Zirconium-mediated multicomponent reactions of 1,3-butadiynes with ylidenemalononitriles to form functionalized 1,8-naphthyridine and cyclopenta[b]pyridine derivatives

Article abstract of DOI:10.1002/chem.201405899

Zirconocene-mediated multicomponent reactions of 1,3-butadiynes with ylidenemalononitriles in the absence or presence of CuCl have been developed. In the absence of CuCl, 1,3-butadiyne couples with three molecules of ylidenemalononitriles to yield azazirconacycles bearing a hexahydro-1,8-naphthyridine skeleton with high stereoselectivity. In the presence of CuCl, cyclopenta[b]-pyridine or cyclopenta[ b ]quinolin-1-one derivatives are obtained via transmetalation of Zr-C bond to Cu-C bond as the key reaction step. These domino-type reactions proceed with high chemo-, regio- and/or stereoselectivities, and allowing the formation of multiple C-N and C-C bonds in a single operation.

Full text of DOI:10.1002/chem.201405899

DOI: 10.1002/chem.201405899
Communication
&
Synthetic Methods |Hot Paper|
Zirconium-Mediated Multicomponent Reactions of 1,3-Butadiynes
with Ylidenemalononitriles to Form Functionalized 1,8-
Naphthyridine and Cyclopenta[b]pyridine Derivatives
[
a]
Shasha Yu, Renhong Sun, Haoyi Chen, Xin Xie, and Yuanhong Liu*
[3b,c]
triles bearing additional functional groups.
Ylidenemalono-
Abstract: Zirconocene-mediated multicomponent reac-
tions of 1,3-butadiynes with ylidenemalononitriles in the
absence or presence of CuCl have been developed. In the
absence of CuCl, 1,3-butadiyne couples with three mole-
cules of ylidenemalononitriles to yield azazirconacycles
bearing a hexahydro-1,8-naphthyridine skeleton with high
stereoselectivity. In the presence of CuCl, cyclopenta[b]-
pyridine or cyclopenta[b]quinolin-1-one derivatives are ob-
tained via transmetalation of ZrÀC bond to CuÀC bond as
the key reaction step. These domino-type reactions pro-
ceed with high chemo-, regio- and/or stereoselectivities,
and allowing the formation of multiple CÀN and CÀC
bonds in a single operation.
nitriles can be viewed as activated alkenes as well as functional
nitriles, which usually act as Michael acceptors to engage in
conjugate addition reactions. However, with the exception of
[4]
functional group transformations, reactions involving prefer-
[5]
ential reaction of the CꢀN bond are quite rare. In addition, to
our knowledge there is no report of Zr- or Ti-promoted direct
[6,7]
coupling of alkynes with ylidenemalononitriles.
Herein we
report an unprecedented zirconium-mediated multicomponent
coupling reaction of 1,3-butadiynes with ylidenemalononitriles,
initiated by preferential insertion of the CꢀN moiety into zirco-
nium–butadiyne complexes, which provides a straightforward
route for the synthesis of 1,8-naphthyridine derivatives with
high levels of chemo- and stereocontrol. It turns out that three
molecules of the ylidenemalononitrile are incorporated into
the products, and one of the diastereomers out of eight possi-
bilities is obtained with high diastereomeric purity after
column chromatography. Moreover, in the presence of a trans-
metalation reagent, 5-amino-3,4-dihydro-2H-cyclopenta[b]pyri-
dine or cyclopenta[b]quinolin-1-one derivatives are obtained,
which depend on the substitution patterns of the ylidenemalo-
nonitriles (Scheme 1).
