Nickel-catalyzed multi-component coupling reaction of aldimine, alkyne, and dimethylzinc via dimerization of butadiene

Article abstract of DOI:10.1016/j.tetlet.2009.04.086

In the presence of a Ni/phosphine ligand catalyst, dimethylzinc, alkyne, butadiene, aldehyde, and primary amine were successively combined via dimerization of butadiene to provide (3E,7E,10Z)-dodecatrienylamine in good yields with excellent regio and ster

Full text of DOI:10.1016/j.tetlet.2009.04.086

Tetrahedron Letters 50 (2009) 3982–3984
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Tetrahedron Letters
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Nickel-catalyzed multi-component coupling reaction of aldimine, alkyne,
and dimethylzinc via dimerization of butadiene
b
b
a
Masanari Kimura a, , Mariko Togawa , Yasushi Tatsuyama , Kimiko Matsufuji
*
a Department of Applied Chemistry, Faculty of Engineering, Nagasaki University, 1-14 Bunkyo-machi, Nagasaki 852-8521, Japan
b Graduate School of Science and Technology, Nagasaki University, 1-14 Bunkyo-machi, Nagasaki 852-8521, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
In the presence of a Ni/phosphine ligand catalyst, dimethylzinc, alkyne, butadiene, aldehyde, and primary
amine were successively combined via dimerization of butadiene to provide (3E,7E,10Z)-dodecatrienyl-
amine in good yields with excellent regio and stereoselectivities.
Received 21 February 2009
Revised 12 April 2009
Accepted 23 April 2009
Available online 3 May 2009
Ó 2009 Elsevier Ltd. All rights reserved.
Keywords:
Nickel
Diene
Alkyne
Aldimine
Dimethylzinc
Multi-component coupling reaction can be challenging, yet of-
fers one of the most efficient and versatile synthetic strategies
for C–C bond formation.1 For the oligomerization and polymeriza-
tion of butadiene, the use of a Ni/phosphine ligand catalyst allowed
amines provided 3,6-octadienylamines, whereas aliphatic amines
furnished 3,7,10-dodecatrienylamines via bis-butadiene Ni(0)
complex. Herein, we disclose that the Ni/phosphine ligand catalyst
can readily promote the dimerization of butadiene to generate
the formation of g1
,g
3-allylnickel species, which then reacted with
g1 3-allylnickel species (as an octadienyl carbanion), followed
,g
aldehydes to provide complex mixtures of regio- and stereoiso-
mers of dienyl and trienyl homoallyl alcohols.2 Unfortunately, pre-
cise control of the nucleophilic allylation of carbonyls by
butadiene, by virtue of oxidative cyclization of butadiene with
Ni(0) complexes, has proved to be extremely problematic so far
(Scheme 1).3
Recently, we have developed a highly regio- and stereo-con-
trolled methodology of C–C bond formation featuring a Ni-cata-
lyzed, five-component coupling reaction involving dimethylzinc,
alkyne, butadiene, aldehydes, and primary amines.4 The reaction
scheme, however, was dependent on the type of amines: aromatic
by a multi-component coupling reaction involving alkyne, aldi-
mines, and dimethylzinc to afford (3E,7E,10Z)-dodecatrienylamine
in excellent yields, irrespective of the amine.
The coupling reaction was carried out as follows. A mixture of
p-anisidine and benzaldehyde in dry THF was stirred at room tem-
perature. Into a flask containing nickel catalyst and phosphine li-
gand purged with nitrogen were successively added THF, the
above prepared solution via cannula, butadiene, 3-hexyne, and
dimethylzinc, and the reaction mixture was stirred at room tem-
perature.5 As summarized in Table 1, the reaction course was sig-
nificantly influenced by phosphine ligands. In the presence of PPh3,
the reaction was predominated over the multi-component cou-
pling involving dimerization of two molecules of butadiene provid-
ing dodecatrienylamine 2a in excellent yield (Table 1, run 2).
Other bidentate phosphine ligands such as dppe, dppp, dppb,
and dppf displayed similar reactivities affording 2a in good to
excellent yields (Table 1, runs 2–6). In the absence of phosphine li-
gands, however, the Ni catalyst promoted the five-component suc-
cessive coupling reactions of dimethylzinc, alkyne, butadiene,
aldehyde, and amine to afford dienylamine 1a in a high yield (Table
1, run 1).
RCHO
Ni(0)
PPh3
R
Ni
Ph3P
HO
highly complex mixture of
regio- and stereoisomers,
oligomers of diene, etc.
Scheme 1. Ni/PPh3-promoted C–C bond formation via bis-p allylnickel.
