Nickel-Catalyzed [2+2+2] Cycloaddition of Alkyne-Nitriles with Alkynes Assisted by Lewis Acids: Efficient Synthesis of Fused Pyridines

Article abstract of DOI:10.1002/chem.201603829

A Ni/BPh₃catalyzed [2+2+2] cycloaddition of alkyne-nitriles with alkynes has been developed, which provides an efficient route to fused pyridines under mild reaction conditions. Mechanistic studies indicate that an azanickelacycle via heterocoupling of an alkyne with a nitrile moiety is possibly formed as a key reaction intermediate. The Lewis acid catalyst is crucial to the successful transformation, which is suggested to promote the oxidative cyclization process.

Full text of DOI:10.1002/chem.201603829

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Accepted Article
Title: Nickel-Catalyzed [2+2+2] Cycloaddition of Alkyne-nitriles with Alkynes Assis-
ted by Lewis Acid: Efficient Synthesis of Fused Pyridines
Authors: Xu You; Xin Xie; Gaonan Wang; Meijun Xiong; Renhong Sun; Haoyi Chen;
Yuanhong Liu
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To be cited as: Chem. Eur. J. 10.1002/chem.201603829
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Chemistry - A European Journal
10.1002/chem.201603829
Nickel-Catalyzed [2+2+2] Cycloaddition of Alkyne-nitriles with Alkynes Assisted by
Lewis Acid: Efficient Synthesis of Fused Pyridines
Xu You, Xin Xie, Gaonan Wang, Meijun Xiong, Renhong Sun, Haoyi Chen
and Yuanhong Liu*
State Key Laboratory of Organometallic Chemistry,
Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences,
345 Lingling Lu, Shanghai 200032, People’s Republic of China
Fax: (+86) 021-64166128, E-mail: yhliu@sioc.ac.cn
1,3-Bis(2,6-diisopropylphenyl)-1,3-dihydro-2H-imidazol-2-ylidene
Abstract: A Ni/BPh3 catalyzed [2+2+2] cycloaddition of alkyne-nitriles with alkynes has
been developed, which provides an efficient route to fused pyridines under mild reaction
conditions. Mechanistic studies indicate that an azanickelacycle via heterocoupling of an
alkyne with a nitrile moiety is possibly formed as a key reaction intermediate. The Lewis
acid catalyst is crucial to the successful transformation, which is suggested to promote the
oxidative cyclization process.
Keywords: nickel ·cycloaddition ·alkynes ·nitriles ·pyridines
Pyridines constitute an important class of heterocycles, which appear as key structural
subunits in numerous natural products and pharmaceutical molecules, and also serve as
attractive building blocks in organic synthesis.[1] Transition-metal-catalyzed [2+2+2]
1
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Chemistry - A European Journal
10.1002/chem.201603829
cycloaddition of two alkynes with a nitrile represents a powerful and atom-economic
strategy for the straightforward synthesis of multi-substituted pyridines.[2] Various
transition metal systems such as Co,[3] Ru,[4] Rh,[5] and more recently, Ni,[6] Fe,[7] Ir [8] and
Nb[9] have been developed in this field. To solve the regioselectivity issue, the
preassembled substrates containing two or three unsaturated units are usually used in these
reactions. However, most of the studies concentrated on the cycloaddition of the
preassembled diynes with nitriles, while the reactions of alkyne-nitriles with alkynes were
less common. So far only two catalytic systems have been developed with Co[3a,c-d,f-g] and
Fe-based[7a] transformations, however, they have certain drawbacks. For example,
Co-catalyzed reactions usually suffer from elevated temperatures, irradiation conditions,
unconvenient manipulations, and most of the reactions restricted to terminal alkyne-nitriles.
The only report with Fe catalysis limited to internal alkynes as the alkyne component etc.
Therefore, the development of efficient catalytic systems which enable the reaction to
occur under mild reaction conditions with wide functional group tolerance is highly
desired.