The development of reliable and highly selective reactions, in-
cluding chemo-, regio- and stereoselective reactions, continues
to be an important challenge in organic synthesis, especially,
in the synthesis of complex molecules. In general, the selectivi-
ty can be affected by various factors, such as the structural fea-
tures of the reactants, metal reagents, ligands, reaction condi-
tions, or additives. In this regard, coupling reactions of two un-
saturated compounds mediated by early transition metals such
as Zr or Ti, leading to the formation of metallacycles, usually
display satisfactory chemo- and regioselectivities, due to highly
selective transition states brought about by the interactions of
[
1]
the metal reagents and substrates. The thus-generated metal-
lacycles are useful intermediates for the construction of
carbon–carbon and carbon–heteroatom bonds. Zr- or Ti-medi-
ated coupling reactions of alkynes with nitriles are of particular
interest, as they can provide a versatile and efficient route for
the formation of highly valuable heterocycles via further trans-
[
2,3]
Scheme 1. Zr-mediated coupling reactions of 1,3-butadiynes with ylidene-
malononitriles.
formations of the resultant azametallacycles.
Although
much progress has been achieved in this field, there have
been few reports of the coupling reactions of alkynes with ni-
Recently, our group developed a very convenient synthetic
method for monozirconation of bulky silyl- or tert-butyl-substi-
[
a] Dr. S. Yu, R. Sun, H. Chen, X. Xie, Prof. Y. Liu
State Key Laboratory of Organometallic Chemistry
Shanghai Institute of Organic Chemistry
Chinese Academy of Sciences
[8a]
[8]
tuted 1,3-butadiynes using the Negishi reagent [Cp ZrBr ].
2
2
The resulting zirconocene–butadiyne complexes can be de-
scribed as a highly strained zirconacyclocumulene 3, which is
possibly in equilibrium with the three-membered alkynylzirco-
nacyclopropene 2, although the equilibrium is shifted towards
3
45 Lingling Lu, Shanghai 200032 (P. R. China)
Fax: (+86)021-64166128
E-mail: yhliu@mail.sioc.ac.cn
3
(Table 1). Zirconacyclocumulene 3 undergoes a series of in-
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/chem.201405899.
teresting and unusual multicomponent reactions with aldehy-
Chem. Eur. J. 2014, 20, 1 – 6
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Table 1. Zirconium-mediated multicomponent reactions of 1,3-butadiynes
with ylidenemalononitriles.
1
2
o
[a]
Entry
R
R
T [ C] t [h] Product Yield [%]
1
2
TIPS (1a)
TIPS (1a)
TIPS (1a)
TBS (1b)
Ph
Ph
Ph
Ph
RT
80
5
5
5
2
2
2
2
2
4a
4a
4a
4b
4c
4d
4e
4 f
67 (7.2:1)
70 (9.1:1)
67
47
42
52 (7.7:1)
48
52 (10:1)
[
[
[
[
[
[
b]
b]
b]
b]
b]
b]
3
4
5
6
7
8
110
110
110
110
110
110
TBDPS (1c) Ph
TPS (1d)
TIPS (1a)
TIPS (1a)
Ph
p-ClC H
6 4
p-MeOC
6
H
4
[a] Yield of isolated product. The diastereomeric ratio is shown in the paren-
thesis; [b] in a sealed tube. TIPS=Si(iPr)
Bu(Ph) ; TPS=Si(Ph)
3
; TBS=SitBuMe
2
; TBDPS=Sit-
2
3
.
Figure 1. Molecular structure of the major diastereomer of 4a. Thermal ellip-
soids are set at 30% probability. Hydrogen atoms are omitted for clarity. Se-
lected bond lengths [ꢁ] and angles [8]: Zr1ÀN1 2.464(2), Zr1ÀN2 2.160(2),
Zr1ÀC20 2.395(2), C15ÀN1 1.292(3), C15ÀN2 1.336(3), C18ÀN2 1.375(3), C17À
C18 1.376(4), C19ÀC20 1.368(4), C29ÀN3 1.124(4); C18-N2-Zr1 132.00(16), N1-
C15-N2 112.2(2), C19-C20-Zr1 121.67(17).
[
8a]
[8b]
[8b]
[8c]
des, carbamoyl cyanides, aroyl cyanides, and nitriles.
