Highly efficient synthesis of stereodefined multisubstituted 1,4-dicyano-and 1-cyano-1,3-butadienes and their reactions with organolithium reagents

Article abstract of DOI:10.1002/chem.200700028

Stereodefined multisubstituted 1-cyano- and 1,4-dicyano-1,3-butadiene derivatives were obtained in excellent yields of the isolated product from their corresponding monohalo-and dihalobutadienes and CuCN. This reaction proceeded with high stereose-lectivi

Full text of DOI:10.1002/chem.200700028

DOI: 10.1002/chem.200700028
Highly Efficient Synthesis of Stereodefined Multisubstituted 1,4-Dicyano-
and 1-Cyano-1,3-butadienes and Their Reactions with Organolithium
Reagents
Congyang Wang,[a] Chao Wang,[a] Qifeng Wang,[b] Zhihui Wang,[a] Hui Sun,[a]
Xiangyu Guo,[a] and Zhenfeng Xi*[a, c]
Abstract: Stereodefined multisubstitut-
ed 1-cyano- and 1,4-dicyano-1,3-buta-
diene derivatives were obtained in ex-
cellent yields of the isolated product
from their corresponding monohalo-
and dihalobutadienes and CuCN. This
reaction proceeded with high stereose-
lectivity and retention of the stereo-
chemistry of the starting halobuta-
dienes. A study of the utility of the
thus-obtained 1-cyano- and 1,4-dicya-
no-1,3-butadiene derivatives was dem-
onstrated by their reactions with orga-
nolithium reagents. 2H-Pyrrole or imi-
nocyclopentadiene derivatives were
formed in high yields from 1-cyano-4-
halo-1,3-butadienes and organolithium
reagents. When 1,4-dicyano-1,3-buta-
dienes were treated with organolithium
reagents followed by trapping with
electrophiles, a tandem process took
place to afford 2H-pyrrolyl nitriles in
excellent yields. Reduction of 1,4-di-
cyano-1,3-butadiene derivatives with
LiAlH4 showed novel reaction patterns
relative to normal nitriles.
Keywords: butadienes · lithiation ·
nitriles · stereoselectivity · synthetic
methods
Introduction
tion to generate nitrogen-containing heterocycles, such as
pyridines (Scheme 1).[5,6] We have recently reported reac-
tions of 1,4-dilithio- and 1-lithio-1,3-butadienes 1 with orga-
The addition reaction of organolithium reagents to organo-
nitriles provides an important synthetic protocol.[1–4] As a
conventional pathway,[3,4] the addition reaction intermedi-
ates, N-lithioketimines, when generated in situ are intramo-
lecularly trapped by an organohalide moiety positioned at
the other end of the molecule through nucleophilic substitu-
[a] Dr. C. Y. Wang, C. Wang, Dr. Z. Wang, H. Sun, X. Guo,
Prof. Dr. Z. Xi
Scheme 1. The conventional way to nitrogen-containing heterocycles
from N-lithioketimines generated from organolithium reagents and ni-
triles.
Beijing 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)
Fax : (+86)10-6275-1708
E-mail: zfxi@pku.edu.cn
nonitriles that afford pyridines 2 and/or pyrroles 3 through
an unprecedented cycloaddition reaction (Scheme 2).[7,8] In
our unusual cycloaddition reaction without a nucleophilic
substitution step, N-lithioketimine 4 was proposed to be the
key intermediate (Scheme 2).[7,8]
To extend the scope of these synthetically useful reactions
and to further investigate the reaction mechanisms, we plan-
ned to treat 1-cyano-1,3-dienes 7 and 8 and 1,4-dicyano-1,3-
dienes 9 with various organolithium reagents (Scheme 3).
We expected these reactions to lead to the formation of a
[b] Q. Wang
Institute of Chemistry
Chinese Academy of Sciences
Beijing 100080 (China)
[c] Prof. Dr. Z. Xi
State Key Laboratory of Organometallic Chemistry
Shanghai Institute of Organic Chemistry
Chinese Academy of Sciences, Shanghai 200032 (China)
Supporting information for this article is available on the WWW
under http://www.chemeurj.org/ or from the author.
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FULL PAPER
variety of multisubstituted 1,4-dicyano- or 1-cyano-1,3-diene
derivatives, we investigated reactions of these cyanodienes
with organolithium reagents as a demonstration of such
useful and important molecules. Their reaction with organo-
lithium reagents did show unique properties. We expect
these multisubstituted 1,4-dicyano- or 1-cyano-1,3-diene de-
rivatives will be widely applicable in organic synthesis and
in the synthesis of organomaterials.
Results and Discussion
Synthesis of stereodefined multisubstituted 1-cyano-1,3-bu-
tadiene and 1,4-dicyano-1,3-butadiene derivatives: 1-Halo-
and 1,4-dihalo-1,3-butadienes can be readily obtained in ex-
cellent yields by the halogenation of metallacyclopenta-
dienes.[16,17] When diene halide 14 was treated with
1.2 equivalents of CuCN in N,N-dimethylformamide (DMF)
at reflux over one hour, the dienenitrile 7 was obtained in
excellent yield of the isolated product and with perfect ste-
reoselectivity (representative examples are given in
Table 1). Both iododienes and bromodienes could be used
in this type of reaction. The vinyl chloride moiety was inert
under the reaction conditions and 4-chlorodienenitrile 8a,b
was formed as the sole product in 94 and 91% yield of the
isolated product, respectively (Table 1, entries 7 and 8).
1,4-Dicyano-1,3-butadienes could be also obtained follow-
ing the same method. When diiodide 15 was treated with
2.4 equivalents of CuCN for a prolonged reaction time, the
dienedinitrile 9 was obtained in excellent yield and with per-
fect stereoselectivity (representative results are shown in
Table 2). Both symmetrical and unsymmetrical dienedini-
triles can be obtained (Table 2, entries 1–3). Dienedihalides
with an aliphatic cycle or with one aryl iodide moiety both
led to the corresponding dienedinitriles 9d–f in excellent
yield of the isolated products (Table 2, entries 4–6). Tri- or
disubstituted dienedinitriles could be also prepared from
their corresponding diiodides in excellent yields (Table 2,
entries 7–10). It is noteworthy that no isomerization of the
C=C bonds was observed in all cases. This result is in con-
trast to the reported isomerization problem for alkenyl hal-
ides. For example, Prochµzka et al. reported that (Z)-1-
bromo-1-propene when treated with CuCN in DMF gave
(E)- and (Z)-2-butenenitrile in 60 and 27% yield, respecti-
vely.[14a] In our case, the butadienyl halides underwent the
coupling reaction with retention of stereoselectivity.
Scheme 2. Reaction of 1,4-dilithio- and 1-lithio-1,3-dienes with organo-
nitriles.
ACHTREUNG
Scheme 3. Expected reactions of 1,4-dicyano- and 1-cyano-1,3-dienes with
organolithium reagents.
wide variety of N-lithioketimines, such as 10–13, which
might lead to structurally important products, including pyri-
dines 2 and pyrroles 3, upon further manipulation.
However, ironically, we found that, although a,b-unsatu-
rated nitriles are versatile intermediates in organic synthesis
and can invoke various functional group transformations
and be used to construct useful carbocycles or heterocy-
cles,[9–11] no general synthetic method for 1,4-dicyano- or 1-
cyano-1,3-diene derivatives has been reported. In fact, for
the preparation of alkenyl nitriles, especially for aryl nitriles,
there are several methods, including the Horner–Wads-
worth–Emmons olefination of carbonyl compounds with a-
cyano phosphonates,[12] the synthesis of dienenitriles by the
1,4-addition of organocopper and alkyl argintate reagents to
enynenitriles,[13] and the substitution of alkenyl or aryl hal-
ides using CuCN.[14,15] After applying and modifying several
known procedures, we found that the substitution of the hal-
ogen atom using CuCN was the best choice for our target
multisubstituted monocyano- and dicyanobutadienes. Thus,
a synthetically useful method for the preparation of 1,4-di-
cyano- and 1-cyano-1,3-dienes of diverse structures and sub-
stitution patterns was first developed. With ready access to a
When 1,4-dibromo-1,3-diene 16 was used as the starting
material, a mixture of monocyano- and dicyanodienes were
formed as the products. Neither largely excessive amounts
of CuCN nor prolonged reaction times could be used to
obtain the dienedinitrile as the sole product. On the other
hand, many attempts were carried out to stop the reaction
at the first cyanation step to afford 4-bromodienenitrile 8c,
which is also very useful for preparing further functionalized
dienenitriles. The amount of CuCN was found to be crucial
for the reaction selectivity. Finally, dibromodiene 16 was
transferred into the 4-bromodienenitrile 8c in 62% yield of
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Z. Xi et al.