As shown in Table 2, our multi-component coupling reaction
involving the Ni/phosphine ligand catalyst was applied to a wide
* Corresponding author. Tel.: +81 95 819 2677; fax: +81 95 819 2684.
E-mail address: masanari@nagasaki-u.ac.jp (M. Kimura).
0040-4039/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2009.04.086

M. Kimura et al. / Tetrahedron Letters 50 (2009) 3982–3984
3983
Table 1
Table 3
Ni-catalyzed multi-component connection reaction of aldimine, alkyne, butadiene,
Ni-catalyzed multi-component connection reaction of various aminesa
and Me2Zna
R1
PhCHO
R1
Me2Zn
R1
R2NH2
Et
PhCHO
PMPNH2
Me2Zn
Et
Et
cat. Ni(acac)2
Et
R1
Ph
NHR2
cat. Ni
Et
Ph
Et
Ph
PPh3
2
Me
r.t., 48 h
2
2
Me
NHPMP Me
NHPMP
1a
2a
Run
Alkyne
R1
Amine
R2
Yield of 2 (%)
Run
Ligand
Time (h)
Yield (%)
1a
2a
1
2
3
4
5
Et
Et
Et
Et
Ph
C6H5
2h: 78
2i: 88
p-BrC6H5
p-ClC6H5
Bn
1
2
3
4
5
6
None
PPh3
dppe
dppp
dppb
dppf
3
3
24
24
24
6
91
0
0
0
0
0
2j:63
87
85
72
63
87
2k: 74 (94)b
2l: 73
p-MeOC6H5
a
Reaction conditions: PhCHO (1 mmol), amine (2 mmol) in THF (2 mL) at room
temperature, and then Ni(acac)2 (0.1 mmol), PPh3 (0.2 mmol) in THF (3 mL), alkyne
(4 mmol), butadiene (4 mmol), Me2Zn (3.6 mmol) at room temperature.
0
a
Reaction conditions: PhCHO (1 mmol), PMPNH2 (2 mmol) in THF (2 mL) at room
b
2k was obtained in 94% in the absence of PPh3.
temperature, and then Ni(acac)2 (0.1 mmol), PPh3 (0.2 mmol), or bidentate phos-
phine ligand (0.1 mmol) in THF (3 mL), 3-hexyne (4 mmol), butadiene (4 mmol),
Me2Zn (3.6 mmol) at room temperature.
imine underwent the coupling reaction to afford the corresponding
amino alcohols (Table 2, runs 11 and 12).
In the presence of PPh3, aldimine composed of aromatic amine
tends to undergo dimerization of butadiene to provide trienylam-
ines 2h–2j in excellent yields (Table 3, runs 1–3). On the other
hand, aliphatic amine gave trienylamine 2, irrespective of the pres-
ence of PPh3; for example, benzylamine-imine provided trienyl-
amine 2k exclusively, even in the absence of PPh3 (Table 3, run
4). Diphenylacetylene served as a capable carbon source in provid-
ing the desired coupling product 2, as well as 3-hexyne (Table 3,
run 5).
Table 2
Ni-catalyzed multi-component connection reaction of various aldehydesa
Et
Et
Et
RCHO
PMPNH2
Me2Zn
Et
cat. Ni
Et
Et
R
R
2
Me
Me
NHPMP
NHPMP
1
2
Run
Aldehyde
R
PPh3 (mmol)
Time (h)
Yield (%)
The proposed reaction mechanism for the multi-component
coupling reaction catalyzed by Ni/phosphine ligand catalyst is
1
2
1
2
3
4
5
6
7
8
p-MeOC6H5
p-MeOC6H5
p-ClC6H5
p-ClC6H5
n-C5H11
n-C5H11
i-Pr
0
0.2
0
0.2
0
0.2
0
2
3
1
3
1
3
1
3
1b: 88
0
1c: 97
0
1d: 87
0
1e: 84
0
2b: 0
68
2c: 0
77
2d: 0
64
2e: 0
74
PPh3
Ni0
IV
Ni
Ph3P
Ni0
VI
; vacant site
Me2Zn
I
i-Pr
0.2
R
R
R
O
OH
9
0
3
6
2
6
1f: 71
2f: 0
78
N
Me2Zn
N
Me2Zn
N
R'
R = alkyl
R'
R'
R = aryl
10
11
0.2
0
0
R = aryl, alkyl
O
OH
1g: 86
2g: 0
86
Ni0
RN
Ni0
R'
R'
RN
12
0.2
0
II
ZnMe2
a
ZnMe2
Reaction conditions: PhCHO (1 mmol), PMPNH2 (2 mmol) in THF (2 mL) at room
temperature, and then Ni(acac)2 (0.1 mmol), PPh3 (0.2 mmol or none) in THF (3 mL),
3-hexyne (4 mmol), butadiene (4 mmol), Me2Zn (3.6 mmol) at room temperature
for 3 h.