Treatment of TIPS-substituted zirconium species 2a/3a, de-
rived from the 1,4-bis[tri(isopropyl)silyl]buta-1,3-diyne 1a, with
4
equivalents of 2-benzylidenemalononitrile at room tempera-
ture for 5 h, afforded the a-alkynylazazirconacycle 4a incorpo-
rating a hexahydro-1,8-naphthyridine skeleton in 67% yield as
a mixture of two diastereomers with a ratio of 7.2:1 (Table 1,
entry 1). Increasing the reaction temperature to 808C resulted
in a 70% yield of 4a with a diastereomeric ratio of 9.1:1
nitrogen on the hydropyridinyl ring coordinates with Zr to
form a four-membered chelate ring. The bond lengths of Zr1À
C20 (2.395(2) ꢁ) and Zr1ÀN2 (2.160(2) ꢁ) are in the range of
[2i,j]
(
Table 1, entry 2). Interestingly, further increasing the reaction
single bonds, whereas the Zr1ÀN1 distance (2.464(2) ꢁ) sug-
[2o]
temperature to 1108C allowed the isolation of 4a as a single
diastereomer in 67% yield (Table 1, entry 3). The results indicat-
ed that the stereoselectivity could be improved at higher reac-
gests a dative interaction. The bond lengths of the C19ÀC20
(1.368(4) ꢁ) and C17ÀC18 (1.376(4) ꢁ) demonstrate strong C=C
double bond character and C15ÀN1 (1.292(3) ꢁ) corresponds
to an imine moiety. The minor isomer was assigned to be a C1
[
9]
tion temperature. The structure and the relative stereochem-
istry of the major as well as the minor diastereomers of 4a
were unambiguously confirmed by X-ray crystallographic anal-
[10]
epimer, according to X-ray crystallographic analysis.
To release the organic moiety from the zirconium com-
[
10]
ysis. Complex 4a is quite stable towards air and water and
plexes, we carried out demetalation reactions. Hydrolysis of 4e
[10]
can be easily isolated by silica-gel chromatography after
with 3m HCl solution at 508C afforded the desired enyne 5a
quenching the mixture with saturated NaHCO solution. TBS-,
in 46% yield, along with an unexpected polycyclic compound
3
TBDPS- and TPS-substituted butadiynes also afforded the cor-
responding zirconacycles 4b–d as single isomers or with high
stereoselectivity at 1108C after separation (Table 1, entries 4–6).
Arylidenemalononitriles bearing Cl or OMe functional groups
were compatible with this reaction to give 4e and 4 f in 48
and 52% yields, respectively (Table 1, entries 7 and 8). The
presence of a five-membered azazirconacycle in 4 indicated
that one of the CN groups of ylidenemalononitrile preferential-
ly reacted with zirconocene–butadiyne complex at the initial
step. Ylidenemalononitriles have been reported to react with
6a in 39% yield (Scheme 2). Interestingly, hydrolysis of 4c,
bearing TBDPS groups, afforded 6b as the sole product in
[10]
[
6b]
zirconacyclopentanes or -pentenes directly, or to act as elec-
trophiles in zirconacycle-mediated reactions in the presence of
[
6a]
CuCl. In these reactions, ylidenemalononitriles act as Michael
acceptors while CN groups remain intact.
The X-ray crystal structure of the major isomer of 4a
(Figure 1) unambiguously verified the structure and the stereo-
chemistry of the fused azazirconacyclopentene complex 4. The
Scheme 2. Demetalation experiments.
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7
6% yield. In these reactions, the ZrÀN bond in com-
Table 2. Zirconium-mediated multicomponent reactions of 1,3-butadiynes with ylide-
nemalononitriles in the presence of CuCl.
plex 4 might be cleaved preferentially to give an al-
kenylzirconium intermediate 7, which undergoes in-
tramolecular cyclization by attack of the ZrÀC bond
to the CN group followed by hydrolysis, to afford the
polycyclic product 6. The ZrÀC bond of 7 derived
from TBDPS-substituted butadiyne might be more
stable towards hydrolysis, thus the cyclization to 6
became the predominant pathway. Iodination of the
complex 4a with 2 equiv of iodine gave iodinated
[a]
[
10]
product 8 in 80% yield (Scheme 2).
