Grignard reagent mediated reaction of Cp2Zr(II)-ethylene complex with imines

Article abstract of DOI:10.1039/b007456j

Imines which do not react with Grignard reagents reacted with EtMgBr in the presence of a catalytic amount of Cp₂ZrCl₂ to give ethylated products in excellent yields; the stoichiometric reaction of the imines and the zirconocene-ethy

Full text of DOI:10.1039/b007456j

Grignard reagent mediated reaction of Cp2Zr(II)–ethylene complex with
imines†
Tamotsu Takahashi,* Yuanhong Liu, Chanjuan Xi and Shouquan Huo
Catalysis Research Center and Graduate School of Pharmaceutical Sciences, Hokkaido University; and CREST,
Science and Technology Corporation (JST), Sapporo 060-0811, Japan. E-mail: tamotsu@cat.hokudai.ac.jp
Received (in Cambridge, UK) 13th September 2000, Accepted 2nd November 2000
First published as an Advance Article on the web 11th December 2000
Imines which do not react with Grignard reagents reacted
with EtMgBr in the presence of a catalytic amount of
Cp2ZrCl2 to give ethylated products in excellent yields; the
stoichiometric reaction of the imines and the zirconocene–
ethylene complex did not give the ethylated product,
whereas addition of MeMgBr or BuMgCl to the mixture
afforded the ethylated product after hydrolysis.
the coupling product (only 7% of 4c) after hydrolysis. It puzzled
us, however, that when an additional amount of EtMgBr (1 eq.)
was added to the reaction mixture, the desired product 4c was
obtained in 64% yield. Moreover, addition of 4 eq. of EtMgBr
to the mixture gave an excellent yield of 4c (93%) [eqn. (2)].
(2)
We have found that a zircononcene–ethylene complex
Cp2Zr(CH2NCH2)
(2)1
and
its
ate
complex
[Cp2ZrEt(CH2NCH2)]MgBr2 prepared from Cp2ZrEt2 (1) and
zirconacyclopentanes1 were involved in the zirconium-cata-
lysed reaction of olefins with EtMgBr3 which was first reported
by Dzhemilev.4 In order to extend this type of reaction we
investigated a catalytic and a stoichiometric reaction of imine
with EtMgBr in the presence of zirconocene. In this paper we
would like to report a zirconium-catalysed reaction of imine
with EtMgBr and the unusual effect of addition of Grignard
reagents on the formation of a new C–C bond in the
stoichiometric reaction of imines with the zirconocene–ethyl-
ene complex.
Imines 3a–d, easily prepared from the corresponding alde-
hydes and amines, do not react with EtMgBr in THF at even
50 °C to give addition products. When 20 mol% Cp2ZrCl2 was
added to the mixture of the imines and EtMgBr in THF, the
reaction proceeded smoothly at rt to produce substituted amine
derivatives 4 in excellent yields after hydrolysis. The results are
shown in Table 1. At least 3 eq. of EtMgBr was needed to finish
the reaction, and the use of 10 mol% of Cp2ZrCl2 decreased the
yield of products 4 [eqn. (1)].
It is noteworthy that the use of different Grignard reagents
also afforded only the same ethylated product 4c, with improved
yields as shown in Table 2.
It is interesting that the reaction of 3a with 2 gave the
ethylated product 4a in 57% yield after hydrolysis. This
indicates that the azazirconacylopentane 5a was formed in the
case of 3a. A similar effect of addition of a Grignard reagent
was also observed. In fact, addition of 1 eq. of MeMgBr to the
mixture of 3a and 2 afforded 4a in 75% yield after hydrolysis.
When 4 eq. of EtMgBr was added to the mixture of 3a and 2, the
product 4a was formed in 97% yield after hydrolysis.
These results suggest that there is an equilibrium between
azazirconacyclopentane 5 and imine 3 and that the position of
the equilibrium lies to the left under the conditions used here. If
an irreversible step such as ring-opening and b-hydrogen
abstraction is involved in the reaction, in other words, when
additional Grignard reagents are added, the reaction goes to the
right as expected to give the ethylated products. Deuterolysis
instead of hydrolysis of the reaction mixture after addition of 4
eq. of MeMgBr to a mixture of 3c and 2 afforded deuterated
product 4c DCH2CH2(t-Bu)CHNDCH2Ph (65% D) [eqn. (3)].
This strongly suggests that the complex 6c is the reaction
product of MeMgBr with a mixture of 3c and 2. When 6c was
treated with 2 eq. of CuCl for 6 h at rt, ethylated imine
tBu(Et)CHNNCHPh (7) was obtained in 48% yield after
hydrolysis.
(1)
We investigated the stoichiometric reactions of imines with
the zirconocene–ethylene complex. And quite surprisingly, we
found that the stoichiometric reaction of 3c with 2 did not give
We also carried out the reactions of a mixture of Cp2ZrEt2
and imine 3a with various electrophiles5,6 and the results are
summarized in Table 3.
Table 1 Zirconium-catalysed addition of EtMgBr to iminesa
Table 2 The effect of addition of Grignard reagents under stoichiometric
conditions
Grignard
reagents
Yield of 4c (%)a
1 eq. of RMgXb
Yield of 4c (%)a
4 eq. of RMgXb
MeMgBr
EtMgBr
n-BuMgCl
sec-BuMgCl
t-BuMgCl
40
64
38
22
7
70a
93
64
96
15
† Electronic supplementary information (ESI) available: reaction proce-
dures and NMR data. See http://www.rsc.org/suppdata/cc/b0/b007456j/
a GC yields of ethylated product 4c. b Amount of addition of RMgX.
DOI: 10.1039/b007456j
Chem. Commun., 2001, 31–32
31
This journal is © The Royal Society of Chemistry 2001

