclopentadiene deriva-
tives and indenimine derivatives has been realized from
alkynes and isocyanates mediated by zirconocene and
BF3 or from alkynes and isothiocyanates mediated by
zirconocene and EtAlCl2. Similarly, butadiene-tethered
1,6-bisamide derivatives were prepared via a one-pot four-
component procedure from alkynes and isocyanates medi-
ated by zirconocene and EtAlCl2. This success indicated
that novel and synthetically useful methodologies could be
developed by combining transition metal mediated C–C
bond forming reactions with Lewis acid-mediated organic
transformations. Electrophilic cyclization of multisubsti-
tuted unsaturated 1,6-bisamides derivatives afforded cyclic
iminoethers in excellent yields with perfect selectivity.
Only one of the amide groups took part in the electrophilic
cyclization.
LA
ZrCp2
Ar-N=C=O
first
O
LA
ZrCp2
insertion
NAr
1
12
second
insertion
LA
Ar-N=C=O
NAr
O
LA
O
NHAr aq. NaHCO3
O
ZrCp2
O
LA
NHAr
NAr
14
5
Scheme 4. A proposed reaction mechanism for the formation of bisamides
via double insertion of ArNCO.
LA
AlCl2
O C NAr
Ar-N=C=O
trans-
and/or
ZrCp2
AlCl
4. Experimental section
4.1. General
M
metallation
16
1
15
double
M = AlCl2,
Cp2Zr
double
insertion
LA
Ar-N=C=O
insertion
Unless otherwise noted, all starting materials were commer-
cially available and were used without further purification.
All reactions involving organometallic compounds were
run under a slightly positive pressure of dry N2 with use of
standard Schlenk techniques. Zirconocene dichloride was
obtained from Aldrich and Alfa-Aesar. PhMgBr, EtAlCl2,
boron trifluoride diethyl etherate (BF3$Et2O), and n-BuLi
were purchased from Acros. Toluene was refluxed and
distilled from sodium benzophenone ketyl under a nitrogen
NAr
NAr
OAlCl2
NAr
LA
O
AlCl
OM
17
O
LA
aq. NaHCO3
NAr
aq. NaHCO3
18
O
1
atmosphere. H and 13C NMR spectra were recorded on
NHAr
O
a JEOL-300 MHz spectrometer. GC analysis was performed
on a gas chromatograph (Shimadzu 14B) equipped with
a flame ionization detector and a capillary column (CBP1-
M25-25). GC yields were determined using suitable hydro-
carbons as internal standards.
5
NHAr
Scheme 5. Proposed reaction mechanisms for the formation of bisamides
via transmetalation followed by double insertion of ArNCO.

Q. Hu et al. / Tetrahedron 63 (2007) 6614–6624
6619
4.2. General procedure for the preparation of multiply
substituted iminocyclopentadiene derivatives from
zirconacyclopentadiene/RNCO/BF3$Et2O
6H), 6.68–7.37 (m, 4H). 13C NMR (CDCl3, Me4Si):
d 14.0, 14.4, 14.6, 23.0, 23.7, 24.1, 26.0, 27.5, 28.2, 115.7,
112.0, 123.8, 131.1, 131.3, 147.3, 150.3, 154.4, 171.2.
HRMS calcd for C23H32NCl: 401.1718, found: 401.1721.
An alkyne (4.0 mmol) was added into a toluene solution of
[Cp2ZrBu2] (Negishi reagent),16 prepared in situ from
Cp2ZrCl2 (2.0 mmol, 0.58 g) and n-BuLi (4.0 mmol,
2.6 mL, 1.60 M hexane solution) in toluene (20 mL) at
ꢀ78 ꢁC. The reaction mixture was then stirred at room
temperature for 1 h to afford zirconacyclopentadiene. Iso-
cyanate (4.0 mmol) was added to this solution at room tem-
perature, then BF3$Et2O (8.0 mmol, 1.0 mL) was added to
this solution at ꢀ78 ꢁC. After the reaction mixture was
stirred at 0 ꢁC for 1 h, the temperature was allowed rising
to 80 ꢁC and maintaining for another 1 h. The above reaction
mixture was quenched with saturated aqueous NaHCO3 and
extracted with n-hexane. The extract was washed with water
and brine, and dried over Na2SO4. The solvent was then
evaporated in vacuo to give red-brown oil, which was puri-
fied by column chromatography to the products.
4.3.4. (2,6-Dichloro-phenyl)-(2,3,4,5-tetrapropyl-cyclo-
penta-2,4-dienylidene)-amine (2d). Red liquid, 61%. H
1
NMR (CDCl3, Me4Si): d 0.45 (br, 3H), 0.98 (t, J¼7.2 Hz,
9H), 1.46–1.48 (m, 8H), 2.20 (br, 8H), 6.85–7.30 (m, 3H).
13C NMR (CDCl3, Me4Si): d 14.3, 14.5, 23.0, 23.4, 26.1,
27.1, 28.2, 123.4, 123.7, 124.8, 127.8, 131.2, 145.8, 148.0,
153.7, 174.4. HRMS calcd for C23H31NCl2: 391.1834,
found: 391.1837.
4.3.5. (2,4-Dichloro-phenyl)-(2,3,4,5-tetrapropyl-cyclo-
penta-2,4-dienylidene)-amine (2e). Red liquid, 76%. H
1
NMR (CDCl3, Me4Si): d 0.47 (br, 3H), 0.98 (br, 11H),
1.47–1.65 (m, 8H), 2.20–2.23 (m, 6H), 6.74–7.36 (m, 3H).
13C NMR (CDCl3, Me4Si): d 14.1, 14.3, 14.6, 23.0, 23.4,
23.9, 26.0, 27.3, 28.2, 120.4, 123.7, 124.1, 126.7, 128.2,
129.0, 131.3, 147.0, 147.8, 154.5, 172.9. HRMS calcd for
C23H31NCl2: 391.1834, found: 391.1835.