To our surprise, when these zirconium-mediated
coupling reactions were carried out in THF in the
[
11,12]
presence of CuCl,
penta[b]pyridine derivatives
Table 2). For example, when zirconacycle 2/3 derived
5-amino-3,4-dihydro-2H-cyclo-
[
10]
9
were obtained
(
from TBDPS-substituted butadiyne reacted with 2-
benzylidenemalononitrile in the presence of 2 equiv-
alents of CuCl at 508C, the corresponding cyclopen-
ta[b]pyridine derivative 9a was obtained in 42%
yield by quenching the reaction mixture with saturat-
ed NaHCO solution. After many trials on the quench-
3
ing conditions, the yield of 9a could be improved to
72% by using MeOH as the quenching reagent. It
should be noted that the products 9 are not stable
upon isolation by silica-gel chromatography; there-
fore, an appropriate workup procedure is very impor-
tant in obtaining pure products. Decomposition
could be avoided if the evaporation was carried out
at room temperature (less than 308C), followed by
separation on neutral Al O . Under these conditions,
2
3
the desired 9 could be obtained with high purity. We
next investigated the reaction scope by performing
the reactions with various ylidenemalononitriles. Aryl-
[a] Yields of isolated product are given.
idenemalononitriles bearing electron-withdrawing or -donating
groups such as p-F, p-Cl, p-CF , p-Me and p-MeO groups on the
3
phenyl ring were all compatible for this reaction, furnishing
the corresponding products 9b–f in 38-80% yields (Table 2).
3,4,5-Trimethoxy- and sterically encumbered 1-naphthyl-substi-
tuted arylidenemalononitriles were converted into the corre-
sponding 9g and 9h in 61% and 45% yields, respectively. 2-
Furanyl and 2-thienyl groups were also tolerated well during
the reaction to give the products 9i and 9j in 70% and 54%
Scheme 3. Reaction with diphenyl ylidenemalononitrile.
yields, respectively. Employing Ph Si-substituted butadiyne af-
3
forded the corresponding products 9k and 9l in 60% and
58% yields, respectively. Notably, the results demonstrated
that the cyclization process is highly diastereoselective, as only
trans-9 were obtained in all cases (Table 2).
Interestingly, when diphenyl-substituted ylidenemalononi-
trile was used as the coupling partner, the 1H-cyclopenta[b]-
[
10]
quinolin-1-one derivative 10 was obtained in 58% yield after
quenching the reaction mixture with water (Scheme 3). In this
case, only one equivalent of ylidenemalononitrile was incorpo-
rated into the product.
We tentatively propose the following mechanism for these
novel transformations (Schemes 4 and 5): Zirconacyclocumu-
lene 3 could equilibrate with a-alkynylzirconacyclopropene 2,
Scheme 4. Proposed reaction mechanism for the formation of 4.
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Communication
In summary, we have developed zirconocene-mediated mul-
ticomponent reactions of 1,3-butadiynes with ylidenemalono-
[14]
nitriles in the absence or presence of CuCl. The reactions
were characterized by initial chemo- and regioselective cou-
pling of 1,3-butadiynes with a CN group of ylidenemalononi-
triles on a low-valency zirconocene moiety. The resulting aza-
zirconacyclopentadienes were highly reactive towards addi-
tional ylidenemalononitriles, yielding azazirconacycles bearing
a hexahydro-1,8-naphthyridine skeleton in a stereoselective
manner. In the presence of CuCl, cyclopenta[b]pyridine or cy-
clopenta[b]quinolin-1-one derivatives were obtained through
transmetalation of ZrÀC to CuÀC as the key reaction step. Fur-
ther studies to elucidate the reaction mechanism and to
extend the scope of synthetic utility are currently underway in
our laboratory.