Table 1. Preparation of 1-cyano-1,3-dienes from 1-halodienes and CuCN.
Table 2. Preparation of 1,4-dicyano-1,3-dienes from 1,4-dihalo- 1,3-dienes
and CuCN.
Entry
1
Dihalodiene 15
Dicyanodiene 9
Yield [%][a]
Entry
1
Dienehalide 14
Dienenitrile 7, 8
Yield [%][a]
9a
9b
9c
9d
95
7a
7b
7c
7d
94
2
3
4
90
96
93
2
3
4
85
82
96
5
6
9e
9 f
93
94
5
6
7
7e
7 f
8a
90
98
94
7
9g
97
8
9
9h
9i
98
81
8
8b
91
[a] Yield of the isolated product.
10
9j
90
the isolated product with 1.1 equivalents of CuCN in DMF
at reflux for one hour (Scheme 4).
[a] Yield of the isolated product.
Reactions of multisubstituted 1-cyano-1,3-diene derivatives
with organolithium reagents: As mentioned above, we previ-
ously proposed that pyridine derivatives are formed through
the intramolecular cycloaddition of N-lithioketimines 4 that
are generated in situ from 1-lithio-1,3-diene derivatives 1
and organonitriles (Scheme 2).[3,7,8,18,19] As shown in
Scheme 5, the pyridine derivative 2a was obtained in 91%
Scheme 4. Synthesis of monocyano monobromobutadiene 8c.
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Stereodefined Multisubstituted 1,4-Dicyano- and 1-Cyano-1,3-butadienes
FULL PAPER
Table 3. Reactions of 4-chlorodienenitriles and organolithium reagents.
Entry
Dienenitrile 8
R’Li
Solvent[a]
THF
Yield 2
Yield 3
[%][b]
[%][b]
1
nBuLi
2b
0
3a
90
2
3
4
8a
8a
8a
tBuLi
MeLi
PhLi
THF
THF
THF
2c
2d
2a
0
6
7
3b
3c
3d
91
78
73
Scheme 5. Reaction of 1-cyano-1,3-butadiene with an organolithium re-
agent relative to the reaction of 1-lithio-1,3-butadiene with an organo-
nitrile.
5
PhLi
THF
2e
trace
3e
86
yield of the isolated product from the organolithium reagent
1a and PhCN.[7,8] The same addition intermediate, N-lithio-
ketimine 4a, was assumed to be formed also in the reaction
of 1-cyano-1,3-butadiene 7a with PhLi. However, unfortu-
nately, although the reaction of 7a with PhLi proceeded
smoothly, it afforded the pyridine derivative 2a in a low
yield (Scheme 5). In addition to 2a, several unknown prod-
ucts were also formed in this reaction. The reason why these
two reactions gave different results is not clear yet.
6
7
8
8b
8a
8a
PhLi
nBuLi
PhLi
Et2O
Et2O
Et2O
2e
2b
2a
61
16
61
3e
3a
3d
18
71
27
[a] THF: at reflux; Et2O: room temperature. [b] Yield of the isolated
product.
Surprisingly, when 4-chlorodienenitriles 8a and 8b were
treated with organolithium reagents in THF at reflux, the
five-membered nitrogen-containing heterocycles 2H-pyr-
roles 3 were obtained in high yields (representative results
are given in Table 3). It is noteworthy that only the E isom-
ers of alkenyl 2H-pyrroles 3 were observed, thus indicating
that the reaction proceeded with excellent stereoselectivity.
Interestingly, bulky tBuLi can also undergo a similar pro-
cess, thus smoothly leading to 3b in 91% yield of the isolat-
ed product (Table 3, entry 2). The solvent was found to be
very important for this reaction. When the reaction was car-
ried out in diethyl ether, pyridine derivatives 2 were formed
in addition to products 3 (Table 3, entries 6–8). For example,
the reaction of 8a with nBuLi in THF afforded 3a as the
sole product in 90% yield of the isolated product (Table 3,
entry 1), whereas the same reaction in diethyl ether afforded
a mixture of two products 2b and 3a in 16 and 71% yields
of the isolated products, respectively (Table 3, entry 7). The
reaction of 8b with PhLi gave 3e in 86% yield of the isolat-
ed product with a trace amount of 2e in THF (Table 3,
entry 5). However, 2e became the major product in diethyl
ether (Table 3, entry 6).
Scheme 6. Proposed mechanism for the reaction of 4-chlorodienenitriles
and an organolithium reagent.
the C=C double bond to give the intermediates 5 and 5’,
which subsequently afforded pyridine product 2 through
elimination of LiCl (Scheme 6, path a). The other is the 5-
exo addition of the iminolithium species to the C=C bond to
form the intermediate 6 followed by elimination of LiCl and
hydrogen transfer to afford the final 2H-pyrrole product 3
(Scheme 6, path b).[8]
When 4-bromodienenitrile 8c was treated with nBuLi,
2H-pyrrole 3a was obtained in 75% yield of the isolated
product through a similar process to that described above.
A proposed mechanism for the above reaction is given in
Scheme 6. The nucleophilic addition may take place firstly
to form the N-lithioketimines 11. Indeed, when the reaction
was carried out at À508C for one hour, quenching the reac-
tion mixture did give the linear imine 17 as the sole product
in a quantitative yield. In principle, two pathways can be
considered for intermediate 11 to undergo anionic ring clo-
sure. One is the 6-endo addition of iminolithium species to
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Z. Xi et al.
Table 4. Reaction of dienedinitriles 9 with organolithium reagents.
Nevertheless, when treated with tBuLi, iminocyclopenta-
diene 19a was obtained in a quantitative yield upon quench-
ing with aqueous NaHCO3 (Scheme 7). Neither pyridine 2
Entry
Dienedinitrile 9
R’Li
Electrophile
H+
Yield [%][a]
1
2
nBuLi
nBuLi
20a
100
100
9a
20b
3
4
5
9a
9a
9a
nBuLi
PhLi
MeLi
PhCH2Br
H+
20c
20d
20e
90
93
95
H+
6
nBuLi
H+
20 f
88
7
8
9
9b
9c
PhLi
H+
H+
H+
20g
20h
20i
75
nBuLi
PhLi
85[b]
75[b]
Scheme 7. Reaction of 4-bromodienenitrile 8c with an organolithium re-
agent.
[a] Yield of the isolated product; d.r.=3:2 [b] Solvent: THF.
nor 2H-pyrrole 3, which should arise from the addition of
an organolithium reagent to a nitrile, was observed. The use
of acid chlorides to trap the reaction intermediate afforded
acylimine 19b,c in 88 and 90% yield of the isolated prod-
ucts, respectively. In these cases, a bromine–lithium ex-
change was proposed to take place first to afford the inter-
mediate 18’, which underwent intramolecular attackon the
cyano group of the vinyl lithium reagent generated in situ,
thus giving the cyclic N-lithioketimine intermediate 18. Fur-
ther functionalized products, such as 19, can be formed by
the ready trapping of intermediate 18 by electrophiles.
A proposed mechanism for the above reactions is shown
in Scheme 8. Nucleophilic addition of an organolithium re-
agent to one of the two cyano groups must take place as the
Reactions of multisubstituted 1,4-dicyano-1,3-diene deriva-
tives with organolithium reagents: Although reactions of
1,4-dicyanobutadiene with transition-metal complexes have
been investigated in several cases,[20,11c–d] the reactivity of di-
enedinitriles with main-group-metal compounds has seldom
been explored. We found dienedinitriles 9 reacted with or-
ganolithium reagents followed by quenching with aqueous
NaHCO3 to give 2H-pyrrolyl nitrile derivatives 20 in excel-
lent yield with d.r. values of about 3:2 in all cases, and none
of expected diimine products were observed (representative
results are given in Table 4). Dienedinitriles with an aliphat-
ic cycle 9b or with one aryl nitrile moiety 9c both led to the
final products in high yields (Table 4, entries 6–9). Both ali-
phatic and aromatic organolithium reagents can be applied
to this reaction. Trapping the reaction mixture with carbon
electrophiles afforded the alkylated 2H-pyrrolyl nitrile de-
rivative 20b,c solely (Table 4, entries 2 and 3).
Scheme 8. Proposed mechanism for reaction of dienedinitrile 9 with an
organolithium reagent.
first step to form N-lithioketimine intermediate 21, which
underwent an intramolecular Michael addition to give the
2H-pyrrolyl lithium intermediate 22. Trapping the inter-
mediate 22 with electrophiles afforded the product 20 even-
tually. Thus, the 2H-pyrrolyl nitrile derivatives 20 can be
readily constructed through this tandem process in one pot.