On the other hand, nickel-catalyzed [2+2+2] cycloaddition to pyridines continues to be
attractive and challenging due to the low rates of alkyne-nitrile heterocoupling,[10]
competitive alkyne cyclotrimerizations,[10] dimerization of nitriles,[10] or carbocyanation of
alkynes with nitriles[11]. Several new achievements have recently been developed. Louie et
al demonstrated that a combination of Ni(COD)2 with electron-donating N-heterocyclic
carbene
(NHC)[6a-c,e-g]
or
bulky
Xantphos
ligands
(Xantphos
catalyzed
=
4,5-bis(diphenylphosphino)-9,9-dimethylxanthene)[6d]
effectively
the
2
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10.1002/chem.201603829
cycloaddition of diynes with nitriles at room temperature (Scheme 1, eq 1). In contrast to
Co-catalyzed [2+2+2] cycloadditions, these reactions were proposed to proceed through
the heterocoupling mechanism involving the initial oxidative cyclization of an alkyne and
nitrile with nickel(0).[6f] It was found that the ligand played an important role in the
achievement of these transformations, which was suggested to promote the formation of an
azanickelacycle or the reductive elimination of C-N bond through electronic or steric
effects of the ligand. However, the related nickel-catalyzed cycloaddition of alkyne-nitriles
with alkynes to pyridines has not been report yet. During our studies, we observed a
dramatic effect of a Lewis acid cocatalyst, which facilitated the desired cycloaddition of
alkyne-nitriles with alkynes significantly with the use of the normal phosphine ligands, and
allowed the reaction to proceed under mild reaction conditions (Scheme 1, eq 2). It is
important to note that without the Lewis acid cocatalyst, the desired [2+2+2] cycloaddition
cannot proceed even employing the special phosphine or NHC ligands. Compared with the
Louie’s reaction, here the key intermediate of azanickelacycle is possibly formed via
enhancement of the electrophilicity of the cyano group (Scheme 1, eq 3). Interestingly, it is
well known that Lewis acid could accelerate the nickel-catalyzed carbocyanation of the
alkynes with nitriles via cleavage of the R-CN bond,[11c-f] however, such reaction was not
observed in our reaction. Herein, we report these results.
3
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R1
Ln
Louie's reaction:
R1
R1
+
N
Ni
Ni(0)/Ln
N
N
(1)
R2
R3
R3
R2
R3
R2
L = NHC, Xantphos
intramolecular
This work: unknown for Ni
R1
N
R1
R3
R3
R2
R3
R2
R1
Ni(0)/Ln/Lewis acid
rt or 50 oC
(2)
(3)
+
Ni
Ln
N
N
R2
L = normal phosphine ligands
intermolecular
Louie's strategy: ligand-assisted coupling
challenging task due to:
oxidative
cyclization
i) low rates of alkyn-nitrile heterocoupling
ii) competitive alkyne cyclotrimerization
iii) competitive carbocyanation
NiLn
NiLn
N
N
Our strategy: Lewis acid promoted coupling
enhancement of the electrophilicity of the cyano group
Scheme 1. Nickel-catalyzed [2+2+2] cycloaddition to pyridines.
At the beginning, we chose the Ni(0)-catalyzed cycloaddition of benzene-tethered
alkyne-nitrile 1a[12] with 3-hexyne as the model reaction for the optimization of the
reaction conditions (Table 1). It was anticipated that such transformation would afford
highly valuable indenopyridines. Treatment of 1a and one equivalent of 3-hexyne with 5
mol% of Ni(COD)2 and 10 mol% of various phosphine ligands including Xantphos and IPr
o
(1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene) in toluene at 50 C for 24 h did not
afford the desired cycloaddition product (Table 1, entries 1-3). After a lot of efforts, we
found that the desired indeno[1,2-b]pyridine 2a could be obtained at room temperature in
66% yield by adding 20 mol% of AlMe2Cl (entry 4). Inspired by this result, different
Lewis acids were examined in order to improve the yield of 2a. To our delight, the best
yield of 2a could be achieved using BPh3 as the Lewis acid and PMePh2 as the ligand
4
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10.1002/chem.201603829
(88%, entry 7). We suggested that Lewis acid might increase the electrophilicity of the
cyano group, thereby facilitated the oxidative cyclization of the alkyne and nitrile moiety
with Ni(0).[13] A variety of ligands were also screened, among them, PBu3 shown
comparative activity with that of PMePh2, leading to 2a in 82% yield (entry 14). Other
ligands such as PPh3, Xantphos, bipy, PCy3 and dppp were less effective (entries 9-13). In
the absence of a ligand, the yield of 2a was sharply reduced to 12% (entry 15). Control
experiment run without nickel catalyst resulted in no formation of 2a (entry 16). A larger
scale reaction was also performed (1 mmol scale), and the desired 2a was still formed in
high yield (entry 17).
Table 1. Optimization studies for Ni(0)-catalyzed cycloaddition of alkyne-nitrile 1a with
3-hexyne.