Acknowledgements
Scheme 5. Proposed reaction mechanism for the formation of 9 and 10.
We thank the National Natural Science Foundation of China
(
Grant Nos. 21125210, 21121062), the Chinese Academy of Sci-
[
8a]
ence, and the Major State Basic Research Development Pro-
gram (Grant No. 2011CB808700) for financial support.
which is more reactive than 3. An S 2’-type addition of one
E
of the CN groups on ylidenemalononitrile to the less-hindered
propargyl zirconium moiety in complex 2 takes place to deliver
an azazirconacyclocumulene 12, which isomerizes to azazirco-
Keywords: butadiynes · domino reactions · heterocycles ·
multicomponent reactions · zirconium
2
nacyclopentadiene 13 (Scheme 4). The CN group trans to R
would react with 2/3 preferentially due to steric reasons. The
high stereoselectivity of the cyclized product may also support
the selective reaction of one of the two CN groups. However,
[
1] For reviews, see: a) Titanium and Zirconium in Organic Synthesis (Ed.: I.
Marek), Wiley-VCH, Weinheim, Germany, 2002; b) T. Takahashi, K. Kanno,
Metallocenes in Regio- and Stereoselective Synthesis in Topics in Organo-
metallic Chemistry, Vol. 8 (Ed.: T. Takahashi), Springer: Berlin, 2005,
p. 217; c) W. Zhang, S. Zhang, Z. Xi, Acc. Chem. Res. 2011, 44, 541.
2
we still could not exclude that the CN group cis to R may also
react with zirconium complex 2/3. In the absence of CuCl,
attack of the nitrogen in intermediate 13 at the CN moiety of
the second molecule of ylidenemalononitrile gives adduct 14,
which undergoes aza-conjugate addition with the third mole-
cule of ylidenemalononitrile followed by twice intramolecular
conjugate addition leading to zirconacycle 4 bearing a 1,8-
naphthyridine skeleton (Table 1 and Scheme 4). The course for
the stereoselectivity was not clear yet. The high stereoselectiv-
ity observed at high temperature may be associated with the
reaction reversibility in several addition steps, leading to the
most thermodynamically stable stereoisomers under the reac-
tion conditions.
[
2] For Zr-mediated coupling reactions of alkynes with nitriles, see: a) S. L.
Buchwald, B. T. Watson, J. Am. Chem. Soc. 1987, 109, 2544; b) T. Takaha-
shi, C. Xi, Z. Xi, M. Kageyama, R. Fischer, K. Nakajima, E. Negishi, J. Org.
Chem. 1998, 63, 6802; c) Y. Liu, B. Yan, Organometallics 2006, 25, 544;
d) R. Choukroun, C. Lorber, L. Vendier, Organometallics 2007, 26, 3784;
e) J. Zhao, S. Zhang, W. Zhang, Z. Xi, Organometallics 2011, 30, 3464;
For the formation of heterocycles, see: f) S. L. Buchwald, B. T. Watson,
R. T. Lum, W. A. Nugent, J. Am. Chem. Soc. 1987, 109, 7137; g) T. Takaha-
shi, F. Tsai, Y. Li, H. Wang, Y. Kondo, M. Yamanaka, K. Nakajima, M.
Kotora, J. Am. Chem. Soc. 2002, 124, 5059; h) X. Sun, C. Wang, Z. Li, S.
Zhang, Z. Xi, J. Am. Chem. Soc. 2004, 126, 7172; i) S. Zhou, D. Liu, Y. Liu,
Organometallics 2004, 23, 5900; j) W. Zhang, S. Zhang, X. Sun, M. Nish-
iura, Z. Hou, Z. Xi, Angew. Chem. Int. Ed. 2009, 48, 7227; Angew. Chem.