4.3. General procedure for the preparation of multiply
substituted iminocyclopentadiene derivatives from
zirconacyclopentadiene/RNCS/EtAlCl2
4.3.6. (4-Methyl-phenyl)-(2,3,4,5-tetrapropyl-cyclo-
penta-2,4-dienylidene)-amine (2f). Red liquid, from
ArNCO 45% isolated yield, from ArNCS 85% isolated
An alkyne (4.0 mmol) was added into a toluene solution of
[Cp2ZrBu2] (Negishi reagent),16 prepared in situ from
Cp2ZrCl2 (2.0 mmol, 0.58 g) and n-BuLi (4.0 mmol,
2.6 mL, 1.60 M hexane solution) in toluene (20 mL) at
ꢀ78 ꢁC. The reaction mixture was then stirred at room tem-
perature for 1 h to afford zirconacyclopentadiene. Isothio-
cyanate (2.6 mmol) was added to this solution at room
temperature and then EtAlCl2 (8.0 mmol, 8.8 mL, 0.9 M
hexane solution) was added to this solution at ꢀ78 ꢁC. After
stirring at room temperature for 1 h, the reaction mixture was
quenched with saturated aqueous NaHCO3 and extracted
with n-hexane. The extract was washed with water and brine,
and dried over Na2SO4. The solvent was then evaporated in
vacuo to give red-brown oil, which was purified by column
chromatography to the products.
1
yield. H NMR (CDCl3, Me4Si): d 0.40 (t, J¼7.2 Hz, 3H),
0.88–1.00 (m, 11H), 1.36–1.65 (m, 8H), 2.13–2.31 (m,
9H), 6.69–7.26 (m, 4H). 13C NMR (CDCl3, Me4Si):
d 13.9, 14.4, 14.6, 20.8, 23.1, 23.7, 24.1, 26.1, 27.5, 28.2,
28.3, 118.2, 124.0, 128.7, 131.4, 146.8, 148.9, 153.6, 170.7.
HRMS calcd for C24H35N: 337.2770, found: 337.2769.
4.3.7. (4-Methoxyl-phenyl)-(2,3,4,5-tetrapropyl-cyclo-
penta-2,4-dienylidene)-amine (2g). Red liquid, 35% iso-
1
lated yield. H NMR (CDCl3, Me4Si): d 0.44 (t, J¼7.2 Hz,
3H), 0.86–1.02 (m, 11H), 1.36–1.53 (m, 6H), 1.63–1.68
(m, 2H), 2.14–2.30 (m, 6H), 3.79 (s, 3H), 6.73–7.26 (m,
4H). 13C NMR (CDCl3, Me4Si): d 14.0, 14.4, 14.6, 23.1,
23.6, 24.1, 26.1, 27.6, 28.2, 55.6, 113.7, 119.6, 123.7,
131.5, 144.8, 146.7, 153.7, 156.0, 171.2. HRMS calcd for
C24H35NO: 353.2719, found: 353.2716.
4.3.1. (2-Chloro-phenyl)-(2,3,4,5-tetrapropyl-cyclo-
penta-2,4-dienylidene)-amine (2a). Red liquid, 75% iso-
lated yield. 1H NMR (CDCl3, Me4Si): d 0.41 (br, 3H),
0.97–1.00 (m, 11H), 1.45–1.64 (m, 8H), 2.17–2.29 (m, 6H),
6.80–7.35 (m, 4H). 13C NMR (CDCl3, Me4Si): d 14.1, 14.4,
14.6, 23.0, 23.5, 24.0, 26.1, 27.4, 28.2, 119.6, 122.9, 123.8,
124.3, 126.5, 129.3, 131.3, 147.4, 148.2, 154.0, 172.2.
HRMS calcd for C23H32NCl: 357.2223, found: 357.2224.
4.3.8. (2-Chloro-phenyl)-(2,3,4,5-tetraethyl-cyclopenta-
2,4-dienylidene)-amine (2h). Red liquid, 75% isolated
yield. 1H NMR (CDCl3, Me4Si): d 0.58–0.62 (m, 3H),
1.07–1.13 (m, 9H), 1.72–1.74 (m, 2H), 2.22–2.38 (m, 6H),
6.82–7.34 (m, 4H). 13C NMR (CDCl3, Me4Si): d 14.2,
14.4, 14.6, 15.6, 17.1, 18.0, 18.8, 119.6, 122.9, 124.0,
125.2, 126.5, 129.3, 132.3, 148.2, 155.4, 171.8. HRMS calcd
for C19H24NCl: 301.1597, found: 301.1593.
4.3.2. (3-Chloro-phenyl)-(2,3,4,5-tetrapropyl-cyclo-
penta-2,4-dienylidene)-amine (2b). Red liquid, 64% iso-
1
lated yield. H NMR (CDCl3, Me4Si): 0.46 (t, J¼7.2 Hz,
4.3.9. (2,4-Dichloro-phenyl)-(2,3,4,5-tetraethyl-cyclo-
penta-2,4-dienylidene)-amine (2i). Red liquid, 75% iso-
lated yield. 1H NMR (CDCl3, Me4Si): d 0.62 (br, 3H),
1.11 (br, 9H), 1.73 (br, 2H), 2.29 (br, 6H), 6.76–7.36 (m,
3H). 13C NMR (CDCl3, Me4Si): d 14.2, 14.3, 14.6, 15.6,
17.1, 18.0, 18.9, 120.4, 123.7, 125.0, 126.7, 128.4, 129.0,
132.3, 146.9, 148.6, 155.9, 172.5. HRMS calcd for
C19H23NCl2: 355.1208, found: 355.1214.
3H), 0.90–1.00 (m, 11H), 1.45–1.63 (m, 8H), 2.14–2.23 (m,
6H), 6.69–7.25 (m, 4H). 13C NMR (CDCl3, Me4Si): d 13.9,
14.4, 14.6, 23.0, 23.8, 24.0, 26.0, 27.4, 28.2, 116.4, 118.2,
122.6, 123.9, 129.2, 131.2, 133.9, 147.4, 152.5, 154.5, 171.2.
HRMS calcd for C23H32NCl: 357.2223, found: 357.2228.
4.3.3. (4-Bromo-phenyl)-(2,3,4,5-tetrapropyl-cyclopenta-
2,4-dienylidene)-amine (2c). Red liquid, 81% isolated
1
yield. H NMR (CDCl3, Me4Si): d 0.45 (t, J¼7.2 Hz, 3H),
4.3.10. (2-Chloro-phenyl)-(2,3,4,5-tetraphenyl-cyclo-
penta-2,4-dienylidene)-amine (2j). Dark solid, 91%
0.89–1.00 (m, 11H), 1.47–1.61 (m, 8H), 2.17–2.26 (m,

6620
Q. Hu et al. / Tetrahedron 63 (2007) 6614–6624
1
isolated yield, mp: 189–190 ꢁC. H NMR (CDCl3, Me4Si):
d 6.47–7.38 (m, 24H). 13C NMR (CDCl3, Me4Si): d 120.5,
123.0, 124.3, 125.9, 126.2, 127.0, 127.3, 127.5, 128.6,
129.8, 130.1, 131.3, 132.5, 132.8, 133.4, 133.6, 134.0, 147.2,
148.5, 153.9, 169.6. HRMS calcd for C35H24NCl: 493.1597,
found: 493.1592. Anal. Calcd for C35H24ClN: C, 85.09%; H,
4.90%; N, 2.84%. Found: C, 85.21%; H, 4.93%; N, 2.76%.