Interestingly, better stereoselectivity was observed on the
addition of ligands to the reaction mixture (Table 5). For ex-
ample, when dienedinitrile 9a was treated with nBuLi in the
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Stereodefined Multisubstituted 1,4-Dicyano- and 1-Cyano-1,3-butadienes
FULL PAPER
Table 5. Ligandꢁs effect on reaction of dienedinitrile 9a with nBuLi.
Table 6. Reaction of different conjugated enenitriles with LiAlH4.
Entry
Substrate
T [8C]
Product
Yield [%][a]
1
2
23
0
24
89[b]
Ligand
Yield [%][a]
d.r.[b]
7a
30
30
25a 85
25b 80
none
66
76
96
71
59:41
76:24
83:17
75:25
TMEDA[c]
sparteine[c]
sparteine[d]
[a] Yield of the isolated product. [b] Detected by HPLC. [c] 1.0 equiva-
lents. [d] 0.1 equivalents.
3
4
8c
9a À30
2 f
75
absence of a ligand, d.r.=59:41 for the final product 20a.
When the reaction was carried out with 1.0 equivalents of
TMEDA, the diastereoisomeric ratio increased to 76:24. In
the presence of 1.0 equivalents of sparteine, the reaction
was completed at À788C within one hour and d.r.=83:17,
which showed an obvious increase both in the reactivity and
stereoselectivity. Furthermore, the product was obtained in
71% yield of the isolated product and d.r.=75:25, even with
0.1 equivalents of sparteine.
5
6
9d À30
9 f À30
20j 65[c]
20k 51[c]
Reduction of 1,4-dicyano- and 1-cyano-1,3-diene derivatives
with lithium aluminum hydride: The reduction of organoni-
triles has been a fundamental synthetic method in organic
[a] Yield of the isolated product; solvent: Et2O, 1 h. [b] Two isomers:
d.r.=3:1. [c] Two isomers: d.r.=1:1.
ꢀ
synthesis. However, when both a C N bond and another un-
saturated chemical bond, such as the C=C bond, exist in the
same molecule, selective reduction of the unsaturated bonds
is desired.[21,22] Simple nitrile groups are known to be re-
duced to primary amines by LiAlH4.[21] In the case of a,b-
ꢀ
unsaturated nitriles, both reduction of the C N and C=C
bonds are reported in different substrates.[22] When we treat-
ed unsaturated nitriles 23 with 1.0 equivalents of LiAlH4 in
diethyl ether, the C=C bond was selectively reduced to give
24 in 89% yield of the isolated product (Table 6, entry 1).
However, on the contrary, treatment of dienenitrile 7a with
1.0 equivalents of LiAlH4 afforded the primary amine 25a
as the sole product in 85% yield of the isolated product
(Table 6, entry 2). This selectivity is in sharp contrast to the
result obtained with a,b-unsaturated nitrile 23. In a similar
manner, 4-bromodienenitrile 8c was reduced to its corre-
sponding amine 25b, and no product with a reduced C=C
bond was observed (Table 6, entry 3).
Scheme 9. Proposed mechanism for the reaction of dienedinitrile 9 with
LiAlH4.
Very interestingly, the reaction of dienedinitriles 9a with
1.0 equivalents of LiAlH4 afforded a cyclic product, the pyri-
dine derivative 2 f, in 75% yield of the isolated product
(Table 6, entry 4). Furthermore, different types of cyclic
products other than the above-described pyridine deriva-
tives, such as the 2H-pyrrole derivatives 20j and 20k, were
obtained, respectively, from the reaction of 9d and 9 f with
1.0 equivalents of LiAlH4.
ꢀ
The reduction of the C N bond into an imino anion is as-
sumed to be the first step in the formatin of intermediate
26. This linear intermediate 26 may then undergo 6-endo in-
tramolecular addition to form the cyclic intermediate 27
(Scheme 9, path a). Elimination of MCN finally afforded the
pyridine product 2 f.[23] On the contrary, when dienedinitrile
9d was treated with 1.0 equivalents of LiAlH4 (Table 6,
entry 5), the 2H-pyrrole derivative 20j, which is obtained
A proposed reaction mechanism for the above-described
novel reduction–cyclization process is shown in Scheme 9.
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Z. Xi et al.
Dienenitrile 7a: Colorless liquid obtained in 94% yield of the isolated
from the 5-exo addition of the imino anion generated in
situ, was obtained as the major product (Scheme 9, path b).
Although the reason for such regioselectivity is not yet
clear, the conformation of the cyclic dienedinitrile 9d may
play an important role in the reaction. In the case of diene-
dinitrile 9 f, the 2H-pyrrole derivative 20k was obtained as
the major product in moderate yield (Table 6, entry 6). The
dearomatization step in the formation of pyridine is unfavor-
able, which is considered to be the main reason for the se-
lectivity in the formation of 2H-pyrrole derivative 20k.
1
product (232 mg). H NMR (CDCl3, TMS): d=0.86–0.98 (m, 12H), 1.28–
1.66 (m, 8H), 2.07–2.25 (m, 8H), 5.48 ppm (t, J=7.5 Hz, 1H); 13C NMR
(CDCl3, TMS): d=13.47, 13.88, 13.94, 14.22, 21.14, 21.77 (2 CH2), 22.54,
30.11, 30.73, 31.99, 110.37, 120.16, 132.35, 139.37, 161.85 ppm; HRMS
calcd for C17H29N 247.2300; found 247.2305.
Dienenitrile 7b: Colorless solid obtained in 85% yield of the isolated
1
product (220 mg). M.p. 60–618C; H NMR (CDCl3, TMS): d=1.75 (d, J=
1.2 Hz, 3H), 2.02 (d, J=1.2 Hz, 3H), 6.79 (s, 1H), 7.02–7.30 ppm (m,
10H); 13C NMR (CDCl3, TMS): d=17.20, 18.19, 105.67, 120.39, 127.43,
127.91, 127.94, 128.69, 129.44, 129.76, 130.95, 135.95, 137.32, 142.23,
156.67 ppm; HRMS calcd for C19H17N 259.1361; found 259.1360.
Dienenitrile 7c: Colorless liquid obtained in 82% yield of the isolated
product (235 mg). 1H NMR (CDCl3, TMS): d=0.95 (t, J=7.5 Hz, 3H),
1.25 (t, J=7.5 Hz, 3H), 2.10 (q, J=7.5 Hz, 2H), 2.37 (q, J=7.5 Hz, 2H),
6.75 (s, 1H), 7.03–7.28 ppm (m, 10H); 13C NMR (CDCl3, TMS): d=
12.49, 13.25, 23.54, 23.69, 112.86, 119.63, 127.39, 127.89, 127.95, 128.67,
129.41, 129.77, 132.13, 136.11, 137.41, 140.92, 161.57 ppm; HRMS calcd
for C21H21N 287.1674; found 287.1673.
Conclusion
In conclusion, we have realized a practical synthesis of 1-
cyano- and 1,4-dicyano-1,3-dienes from readily available
starting materials and CuCN in yields of 81–98% and with
excellent stereoselectivities. This method provides rapid
access to multisubstituted, stereodefined dienenitrile/dini-
triles, which are expected to have wide applications in syn-
thetic chemistry and the field of organomaterials. The utility
of these unsaturated nitriles in organic synthesis is demon-
strated by their reactions with organolithium reagents. 2H-
Pyrrole or iminocyclopentadiene derivatives were formed in
good-to-excellent yields from 4-halodienenitriles and orga-
nolithium reagents. 2H-Pyrrolyl nitrile derivatives are readi-
ly constructed from dienedinitriles and organolithium re-
agents in high yields through tandem processes in one pot.
The reduction of these unsaturated nitriles with LiAlH4 af-
forded amine, pyridine, or pyrrole derivatives, in which un-
precedented reaction patterns relative to normal nitriles
were observed. Further exploration of the reactivity of dien-
enitrile/dinitriles as useful building blocks in synthetic
chemistry is being carried out in our group.
Dienenitrile 7d: Colorless liquid obtained in 96% yield of the isolated
product (208 mg). 1H NMR (CDCl3, TMS): d=0.92–0.97 (m, 6H), 1.39–
1.71 (m, 8H), 2.06–2.33 (m, 8H), 5.65 ppm (t, J=7.5 Hz, 1H); 13C NMR
(CDCl3, TMS): d=13.37, 13.85, 21.82, 22.43, 26.60, 27.02, 29.09, 29.75,
31.20, 31.95, 105.58, 120.29, 129.39, 138.16, 160.21 ppm; HRMS calcd for
C15H23N 217.1831; found 217.1831.