Table 3 Reactions of a mixture of Cp2ZrEt2 and 3a with electrophilesa
zirconocene–ethylene complex 2 from Cp2ZrCl2 and two eq. of
EtMgBr; (2) coupling with imine 3 to form azazirconacyclo-
pentane 5; (3) ring-opening reaction by EtMgBr; and (4) b-
elimination to regenerate zirconocene–ethylene complex 2 and
to release metalated amine 9.7 The ring-opening reaction
occurred exclusively on the Zr–N bond, because no deuterium
incorporation was found in the Et group of products 4 in the
catalytic reaction when the reaction mixture was quenched with
MeOD. As expected, this catalytic reaction did not proceed with
MeMgBr. When higher magnesium alkyls, namely, n-PrMgBr
and n-BuMgCl, were used, the formation of addition products
was not observed from the reaction with imine 3a, indicating no
coupling reaction between the zirconocene-substituted olefin
complex and the imine.
(3)
We have developed several zirconium-catalyzed reactions, in
which a zirconocene–olefin complex acts as the key catalytic
species. In the light of our previous work, a plausible
mechanism for this catalytic addition of EtMgBr to imines is
shown in Scheme 1, which involves: (1) generation of
Notes and references
1 T. Takahashi, T. Seki, Y. Nitto and M. Saburi, 37th Symposium on
Organometallic Chemistry, Japan, Osaka, 1990, 172; T. Takahashi, T.
Seki, M. Saburi and E. Negishi, XIVth International Conference on
Organometallic Chemistry, Detroit, MI, 1990, B17; T. Takahashi, T.
Seki, Y. Nitto, M. Saburi, C. J. Rousset and E. Negishi, J. Am. Chem.
Soc., 1991, 113, 6266.
2 T. Takahashi, N. Suzuki, M. Hasegawa, Y. Nitto, M. Kageyama and M.
Saburi, 38th Symposium on Organometallic Chemistry, Japan, Kyoto,
1991, 232. See also T. Takahashi, N. Suzuki, M. Kageyama, Y. Nitto, M.
Saburi and E. Negishi, Chem. Lett., 1991, 1579. For the structure of
zirconium–olefin ate complex, see H. Lee, T. Hascall, P. J. Desrosiers
and G. Parkin, J. Am. Chem. Soc., 1998, 120, 5830.
3 For related catalytic reactions involving zirconocene, see also K. S.
Knight and R. M. Waymouth, J. Am. Chem. Soc., 1991, 113, 6268; A. H.
Hoveyda and Z. Xu, J. Am. Chem. Soc., 1991, 113, 5079; D. P. Lewis,
P. M. Muller and R. J. Whitby, Tetrahedron Lett., 1991, 32, 6797.
4 U. M. Dzhemilev, O. S. Vostrikova and R. M. Sultanov, Izv. Akad. Nauk
SSSR, Ser. Khim., 1983, 218; U. M. Dzhemilev and O. S. Vostrikova,
J. Organomet. Chem., 1985, 285, 43.
5 K. Kasai, M. Kotora, N. Suzuki and T. Takahashi, J. Chem. Soc., Chem.
Commun., 1995, 109.
6 T. Takahashi, M. Kotora and Z. Xi, J. Chem. Soc., Chem. Commun.,
1995, 1503.
Scheme 1
7 Y. Zhang, J. Jiang and Y. Chen, Tetrahedron Lett., 1987, 28, 3815.
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Chem. Commun., 2001, 31–32