5 mol% Ni(COD)2
10 mol% ligand
20 mol% LA
OTBS
OTBS
Ph
Et
Et
Et
Et
+
Ph
toluene, 24 h
CN
N
1.0 equiv
1a
2a
Entry
1
Ligand
LA
Temp (oC)
Yield (%)[a]
- (97)
PMePh2
-
-
50
50
2[b]
Xantphos
- (77)
[c]
3
4
5
6
IPr
-
50
rt
-
PMePh2
PMePh2
PMePh2
AlMe2Cl
66
14
17
TMSOTf
B(C5F5)3
rt
rt
5
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7
PMePh2
PMePh2
PPh3
BPh3
BPh3
BPh3
BPh3
BPh3
BPh3
BPh3
BPh3
BPh3
BPh3
BPh3
rt
rt
rt
rt
rt
rt
rt
rt
rt
rt
rt
88
8[d]
9
52
58
7
10[b]
11[b]
12
Xantphos
bipy
8
PCy3
41
33
82
12
- (92)
89
13[b]
14
dppp
PBu3
15
-
16[e]
17[f]
PMePh2
PMePh2
[a] Isolated yields. Unless noted, all the reactions were carried out on 0.3 mmol scale. The
yields of recovered 1a are shown in parentheses. [b] 5 mol% ligand was used. [c] The
reaction was not clean and no desired product was formed. [d] 10 mol% BPh3 was used. [e]
In the absence of Ni(COD)2. [f] 1 mmol scale.
In light of the above investigations, we chose entry 7 in Table 1 as the optimized
conditions to explore the substrate scope of this reaction. First, the scope of alkynes was
examined using 1a as the reaction partner (Table 2). Under the standard reaction conditions,
1a underwent cycloadditions smoothly with symmetrically substituted alkynes such as
5-decyne or the alkyne bearing -CH2OTBS functional groups to give the corresponding
indenopyridines 2b and 2c in 76% and 82% yields, respectively. However, when
o
diphenylacetylene was used, only 45% of 2d was obtained at 50 C. Undoubtedly, the
reaction of 1a with a propyl methyl-substituted alkyne afforded 2e as a 1:1 mixtures of
6
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10.1002/chem.201603829
regioisomers. High to excellent regioselectivity were observed for phenyl alkyl alkynes,
possibly due to the polarity of these alkynes. The regioselectivity in these cases is opposite
to that observed in Fe-catalyzed cycloaddition reactions.[7a] When enyne or butadiynes[3d]
were employed, the corresponding 2h-2j were isolated in high yields as a single
regioisomer, in which an alkenyl or alkynyl group located at the-position of the pyridine
ring. The high regioselectivity can be explained by the directing effects of these
unsaturated groups caused by their coordination with the metal center during the insertion
of alkyne to azanickelacycle. To our delight, terminal alkynes bearing normal alkyl, benzyl,
cyanoalkyl, chloroalkyl or cyclopropyl functional groups were all compatible to give
2k-2p in 61-89% yields as a mixture of two regioisomers, while the alkyl substituent is
located at the -position of the newly formed pyridine ring in the major regioisomer.
Especially, no cycloaddition derived from the reaction of 5-hexynenitrile with the alkyne
moiety of 1a was observed in the case of 2n. It was important to note that when terminal
alkynes were used as the monoalkyne components in metal-catalyzed [2+2+2]
cycloaddition reactions, usually low product yields were observed,[3a,c,e,g] possibly due to
the rapid trimerization or oligiomerization of these alkynes under the catalytic conditions.
In our reaction system, the heterocoupling of an alkyne and a nitrile might be much faster
than alkyne trimerization or oligiomerization due to the enhanced electrophilicity of the
cyano group through coordination with Lewis acid. It was worth mentioning that both
regioisomers obtained in above reactions could be easily separated by column
chromatography. The structure and regiochemistry of these indenopyridine products were
confirmed by X-ray crystallographic analyses of 2g, 2h, 2j, and the major isomer of 2f,
7
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2k.[14] Next, the scope of substrates 1 bearing different functionalities at their alkyne
terminus were examined. Both of the electron-rich and electron-deficient substituents on
the aromatic rings of aryl alkynes were well tolerated. In the case of 2r, no activation of
aryl-halogen bond was observed. 2-Thienyl- or alkenyl-substituted alkyne converted into 2t
and 2u in good yields. The alkynes bearing linear or cyclic alkyl groups were also well
suited. However, when terminal alkyne was employed, only complicated reaction mixture
was observed.
