Nickel-catalyzed cross-coupling reaction of aryl halides with allylic zirconium reagents generated in situ from zirconocene(alkene) complexes

Article abstract of DOI:10.1055/s-2005-871542

Allylic zirconium reagents that are generated in situ via allylic C-H bond activation of alkenes proved to serve as metal counterparts in nickel-catalyzed cross-coupling reactions. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2005-871542

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1787
Nickel-Catalyzed Cross-Coupling Reaction of Aryl Halides with Allylic
Zirconium Reagents Generated in situ from Zirconocene(alkene) Complexes
????? oji Hirano, Kazuya Fujita, Hideki Yorimitsu, Koichiro Oshima*
Department of Material Chemistry, Graduate School of Engineering, Kyoto University, Kyoto-daigaku Katsura, Nishikyo-ku,
Kyoto 615-8510, Japan
E-mail: oshima@orgrxn.mbox.media.kyoto-u.ac.jp
Received 1 April 2005
zirconocene(propene) was formed. Diisopropyl ketone
Abstract: Allylic zirconium reagents that are generated in situ via
(3.0 mmol) was added to the solution of zirconocene(pro-
pene), which resulted in reduction of the ketone and af-
allylic C–H bond activation of alkenes proved to serve as metal
counterparts in nickel-catalyzed cross-coupling reactions.
forded allylzirconium 2a. The cross-coupling reactions of
Key words: zirconium, cross-coupling, nickel, C–H bond activa-
3-iodoanisole (1.0 mmol) with 2a under several sets of
tion, allylic metal
conditions were surveyed (Table 1). Use of palladium cat-
alysts suffered from lower conversion as well as the for-
mation of biaryl 6 (Table 1, entries 1–3). A nickel catalyst
Allylic metals are among the most important reagents in
NiBr2(PPh3)2 proved to be the best (Table 1, entry 4). The
organic synthesis.1 Thus, the preparation of allylic metals
nickel catalyst effected the cross-coupling reaction even
has been well investigated. Recently, we developed zir-
at 25 °C, which suppressed the isomerization of 4 into 5
conium-mediated allylic C–H bond activation of the co-
(Table 1, entry 5).
ordinating alkenes of zirconocene(alkene) complexes to
form 1 (Scheme 1).2 After selective removal of the
hydride moiety by using diisopropyl ketone, allylic zirco-
nium reagents 2 were applied to carbonyl allylation3 and
radical allylation.4 Here, we report their application in
cross-coupling reactions.5 Such reactions with allylic
zirconium reagents are quite rare.6,7
For the crotylation reaction, tri(2-furyl)phosphine proved
to be the best ligand (Table 2). A higher temperature facil-
itated the reaction without troublesome isomerization into
styrene derivatives. Good branched/linear selectivity was
observed in the crotyl-coupling reaction; not only aryl io-
dides but also aryl bromide and chloride underwent the
cross-coupling reaction.
H
Cp2Zr
Cp2Zr
Cp2ZrCl2
+
O
Cp2Zr
OCHiPr2
Cp2ZrCl2 (2.0 mmol)
Mg (3.0 mmol)
1-alkene (4.0 mmol)
iPr
iPr Cp2Zr
1
R
R
R
R
MgBr
THF
0 °C, 3 h
(3.0 mmol)
25 ºC
OH
2
R
PhCHO
Ph
2
ref.3
R
R
O
O
5 mol% NiCl2
OCHiPr2
1-Np
R
10 mol% P(2-furyl)3
I
O
+
iPr
iPr
Cp2Zr
1-Np
5 O
R
3b
R'
(1.0 mmol)
THF, reflux, 3 h
9
10
cat. Et3B
R'
2
ref.4
Ar
R
O
5 O
Ph
tBu
Ar–X
cross-coupling
9a, 50%; 10a, 12%
9b, 59%; 10b, 18%
R
This work
Scheme 2
Scheme 13,4
Allylic Zirconium reagents could be alternatively pre-
pared directly from alkene (Scheme 2). Cp2ZrCl2 (0.58 g,
2.0 mmol) was treated with magnesium metal (73 mg, 3.0
mmol, activated with 26 mg of 1,2-dibromoethane) in
THF (1 mL) at 25 °C for 15 min. After the solution was
cooled to 0 °C, a solution of 1-alkene (4.0 mmol) in THF
(4 mL) was added. The reaction mixture was stirred for 3
h at 0 °C to form the zirconocene(1-alkene) complex. The
mixture was transferred to another reaction flask under ar-
gon to remove remaining metallic magnesium. Diisopro-
pyl ketone (0.43 mL, 3.0 mmol) in THF (5 mL) was added
to the complex and the whole mixture was stirred for 3 h
As our first attempt, we examined the preparation and use
of unsubstituted allylzirconium reagent 2a (R = H) for
cross-coupling reactions. A THF solution of C3H7MgBr
(4.0 mmol) was added to Cp2ZrCl2 (2.0 mmol) also in
THF (10 mL). The addition was carried out at 0 °C and
after stirring for 30 minutes at the same temperature,
SYNLETT 2005, No. 11, pp 1787–1788
0
7
.0
7
.2
0
0
5
Advanced online publication: 14.06.2005
DOI: 10.1055/s-2005-871542; Art ID: Y00705ST
© Georg Thieme Verlag Stuttgart · New York