Dienenitrile 7e: Colorless liquid obtained in 90% yield of the isolated
product (221 mg). 1H NMR (CDCl3, TMS): d=0.88–0.96 (m, 6H), 1.29–
1.67 (m, 12H), 2.08–2.31 (m, 8H), 5.64 ppm (t, J=7.5 Hz, 1H); 13C NMR
(CDCl3, TMS): d=13.87, 13.97, 22.05, 22.38, 26.60, 27.02, 27.44, 29.04,
29.80, 30.72, 31.14, 31.36, 105.76, 120.32, 129.61, 137.92, 159.96 ppm;
HRMS calcd for C17H27N 245.2144; found 245.2142.
Dienenitrile 7 f: Colorless liquid obtained in 98% yield of the isolated
product (187 mg). 1H NMR (CDCl3, TMS): d=0.91–0.97 (m, 6H), 1.32–
1.62 (m, 8H), 2.27–2.37 (m, 4H), 5.38–5.56 (m, 2H), 6.86–6.95 ppm (m,
1H); 13C NMR (CDCl3, TMS): d=13.84 (2CH3), 22.29, 22.98, 27.20,
29.88, 30.52, 31.23, 112.89, 118.79, 119.03, 135.33, 153.27 ppm; HRMS
calcd for C13H21N 191.1674; found 191.1672.
4-Chlorodienenitrile 8a: Colorless liquid obtained in 94% yield of the
isolated product (264 mg). 1H NMR (CDCl3, TMS): d=0.93–1.01 (m,
12H), 1.37–1.73 (m, 8H), 1.98–2.12 (m, 2H), 2.24–2.47 ppm (m, 6H);
13C NMR (CDCl3, TMS): d=13.38, 13.52, 14.33, 14.58, 20.81, 20.85, 21.53,
21.62, 31.71, 33.56, 34.14, 37.06, 113.33, 119.41, 133.15, 135.73,
156.57 ppm; HRMS calcd for C17H28N35Cl 281.1910; found 281.1912.
4-Chlorodienenitrile 8b: Colorless liquid obtained in 91% yield of the
isolated product (205 mg). 1H NMR (CDCl3, TMS): d=1.02–1.08 (m,
6H), 1.16–1.22 (m, 6H), 2.06–2.51 ppm (m, 8H); 13C NMR (CDCl3,
TMS): d=11.81, 12.48, 12.85, 12.90, 23.13, 24.30, 25.01, 28.67, 114.35,
119.15, 134.37, 135.59, 156.67 ppm; HRMS calcd for C13H20N35Cl
225.1284; found 225.1286.
Experimental Section
General: The nucleophilic substitution reactions of butadiene halides
with cuprous cyanide were carried out in air. The reactions of butadiene-
dinitrile with organolithium reagents were conducted under a slightly
positive pressure of dry, prepurified nitrogen using standard Schlenk
techniques when appropriate. Unless otherwise noted, all starting materi-
als were commercially available and were used without further purifica-
tion. Diethyl ether was heated to reflux and distilled from sodium benzo-
phenone ketyl under a nitrogen atmosphere. All the organolithium re-
agents were obtained from Acros Organics.
1H and 13C NMR spectra were recorded at 300 and 75.4 MHz, respective-
ly, in CDCl3 (containing 0.1% tetramethylsilane (TMS)) on a JEOL
JNM-AL300 NMR spectrometer. All the butadiene halides were synthe-
sized by a previously reported procedure.[24]
A typical procedure for the preparation of,4-dicyano-1,3-butadienes 9a–j
from the corresponding 1,4-dihalo-1,3-butadienes: CuCN (2.4 mmol) was
added to
a solution of 1,4-dihalo-1,3-butadiene (1.0 mmol) in DMF
(5 mL) at room temperature. The reaction mixture was heated to reflux
and stirred for 6 h to generate 1,4-dicyano-1,3-butadiene, the formation
of which was monitored by GC analysis or by TLC. The reaction mixture
was then filtered, and the solvent was evaporated in vacuo to give a
blackoil, which was purified by column chromatography (silica gel,
Et2O/hexane 1:20) to afford 9a–j.
Dienedinitrile 9a: Colorless liquid obtained in 95% yield of the isolated
A typical procedure for the preparation of 1-cyano-1,3-buatadienes 7a–f
1
product (258 mg). H NMR (CDCl3, TMS): d=0.96–1.03 (m, 12H), 1.42–
and 8a,bfrom their corresponding 1-halo-1,3u-btadienes
: CuCN
1.49 (m, 4H), 1.61–1.73 (m, 4H), 2.29–2.33 ppm (m, 8H); 13C NMR
(CDCl3, TMS): d=13.02, 13.85, 20.59, 20.92, 31.47, 32.51, 114.27, 118.09,
155.70 ppm; HRMS calcd for C18H28N2 272.2253; found 272.2255.
(1.2 mmol) was added to a solution of 1-halo-1,3-butadiene (1.0 mmol) in
DMF (5 mL) at room temperature. The reaction mixture was heated to
reflux and stirred for 1 h to generate 1-cyano-1,3-butadiene, the forma-
tion of which was monitored by GC analysis or TLC. The reaction mix-
ture was then filtered, and the solvent was evaporated in vacuo to give a
blackoil, which was purified by column chromatography (silica gel,
Et2O/hexane 1:30) to afford 7a–g and 8a,b.
Dienedinitrile 9b: Colorless solid obtained in 90% yield of the isolated
product (144 mg). M.p. 49–508C; 1H NMR (CDCl3, TMS): d=1.97 ppm
(s, 12H); 13C NMR (CDCl3, TMS): d=16.35, 17.32, 107.30, 118.50,
154.13 ppm; HRMS calcd for C10H12N2 160.1001; found 160.1000.
6490
www.chemeurj.org
ꢀ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2007, 13, 6484 – 6494

Stereodefined Multisubstituted 1,4-Dicyano- and 1-Cyano-1,3-butadienes
FULL PAPER
Dienedinitrile 9c: Colorless solid obtained in 96% yield of the isolated
product (300 mg). M.p. 105–1068C; 1H NMR (CDCl3, TMS): d=1.07–
1.12 (m, 3H), 1.31–1.36 (m, 3H), 2.26 (br, 2H), 2.46–2.54 (m, 2H), 7.06–
7.31 ppm (m, 10H); 13C NMR (CDCl3, TMS): d=12.06, 12.53, 23.65,
24.28, 115.87, 117.28, 118.39, 118.54, 128.64 (2CH), 128.78 (2CH), 129.03,
129.38 (2CH), 129.65, 129.80 (2CH), 133.15, 134.41, 154.83, 156.72 ppm;
HRMS calcd for C22H20N2 312.1627; found 312.1617.
A typical procedure for the preparation of pyrridine derivatives 2 and
2H-pyrrole derivatives 3 from dienenitrile 7a or 4-halodienenitrile 8 and
organolithium reagents: An organolithium reagent, such as nBuLi
(1.2 mmol, 1.5m in pentane), was added to dienenitrile 7a or 4-haoldiene-
nitrile 8 (1.0 mmol) in a solution of a diethyl ether or THF (5 mL) at
À788C. The reaction mixture was then stirred at room temperature (or at
reflux in THF) for 1 h to generate pyridine 2 and/or 2H-pyrrole 3, the
formation of which was monitored by GC analysis or TLC. The reaction
mixture was then quenched with saturated aqueous NaHCO3 solution
and extracted with diethyl ether. The extract was washed with brine and
dried over MgSO4. The solvent was evaporated in vacuo to give a yellow
oil, which was purified by column chromatography (silica gel, Et2O/
hexane 1:10) to afford pyridine 2 and/or 2H-pyrrole 3.
Dienedinitrile 9d: Colorless liquid obtained in 93% yield of the isolated
product (225 mg). 1H NMR (CDCl3, TMS): d=1.00 (t, J=7.5 Hz, 6H),
1.50–1.71 (m, 6H), 1.93–2.11 (m, 4H), 2.23–2.39 (m, 4H), 2.83–2.88 ppm
(m, 2H); 13C NMR (CDCl3, TMS): d=13.39, 21.51, 27.41, 31.91, 32.01,
111.07, 118.38, 155.48 ppm; HRMS calcd for C16H22N2 242.1783; found
242.1778.