2
009, 121, 7363; k) S. Zhang, X. Sun, W. Zhang, Z. Xi, Chem. Eur. J. 2009,
In the presence of CuCl, ring-opening of zirconacyclopenta-
diene 13 by transmetalation of the ZrÀC bond to a CuÀC bond
occurs to afford vinyl copper species 17 (Scheme 5). Intramo-
lecular addition of CuÀC to the CN group provides five-mem-
1
1
5, 12608; l) S. Zhang, W. Zhang, J. Zhao, Z. Xi, J. Am. Chem. Soc. 2010,
32, 14042; m) S. Zhang, W. Zhang, Z. Xi, Chem. Eur. J. 2010, 16, 8419;
n) S. Zhang, W. Zhang, J. Zhao, Z. Xi, Chem. Eur. J. 2011, 17, 2442; o) J.
Zhao, S. Zhang, W. Zhang, Z. Xi, Organometallics 2012, 31, 8370.
[
13]
[3] For Ti-mediated coupling reactions of alkynes with nitriles, see: a) P.
Binger, F. Sandmeyer, C. Krꢂger, Organometallics 1995, 14, 2969. For the
formation of heterocycles, see: b) D. Suzuki, Y. Nobe, Y. Watai, R. Tanaka,
Y. Takayama, F. Sato, H. Urabe, J. Am. Chem. Soc. 2005, 127, 7474; c) X.
You, X. Xie, R. Sun, H. Chen, S. Li, Y. Liu, Org. Chem. Front. 2014, 1, 940.
bered diimine species 18, which undergoes conjugate addi-
tion with the second molecule of ylidenemalononitrile fol-
lowed by intramolecular addition to the azadiene moiety, to
afford the most stable trans-product 9 after quenching with
MeOH (Table 2 and Scheme 5). When diphenyl ylidenemalono-
nitrile was used as the coupling partner, the intermolecular
conjugate addition of diimine species 22 might be prevented
due to the steric effect of the two aryl groups in dinitrile and
[
4] X. Xin, D. Xiang, J. Yang, Q. Zhang, F. Zhou, D. Dong, J. Org. Chem.
013, 78, 11956.
5] S. Kamijo, T. Jin, Y. Yamamoto, J. Org. Chem. 2002, 67, 7413.
2
[
[6] For the reactions of zirconacycles with ylidenemalononitriles, see: a) T.
Takahashi, Y. Li, F. Y. Tsai, K. Nakajima, Organometallics 2001, 20, 595;
b) Y. Liu, B. Shen, M. Kotora, K. Nakajima, T. Takahashi, J. Org. Chem.
22. Instead, 22 undergoes a 6p-electrocyclic reaction to give
2
002, 67, 7019.
a cyclized intermediate 23, which might be aromatized to
[
7] For titanium-mediated cyclodimerization of ylidenemalononitriles, see:
afford 10 after quenching by H O in the air (Schemes 3 and 5).
A. Sera, T. Tsuzuki, E. Satoh, K. Itoh, Bull. Chem. Soc. Jpn. 1992, 65, 3068.
2
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Communication
[
[
8] a) X. Fu, S. Yu, G. Fan, Y. Liu, Y. Li, Organometallics 2012, 31, 531; b) S.
Yu, X. You, Y. Liu, Chem. Eur. J. 2012, 18, 13936; c) X. You, S. Yu, Y. Liu,
Organometallics 2013, 32, 5273.
9] Other stereoisomers might also be formed, albeit only in very small
amounts, as indicated by TLC.
K. Nakajima, T. Takahashi, J. Org. Chem. 2000, 65, 945; j) T. Takahashi, Y.
Li, P. Stepnicka, M. Kitamura, Y. Liu, K. Nakajima, M. Kotora, J. Am. Chem.
Soc. 2002, 124, 576; k) C. Chen, C. Xi, C. Lai, R. Wang, X. Hong, Eur. J.
Org. Chem. 2004, 647; l) C. Chen, C. Xi, Y. Jiang, X. Hong, J. Am. Chem.
Soc. 2005, 127, 8024; m) L. Dufkovꢃ, M. Kotora, I. Cꢄsa rˇ ovꢃ, Eur. J. Org.