1788
K. Hirano et al.
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Table 1 Palladium- and Nickel-Catalyzed Allylation of 3-Iodoanisole
O
OCHiPr2
Cp2ZrCl2
iPr
iPr Cp2Zr
Cp2Zr
+
THF
nC3H7MgBr
2a
Ar = 3-methoxyphenyl
Ar
5 mol% catalyst, 2a
Ar
Ar
Ar
+
+
Ar
I
THF, temp., 3 h
3a
4
5
6
Entry
Catalyst
Temperature
65 °C
4
5
6
3a
5%
a
a
1
2
3
4
5
Pd(dba)/PPh3
Pd(dba)/PPh3
PdCl2(PPh3)2
NiBr2(PPh3)2
NiBr2(PPh3)2
61%
–
2%
–
7%
–
25 °C
96%
21%
–
65 °C
46%
76%
84%
–
7%
–
65 °C
9%
–
25 °C
–
–
a Pd2(dba)3·CHCl3 (2.5 mol%), PPh3 (10 mol%).
Table 2 Cross-Coupling of Aryl Halides with Crotylzirconium
Reagent
References
(1) Yamamoto, Y.; Asao, N. Chem. Rev. 1993, 93, 2207.
(2) (a) Fujita, K.; Yorimitsu, H.; Oshima, K. Chem. Rec. 2004,
4, 110. (b) Fujita, K.; Yorimitsu, H.; Shinokubo, H.;
Matsubara, S.; Oshima, K. J. Am. Chem. Soc. 2001, 123,
12115. (c) Fujita, K.; Shinokubo, H.; Oshima, K. Angew.
Chem. Int. Ed. 2003, 42, 2550. (d) Fujita, K.; Yorimitsu, H.;
Shinokubo, H.; Oshima, K. J. Am. Chem. Soc. 2004, 126,
6776.
O
OCHiPr2
Cp2ZrCl2
iPr
iPr Cp2Zr
Cp2Zr
+
THF
nC4H9MgBr
2b
5 mol% NiCl2,
10 mol% P(2-furyl)3, 2b
Ar
Ar
Ar
+
X
(3) Fujita, K.; Yorimitsu, H.; Shinokubo, H.; Oshima, K. J. Org.
Chem. 2004, 69, 3302.
THF, reflux, 3 h
3
7
8
(4) Hirano, K.; Fujita, K.; Shinokubo, H.; Oshima, K. Org. Lett.
2004, 6, 593.
Entry ArX
7, yield
8, yield
8a, 6%
8b, 12%
8c, 10%
(5) Reviews on organozirconiums in cross-coupling reactions:
(a) Negishi, E. Dalton Trans. 2005, 827. (b) Negishi, E.;
Liu, F. In Metal-catalyzed Cross-coupling Reactions, Vol. 1;
Diederich, F.; Stang, P. J., Eds.; Wiley-VCH: Weinheim,
1998, Chap. 1. (c) Negishi, E.; Zeng, X.; Tan, Z.; Qian, M.;
Hu, Q.; Huang, Z. In Metal-catalyzed Cross-coupling
Reactions, Vol. 2; Diederich, F.; Stang, P. J., Eds.; Wiley-
VCH: Weinheim, 2004, Chap. 15.
1
2
3
3-Iodoanisole (3a)
7a, 82%
7b, 86%
1-Iodonaphthalene (3b)
3-Bromo-a,a,a-trifluorotoluene 7c, 70%
(3c)
4
1-Chloronaphthalene (3d)
7b, 56%
8b, 8%
(6) Copper-catalyzed coupling reactions: Sato, A.; Ito, H.;
Yamaguchi, Y.; Taguchi, T. Tetrahedron Lett. 2000, 41,
10239.
(7) Generation of allylic zirconium reagents from allylic ethers:
(a) Ito, H.; Taguchi, T.; Hanzawa, Y. Tetrahedron Lett.
1992, 33, 1295. (b) Sato, A.; Ito, H.; Taguchi, T. J. Org.
Chem. 2005, 71, 709; and references cited therein.
at 25 °C. 1-Iodonaphthalene (3b, 0.15 mL, 1.0 mmol) and
NiCl2(trifurylphosphine)2 (0.050 mmol prepared in situ)
were finally added, and the mixture was stirred for 3 h at
reflux. Usual workup followed by silica gel column puri-
fication afforded the corresponding cross-coupled prod-
ucts 9 and 10. The reaction conditions were so mild that
functional groups such as ether and ester moieties sur-
vived under the reaction conditions.
Acknowledgment
This work was supported by Grants-in-Aid for Scientific Research
and COE Research from the Ministry of Education, Culture, Sports,
Science, and Technology, Japan. K.F. acknowledges JSPS for
financial support.
Synlett 2005, No. 11, 1787–1788 © Thieme Stuttgart · New York