V
R'
ZnMe
Ni
Me
Ni
N
N
Me
MeZn
R
variety of aldehydes. For aromatic aldehydes with an electron-
donating group or a halogen (Table 2, runs 1–4), the multi-compo-
nent coupling reaction proceeded smoothly, in which the presence
of PPh3 accelerated the dimerization of butadiene to exclusively af-
ford trienylamines 2. For aliphatic aldehydes, the presence of PPh3
favored the formation of trienylamine 2, whereas its absence fa-
vored dienylamine 1 (Table 2, runs 5–8). The stability of the pres-
ent reaction in the presence of water, which is generated during
the in situ formation of an aldimine between the aldehyde and pri-
mary amine, encouraged us to investigate in detail our coupling
reaction using cyclic hemiacetals.6 Depending on the catalytic sys-
tem, 2-hydroxy-1-oxacyclopentane-p-anisidine imine afforded
dienylamino alcohol 1f or trienylamino alcohol 2f (Table 2, runs
III
VII
R
R'
alkyne
alkyne
R"
R'
NiMe
NiMe
N
ZnMe
R"
R
R"
N
R
MeZn
R"
R'
- Ni0
- Ni0
2
1
Scheme 2. Ni-catalyzed selective coupling reaction of 2,3-butadiene, aldimine,
9
and 10); similarly, 2-hydroxy-1-oxacyclohexane-p-anisidine
alkyne, and Me2Zn.

3984
M. Kimura et al. / Tetrahedron Letters 50 (2009) 3982–3984
2. (a) Ziegler, K.; Wilms, H. Justus Liebigs Ann. Chem. 1950, 567, 1; (b) Jolly, P. W.;
Jonas, K.; Krüger, C.; Tsay, Y.-H. J. Organomet. Chem. 1971, 33, 109; (c) Benn, R.;
Büssemeier, B.; Holle, S.; Jolly, P. W.; Mynott, R.; Tkatchenko, I.; Wilke, G. J.
Organomet. Chem. 1985, 279, 63; (d) Heimbach, P.; Kluth, J.; Schenkluhn, H.;
Weimann, B. Angew. Chem., Int. Ed. 1980, 19, 569.
3. (a) Baker, R. Chem. Rev. 1973, 73, 487; (b) Akutagawa, S. Bull. Chem. Soc. Jpn.
1976, 49, 3646; (c) Baker, R.; Crimmin, M. J. J. Chem. Soc., Perkin Trans. 1 1979,
1264; (d) Wilke, G. Angew. Chem., Int. Ed. 1988, 27, 185.
shown in Scheme 2. Aromatic amine-imines would react with
mono butadiene-Ni(0) species I, in the presence of dimethylzinc,
to form azanickelacyclo intermediate III providing dienylamine 1
by virtue of the insertion of alkyne. On the other hand, for less
reactive aliphatic amine-imines, the potential of I to undergo
oxidative cyclization might be insufficient to lead to III.7 Thus, a
small equilibrium concentration and the less populated bis-butadi-
ene-nickel(0) complex IV are assumed to display higher reactivity
than I owing to its greater polarizability, and would be followed by
cis-insertion of an alkyne at the terminal carbon of the allylnickel
moiety giving rise to trienylamine 2 through azanickelacycle
intermediate VII.8 The reaction feature of these multi-component
coupling reactions is consistent with the insertion of alkynes
4. Kimura, M.; Kojima, K.; Tatsuyama, Y.; Tamaru, Y. J. Am. Chem. Soc. 2006, 128,
6332.
5. See Supplementary data for details.
6. (a) Kimura, M.; Miyachi, A.; Kojima, K.; Tanaka, S.; Tamaru, Y. J. Am. Chem. Soc.
2004, 126, 14360; (b) Shimizu, M.; Kimura, M.; Watanabe, T.; Tamaru, Y. Org.
Lett. 2005, 7, 637; (c) Kojima, K.; Kimura, M.; Tamaru, Y. Chem. Commun. 2005,
4717; (d) Kimura, M.; Mori, M.; Mukai, N.; Kojima, K.; Tamaru, Y. Chem.
Commun. 2006, 2813; (e) Kojima, K.; Kimura, M.; Ueda, S.; Tamaru, Y.