J¼7.2 Hz, 3H), 1.59–1.71 (m, 4H), 2.28–2.58 (m, 4H),
6.28–7.44 (m, 8H). 13C NMR (CDCl3, Me4Si): d 14.4,
14.6, 21.7, 23.4, 26.1, 28.0, 118.8, 119.6, 123.1, 124.4,
124.6, 126.3, 127.3, 129.1, 129.9, 131.0, 137.6, 146.1, 149.3,
149.5, 168.4. HRMS calcd for C21H22NCl: 323.1441, found:
323.1446.
4.5.2. (4-Methyl-phenyl)-(2,3-dipropyl-inden-1-ylidene)-
amine (4b). Orange liquid, from ArNCO 48% isolated yield,
from ArNCS 69% isolated yield. 1H NMR (CDCl3, Me4Si):
d 0.98 (t, J¼7.2 Hz, 3H), 1.04 (t, J¼7.2 Hz, 3H), 1.56–1.71
(m, 4H), 2.38 (s, 3H), 2.46–2.56 (m, 4H), 6.35–7.24 (m, 8H).
13C NMR (CDCl3, Me4Si): d 14.4, 14.5, 21.0, 21.7, 23.5,
26.1, 28.0, 118.2, 118.6, 125.1, 125.8, 128.7, 129.6, 130.4,
133.0, 137.8, 146.3, 148.3, 149.6, 166.8. HRMS calcd for
C22H25N: 303.1987, found: 303.1982.
4.3.11. (2-Chloro-phenyl)-(2,4-dibutyl-3,5-diphenyl-
cyclopenta-2,4-dienylidene)-amine (2k). Red liquid, 64%
isolated yield. H NMR (CDCl3, Me4Si): d 0.52–0.60 (br,
1
3H), 0.83 (t, J¼7.2 Hz, 3H), 0.96–1.06 (m, 4H), 1.27–1.34
(m, 2H), 1.53–1.64 (m, 2H), 1.75 (br, 2H), 2.17–2.45 (m,
2H), 6.37–7.46 (m, 14H). 13C NMR (CDCl3, Me4Si):
d 13.4, 14.0, 22.3, 22.8, 24.0, 26.0, 30.3, 32.9, 121.0,
124.0, 124.2, 124.7, 125.8, 128.9, 127.2, 127.5, 128.2, 128.4,
128.6, 129.3, 134.5, 134.7, 135.3, 147.06, 147.10, 156.8,
170.4. HRMS calcd for C31H32NCl: 453.2223, found:
453.2209.
4.5.3. (2,4-Dichloro-phenyl)-(2,3-dipropyl-inden-1-
ylidene)-amine (4c). Orange liquid, 65% isolated yield.
1H NMR (CDCl3, Me4Si): d 0.97–1.07 (m, 6H), 1.58–1.72
(m, 4H), 2.46–2.55 (m, 4H), 6.35–7.44 (m, 7H). 13C NMR
(CDCl3, Me4Si): d 14.3, 14.5, 21.6, 23.3, 26.0, 28.0, 119.0,
120.5, 123.9, 124.3, 126.3, 127.6, 128.97, 128.99, 129.6,
131.2, 137.4, 146.1, 147.5, 149.9, 168.9. HRMS calcd for
C21H21NCl2: 357.1051, found: 357.1052.
4.4. General procedure for the preparation of multiply
substituted indenyl imine derivatives from zircona-
cyclopentadiene/RNCO/BF3$Et2O
An alkyne (2.0 mmol) was added to a solution of
[Cp2ZrPh2]17 in toluene, prepared in situ from Cp2ZrCl2
(2.0 mmol, 0.58 g) and PhLi (4.0 mmol, 2.0 mL, 2.0 M di-
butyl ether) in toluene (20 mL) at 0 ꢁC. The reaction mixture
was then stirred at 100 ꢁC for 9 h to afford zirconaindene.
The solution was cooled to room temperature and isocyanate
(4.0 mmol) was added. Then BF3$Et2O (8.0 mmol, 1.0 mL)
was added to this solution at ꢀ78 ꢁC. After the reaction mix-
ture was stirred at 0 ꢁC for 1 h, the temperature was allowed
rising to 80 ꢁC and maintaining for another 1 h. The above
reaction mixture was quenched with saturated aqueous
NaHCO3 and extracted with n-hexane. The extract was
washed with water and brine, and dried over Na2SO4. The
solvent was then evaporated in vacuo to give red-brown
oil, which was purified by column chromatography to the
products.
4.5.4. (4-Methoxyl-phenyl)-(2,3-dipropyl-inden-1-
ylidene)-amine (4d). Orange liquid, 28% isolated yield.
1H NMR (CDCl3, Me4Si): d 0.99 (t, J¼7.2 Hz, 3H), 1.05
(t, J¼7.2 Hz, 3H), 1.58–1.68 (m, 4H), 2.46–2.57 (m, 4H),
3.85 (s, 3H), 6.41–7.26 (m, 8H). 13C NMR (CDCl3,
Me4Si): d 14.4, 14.5, 21.7, 23.5, 26.1, 28.0, 55.5, 114.3,
118.6, 119.6, 125.0, 125.9, 128.65, 130.4, 137.9, 145.4,
146.3, 148.3, 156.4, 167.3. HRMS calcd for C22H25NO:
319.1936, found: 319.1938.
4.5.5. (4-Methyl-phenyl)-(2,3-dibutyl-inden-1-ylidene)-
amine (4e). Red liquid, 51% isolated yield. 1H NMR
(CDCl3, Me4Si): d 0.94 (t, J¼7.2 Hz, 3H), 0.97 (t, J¼
7.2 Hz, 3H), 1.37–1.62 (m, 8H), 2.38 (s, 3H), 2.47–2.57
(m, 4H), 6.35–7.16 (m, 8H). 13C NMR (CDCl3, Me4Si):
d 14.0, 14.1, 21.0, 23.0, 23.1, 23.8, 25.7, 30.5, 32.5, 118.2,
118.5, 125.1, 125.8, 128.8, 129.6, 130.4, 133.0, 137.9, 146.3,
148.4, 149.6, 166.8. HRMS calcd for C24H29N: 331.2300,
found: 331.2302.