Pyridine 2a:[7] Colorless liquid obtained in 32% yield of the isolated
Dienedinitrile 9e: Colorless liquid obtained in 93% yield of the isolated
product (221 mg). 1H NMR (CDCl3, TMS): d=0.93 (t, J=7.2 Hz, 3H),
1.06 (t, J=7.2 Hz, 3H), 1.29–1.42 (m, 2H), 1.63–1.78 (m, 2H), 2.42 (t, J=
7.5 Hz, 2H), 2.57 (t, J=7.5 Hz, 2H), 7.29–7.32 (m, 1H), 7.43–7.49 (m,
1H), 7.60–7.65 (m, 1H), 7.71–7.73 ppm (m, 1H); 13C NMR (CDCl3,
TMS): d=13.45, 13.98, 20.79, 21.56, 32.05, 35.73, 111.65, 116.01, 117.43,
118.09, 128.80, 129.06, 132.90, 133.25, 144.32, 155.13 ppm; HRMS calcd
for C16H18N2 238.1470; found 238.1474.
product (103 mg). 1H NMR (CDCl3, TMS): d=0.78 (t, J=7.5 Hz, 3H),
0.96–1.10 (m, 9H), 1.30–1.80 (m, 8H), 2.44–2.50 (m, 2H), 2.57–2.63(m,
G
4H), 2.71–2.77 (m, 2H), 7.29–7.39 ppm (m, 5H); 13C NMR (CDCl3,
TMS): d=14.43, 14.57, 14.92, 15.02, 23.69, 24.53, 24.58 (2CH2), 31.00,
31.39, 31.47, 37.48, 127.13, 127.95 (2CH), 128.88 (2CH), 131.20, 132.34,
142.44, 148.19, 156.52, 157.14 ppm.
Pyridine 2b: Colorless liquid obtained in 16% yield of the isolated prod-
uct (48 mg). 1H NMR (CDCl3, TMS): d=0.92–1.07 (m, 15H), 1.36–1.57
(m, 8H), 1.61–1.78 (m, 4H), 2.49–2.54 (m, 6H), 2.66–2.73 ppm (m, 4H);
13C NMR (CDCl3, TMS): d=14.14, 14.44, 14.88 (2CH3), 14.99, 23.12,
23.55, 24.50, 24.57 (2CH2), 30.94 (2CH2), 31.43, 32.62, 35.17, 37.39,
130.66, 130.72, 147.51, 156.78, 156.98 ppm; HRMS calcd for C21H37N
303.2926; found 303.2922.
Dienedinitrile 9 f: Colorless liquid obtained in 94% yield of the isolated
product (197 mg). 1H NMR (CDCl3, TMS): d=0.98 (t, J=7.5 Hz, 3H),
1.27 (t, J=7.5 Hz, 3H), 2.46 (q, J=7.5 Hz, 2H), 2.61 (q, J=7.5 Hz, 2H),
7.30–7.33 (m, 1H), 7.44–7.49 (m, 1H), 7.61–7.73 ppm (m, 2H); 13C NMR
(CDCl3, TMS): d=11.93, 12.90, 23.53, 26.91, 111.73, 116.82, 117.34,
117.94, 128.86, 129.04, 132.96, 133.14, 143.87, 155.73 ppm; HRMS calcd
for C14H14N2 210.1157; found 210.1157.
Pyridine 2d: Colorless liquid obtained in 6% yield of the isolated prod-
uct (16 mg). 1H NMR (CDCl3, TMS): d=0.98–1.07 (m, 12H), 1.41–1.56
(m, 6H), 1.63–1.75 (m, 2H), 2.47–2.54 (m, 9H), 2.64–2.69 ppm (m, 2H);
13C NMR (CDCl3, TMS): d=14.51, 14.80, 14.85, 14.96, 22.53, 23.48, 23.81,
24.43, 24.62, 30.89, 31.30, 31.42, 37.56, 130.96, 131.36, 147.44, 153.46,
156.80 ppm; HRMS calcd for C18H31N 261.2457; found 261.2462.
Pyridine 2e:[8] Colorless liquid obtained in 61% yield of isolated product
(163 mg). 1H NMR (CDCl3, TMS): d=0.99 (t, J=7.5 Hz, 3H), 1.13–1.31
(m, 9H), 2.56 (q, J=7.5 Hz, 2H), 2.68–2.75 (m, 4H), 2.83 (q, J=7.5 Hz,
2H), 7.33–7.42 ppm (m, 5H); 13C NMR (CDCl3, TMS): d=14.78, 15.34,
15.44, 15.57, 21.43, 21.78, 21.98, 28.28, 127.21, 127.98 (2CH), 128.86
(2CH), 132.53, 133.43, 142.18, 149.44, 156.59, 158.24 ppm.
Dienedinitrile 9g: Colorless liquid obtained in 97% yield of isolated
product (210 mg). 1H NMR (CDCl3, TMS): d=0.95 (t, J=7.2 Hz, 3H),
1.12 (t, J=7.5 Hz, 3H), 1.21 (t, J=7.5 Hz, 3H), 1.32–1.45 (m, 2H), 1.57–
1.67(m, 2H), 2.35–2.42 (m, 4H), 2.67 (q, J=7.5 Hz, 2H), 6.92 ppm (s,
R
1H); 13C NMR (CDCl3, TMS): d=12.82, 13.30, 13.70, 21.81, 22.13, 23.56,
30.21, 36.60, 116.92, 117.39, 117.76, 119.01, 140.45, 151.64 ppm; HRMS
calcd for C14H20N2 216.1627; found 216.1624.
Dienedinitrile 9h: Colorless liquid obtained in 98% yield of the isolated
product (333 mg). 1H NMR (CDCl3, TMS): d=0.85 (t, J=6.9 Hz, 3H),
1.22–1.35 (m, 6H), 1.47–1.55 (m, 2H), 2.21–2.27 (m, 2H), 5.66 (t, J=
1.5 Hz, 1H), 7.07–7.33 ppm (m, 10H); 13C NMR (CDCl3, TMS): d=
13.98, 22.41, 26.87, 28.67, 31.34, 35.64, 100.26, 115.24, 116.16, 118.08,
128.64 (2CH), 128.91 (2CH), 129.20 (3CH), 129.76 (2CH), 129.82,
132.69, 133.96, 153.49, 164.77 ppm; HRMS calcd for C24H24N2 340.1940;
found 340.1936.
2H-Pyrrole 3a: Colorless liquid obtained in 90% yield of the isolated
1
product (273 mg). H NMR (CDCl3, TMS): d=0.73–0.97 (m, 15H), 1.35–
1.73 (m, 10H), 1.95–2.25 (m, 8H), 2.43–2.48 (m, 2H), 5.04 (dt, 1J=
15.6 Hz, 2J=1.5 Hz, 1H), 5.62 ppm (dt, 1J=15.6 Hz, 2J=6.6 Hz, 1H);
13C NMR (CDCl3, TMS): d=13.66, 13.99, 14.27, 14.46, 14.87, 16.25, 21.88,
22.91, 23.11, 25.80, 27.14, 28.97, 29.65, 30.76, 36.23, 83.44, 129.78, 130.61,
135.89, 164.14, 176.81 ppm; HRMS calcd for C21H37N 303.2926; found
303.2933.
Dienedinitrile 9i: Colorless liquid obtained in 81% yield of the isolated
product (221 mg). 1H NMR (CDCl3, TMS): d=0.89 (t, J=6.9 Hz, 6H),
1.30–1.50 (m, 16H), 2.30–2.36 (m, 4H), 5.43 ppm (t, J=1.2 Hz, 2H);
13C NMR (CDCl3, TMS): d=14.01, 22.48, 26.87, 28.73, 31.43, 35.56, 98.69,
115.61, 163.33 ppm; HRMS calcd for C18H28N2 272.2253; found 272.2257.
2H-Pyrrole 3b: Colorless liquid obtained in 91% yield of the isolated
product (276 mg). 1H NMR (CDCl3, TMS): d=0.63–1.00 (m, 12H), 1.30
(s, 9H), 1.38–1.74 (m, 6H), 1.95–2.24 (m, 6H), 2.32–2.37 (m, 2H), 4.99
(dt, 1J=15.6 Hz, 2J=1.5 Hz, 1H), 5.59 ppm (dt, 1J=15.6 Hz, 2J=6.6 Hz,
1H); 13C NMR (CDCl3, TMS): d=13.59, 14.45, 14.67, 15.00, 15.75, 21.59,
23.74, 25.79, 28.99, 29.04 (3CH3), 29.11, 35.93, 35.95, 81.59, 130.09,
130.42, 136.17, 165.79, 181.73 ppm; HRMS calcd for C21H37N 303.2926;
found 303.2930.