Tetrahedron 2006, 62, 7512; (f) Kimura, M.; Tatsuyama, Y.; Kojima, K.;
Tamaru, Y. Org. Lett. 2007, 9, 1871.
7. (a) Kimura, M.; Matsuo, S.; Shibata, K.; Tamaru, Y. Angew. Chem., Int. Ed. 1999,
38, 3386; (b) Kimura, M.; Ezoe, A.; Mori, M.; Tamaru, Y. J. Am. Chem. Soc. 2005,
127, 201.
toward a
p-allylnickel(II) complex to form 1,4-pentadienyl nickel
intermediate.9 In the presence of PPh3, the butadiene would
quickly dimerize to give more nucleophilic bis-p-allylnickel
species VI,10 which would readily participate in the reaction with
aldimines to provide trienylamine 2 via insertion of an alkyne
involving a similar allylnickel intermediate VII, irrespective of
the nature of the primary amines.
8. Under similar catalytic system, exposure of same amount of p-anisidine
(0.5 mmol) and benzylamine (0.5 mmol) to PhCHO (1 mmol) provided
a
mixture of dienylamine 1a (86%) and trienylamine 2a (76%) (Eq 1).
Dienylamine 1a was successfully formed from p-anisidine, whereas
trienylamine 2a was produced by benzylamine. This result implies the
reaction feature depends on the electrophilicity of aldimine generated from
aromatic amine or aliphatic amine as shown in Scheme 2. It seems to rule out
the alternative reaction mechanism that amine or the corresponding aldimine
acts as a ligand to enhance the nucleophilicity of allylnickel species.
In summary, we have developed
a Ni-catalyzed multi-
component coupling reaction with alkyne, aldimines, and dim-
ethylzinc to afford (3E,7E,10Z)-dodecatrienylamine in excellent
yields via g1 3-allylnickel species, involving the dimerization
,g
Et
Et
PMPNH2
BnNH2
PhCHO
of butadiene induced by phosphine ligands. The applicability
and scope of this method for the asymmetric syntheses of terp-
enes and physiologically active molecules are currently under
investigations.
(0.5 mmol)
(0.5 mmol)
(4 mmol)
Et
(1 mmol)
(4 mmol)
Ni(acac)2
(0.1 mmol)
Et
Et
Ph
Et
Ph
Me2Zn
(2.4 mmol)
r.t., 20 h
2
Me
NHPMP
Me
NHBn
Acknowledgment
1a (86%)
2a (76%)
We thank financial support from the Ministry of Education, Cul-
ture, Sports, Science, and Technology, of the Japanese Government.
9. (a) Jolly, P. W.. In Comprehensive Organometallic Chemistry; Wilkinson, G., Stone,
F. G. A., Abel, E. W., Eds.; Pergamon Press: Oxford, 1982; Vol. 8, (b) Billington, D.
C.. In Comprehensive Organic Synthesis; Trost, B. M., Fleming, I., Eds.; Pergamon
Press: Oxford, 1991; Vol. 2, p 423; (c) Chiusoli, G. P. Acc. Chem. Res. 1973, 6, 422;
(d) Casser, L.; Chiusoli, G. P.; Guerrieri, F. Synthesis 1973, 509; (e) Llebaria, A.;
Moreto, J. J. Organomet. Chem. 1993, 452, 1; (f) Ikeda, S.; Cui, D.-M.; Sato, Y. J.
Org. Chem. 1994, 59, 6877; (g) Cui, D.-M.; Tsuzuki, T.; Miyake, T.; Ikeda, S.; Sato,
Y. Tetrahedron 1998, 54, 1063.
Supplementary data
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.tetlet.2009.04.086.
10. G. Wilke et al. have been established that a Ni(0) complex containing two
molecules of butadiene and PPh3 readily undergoes intramolecular
rearrangement to give bis(
The Organic Chemistry of Nickel; Academic Press: New York, 1974; Vols. I and II,
Ni-catalyzed nucleophilic allylation of carbon monoxide via bis- -allylnickel in
the presence of PPh3 ligand has been reported: (b) Takimoto, M.; Mori, M. J. Am.
Chem. Soc. 2002, 124, 10008; (c) Takimoto, M.; Nakamura, Y.; Kimura, K.; Mori,
M. J. Am. Chem. Soc. 2004, 126, 5956; (d) Takimoto, M.; Kajima, Y.; Sato, Y.;
Mori, M. J. Org. Chem. 2005, 70, 8605.
p-allyl)nickel species: (a) Jolly, P. W.; Wilke, G.. In
References and notes
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Weinheim, 2005.