4.5. General procedure for the preparation of multiply
substituted indenyl imines derivatives from zircona-
cyclopentadiene/RNCS/EtAlCl2
An alkyne (2.0 mmol) was added to a solution of
[Cp2ZrPh2]17 in toluene, prepared in situ from Cp2ZrCl2
(2.0 mmol, 0.58 g) and PhLi (4.0 mmol, 2.0 mL, 2.0 M di-
butyl ether) in toluene (20 mL) at 0 ꢁC. The reaction mixture
was then stirred at 100 ꢁC for 9 h to afford zirconaindene.
The solution was cooled to room temperature and isothio-
cyanate (2.6 mmol) was added. Then EtAlCl2 (8.0 mmol,
8.8 mL, 0.9 M hexane solution) was added to this solution
at ꢀ78 ꢁC. After stirring at 80 ꢁC for 1 h, the reaction mix-
ture was quenched with saturated aqueous NaHCO3 and
extracted with n-hexane. The extract was washed with water
and brine, and dried over Na2SO4. The solvent was then
evaporated in vacuo to give red-brown oil, which was puri-
fied by column chromatography to the products.
4.5.6. (2-Chloro-phenyl)-(2,3-dibutyl-inden-1-ylidene)-
amine (4f). Orange liquid in 59% isolated yield. H NMR
1
(CDCl3, Me4Si): d 0.94 (t, J¼7.2 Hz, 3H), 0.98 (t,
J¼7.2 Hz, 3H), 1.39–1.67 (m, 8H), 2.50–2.58 (m, 4H),
6.28–7.44 (m, 8H). 13C NMR (CDCl3, Me4Si): d 14.0,
14.1, 22.9, 23.1, 23.8, 25.7, 30.5, 32.3, 118.8, 119.6,
123.1, 124.4, 124.5, 126.2, 127.3, 129.1, 129.9, 131.0, 137.6,
146.1, 148.9, 149.5, 168.3. HRMS calcd for C23H26NCl2:
351.1754, found: 351.1756.
4.6. General procedure for the preparation of multiply
substituted hexa-2,4-dienedioic acid bisamide deriva-
tives (5a–f)
4.5.1. (2-Chloro-phenyl)-(2,3-dipropyl-inden-1-ylidene)-
amine (4a). Orange liquid, 63% isolated yield. H NMR
(CDCl3, Me4Si): d 1.01 (t, J¼7.2 Hz, 3H), 1.03 (t,
An alkyne (4.0 mmol) was added into a toluene solution of
[Cp2ZrBu2] (Negishi reagent),16 prepared in situ from
Cp2ZrCl2 (2.0 mmol, 0.58 g) and n-BuLi (4.0 mmol,
1

Q. Hu et al. / Tetrahedron 63 (2007) 6614–6624
6621
2.6 mL, 1.60 M hexane solution) in toluene (20 mL) at
ꢀ78 ꢁC. The reaction mixture was then stirred at room
temperature for 1 h to afford zirconacyclopentadiene. Iso-
cyanate (4.0 mmol) and EtAlCl2 (8.0 mmol, 8.8 mL, 0.9 M
hexane solution) were added to this solution at ꢀ78 ꢁC.
After stirring the reaction mixture at ꢀ30 ꢁC for 1 h, the
above reaction mixturewas quenched with saturated aqueous
NaHCO3 and extracted with Et2O. The extract was washed
with water and brine, and dried over Na2SO4. The solvent
was then evaporated in vacuo to give yellow oil, which was
purified by column chromatography to the products.
C28H32N2O2Cl2: 498.1841, found: 498.1831. Anal. Calcd
for C28H32N2O2Cl2: C, 67.33%; H, 6.46%; N, 5.61%.
Found: C, 67.58%; H, 6.54%; N, 5.42%.
4.6.6. Compound 5f. White solid, 62% isolated yield, mp:
1
101–102 ꢁC. H NMR (CDCl3, Me4Si): d 1.55–1.85 (m,
4H), 2.42–2.61 (m, 4H), 6.76–7.49 (m, 18H), 8.39 (m,
1H), 8.41 (m, 1H). 13C NMR (CDCl3, Me4Si): d 28.7,
36.0, 120.2, 122.2, 123.8, 127.5, 128.2, 129.0, 129.7,
130.0, 134.8, 136.8, 151.9, 166.4. HRMS calcd for
C34H28N2O2Cl2: 566.1528, found: 566.1528. Anal. Calcd
for C34H28N2O2Cl2: C, 71.96%; H, 4.97%; N, 4.94%.
Found: C, 72.13%; H, 5.06%; N, 4.83%.
4.6.1. (2Z,4Z)-N1,N6-Bis(4-phenyl)-2,3,4,5-tetrapropyl
hexa-2,4-dienediamide (5a). White solid, 65% isolated
1
yield, mp: 184–185 ꢁC. H NMR (CDCl3, Me4Si): d 0.82–
4.7. General procedure for the preparation of multiply
substituted hexa-2,4-dienedioic acid bisamide deriva-
tives (5) and multiply substituted penta-2,4-dienoic acid
amide derivatives (6)
1.94 (m, 12H), 1.27–1.46 (m, 8H), 2.09–2.13 (m, 4H),
2.29–2.32 (m, 4H), 7.08–7.62 (m, 10H), 9.24 (s, 2H). 13C
NMR (CDCl3, Me4Si): d 14.1, 14.7, 21.6, 22.1, 32.6, 37.0,
119.9, 124.1, 128.9, 134.3, 138.3, 142.3, 170.4. HRMS calcd
for C30H40N2O2: 460.3090, found: 460.3083. Anal. Calcd
for C30H40N2O2: C, 78.22%; H, 8.75%; N, 6.08%. Found:
C, 78.45%; H, 8.79%; N, 6.01%.
The procedure was basically the same as above. Depending
on the substituents of the Ar group of ArNCO, mono-amide
and/or bisamide derivatives were obtained as mixtures.