Dienedinitrile 9j: Colorless liquid obtained in 90% yield of the isolated
product (194 mg). 1H NMR (CDCl3, TMS): d=0.95 (t, J=7.5 Hz, 6H),
1.31–1.44 (m, 4H), 1.54–1.64 (m, 4H), 2.36 (t, J=7.5 Hz, 4H), 6.97 ppm
(s, 2H); 13C NMR (CDCl3, TMS): d=13.67, 21.91, 30.05, 34.36, 116.74,
120.59, 138.41 ppm; HRMS calcd for C14H20N2 216.1627; found 216.1625.
A typical procedure for the preparation of 4-bromodienenitrile 8c from
1,4-dibromo-1,3-butadiene: CuCN (1.1 mmol) was added to 1,4-dibromo-
1,3-butadiene (1.0 mmol) in a solution of DMF (5 mL). The reaction mix-
ture was heated to reflux and stirred for 1 h to generate 4-bromodiene-
mononitrile, the formation of which was monitored by GC analysis or
TLC. The reaction mixture was filtered, and the solvent was evaporated
in vacuo to give a blackoil, which was purified by column chromatogra-
phy (silica gel, Et2O/hexane 1:30) to afford 8c.
2H-Pyrrole 3c: Colorless liquid obtained in 78% yield of the isolated
1
product (204 mg). H NMR (CDCl3, TMS): d=0.79–1.02 (m, 12H), 1.33–
1
2
1.65 (m, 6H), 1.91–2.25 (m, 11H), 5.07 (dt, J=15.6 Hz, J=1.5 Hz, 1H),
1
2
5.64 ppm (dt, J=15.6 Hz, J=6.6 Hz, 1H); 13C NMR (CDCl3, TMS): d=
13.66, 14.18, 14.44, 14.85, 16.48, 17.43, 21.92, 22.91, 25.80, 27.19, 28.94,
36.37, 83.52, 129.39, 130.84, 135.91, 164.28, 173.40 ppm; HRMS calcd for
C18H31N 261.2457; found 261.2457.
4-Bromodienenitrile 8c: Colorless liquid obtained in 62% yield of the
isolated product (202 mg). 1H NMR (CDCl3, TMS): d=0.93–1.02 (m,
12H), 1.38–1.74 (m, 8H), 1.96–2.61 ppm (m, 8H); 13C NMR (CDCl3,
TMS): d=13.24, 13.62, 14.34, 14.69, 20.84, 21.44, 21.61 (2CH2), 31.75,
33.69, 34.71, 39.17, 113.33, 119.32, 126.75, 138.88, 158.04 ppm; HRMS
calcd for C17H28N79Br 325.1405; found 325.1407.
2H-Pyrrole 3d: Colorless liquid obtained in 73% yield of the isolated
1
product (236 mg). H NMR (CDCl3, TMS): d=0.76–1.12 (m, 14H), 1.19–
1.31 (m, 2H), 1.45–1.57 (m, 2H), 1.71–1.79 (m, 1H), 1.98–2.40 (m, 7H),
5.18 (dt, 1J=15.6 Hz, 2J=1.5 Hz, 1H), 5.72 (dt, 1J=15.6 Hz, 2J=6.6 Hz,
1H), 7.38–7.40 (m, 3H), 7.60–7.63 ppm (m, 2H); 13C NMR (CDCl3,
Chem. Eur. J. 2007, 13, 6484 – 6494
ꢀ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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Z. Xi et al.
TMS): d=13.62, 14.04, 14.45, 14.90, 16.41, 21.98, 22.61, 25.82, 27.61,
29.15, 36.56, 83.97, 127.68 (2CH), 128.19 (2CH), 128.90, 129.06, 131.16,
135.50, 136.56, 166.08, 174.51 ppm; HRMS calcd for C23H33N 323.2613;
found 323.2612.
room temperature for 1 h. The reaction was quenched with saturated
aqueous NaHCO3 solution. Subsequent work-up afforded 2H-pyrrole
20b,c.
2H-Pyrrole 20a: Colorless liquid obtained in 100% yield of the isolated
2H-Pyrrole 3e:[8] Colorless liquid obtained in 86% yield of the isolated
1
product (330 mg). H NMR (CDCl3, TMS): d=0.67–1.05 (m, 17H), 1.21–
product (230 mg). 1H NMR (CDCl3, TMS): d=0.60 (t, J=7.2 Hz, 3H),
1.84 (m, 14H), 2.03–2.51 (m, 6H), 2.73–3.08 ppm (m, 1H); 13C NMR
(CDCl3, TMS): d=13.53, 13.55, 13.90, 13.92, 14.00, 14.13, 14.40 (2CH3),
15.03, 15.07, 15.71, 16.11, 20.88, 21.13, 21.29, 21.39, 22.90, 22.94, 23.06
(2CH2), 27.09, 27.21, 28.38, 28.71, 29.04, 29.09, 29.74, 29.88, 30.52, 30.58,
36.41, 36.54, 37.93, 38.51, 81.67, 82.08, 120.34, 120.69, 139.58, 139.61,
159.81, 161.09, 178.64, 179.12 ppm; HRMS calcd for C22H38N2 330.3035;
found 330.3030.
1
2
0.92 (t, J=7.5 Hz, 3H), 1.12 (t, J=7.5 Hz, 3H), 1.68 (dd, J=6.3 Hz, J=
1.5 Hz, 3H), 2.14–2.47 (m, 6H), 5.29 (dq, 1J=15.6 Hz, 2J=1.5 Hz, 1H),
5.70 (dq, J1 =15.6 Hz, 2J=6.6 Hz, 1H), 7.38–7.43 (m, 3H), 7.60–7.64 ppm
(m, 2H); 13C NMR (CDCl3, TMS): d=7.56, 13.24, 14.36, 18.22, 18.58,
19.58, 27.20, 84.13, 124.55, 127.72 (2CH), 128.24 (2CH), 129.01, 130.90,
136.23, 137.13, 166.40, 174.81 ppm.
Imine 17: nBuLi ( 1.2 mmol, 1.5m in pentane) was added to 4-haoldiene-
nitrile 8a (1.0 mmol) in a solution of diethyl ether (5 mL) at À508C. The
reaction mixture was stirred at À508C for 1 h and quenched with saturat-
ed aqueous NaHCO3 solution, subsequent work-up generated imine 17.
A colorless liquid was obtained in 100% yield of the isolated product
(339 mg). 1H NMR (CDCl3, TMS): d=0.88–0.98 (m, 15H), 1.32–1.63 (m,
12H), 1.92–2.66 (m, 10H), 8.82 ppm (br, 1H); 13C NMR (CDCl3, TMS):
d=13.54, 13.95, 14.00, 14.60, 14.77, 21.05, 21.70, 21.77, 22.52, 22.71, 28.03,
31.87, 35.07, 36.73, 37.21 (2CH2), 131.98, 137.55, 138.57, 138.71,
184.26 ppm; HRMS calcd for C21H38N35Cl 339.2693; found 339.2690.
2H-Pyrrole 20b: Colorless liquid obtained in 100% yield of the isolated
product (369 mg). 1H NMR (CDCl3, TMS): d=0.55–0.82 (m, 8H), 0.92–
1.10 (m, 11H), 1.29–2.06 (m, 12H), 2.13–2.48 (m, 7H), 2.62–2.97 (m,
1H), 4.92–5.19 (m, 2H), 5.67–6.10 ppm (m, 1H); 13C NMR (CDCl3,
TMS): d=13.93 (2CH3), 14.02 (2CH3), 14.26, 14.28, 14.56, 14.61, 15.08,
15.10, 15.66, 15.71, 19.25, 20.20, 21.59, 21.62, 22.97, 23.03 (2CH2), 23.11,
27.20, 27.24, 29.70, 29.79, 29.84, 29.89, 30.60, 30.64, 33.65, 33.72, 34.29,
37.01, 37.38, 40.15, 45.64, 45.66, 85.31, 85.36, 117.99, 118.29, 122.10,
122.22, 133.80, 134.66, 139.94, 140.00, 161.89, 162.06, 178.75, 179.06 ppm;
HRMS calcd for C25H42N2 370.3348; found 370.3335.