8
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Table 2. Ni/BPh3-catalyzed cycloaddition of benzene-tethered alkyne-nitriles with alkynes.[a]
5 mol% Ni(COD)2
10 mol% PMePh2
20 mol% BPh3
OTBS
R1
OTBS
R3
R2
R2
R3
+
R1
toluene, rt, 24 h
CN
N
1.0 equiv
TBSO
1
2
TBSO
TBSO
Ph
Ph
R
Ph
Me
Bu
Bu
N
N
N
Pr
R
2c, R = CH2OTBS, 82%
2d, R = Ph, 45%[b]
2e, 81% (1:1)
2b, 76%
TBSO
TBSO
Ph
TBSO
Ph
Ph
NBn2
Me
C5H11
N
N
N
Ph
Ph
2f, 70% (6:1)
2g, 63%[c]
2h, 75%[c]
Ph
Et
TBSO
R1
TBSO
TBSO
Ph
Ph
Pr
H
N
N
N
R
Et
2q, R1 = p-MeOC6H4, 81%
2r, R1 = p-ClC6H4, 80%[d]
2s, R1 = p-CF3C6H4, 86%
2i, 73%[c]
Pr
2k, R = Pr, 89% (2:1)
2l, R = Hex, 76% (1.5:1)
TBSO
Ph
2t, R1 = 2-thienyl, 80%
2u, R1 = cyclohexenyl, 77%[d]
2v, R1 = n-C3H7, 64%[d]
2w, R1 = cyclopropyl, 71%
2x, R1 = H, messy
2m, R = Bn, 79% (1.8:1)
2n, R = (CH2)3CN, 66% (2.1:1)
2o, R = (CH2)3Cl, 61% (1.3:1)
2p, R = cyclopropyl, 89% (8:1)
N
2j, 84%
[a] The yields are given for the isolated products. Only the structure of the major regioisomer is
shown. The ratio of two regioisomers is shown in the paretheses. [b] 10 mol% Ni(COD)2, 20 mol%
PMePh2, 20 mol% BPh3 and 1.5 equiv of alkyne were used. The reaction was carried out at 50 oC
for 32 h. [c] 10 mol% Ni(COD)2, 20 mol% PMePh2 and 40 mol% BPh3 were used. [d] 50 oC, 24 h.
The reaction was also successfully expanded to linear alkyne-nitriles using PBu3 as the
ligand (Table 3).[15] A wide variety of C, N or O-linked alkyne-nitriles were compatible. It
9
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was noted that in some cases, pyridines 5 derived from self-cycloaddition of alkyne-nitrile
3 were also observed. 5 was obtained as a single regioisomer in which phenyl group
located at the -position of the pyridine ring. Internal alkyne substrates, whenever
substituted with phenyl or alkyl group reacted with 3-hexyne or diphenylacetylene to
afford 4a-4d in 42-74% yields. Terminal alkyne also worked, albeit with a low yield of 4e.
Alkyne-nitriles bearing either a sulphonamide or oxygen tether coupled well with alkynes
to give 4f-4j in 44-80% yields. Substrate with a four-atom linkage between the alkyne
and cyano group transformed into the pyridine 4k smoothly. The reaction of
(o-alkynyl)benzyl nitrile with internal or terminal alkynes proceeded efficiently to afford
9H-indeno[2,1-b]pyridines 4l or 4m in high yields.
10
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Table 3. Scope of the alkyne-nitriles.[a]
5 mol% Ni(COD)2
10 mol% PBu3
20 mol% BPh3
R1
N
R2
X
R2
X
R4
R3
R1
R3
R4
+
toluene, 50 oC, 24 h
N
3, 1.3 equiv, X = C, N, O
4
C5H11
Ph
Ph
Et
Et
R
R
Et
Et
MeO2C
MeO2C
MeO2C
MeO2C
MeO2C
MeO2C
N
Et
N
Et
N
N
4a, R = Et, 50% (47%)
4b, R = Ph, 42% (49%)[b]
4c, 67% (26%)
4d, 74%
4e,[c] 31%(-)[d]
Ph
Ph
Et
Ph
Ph
Ph
Ph
Et
Et
Et
Et
Et
O
Ts N
Ts N
O
N
N
Et
N
Et
N
4h,[e] 44% (58%)
4i, 49% (-)[d,e]
4g, 80%
4f, 57% (34%)
Et
Ph
Ph
Ph
Ph
Ph
Pr
Et
N
H
Bn
Et
Et
N
N
Ts N
4j, 74%[f]
N
Pr
N
4m, 86%[c,f,g]
4k, 42% (-)[d]
4l, 94%[c,g]
Ph
[a] Isolated yields. The yields of byproduct 5 based on 3 are
shown in the parentheses. [b] 60 C, 24 h. [c] 10 mol%
o
X
PMePh2 was used as the ligand. [d] The byproducts were
not clean. [e] 10 mol% PPh3 was used as the ligand. [f] Two
regioisomers were obtained with a ratio of 1:1. [g] rt, 24 h.