4.6.2. (2Z,4Z)-N1,N6-Bis(2-chlorophenyl)-2,3,4,5-tetra-
propyl hexa-2,4-dienediamide (5b). White solid, 80% iso-
4.7.1. (2Z,4Z)-N1,N6-Bis(4-methylphenyl)-2,3,4,5-tetra-
propyl hexa-2,4-dienediamide (5g). White solid, 34% iso-
1
1
lated yield, mp: 130–131 ꢁC. H NMR (CDCl3, Me4Si):
lated yield. H NMR (CDCl3, Me4Si): d 0.86 (t, J¼7.2 Hz,
d 0.89 (t, J¼7.2 Hz, 6H), 0.92 (t, J¼7.2 Hz, 6H), 1.33–
1.57 (m, 8H), 2.15–2.22 (m, 4H), 2.35 (t, J¼7.8 Hz, 4H),
6.99–8.27 (m, 8H), 8.88 (s, 2H). 13C NMR (CDCl3,
Me4Si): d 14.1, 14.8, 21.6, 22.0, 32.5, 37.0, 122.7, 123.8,
124.7, 127.5, 129.2, 133.4, 134.9, 144.1, 169.8. HRMS calcd
for C30H38N2O2Cl2: 528.2310, found: 528.2310. Anal.
Calcd for C30H38N2O2Cl2: C, 68.24%; H, 7.28%; N,
5.22%. Found: C, 68.04%; H, 7.23%; N, 5.29%.
6H), 0.87 (t, J¼7.2 Hz, 6H), 1.30–1.50 (m, 8H), 2.09–2.15
(m, 4H), 2.25–2.33 (m, 10H), 7.09–7.51 (m, 8H), 9.06 (s,
2H). 13C NMR (CDCl3, Me4Si): d 14.1, 14.7, 20.9, 21.6,
22.1, 32.6, 37.0, 119.9, 129.3, 133.6, 134.4, 135.8, 142.1,
170.2. HRMS calcd for C32H44N2O2: 488.3403, found:
488.3407.
4.7.2. (2Z,4Z)-N1,N6-Bis(4-fluorophenyl)-2,3,4,5-tetra-
propyl hexa-2,4-dienediamide (5h). White solid, 26% iso-
1
4.6.3. (2Z,4Z)-N1,N6-Bis(2,4-dichlorophenyl)-2,3,4,5-
tetrapropyl hexa-2,4-dienediamide (5c). White solid,
lated yield. H NMR (CDCl3, Me4Si): d 0.85 (t, J¼7.2 Hz,
6H), 0.87 (t, J¼7.2 Hz, 6H), 1.22–1.50 (m, 8H), 2.10–2.20
(m, 4H), 2.26–2.34 (m, 4H), 6.96–7.59 (m, 8H), 9.30 (s,
2H). 13C NMR (CDCl3, Me4Si): d 14.1, 14.7, 21.6, 22.1,
32.6, 37.0, 115.5 (d, J¼22.3 Hz, 2C), 121.6 (d, J¼8.1 Hz,
2C), 134.2, 134.3 (d, J¼3.1 Hz, 1C), 142.3, 159.3 (d,
J¼241.1 Hz, 1C), 170.4. HRMS calcd for C30H38N2O2F2:
496.2901, found: 496.2902.
1
89% isolated yield, mp: 133–134 ꢁC. H NMR (CDCl3,
Me4Si): d 0.89 (t, J¼7.5 Hz, 6H), 0.92 (t, J¼7.5 Hz, 6H),
1.34–1.51 (m, 8H), 2.14–2.20 (m, 4H), 2.34 (t, J¼7.8 Hz,
4H), 7.21–8.24 (m, 6H), 8.88 (s, 2H). 13C NMR (CDCl3,
Me4Si): d 14.1, 14.8, 21.6, 22.0, 32.5, 37.0, 123.4, 124.4,
127.7, 128.9, 129.2, 133.3, 133.7, 144.4, 169.8. HRMS calcd
for C30H36N2O2Cl4: 596.1531, found: 596.1518. Anal.
Calcd for C30H36N2O2Cl4: C, 60.21%; H, 4.68%; N,
6.06%. Found: C, 60.36%; H, 4.59%; N, 6.12%.
4.7.3. (2Z,4Z)-N1,N6-Bis(4-chlorophenyl)-2,3,4,5-tetra-
propyl hexa-2,4-dienediamide (5i). White solid, 23% iso-
1
lated yield. H NMR (CDCl3, Me4Si): d 0.86 (t, J¼7.2 Hz,
4.6.4. (2Z,4Z)-N1,N6-Bis(2-chlorophenyl)-2,3,4,5-tetra-
ethyl hexa-2,4-dienediamide (5d). White solid, 71% iso-
lated yield. 1H NMR (CDCl3, Me4Si): d 1.03–1.08 (m,
12H), 2.24–2.46 (m, 8H), 7.01–8.30 (m, 8H), 8.86 (s, 2H).
13C NMR (CDCl3, Me4Si): d 12.8, 13.3, 23.4, 27.3, 122.6,
123.7, 124.8, 127.5, 129.2, 134.2, 134.9, 144.5, 169.7.
HRMS calcd for C26H30N2O2Cl2: 472.1684, found:
472.1686.
12H), 1.24–1.49 (m, 8H), 2.08–2.13 (m, 4H), 2.30 (t,
J¼7.8 Hz, 4H), 7.25–7.57 (m, 8H), 9.17 (s, 2H). 13C NMR
(CDCl3, Me4Si): d 14.1, 14.7, 21.6, 22.1, 32.6, 37.0, 121.1,
128.9, 129.1, 134.2, 136.8, 142.6, 170.5. HRMS calcd for
C30H38N2O2Cl2: 528.2310, found: 528.2303.
4.7.4. 2,3,4-Tripropyl-octa-2,4-dienoic acid (4-methyl-
phenyl)-amide (6a). White solid, 21% isolated yield. H
1
NMR (CDCl3, Me4Si): d 0.81 (t, J¼7.5 Hz, 3H), 0.89–
0.97 (m, 9H), 1.23–1.51 (m, 8H), 1.93–1.98 (m, 2H),
2.00–2.18 (m, 4H), 2.29 (s, 3H), 2.34–2.39 (m, 2H), 5.47
(t, J¼7.2 Hz, 1H), 7.07–7.34 (m, 5H). 13C NMR (CDCl3,
Me4Si): d 13.9, 14.1, 14.8, 20.8, 21.4, 22.2, 22.6, 22.9,
30.2, 32.3, 33.2, 119.4, 129.4, 130.8, 133.4, 134.9, 135.8,
139.9, 144.4, 170.0. HRMS calcd for C24H37NO:
355.2875, found: 355.2871.