A typical procedure for the preparation of iminocyclopentadiene 19a–c
from 4-bromodienenitrile 8c and tBuLi: tBuLi (2.4 mmol, 1.6m in pen-
tane) was added to 4-bromodienenitrile 8c (1.0 mmol) in a solution of di-
ethyl ether (5 mL) at À788C. The reaction mixture was stirred at À788C
for 1 h to generate a cyclic N-lithioketimine intermediate, the formation
of which was monitored by GC analysis or TLC. If the reaction mixture
was not quenched, acyl chloride was added and the reaction mixture was
further stirred at room temperature for 1 h. The reaction mixture was
then quenched with saturated aqueous NaHCO3 solution and extracted
with diethyl ether. The extracts were washed with brine and dried over
MgSO4. The solvent was evaporated in vacuo to give a yellow oil, which
was purified by column chromatography (neutral Al2O3, Et2O/hexane
1:20) to afford iminocyclopentadiene 19a–c.
2H-Pyrrole 20c: Colorless liquid obtained in 90% yield of the isolated
product (378 mg). H NMR (CDCl3, TMS): d=0.32–1.15 (m, 20H), 1.21–
1
1.72 (m, 9H), 2.00–2.61 (m, 9H), 3.28–3.50 (m, 1H), 7.24–7.40 ppm (m,
5H); 13C NMR (CDCl3, TMS): d=13.95 (2CH3), 14.03, 14.09 (2CH3),
14.59 (2CH3), 15.00, 15.19, 15.63, 15.92, 19.74, 20.77, 21.52, 21.73, 22.94,
23.00, 23.03, 23.18, 27.22, 27.25, 29.72, 29.78, 29.85, 30.15, 30.59 (2CH2),
33.16, 33.58 (2CH2), 36.47, 38.88, 41.99, 46.43, 46.87, 85.52, 85.67, 121.93,
122.22, 127.00, 127.09, 128.18 (2CH), 128.20 (2CH), 130.30 (2CH),
130.60 (2CH), 136.42, 137.05, 140.03, 140.21, 162.02, 162.17, 178.91,
179.50 ppm; HRMS calcd for C29H44N2 420.3505; found 420.3494.
2H-Pyrrole 20d: Colorless liquid obtained in 93% yield of the isolated
1
product (326 mg). H NMR (CDCl3, TMS): d=0.78–1.65 (m, 22H), 1.78–
2.51 (m, 6H), 2.85–3.20 (m, 1H), 7.41–7.61 ppm (m, 5H); 13C NMR
(CDCl3, TMS): d=13.55 (2CH3), 14.00, 14.14 (2CH3), 14.18, 15.03, 15.07,
15.86, 16.27, 20.92, 21.13, 21.39, 21.47, 22.52, 22.54, 27.53, 27.68, 28.45,
28.76, 29.18, 29.23, 36.61, 36.72, 38.00, 38.62, 82.19, 82.56, 120.15, 120.46,
127.43 (2CH), 127.60 (2CH), 128.40 (2CH), 128.45 (2CH), 129.38
(2CH), 135.66, 135.72, 139.41, 139.44, 161.58, 162.83, 176.04, 176.70 ppm;
HRMS calcd for C24H34N2 350.2722; found 350.2715.
Iminocyclopentadiene 19a: Colorless liquid obtained in 100% yield of
the isolated product (247 mg). 1H NMR (CDCl3, TMS): d=0.88–1.00 (m,
12H), 1.37–1.52 (m, 8H), 2.18–2.25 (m, 8H), 9.61 ppm (s, 1H); 13C NMR
(CDCl3, TMS): d=14.32, 14.50, 22.92, 24.03, 25.44, 28.28, 126.97, 148.94,
182.43 ppm; HRMS calcd for C17H29N 247.2300; found 247.2297.
Iminocyclopentadiene 19b: Colorless liquid obtained in 88% yield of the
isolated product (309 mg). 1H NMR (CDCl3, TMS): d=0.80 (t, J=
7.2 Hz, 6H), 0.98 (t, J=7.2 Hz, 6H), 1.26–1.50 (m, 8H), 2.02–2.23 (m,
8H), 7.42–7.57 (m, 3H), 7.87–7.89 ppm (m, 2H); 13C NMR (CDCl3,
TMS): d=14.28, 14.53, 22.80, 23.72, 26.30, 28.43, 127.42, 128.49 (2CH),
128.94 (2CH), 132.77, 133.41, 152.12, 170.02, 178.01 ppm; HRMS calcd
for C24H33NO 351.2562; found 351.2559.
2H-Pyrrole 20e: Colorless liquid obtained in 95% yield of the isolated
1
product (274 mg). H NMR (CDCl3, TMS): d=0.66–1.05 (m, 15H), 1.15–
2.36 (m, 16H), 2.71–3.04 ppm (m, 1H); 13C NMR (CDCl3, TMS): d=
13.54, 13.57, 13.97, 14.13, 14.32 (2CH3), 15.02, 15.07, 15.73, 16.25, 17.10,
17.17, 20.85, 21.17, 21.28, 21.42, 22.88 (2CH2), 27.15, 27.24, 28.28, 28.76,
29.00, 29.05, 36.48 (2CH2), 37.81, 38.43, 81.77, 82.21, 120.22, 120.63,
139.59, 139.71, 159.75, 161.22, 175.14, 175.60 ppm; HRMS calcd for
C19H32N2 288.2566; found 288.2565.
Iminocyclopentadiene 19c: Colorless liquid obtained in 90% yield of the
isolated product (273 mg). 1H NMR (CDCl3, TMS): d=0.88 (t, J=
7.2 Hz, 6H), 0.98 (t, J=7.2 Hz, 6H), 1.19 (t, J=7.5 Hz, 3H), 1.31–1.51
(m, 8H), 2.01–2.06 (m, 4H), 2.17–2.22 (m, 4H), 2.55 ppm (q, J=7.5 Hz,
2H); 13C NMR (CDCl3, TMS): d=8.87, 14.30, 14.51, 22.79, 23.72, 26.23,
28.39, 31.38, 127.23, 151.52, 166.46, 186.58 ppm; HRMS calcd for
C20H33NO 303.2562; found 303.2565.
2H-Pyrrole 20 f: Colorless liquid obtained in 88% yield of the isolated
1
product (264 mg). H NMR (CDCl3, TMS): d=0.63–1.11 (m, 11H), 1.20–
2.12 (m, 14H), 2.23–2.31 (m, 2H), 2.50–2.94 ppm (m, 5H); 13C NMR
(CDCl3, TMS): d=13.36, 13.43, 13.75 (4CH3), 20.69, 21.25, 21.69, 21.73,
22.65, 22.70, 22.96, 23.00, 24.91, 25.24, 26.07, 26.16, 26.97, 27.48, 27.91,
29.53, 29.64, 29.90, 30.51, 30.60, 34.12, 34.18, 34.90, 38.00, 77.26, 77.80,
118.84, 120.21, 133.59, 134.17, 161.03, 162.99, 178.46, 179.47 ppm; HRMS
calcd for C20H32N2 300.2566; found 300.2568.
A typical procedure for the preparation of 2H-pyrrole derivatives 20a–i
from 1,4-dicyano-1,3-butadiene 9 and organolithium reagents: nBuLi
(1.2 mmol, 1.5m in pentane) was added to 1,4-dicyano-1,3-butadiene 9
(1.0 mmol) in a solution of diethyl ether (5 mL) at À508C. The reaction
mixture was stirred at room temperature for 1 h to generate a 2H-pyrrole
lithium intermediate, the formation of which was monitored by GC anal-
ysis or TLC. The reaction mixture was quenched with saturated aqueous
NaHCO3 solution and extracted with diethyl ether. The extract was
washed with brine and dried over MgSO4. The solvent was evaporated in
vacuo to give a yellow oil, which was purified by column chromatography
(silica gel, Et2O/hexane 1:10) to afford 20a and 20d–i. For the prepara-
tion of 20b,c: After the addition of nBuLi at À508C, the reaction mix-
ture was stirred at À508C for 1 h. Allyl bromide or benzyl bromide
(1.5 mmol) were added at À508C and the reaction mixture was stirred at
2H-Pyrrole 20g: Colorless liquid obtained in 75% yield of the isolated
product (240 mg). 1H NMR (CDCl3, TMS): d=0.75–1.04 (m, 8H), 1.07–
2.22 (m, 10H), 2.37–2.44 (m, 2H), 2.64–3.06 (m, 3H), 7.37–7.44 (m, 3H),
7.59–7.66 ppm (m, 2H); 13C NMR (CDCl3, TMS): d=13.56, 13.62, 13.83,
13.87, 20.92, 21.40, 21.87, 21.94, 22.83, 22.90, 25.42, 25.73, 26.71, 26.93,
27.20, 27.72, 28.19, 30.01, 34.41, 34.62, 35.27, 38.33, 78.05, 78.54, 118.89,
120.20, 127.82 (2CH), 127.86 (2CH), 128.34 (2CH), 128.38 (2CH),
129.25, 129.44, 133.79, 134.18, 135.59, 135.81, 162.96, 164.67, 175.73,
177.20 ppm; HRMS calcd for C22H28N2 320.2253; found 320.2249.
