Direct observation of noninnocent reactivity of ZnBr2 with alkyl halide complexes of nickel

Article abstract of DOI:10.1021/om034380j

Nickel-catalyzed cross-coupling reactions of alkylzinc reagents with alkyl halides (Negishi couplings) are powerful tools in synthetic organic chemistry. These reactions typically provide the coupled alkane with ZnBr₂ as the final products. We report here that generated ZnBr₂ does not always act innocently but can mediate a halogen abstraction from the nickel alkyl halide complex. Such reactivity warrants consideration in developing mechanisms and catalyst design for these versatile reactions.

Full text of DOI:10.1021/om034380j

© Copyright 2004
Volume 23, Number 4, February 16, 2004
American Chemical Society
Communications
Dir ect Obser va tion of Non in n ocen t Rea ctivity of Zn Br 2
w ith Alk yl Ha lid e Com p lexes of Nick el
Thomas J . Anderson and David A. Vicic*
Department of Chemistry and Biochemistry, University of Arkansas,
Fayetteville, Arkansas 72701
Received December 17, 2003
Sch em e 1. Gen er a l Mech a n ism for Negish i
Cr oss-Cou p lin g of Alk a n es
Summary: Nickel-catalyzed cross-coupling reactions of
alkylzinc reagents with alkyl halides (Negishi couplings)
are powerful tools in synthetic organic chemistry. These
reactions typically provide the coupled alkane with
ZnBr2 as the final products. We report here that gener-
ated ZnBr2 does not always act innocently but can
mediate a halogen abstraction from the nickel alkyl
halide complex. Such reactivity warrants consideration
in developing mechanisms and catalyst design for these
versatile reactions.
Nickel-catalyzed cross-coupling reactions to make new
carbon-carbon bonds have become very powerful tools
in synthetic organic chemistry.1-4 Of particular note,
recent advances of the Negishi cross-coupling reaction
have enabled chemists to catalytically couple two sp3
carbon centers.5-9 Fu has even described catalytic
methods to prepare tertiary sp3 carbon centers with
nickel.9 Palladium is also known to effectively catalyze
C(sp3)-C(sp3) bond formations involving zinc trans-
metalation events.10 The generally accepted mechanism
of the Negishi reaction is outlined in Scheme 1. Among
the important steps of this mechanism is the activation
of an alkyl halide by low-valent nickel to form a
nickel(II) alkyl halide complex. Alkyl iodides and alkyl
bromides are the usual substrates for this oxidative
addition process. When alkyl bromides are used, the
resulting LnNi(alkyl)Br complex subsequently under-
goes transmetalation with an alkylzinc bromide reagent,
* To whom correspondence should be addressed. E-mail: dvicic@
uark.edu.
(1) Terao, J .; Watanabe, H.; Ikumi, A.; Kuniyasu, H.; Kambe, N. J .
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(10) Zhou, J .; Fu, G. C. J . Am. Chem. Soc. 2003, 125, 12527-12530.
10.1021/om034380j CCC: $27.50 © 2004 American Chemical Society
Publication on Web 01/10/2004