4.6.5. Compound 5e. White solid, 59% isolated yield, mp:
127–128 ꢁC. 1H NMR (CDCl3, Me4Si): d 0.86 (t,
J¼7.2 Hz, 6H), 1.35–1.39 (m, 4H), 1.52–1.76 (m, 4H),
2.03–2.11 (m, 2H), 2.22–2.31 (m, 4H), 2.86–2.91 (m, 2H),
6.95–7.61 (m, 8H), 8.41–8.44 (m, 2H). 13C NMR (CDCl3,
Me4Si): d 14.0, 22.3, 28.7, 32.1, 34.1, 121.6, 122.2, 124.2,
127.8, 128.6, 132.4, 134.8, 143.4, 168.2. HRMS calcd for

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Q. Hu et al. / Tetrahedron 63 (2007) 6614–6624
4.7.5. 2,3,4-Tripropyl-octa-2,4-dienoic acid (4-fluoro-
phenyl)-amide (6b). White solid, 40% isolated yield. H
Cp2ZrCl2 (2.0 mmol, 0.58 g) and n-BuLi (4.0 mmol,
2.6 mL, 1.60 M hexane solution) in toluene (20 mL) at
ꢀ78 ꢁC. The reaction mixture was then stirred at room tem-
perature for 1 h to afford zirconacyclopentadiene. 4-Bromo-
phenyl isocyanate (4.0 mmol) and EtAlCl2 (8.0 mmol,
8.8 mL, 0.9 M hexane solution) were added to this solution
at ꢀ78 ꢁC. After being stirred at ꢀ30 ꢁC for 1 h, the above
reaction mixture was treated with I2 (2 mmol) and stirred
for another 1 h before quenching with saturated aqueous
NaHCO3 and extracting with Et2O. The extract was washed
with water and brine, and dried over MgSO4. The solvent
was then evaporated in vacuo to give yellow oil, which
was purified by column chromatography to give the product
1
NMR (CDCl3, Me4Si): d 0.80 (t, J¼7.5 Hz, 3H), 0.90–
0.98 (m, 9H), 1.24–1.49 (m, 8H), 1.95–1.99 (m, 2H),
2.11–2.19 (m, 4H), 2.34–2.39 (m, 2H), 5.46 (t, J¼7.2 Hz,
1H), 7.20–7.43 (m, 5H). 13C NMR (CDCl3, Me4Si):
d 13.9, 14.1, 14.8, 21.4, 22.3, 22.7, 22.9, 30.2, 32.33,
32.38, 33.1, 115.5 (d, J¼22.2 Hz, 2C), 121.0 (d, J¼7.4 Hz,
2C), 130.9, 134.4 (d, J¼2.5 Hz, 1C), 134.7, 139.9, 144.9,
159.2 (d, J¼241.1 Hz, 1C), 170.1. HRMS calcd for
C23H34NOF: 359.2624, found: 359.2637.
4.7.6. 2,3,4-Tripropyl-octa-2,4-dienoic acid (4-chloro-
phenyl)-amide (6c). White solid, 30% isolated yield. H
1
1
6I as yellow oil in 68% isolated yield. H NMR (CDCl3,
NMR (CDCl3, Me4Si): d 0.80 (t, J¼7.5 Hz, 3H), 0.90–
0.98 (m, 9H), 1.20–1.25 (m, 2H), 1.36–1.48 (m, 6H),
1.94–1.97 (m, 2H), 2.10–2.19 (m, 4H), 2.33–2.39 (m, 2H),
5.46 (t, J¼7.2 Hz, 1H), 7.22–7.42 (m, 5H). 13C NMR
(CDCl3, Me4Si): d 13.9, 14.1, 14.8, 21.4, 22.3, 22.7, 22.9,
30.2, 32.3, 32.26, 33.31, 120.5, 128.7, 128.9, 131.1, 134.6,
137.0, 140.0, 145.1, 170.2. HRMS calcd for C23H34NOCl:
375.2329, found: 375.2331.
Me4Si): d 0.92–1.13 (m, 12H), 2.13–2.59 (m, 8H), 7.39–
7.50 (m, 4H), 7.91 (s, 1NH). 13C NMR (CDCl3, Me4Si):
d 12.6, 12.8, 13.0, 14.8, 22.9, 26.1, 27.4, 34.4, 110.1,
116.3, 120.7, 131.9, 135.1, 137.3, 145.7, 148.6, 168.6.
HRMS calcd for C19H25NOBrI: 489.0164, found: 489.0168.
4.10. General procedure for the preparation of mixed
bisamide derivative
4.7.7. 2,3,4-Tripropyl-octa-2,4-dienoic acid (4-bromo-
phenyl)-amide (6d). White solid, 54% isolated yield. H
A monoyne (2.0 mmol) was added into a toluene solution of
[Cp2ZrBu2] (Negishi reagent),16 prepared in situ from
Cp2ZrCl2 (1.0 mmol, 0.29 g) and n-BuLi (2.0 mmol,
1.3 mL, 1.60 M hexane solution) in toluene (10 mL) at
ꢀ78 ꢁC. The reaction mixture was then stirred at room tem-
perature for 1 h to afford zirconacyclopentadiene. The first
isocyanate (1.4 mmol) and EtAlCl2 (5.6 mmol, 6.2 mL,
0.9 M hexane solution) were added to this solution at
ꢀ78 ꢁC and the reaction mixture was stirred at ꢀ35 ꢁC for
1 h. Then, the second isocyanate (1.5 mmol) was added to
the above reaction mixture at ꢀ35 ꢁC. After stirring at
room temperature for 12 h, the above reaction mixture was
quenched with 3 N HCl and extracted with EtOAc. The ex-
tract was washed with water and brine, and dried over
MgSO4. The solvent was then evaporated in vacuo to give
yellow oil, which was purified by column chromatography
to the products.
1
NMR (CDCl3, Me4Si): d 0.80 (t, J¼7.2 Hz, 3H), 0.89–0.98
(m, 9H), 1.18–1.50 (m, 8H), 1.91–1.99 (m, 2H), 2.09–2.18
(m, 4H), 2.33–2.38 (m, 2H), 5.45 (t, J¼7.2 Hz, 1H), 7.21–
7.41 (m, 5H). 13C NMR (CDCl3, Me4Si): d 13.9, 14.1,
14.8, 21.4, 22.3, 22.7, 22.9, 30.2, 32.2, 32.3, 33.1, 116.2,
120.7, 131.1, 131.9, 134.6, 137.4, 139.8, 145.2, 170.2.