6492
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ꢀ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2007, 13, 6484 – 6494

Stereodefined Multisubstituted 1,4-Dicyano- and 1-Cyano-1,3-butadienes
FULL PAPER
2H-Pyrrole 20h: Colorless liquid obtained in 85% yield of the isolated
product (228 mg). 1H NMR (CDCl3, TMS): d=0.38–0.51 (m, 3H), 0.76–
1.27 (m, 7H), 1.36–1.58 (m, 3H), 1.75–1.85 (m, 2H), 2.10–2.40 (m, 2H),
2.82–3.26 (m, 3H), 7.40–7.75 ppm (m, 4H); 13C NMR (CDCl3, TMS): d=
7.34, 7.53, 11.99, 12.51, 13.89, 13.90, 19.71, 20.92, 22.86 (2CH2), 28.10,
29.51, 29.60, 30.03, 30.35, 30.37, 41.11, 42.34, 79.25, 79.63, 120.11, 120.62,
121.20, 121.42, 122.00, 122.39, 128.27 (2CH), 128.83, 129.15, 140.08,
140.16, 152.06, 152.48, 174.81, 175.20 ppm; HRMS calcd for C18H24N2
268.1940; found 268.1931.
(CDCl3, TMS): d=0.40–0.56 (m, 3H), 0.78–1.56 (m, 5H), 2.13–2.41 (m,
2H), 2.82–2.87 (m, 0.5H), 3.23–3.28 (m, 0.5H), 7.27–7.75 (m, 4H), 8.55
(s, 0.5H), 8.58 ppm (s, 0.5H); 13C NMR (CDCl3, TMS): d=7.25, 7.55,
11.97, 12.42, 19.68, 20.80, 27.93, 29.72, 40.58, 41.83, 81.65, 82.03, 119.91,
120.30, 122.05, 122.22, 122.41, 122.45, 128.51, 128.53, 129.24, 129.51,
139.92, 140.01, 151.69, 151.97, 163.94, 164.22 ppm; HRMS calcd for
C14H16N2 212.1314; found 212.1313.
2H-Pyrrole 20i: Colorless liquid obtained in 75% yield of the isolated
product (216 mg). 1H NMR (CDCl3, TMS): d=0.45–0.58 (m, 3H), 0.83–
1.25 (m, 5H), 1.43–3.40 (m, 3H), 7.43–7.97 ppm (m, 9H); 13C NMR
(CDCl3, TMS): d=7.43, 7.61, 11.98, 12.52, 19.83, 21.03, 28.39, 30.48,
41.27, 42.52, 79.61, 79.94, 120.06, 120.60, 122.31, 122.75, 122.94, 123.14,
128.12, 128.29, 128.36, 128.78, 128.87, 128.93, 129.29, 130.46, 130.58,
133.84, 133.94, 139.05, 139.09, 153.06, 153.53, 171.53, 172.00 ppm; HRMS
Acknowledgements
This workwas supported by the National Natural Science Foundation of
China. C.Y.W. thanks the Postdoctorate Research Fund of China
(2005038003) for financial support. The Cheung Kong Scholars Program,
Dow Corning Corporation, Qiu Shi Science & Technologies Foundation,
and BASF are gratefully acknowledged.
calcd for C20H20N2 288.1627; found 288.1628.
A typical procedure for the reaction of different conjugated enenitriles
23, 7a, 8c, 9a, 9d, and 9 f with LiAlH4: LiAlH4 (1.0 mmol, 1.0m in Et2O)
was added to the conjugated enenitrile 23 (or 7a, 8c, 9a, 9d, 9 f;
1.0 mmol) in a solution of diethyl ether (5 mL) at À788C. The reaction
mixture was stirred at 08C (or other proper temperature for different
substrates) for 1 h to generate the final product or intermediate, the for-
mation of which was monitored by GC analysis or TLC. The reaction
mixture was quenched with saturated aqueous NaHCO3 solution and ex-
tracted with diethyl ether. The extract was washed with brine and dried
over MgSO4. The solvent was evaporated in vacuo to give the crude
product, which was purified by column chromatography (silica gel, Et2O/
hexane 1:10 or 100% Et2O) to afford 24, 25a,b, 2 f, and 20j–k.
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Nitrile 24: Colorless solid obtained as two isomers (d.r.=3:1) in a com-
bined yield of 89% of the isolated products (209 mg). Major isomer:
1H NMR (CDCl3, TMS): d=0.80 (t, J=7.5 Hz, 3H), 1.78–1.87 (m, 2H),
2.83–2.94 (m, 1H), 4.04 (d, J=6.9 Hz, 1H), 7.04–7.09 (m, 4H), 7.22–
7.27 ppm (m, 6H); 13C NMR (CDCl3, TMS): d=11.99, 26.06, 44.28,
52.54, 119.83, 127.42, 127.97, 128.13 (2CH), 128.35 (2CH), 128.45 (2CH),
128.63 (2CH), 134.51, 139.05 ppm; HRMS calcd for C17H17N 235.1361;
found 235.1358.
Amine 25a: Colorless liquid obtained in 85% yield of the isolated prod-
uct (213 mg). 1H NMR (CDCl3, TMS): d=0.84–0.95 (m, 12H), 1.21–1.48
(m, 10H), 1.97–2.13 (m, 8H), 3.21 (s, 2H), 4.99 ppm (t, J=7.5 Hz, 1H);
13C NMR (CDCl3, TMS): d=13.94, 14.11, 14.37, 14.60, 21.44, 21.64, 22.27,
23.25, 29.87, 31.26, 31.90, 32.21, 43.60, 127.82, 135.75, 139.91, 140.31 ppm;
HRMS calcd for C17H33N 251.2613; found 251.2611.
Amine 25b: Colorless liquid obtained in 80% yield of the isolated prod-
uct (263 mg). 1H NMR (CDCl3, TMS): d=0.88–0.98 (m, 12H), 1.21–1.69
(m, 10H), 1.86–2.00 (m, 2H), 2.15–2.32 (m, 4H), 2.49–2.54 (m, 2H),
3.06–3.28 ppm (m, 2H); 13C NMR (CDCl3, TMS): d=13.29, 14.45
(2CH3), 14.90, 21.62, 21.65, 21.79, 21.89, 30.49, 33.61, 35.00, 39.08, 43.91,
124.71, 135.94, 136.35, 140.32 ppm; HRMS calcd for C17H32N79Br
329.1718; found 329.1718.
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Pyridine 2 f: Colorless liquid obtained in 75% yield of the isolated prod-
uct (185 mg). 1H NMR (CDCl3, TMS): d=0.97–1.07 (m, 12H), 1.42–1.80
(m, 8H), 2.50–2.59 (m, 6H), 2.69–2.74 (m, 2H), 8.14 ppm (s, 1H);
13C NMR (CDCl3, TMS): d=14.28, 14.45, 14.82, 14.86, 23.28, 24.18, 24.45,
24.53, 30.73, 30.91, 32.46, 37.32, 133.13, 133.18, 147.33, 147.37,
157.82 ppm; HRMS calcd for C17H29N 247.2300; found 247.2311.
2H-Pyrrole 20j: Colorless liquid obtained as two isomers (d.r.=1:1) in a
combined yield of 65% of the isolated products (159 mg). 1H NMR
(CDCl3, TMS): d=0.60–1.16 (m, 8H), 1.21–2.14 (m, 10H), 2.27–2.35 (m,
2H), 2.58–2.99 (m, 3H), 8.08 (s, 0.6H), 8.12 ppm (s, 0.4H); 13C NMR
(CDCl3, TMS): d=13.51, 13.62, 13.71 (2CH2), 20.86, 21.35, 21.72, 21.78,
22.62 (2CH2), 24.84, 25.19, 26.44, 26.49, 27.04, 27.68, 28.11, 30.02, 34.07,
34.40, 34.62, 38.19, 80.92, 81.38, 118.74, 120.10, 133.77, 134.32, 160.84,
162.83, 167.97, 168.67 ppm; HRMS calcd for C16H24N2 244.1940; found
244.1946.
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2H-Pyrrole 20k: Colorless liquid obtained as two isomers (d.r.=1:1) in a
combined yield of 51% of the isolated product (108 mg). 1H NMR
Chem. Eur. J. 2007, 13, 6484 – 6494
ꢀ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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Received: January 9, 2007
Published online: May 11, 2007
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