624 Organometallics, Vol. 23, No. 4, 2004
Communications
Sch em e 2. F or m a tion of Nick el Ben zyl Ca tion 3
fr om In d ep en d en t Rou tes
F igu r e 1. ORTEP diagram of 2. Ellipsoids are shown at
the 50% level. Hydrogen atoms are omitted for clarity.
affording a nickel(II) dialkyl complex, which reductively
eliminates the cross-coupled product and regenerates
low-valent nickel. Mass balance leaves ZnBr2 as a
coproduct.
It seemed feasible to us that ZnBr2 could also par-
ticipate in this reaction by interacting with the organo-
nickel intermediates. As future catalyst development
would need to account for any type of noninnocent
behavior of the coproducts, we set out to prepare well-
defined alkyl halide complexes of nickel so that their
interactions with ZnBr2 could be studied in detail. Con-
sidering that halogen-atom abstraction of the organo-
nickel halides by ZnBr2 was one possible reaction that
could occur, a challenge was to develop a system where
the resulting alkyl cation could be stabilized so that
spectroscopic support for its structure could be obtained.
Simple n-alkyl bromide complexes of nickel were not
targeted as model systems, as the resulting alkyl cation
complexes are known to be highly reactive and short-
lived, generally affording â-hydride elimination products
if left without a reaction partner.11,12 Therefore, benzylic
bromides were studied as viable intermediates of the
Negishi cross-coupling reaction, as nickel benzyl cations
are known to be longer lived and even isolable13,14
species. Importantly, the benzyl architecture can be
used both as an electrophile and as a nucleophile in
cross-coupling reactions, and benzyl sulfonium salts15
and benzyl zinc bromides16 have each been used suc-
cessfully in Negishi couplings with nickel.
F igu r e 2. ORTEP diagram of 3. Ellipsoids are shown at
the 50% level. Hydrogen atoms are omitted for clarity.
complex, whose structure was confirmed by X-ray
crystallography. The ORTEP diagram of 2 is provided
in Figure 1 and shows the square-planar arrangements
of the ligands around nickel. The clean synthesis of 2
allowed for its reactivity with ZnBr2 to be studied by
NMR spectroscopy.
Addition of 1 equiv of ZnBr2 to a THF-d8 solution of
The benzyl bromide complex 2 was prepared under
mild conditions by reacting the convenient Ni0 source
[(dippe)NiH]2 (1; dippe ) (i-Pr2PCH2)2) with benzyl
bromide in benzene solution at room temperature
(Scheme 2). This reaction affords an η1-benzyl bromide
1
2 led to an instant and dramatic change in the H NMR
spectrum (see the Supporting Information). The proton
on the carbon atom ortho to the ipso carbon undergoes
a large upfield shift of about 1.1 ppm, indicative of metal
interactions with the ortho carbons. Such a change in
NMR resonances can be explained by formation of an
η3-benzyl species such as 3, in which the η3-bound metal
shields the ortho hydrogens. The structure of 3 was
eventually confirmed by X-ray crystallography, and the
ORTEP diagram is provided in Figure 2.
Figure 2 clearly shows the fate of the ZnBr2 after
participation in the halogen abstraction event. Upon
halide abstraction, a nickel benzyl cation is formed along
with a stable four-coordinate ZnBr3(THF) counterion.17
(11) Leatherman, M. D.; Svejda, S. A.; J ohnson, L. K.; Brookhart,
M. J . Am. Chem. Soc. 2003, 125, 3068-3081.
(12) Svejda, S. A.; Brookhart, M. Organometallics 1999, 18, 65-74.
(13) Lee, B. Y.; Bazan, G. C.; Vela, J .; Komon, Z. J . A.; Bu, X. J .
Am. Chem. Soc. 2001, 123, 5352-5353.
(14) Ascenso, J . R.; Carrondo, M. A. A. F. d. C. T.; Dias, A. R.; Gomes,
P. T.; Piedade, M. F. M.; Romao, C. C.; Revillon, A.; Tkatchenko, I.
Polyhedron 1989, 8, 2449-2457.
(15) Srogl, J .; Allred, G. D.; Liebeskind, L. S. J . Am. Chem. Soc.
1997, 119, 12376-12377.
(16) Piber, M.; J ensen, A. E.; Rottlaender, M.; Knochel, P. Org. Lett.
1999, 1, 1323-1326.

Communications
Organometallics, Vol. 23, No. 4, 2004 625
Complex 3 can also be made directly from reaction of
(dippe)NiBr2 (4) with BzZnBr in THF solution (Scheme
2). Thus, it appears that even when ZnBr2 is produced
in situ from a transmetalation reaction, halogen atom
abstractions from nickel benzyl bromides can readily
occur.
We have also found that the halogen atom abstraction
event is not limited to dippe ligands. It was important
to establish that phosphines containing different bite
angles undergo similar reactivity, as oftentimes changes
in bite angles can lead to dramatic effects in the
catalytic activity of coupling reactions.18 (dippm)NiBr2
(5; dippm ) bis(diisopropylphosphino)methane) was
found to react similarly with BzZnBr, directly affording
the η3-benzyl cation complex 6 (eq 1). The η1-benzyl
F igu r e 3. ORTEP diagram of 7. Ellipsoids are shown at
the 50% level. Hydrogen atoms are omitted for clarity.
to future catalyst design. It may also help rationalize
some intriguing results in which additives6,17 or excess
ligands9 were found to increase the efficiency of Negishi
couplings. Moreover, Negishi noted that many of the
Pd- or Ni-catalyzed reactions of alkenyl-aluminum or
-zirconium species with alkenyl, aryl, and alkynyl
halides could only be achieved when performed in the
presence of additional ZnCl2,19 although the exact role
of ZnCl2 was not established. Further investigations of
the mechanism of the Negishi couplings are underway.
bromide complex 7 has also been prepared by the
reaction of Ni(COD)2 and BzBr in the presence of dippm
and was found to react instantly with ZnBr2 in THF-d8
solution to afford 6 in quantitative yield by NMR
spectroscopy. Both 6 and 7 have been structurally
characterized, and the ORTEP diagram for 7 is shown
in Figure 3.
The results presented here suggest that the ability
of ZnBr2 to abstract a halogen atom from nickel alkyl
halides should be considered in the developing mecha-
nisms of Negishi-like couplings and may also be relevant
Ack n ow led gm en t. D.A.V. thanks the University of
Arkansas, the Arkansas Biosciences Institute, and the
NIH (Grant No. RR-15569) for support of this work.
Su p p or tin g In for m a tion Ava ila ble: Text, tables, and
figures giving general methods and procedures, NMR spectra,
and X-ray data for all relevant compounds; crystallographic
data are also given as CIF files. This material is available free
of charge via the Internet at http://pubs.acs.org.
OM034380J
(17) Darensbourg, D. J .; Lewis, S. J .; Rodgers, J . L.; Yarbrough, J .
C. Inorg. Chem. 2003, 42, 581-589.
(18) van Leeuwen, P. W. N. M.; Kamer, P. C. J .; Reek, J . N. H.;
Dierkes, P. Chem. Rev. 2000, 100, 2741-2769.
(19) Negishi, E.-I.; Okukado, N.; King, A. O.; Van Horn, D. E.;
Spiegel, B. I. J . Am. Chem. Soc. 1978, 100, 2254-2257.