HRMS calcd for C23H34NOBr: 419.1824, found: 419.1837.
4.8. Procedure for the preparation of (2Z,4E)-4-deutero-
(4-bromophenyl)-2,3,4-tripropylhepta-2,4-dienamide
(6eD)
4-Octyne (4.0 mmol) was added into a toluene solution of
[Cp2ZrBu2] (Negishi reagent), prepared in situ from
Cp2ZrCl2 (2.0 mmol, 0.58 g) and n-BuLi (4.0 mmol, 2.6 mL,
1.60 M hexane solution) in toluene (20 mL) at ꢀ78 ꢁC. The
reaction mixture was then stirred at room temperature for 1 h
to afford zirconacyclopentadiene. 4-Bromophenyl isocya-
nate (4.0 mmol) and EtAlCl2 (8.0 mmol, 8.8 mL, 0.9 M hex-
ane solution) were added to this solution at ꢀ78 ꢁC. After
stirring the reaction mixture at ꢀ30 ꢁC for 1 h, the above re-
action mixture was quenched with DCl (0.3 mL, 20%) and
extracted with Et2O. The extract was washed with water
and brine, and dried over MgSO4. The solvent was then evap-
orated in vacuo to give yellow oil, which was purified by col-
umn chromatography to the products as yellow oil in 47%
4.10.1. (2Z,4Z)-N1-(4-Bromophenyl)-N6-(2,4-dichloro-
phenyl)-2,3,4,5-tetrapropyl hexa-2,4-dienediamide (9a).
White solid, 39% isolated yield, mp: 116–117 ꢁC. 1H
NMR (CDCl3, Me4Si): d 0.79–0.92 (m, 12H), 1.22–1.52
(m, 8H), 2.01–2.22 (m, 6H), 2.42–2.48 (m, 2H), 7.26–7.54
(m, 6H), 7.85 (s, 1H), 8.28 (d, J¼8.7 Hz, 1H), 10.36 (s,
1H). 13C NMR (CDCl3, Me4Si): d 14.0, 14.2, 14.67, 14.69,
21.3, 21.75, 21.84, 22.6, 32.2, 32.8, 36.9, 37.2, 115.8,
120.8, 122.9, 124.0, 128.1, 129.0, 130.0, 131.65, 131.74,
132.7, 136.1, 138.2, 139.4, 147.2, 169.5, 171.1. HRMS calcd
for C30H37BrCl2N2O2: 606.1416, found: 606.1421. Anal.
Calcd for C30H37BrCl2N2O2: C, 59.22%; H, 6.13%; N,
4.60%. Found: C, 59.34%; H, 6.09%; N, 4.45%.
1
isolated yield, D>90%. H NMR (CDCl3, Me4Si): d 0.80
(t, J¼7.2 Hz, 3H), 0.89–0.98 (m, 9H), 1.20–1.47 (m, 8H),
1.92–1.97 (m, 2H), 2.09–2.18 (m, 4H), 2.33–2.38 (m, 2H),
7.19–7.41 (m, 5H). 13C NMR (CDCl3, Me4Si): d 13.9,
14.1, 14.8, 21.4, 22.3, 22.7, 22.8, 30.1, 32.2, 32.3, 33.1,
116.2, 120.7, 131.9, 134.6, 137.4, 139.7, 145.1, 170.2.
HRMS calcd for C23H33DNOBr: 420.1887, found: 420.1874.
4.10.2. (2Z,4Z)-N1-(4-Bromophenyl)-N6-(2-chloro-
phenyl)-2,3,4,5-tetraethyl hexa-2,4-dienediamide (9b).
White solid, 51% isolated yield. 1H NMR (CDCl3, Me4Si):
d 0.95–1.09 (m, 12H), 2.10–2.36 (m, 6H), 2.45–2.57 (m,
2H), 7.12–7.87 (m, 8H), 8.30–8.33 (m, 1H), 10.56 (s, 1H).
13C NMR (CDCl3, Me4Si): d 12.5, 13.0, 13.2, 13.8, 23.3,
23.4, 27.4, 115.7, 120.8, 122.3, 123.6, 125.5, 127.9, 129.3,
131.6, 132.7, 133.9, 136.9, 138.2, 139.9, 147.2, 169.6,
4.9. Procedurefor thepreparationofbutadienyliodide6I
3-Hexyne (4.0 mmol) was added into a toluene solution of
[Cp2ZrBu2] (Negishi reagent), prepared in situ from

Q. Hu et al. / Tetrahedron 63 (2007) 6614–6624
6623
171.0. HRMS calcd for C26H30N2O2BrCl: 516.1179, found:
516.1184.
14.7, 18.0, 20.3, 26.4, 33.6, 74.3, 97.0, 121.5, 123.1,
124.1, 124.7, 125.7, 126.9, 127.1, 127.4, 129.3, 129.4,
134.4, 136.3, 144.7, 154.2, 161.0, 166.1. Isomer 2: 1H
NMR (CDCl3, Me4Si): d 0.79 (t, J¼7.2 Hz, 3H), 1.12 (t,
J¼6.8 Hz, 3H), 1.31 (t, J¼7.7 Hz, 6H), 1.91–2.55 (m, 8H),
6.68–7.81 (m, 8H), 8.70 (s, 1H). 13C NMR (CDCl3,
Me4Si): d 8.7, 12.6, 12.9, 15.1, 17.9, 20.3, 24.9, 32.0, 71.9,
97.1, 122.3, 122.7, 123.8, 125.4, 125.6, 126.5, 126.7,
127.2, 129.1, 129.3, 134.4, 136.7, 145.0, 155.3, 161.2,
166.0. HRMS calcd for C26H29N2O2Cl2I: 598.0651, found:
598.0660. Anal. Calcd for C26H29N2O2Cl2I: C, 52.10%; H,
4.88%; N, 4.67%. Found: C, 52.26%; H, 4.99%; N, 4.61%.
Mp: 118–119 ꢁC.
4.11. General procedure for the preparation of com-
pounds 11
To a THF and H2O (1:1, 5 mL) solution of compound
2 (1.0 mmol) at room temperature was added NBS
(1.0 mmol). The above reaction mixture was then stirred at
room temperature for 3 h to generate compound 11, which
was monitored by GC analysis or by TLC. The above reac-
tion mixture was then extracted with diethyl ether. The ex-
tract was washed with brine and dried over MgSO4. The
solvent was evaporated in vacuo to give a red-orange oil,
which was purified by column chromatography to afford 11.