X
N
N
Ph
5
To understand the reaction mechanism, we carried out the following experiments. First,
we examined the reaction of 1a with a stoichiometric amount of Ni(COD)2 (1 equiv),
PMePh2 (2 equiv) and BPh3 (1 equiv) (Scheme 2, eq 1). Surprisingly, a cyclized N-H imine
6a was formed in 62% yield after hydrolysis by water. Due to the instability of 6a, the
structure of 6a was confirmed by X-ray crystal analysis of its derivative 7a.[14,16] The
appearance of one more phenyl group in 6a indicated that BPh3 acted not only as a Lewis
11
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10.1002/chem.201603829
acid, but also delivered one of its phenyl group to the product in the stoichiometric reaction.
The reaction possibly proceeds by first formation of azanickelacycle 8 followed by
transmetalation and reductive elimination, which was not known yet in Ni-catalysis.[17]
The results implied that oxidative coupling of the alkyne and the nitrile moiety in 1 could
occur in the presence of BPh3, and in catalytic pyridine formation process, insertion of an
alkyne to the resulting azanickelacycle should proceed much faster than transmetalation.
The stoichiometric reaction of 1a with Ni(COD)2 and PMePh2 afforded an orange, air and
moisture sensitive (PMePh2)2Ni(2-alkyne) complex 10 in 85% yield, rather than
2-nitrile[6e] or 2:2-5-en-nitrile[13b] Ni(0) complex (Scheme 2, eq 2). No further
o
cyclization occurred when the reaction was carried out at 50 C. The X-ray crystal
analysis[14] of 10 indicates that the metal center adopts a distorted square-planar geometry,
and the C≡C bond distances (1.270(8) Å), C≡C-C angles (140.7(6)o, 144.4(6)o) are similar
to those reported for other nickel(0)-alkyne phosphine complexes.[18] Treatment of 10 with
one equiv of 3-hexyne and one equiv of BPh3 resulted in the formation of 2a in 81% yield
(Scheme 2, eq 3). Without BPh3, no reaction occurred. The results suggest that the reaction
possibly proceeds via formation of a metal -alkyne complex followed by BPh3-assisted
cycloaddition. Moreover, reaction of the azazirconacyclopentadiene 11 prepared by
Zr-meidated alkyne-nitrile coupling of 1a with NiCl2(PPh3)2 and 3-hexyne afforded the
same product 2a in 32% yield. The formation of azazirconacycle 11 was confirmed by the
isolation of imine 12 through hydrolysis (Scheme 2, eq 4). In this reaction, azanickelacycle
13 is proposed to be formed through transmetalation from Zr to Ni.[19] The results indicate
that a similar azanickelacycle should be generated in Ni-catalyzed reaction, and the
12
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heterocoupling pathway is the most favorable route.[6f] It is also implied that insertion of
alkyne to azanickelacycle can proceed without the aid of BPh3.
1 equiv Ni(COD)2
2 equiv PMePh2
1 equiv BPh3
OTBS
Ph
OTBS
Ph
THF/H2O
50 oC
NH2OH HCl
in THF
(1)
1a
toluene, 50 oC, 3 h
Ph
Ph
N
NH
6a, 62%
HO
Ni(0)
OTBS
7a, 92% (X-ray)
OTBS
Ph
Ph
NiLn
Ph
NiLn
N
N
Ph
8
Ph2B
9
BPh2
TBSO
1 equiv Ni(COD)2
2 equiv PMePh2
(2)
1a
Ni
PMePh2
PMePh2
toluene, rt, 2 h
N
10, 85%
1 equiv
Et
Et
1 equiv BPh3
10
1a
2a, 81%
(3)
toluene, rt, 1 h
OTBS
1 equiv NiCl2(PPh3)2
2 equiv
1.3 equiv
Cp2ZrBu2
Et
Et
Ph
2a, 32%
(4)
50 oC, 12 h
toluene, rt 3 h
ZrCp2
N
11
H2O
OTBS
Ph
OTBS
Ph
Ni(PPh3)2
N
NH
12, 51%
13
Scheme 2. Mechanistic studies
Based on the above observations, we propose the following reaction mechanism for
13
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this cycloaddition reaction (Scheme 3). Initially, a nickel-alkyne complex 14 is formed, in
which the cyano group coordinates to BPh3.[20] Then, oxidative cyclization of the alkyne
and nitrile moiety with Ni(0) occurs to give an azanickelacycle 15. Insertion of an alkyne
to Ni-C bond in 15, which is much faster than transmetalation, results in the formation of
seven-membered azanickelacycle 17. Insertion of an alkyne to Ni-N bond may be
unfavored due to the reduced nucleophilicity of nitrogen moiety, which is considered to be
coordinated with Lewis acid. Reductive elimination of 17 affords the desired product 2 and
regenerates the nickel catalyst. The Lewis acid catalyst is suggested to promote the
oxidative cyclization.
