Evidence for a NiI active species in the catalytic cross-coupling of alkyl electrophiles

Article abstract of DOI:10.1021/ja0483903

Addition of terpyridine to (TMEDA)Ni(CH₃)₂ results in the high-yield formation of (terpyridyl)NiMe (3). This Ni^I organometallic complex was found to be capable of transferring its methyl group to iodocyclohexane to produce methylcyclohexane in high yield. Compound 3 can also serve as an initiator for the catalytic cross-coupling of alkyl electrophiles performed under Negishi-like conditions. Copyright

Full text of DOI:10.1021/ja0483903

Published on Web 06/15/2004
Evidence for a NiI Active Species in the Catalytic Cross-Coupling of Alkyl
Electrophiles
Thomas J. Anderson, Gavin D. Jones, and David A. Vicic*
Department of Chemistry and Biochemistry, UniVersity of Arkansas, FayetteVille, Arkansas 72701
Received March 21, 2004; E-mail: dvicic@uark.edu
The cross-coupling reaction between an organometallic reagent
and an organic halide is one of the most versatile methods for
forming a new carbon-carbon bond. The majority of catalytic cross-
couplings involve some type of a C(sp2)-functionalized partner, and
there are much fewer reports on methods to couple two C(sp3)
partners to form a new alkyl-alkyl bond. However, in recent years,
advances in nickel and palladium chemistry have made possible
the catalytic cross-coupling of simple alkyl electrophiles with simple
alkyl nucleophiles, even using substrates that possess normally
reactive â-hydrogens.1-10 To expand the scope of these current
catalysts to include more sophisticated transformations with alkyl
electrophiles, more fundamental information is needed concerning
the nature of the catalytically active species so that rational
modifications to the catalysts can be made to suit a particular need.
We have been actively trying to develop synthetic methods to
prepare nickel dialkyl complexes in order to determine what factors
favor reductive elimination of saturated alkanes over the competing
â-hydride elimination pathways. While working with polypyridine-
based ligands, an interesting organometallic transformation was
uncovered that sheds new light on the mechanism of a certain class
of alkyl cross-coupling reactions. Reaction of bipyridine with
(TMEDA)Ni(CH3)2 (1, TMEDA ) N,N,N′,N′-tetramethylethylene-
diamine) is well-known to provide the nickel dimethyl complex 2
(eq 1).11 It was found, however, that reaction of 1 with terpyridine
did not provide the related dimethyl complex, but instead led to
the high-yield formation of the monomethyl complex 3 (eq 2). This
paramagnetic metal complex is a rare example of an isolable NiI
organometallic species that is stable at room temperature. Magnetic
susceptibility (µeff ) 1.64 µB in THF) determination by the Evans
NMR method12,13 confirms a product having one unpaired d-
electron. It was also found that 3 exhibits two quasi-reversible waves
in the cyclic voltammogram at -1.47 and -0.92 V vs Ag/Ag+ in
THF solution.
Figure 1. Ball and stick diagram of stacked 3. Hydrogen atoms on the tpy
ligand are omitted for clarity.
the two nickel complexes and the ligand-induced flattening of the
Ni(I) centers.15 The nickel-carbon bond lengths averaged to 1.95-
(13) Å, and a short nickel-nickel contact of 3.18(12) Å was also
observed.
Presumably the formation of 3 arises from a Ni-C bond
homolysis reaction16,17 resulting from distortion of a NiII dialkyl
species from square planarity. In the context of alkane cross-
coupling reactions, the failure of the dimethyl nickel complex to
eliminate a full equiValent of ethane upon addition of terpyridine
ligand suggests that NiII dialkyl intermediates may not be Viable
in the catalytic cross-coupling of saturated alkyl electrophiles using
similar ligands. To probe this possibility, a number of reactions
were performed using alkyl halides as electrophilic substrates in
both stoichiometric and catalytic cross-coupling reactions.
Reaction of complex 3 with 1 equiv of cyclohexyl iodide at room
temperature for 24 h in C6D6 solution indeed showed that transfer
of the metal-bound methyl group to alkyl halides could occur (eq
3). The reaction was monitored by NMR spectroscopy (referenced
to an internal standard), and the yield of methylcyclohexane
1
produced was found to be 79%. Analysis of the volatiles by H
NMR spectroscopy also confirmed that the major product of the
reaction was methylcyclohexane, with no significant amount of
olefinic products resulting from â-hydride elimination reactions.
The inorganic product of the reaction was characterized by
elemental analysis, which was consistent with the mono-iodo NiI
complex 4a. The stoichiometric reaction described in eq 3 is thus
further evidence against a Ni0/NiII redox cycle, as no dispropor-
tionation products were produced during alkyl transfer.
The results described in eq 4 suggest that NiII alkyl halide
complexes derived from the terpyridyl ligand were unstable, similar
to the dimethyl counterparts. Reaction of Ni(COD)2 with 1 equiv
of tpy-based ligand and 1 equiv of alkyl iodide did not lead to any
stable oxidative addition products, but rather led to isolable NiI
iodide complexes. The more soluble 4b has even been structurally
characterized (see Supporting Information).
Complex 3 was found to crystallize as extremely small violet
plates that only weakly diffracted X-rays and afforded an ill-refined
data set (see Supporting Information). A connectivity structure could
be obtained, however, and a structural diagram of 3 is shown in
Figure 1. Of particular note is the “head-to-head” packing14 between
Experiments were also performed to see if a NiI alkyl complex
such as 3 could be a viable precursor in cross-coupling catalysis.
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10.1021/ja0483903 CCC: $27.50 © 2004 American Chemical Society