Chem. 2005, 2491; n) Z. Duan, T. Nishimoto, M. Ogasawara, T. Takahashi,
Synthesis 2005, 2055; o) C. Chen, C. Xi, Z. Ai, X. Hong, Org. Lett. 2006, 8,
4055; p) C. Chen, C. Xi, Y. Liu, X. Hong, J. Org. Chem. 2006, 71, 5373.
[12] For the transmetalation of zirconacyclopentanes or -pentenes with
CuCl, see: a) T. Takahashi, Y. Nishihara, R. Hara, S. Huo, M. Kotora, Chem.
Commun. 1997, 1599; b) Y. Liu, B. Shen, M. Kotora, T. Takahashi, Angew.
Chem. Int. Ed. 1999, 38, 949; Angew. Chem. 1999, 111, 966; c) S. Guo, Y.
Liu, Org. Biomol. Chem. 2008, 6, 2064.
[
10] CCDC-1024766 (the major diastereomer of 4a), 1024768 (the minor dia-
stereomer of 4a), 1024769 (5a), 1026543 (6b), 1024765 (8), 1024767
(
9a) and 1024764 (10) contain the supplementary crystallographic data
for this paper. This data can be obtained free of charge via
www.ccdc.cam.ac.uk/data_request/cif
[
11] For the transmetalation of zirconacyclopentadienes with CuCl, see: a) T.
Takahashi, M. Kotora, K. Kasai, N. Suzuki, Organometallics 1994, 13,
4183; b) T. Takahashi, M. Kotora, Z. Xi, J. Chem. Soc. Chem. Commun.
1
995, 361; c) T. Takahashi, R. Hara, Y. Nishihara, M. Kotora, J. Am. Chem.
[13] For addition of organocopper to a nitrile group, see: J. Zhu, J. Quirion,
H. P. Husson, Tetrahedron Lett. 1989, 30, 5137.
[14] All products were isolated in high purity according to NMR spectra.
Soc. 1996, 118, 5154; d) T. Takahashi, Z. Xi, A. Yamazaki, Y. Liu, K. Nakaji-
ma, M. Kotora, J. Am. Chem. Soc. 1998, 120, 1672; e) T. Takahashi, W.-H.
Sun, Y. Liu, K. Nakajima, M. Kotora, Organometallics 1998, 17, 3841; f) M.
Kotora, C. Xi, T. Takahashi, Tetrahedron Lett. 1998, 39, 4321; g) Y. Yama-
moto, T. Ohno, K. Itoh, Chem. Commun. 1999, 1543; h) T. Takahashi,
W. H. Sun, K. Nakajima, Chem. Commun. 1999, 1595; i) C. Xi, M. Kotora,
Received: October 31, 2014
Published online on && &&, 0000
Chem. Eur. J. 2014, 20, 1 – 6
www.chemeurj.org
5
ꢀ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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These are not the final page numbers! ÞÞ

Communication
COMMUNICATION
Stereoselective zirconocene-mediated
multicomponent reactions of 1,3-buta-
diynes with ylidenemalononitriles in the
absence or presence of CuCl have been
developed. In the absence of CuCl, 1,3-
butadiyne couples with three molecules
of ylidenemalononitriles to yield azazir-
conacycles bearing a hexahydro-1,8-
naphthyridine skeleton. In the presence
of CuCl, cyclopenta[b]pyridine or cyclo-
penta[b]quinolin-1-one derivatives were
obtained.
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Synthetic Methods
S. Yu, R. Sun, H. Chen, X. Xie, Y. Liu*
& – &&
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Zirconium-Mediated Multicomponent
Reactions of 1,3-Butadiynes with
Ylidenemalononitriles to Form
Functionalized 1,8-Naphthyridine and
Cyclopenta[b]pyridine Derivatives
&
&
Chem. Eur. J. 2014, 20, 1 – 6
www.chemeurj.org
6
ꢀ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
ÝÝ These are not the final page numbers!