Ni(COD)2
PMePh2
OTBS
R1
OTBS
N
R1
R3
L2Ni(0)
2
N
1
+
R2
+
L = PMePh2
BPh3
BPh3
reductive
elimination
OTBS
R1
OTBS
NiL2
R1
BPh3
R3
R2
N
17
Ni
L2
N
6
14
Ph3B
OTBS
OTBS
OTBS
R1
R2
R1
R3
R1
NiL2
<<
Ni
N
NiL2
Ph
N
16
L2
N
15
Ph2B
Ph3B
8
BPh3
R2
R3
Scheme 3. Possible reaction mechanism
14
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In summary, we have demonstrated that Ni/LA dual catalysts are highly effective for
[2+2+2] cycloaddition of alkyne-nitriles with alkynes. Not only internal alkynes but also
terminal alkynes participate in the cycloaddition very well, allowing the facile access to
fused pyridines regioselectively under mild reaction conditions. Mechanistic studies
indicated that an azanickelacycle was formed as a key reaction intermediate. The Lewis
acid catalyst is crucial for successful transformation, which is suggested to promote the
formation of an azanickelacycle. Further investigation of the reaction mechanism and
applications of this chemistry are underway in our group.
Acknowledgment
We thank the National Natural Science Foundation of China (Grant Nos. 21125210,
21421091), Chinese Academy of Science for financial support.
Supporting Information Available: Supporting information for this article is available on
the WWW under http://dx.doi.org/
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17
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(Z-7b), 1480605 (E-7b) and 1434666 (10) contain the supplementary crystallographic
data for this paper. These data can be obtained free of charge from the Cambridge
Crystallographic Data Centre.
[15]PMePh2 also worked for linear substrates, however, with a slight lower yields of
in some cases.
4
[16]When alkyne-nitrile 1b substituted with a p-MeOC6H4 group at the alkyne terminus
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be explained by double bond isomerization of alkenylnickel species 9 before reductive
elimination. For cis-trans isomerization of the alkenylnickel species, see: (a) X. Zhang,
18
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[20]For activation of nitrile through coordination with BPh3 in nickel-catalyzed
carbocyanation reactions, see: Ref. 11c, e, f; For isolation and characterization of a
13
Ni(II)-CN-BPh3 complex, see: Ref. 11f. We observed that in the C NMR spectrum,
there is no apparent difference in the carbon resonance of cyano group in 1a and
1a+BPh3 (1:1) in toluene-d8. However, the chemical shift of BPh3 in 11B NMR spectra
shifts from 67.17 ppm in free BPh3 to 60.23 ppm in the mixture of 1a+BPh3 in
toluene-d8, possibly due to the coordination of BPh3 to the cyano group of 1a.
Table of Contents
R1
R3
R3
R2
R1
Ni(0)/Ln/Lewis acid
+
X
X
room temperature
or 50 oC
N
N
R2
36 examples
X = C, N, O
L = normal phosphine ligands
Lewis acid promoted cycloaddition regio- and chemo-selective
19
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Chemistry - A European Journal
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Ni/LA dual catalysis: A Ni/BPh3 catalyzed [2+2+2] cycloaddition of alkyne-nitriles with
alkynes has been developed, which provides an efficient route to fused pyridines under
mild reaction conditions. Mechanistic studies indicate that an azanickelacycle via
heterocoupling of an alkyne with a nitrile moiety is possibly formed as a key reaction
intermediate. The Lewis acid catalyst is crucial to the successful transformation, which is
suggested to promote the oxidative cyclization process.
20
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