Acknowledgements
4.11.1. Compound 11a. White solid, 89% isolated yield,
1
mp: 89–90 ꢁC. H NMR (CDCl3, Me4Si): d 0.85–1.09 (m,
This work was supported by the Natural Science Foundation
of China and the Major State Basic Research Development
Program (2006CB806105). Cheung Kong Scholars Pro-
gramme, Qiu Shi Science and Technologies Foundation,
and Dow Corning Corporation are gratefully acknowledged.
12H), 1.62–1.72 (m, 8H), 2.34–2.38 (m, 8H), 6.76–7.82
(m, 6H), 8.96 (s, 1H). 13C NMR (CDCl3, Me4Si): d 13.9,
14.0, 14.5, 15.1, 17.0, 20.5, 21.5, 21.6, 26.6, 29.7, 34.1,
39.0, 81.9, 97.0, 122.2, 123.4, 125.1, 126.7, 127.2, 127.7,
128.3, 128.78, 128.81, 130.2, 132.7, 134.7, 144.0, 154.7,
162.5, 165.4. HRMS calcd for C30H35N2O2Cl4Br: 674.0636,
found: 674.0636. Anal. Calcd for C30H35N2O2Cl4Br: C,
53.20%; H, 5.21%; N, 4.14%. Found: C, 53.42%; H,
5.19%; N, 4.05%.
Supplementary data
Supplementary data associated with this article can be found
in the online version, at doi:10.1016/j.tet.2007.02.015.
4.11.2. Compound 11b. White solid, 98% isolated yield,
mp: 92–93 ꢁC. 1H NMR (CDCl3, Me4Si): d 0.74 (t,
J¼7.2 Hz, 3H), 1.07 (t, J¼6.8 Hz, 3H), 1.23–1.90 (m, 6H),
1.95–2.03 (m, 2H), 2.42–2.59 (m, 6H), 6.67–7.91 (m, 8H),
9.06 (s, 1H). 13C NMR (CDCl3, Me4Si): d 8.0, 11.4, 12.6,
13.0, 17.8, 20.1, 25.1, 30.4, 83.2, 97.1, 121.8, 122.8,
123.7, 124.7, 125.4, 126.5, 126.6, 128.4, 129.0, 129.1,
134.1, 136.3, 145.1, 154.1, 161.7, 162.3. HRMS calcd for
C26H29N2O2Cl2Br: 550.0789, found: 550.0785. Anal. Calcd
for C26H29N2O2Cl2Br: C, 56.54%; H, 5.29%; N, 5.07%.
Found: C, 56.62%; H, 5.26%; N, 4.89%.
References and notes
1. (a) Santelli, M.; Pons, J. M. Lewis Acids and Selectivity in
Organic Synthesis; CRC: Tokyo, 1996; (b) Lewis Acids in
Organic Synthesis; Yamamoto, H., Ed.; Wiley-VCH:
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2. Multimetallic Catalysts in Organic Synthesis; Shibasaki, M.,
Yamamoto, Y., Eds.; Wiley-VCH: Weinheim, 2004.
3. (a) Jiang, B.; Tilley, T. D. J. Am. Chem. Soc. 1999, 121, 9744;
(b) Suh, M. C.; Jiang, B.; Tilley, T. D. Angew. Chem., Int.
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Organometallics 2001, 20, 5515.
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Spiegel, B. J. J. Am. Chem. Soc. 1978, 100, 2254; (b) van
Horn, D. E.; Valente, L. F.; Idacavage, M. J.; Negishi, E.
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Matsumura, H.; Yamanaka, M.; Takahashi, T. Tetrahedron
2004, 60, 1393.
4.11.3. Compound 11c (1:1 mixture). Colorless oil, 75%
isolated yield. Isomer 1: H NMR (CDCl3, Me4Si): d 0.77
1
(t, J¼7.2 Hz, 3H), 0.97 (t, J¼7.3 Hz, 3H), 1.17 (t,
J¼7.5 Hz, 3H), 1.24 (t, J¼7.8 Hz, 3H), 1.60–2.63 (m, 9H),
6.92–8.06 (m, 9H). 13C NMR (CDCl3, Me4Si): d 7.2, 12.1,
12.6, 13.3, 17.6, 19.5, 20.8, 27.4, 58.0, 94.2, 122.9, 123.0,
123.9, 124.2, 125.3, 126.8, 126.9, 127.5, 129.1, 129.4,
133.9, 134.5, 145.1, 155.8, 162.2, 169.7. HRMS calcd for
1
C26H30N2O2Cl2: 472.1684, found: 472.1682. Isomer 2: H
NMR (CDCl3, Me4Si): d 0.73 (t, J¼7.2 Hz, 3H), 0.98 (t,
J¼7.5 Hz, 3H), 1.20 (t, J¼7.8 Hz, 3H), 1.28 (t, J¼7.5 Hz,
3H), 1.41–2.63 (m, 9H), 6.93–8.19 (m, 9H). 13C NMR
(CDCl3, Me4Si): d 7.1, 11.6, 12.6, 13.4, 17.7, 18.7, 20.4,
27.6, 57.5, 94.2, 122.4, 122.5, 123.9, 124.2, 124.7, 125.7,
127.1, 127.3, 128.9, 129.7, 134.4, 145.3, 154.3, 161.8,
170.8. HRMS calcd for C26H30N2O2Cl2: 472.1684, found:
472.1688.
6. (a) Suzuki, K. Pure Appl. Chem. 1994, 66, 1557; (b) Suzuki, K.;
Hasegawa, T.; Imai, T.; Maeta, H.; Ohba, S. Tetrahedron 1995,
51, 4483; (c) Ohmori, K.; Hatakeyama, K.; Ohrui, H.; Suzuki,
K. Tetrahedron 2004, 60, 1365.
4.11.4. Compound 11d (1:5 mixture). White solid, 60%
isolated yield. Isomer 1: H NMR (CDCl3, Me4Si): d 0.81
(t, J¼7.2 Hz, 3H), 1.09 (t, J¼6.9 Hz, 3H), 1.23 (t,
J¼7.8 Hz, 6H), 1.94–2.52 (m, 8H), 6.92–8.10 (m, 8H),
9.02 (s, 1H). 13C NMR (CDCl3, Me4Si): d 8.2, 12.5, 13.0,
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Y.; Hayashi, T. Tetrahedron Lett. 1996, 37, 3161; (c) Gordon,
1

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