C O M M U N I C A T I O N S
Scheme 1. Possible Mechanism for the Cross-Coupling of
Table 1. Catalytic Alkyl Cross-Coupling Reactions
Saturated Alkyl Electrophiles Mediated by 3
entry
alkyl halide
hexyl-Br
Ph(CH2)3Br
Ph(CH2)3I
iodocyclohexane
iodocyclohexane
product
undecane
Ph(CH2)7CH3
Ph(CH2)7CH3
pentylcyclohexane
pentylcyclohexane
yield (%)a
1
2
3
15
13
60
64
65
4
5b
a Yields based on GC relative to a calibrated internal standard. b Catalyst
employed was Ni(COD)2 and tpy (both 5 mol %).
the reduction of alkyl halides by odd-electron rhodium complexes.19
To our knowledge, this is the first time a NiI species has been
proposed as the catalytically active species in the cross-coupling
of saturated alkyl groups, and these results build upon the seminal
work by Espenson and Kochi, who also observed electron-transfer
reactions between organic halides and nickel complexes.20,21 The
results presented here may also be relevant to the cross-coupling
chemistry involving other ligands such as those derived from
pybox,9 which are also tricoordinating in nature. A survey of new
ligands which may be able to support a similar odd-electron redox
shuttle and provide higher yields for catalytic cross-coupling of
alkanes is currently being undertaken.
The results of this study are provided in Table 1, and show that, in
the presence of a transmetallating agent such as alkylzinc halides,
moderate yield formation of cross-coupled alkane could be achieved
without any overwhelming formation of â-hydride elimination
products. Of note is the greater efficiency of the cross-coupling
reaction using alkyl iodides over alkyl bromides. High yields of a
product containing a relatively bulky tertiary C(sp3) center could
even be achieved using secondary alkyl halides such as iodocy-
clohexane as the electrophile. Use of the commercially available
starting materials Ni(COD)2 and tpy yielded results (entry 4 vs 5)
similar to those seen with 3. The minor products in the catalysis of
alkyl iodides suggest the presence of a radical pathway, as Ph-
(CH2)6Ph and dicyclohexyl were detected for entries 3 and 4,
respectively. Additionally, reaction of 3 with the radical clock iodo-
methylcyclopropane afforded substantial formation of olefinic
Acknowledgment. D.A.V. thanks the University of Arkansas,
the Arkansas Biosciences Institute, and NIH (RR-15569) for support
of this work.
Supporting Information Available: General methods and X-ray
data for all relevant compounds (PDF, CIF). This material is available
free of charge via the Internet at http://pubs.acs.org.
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1
products as detected by H NMR spectroscopy.
In light of the fact that both the NiII alkyl halide and dialkyl
complexes were found to be unstable with respect to their NiI
decomposition products, and the fact that 3 can both transfer its
methyl group to alkyl halides to form a NiI halide complex and to
serve as an initiator for catalytic alkyl cross-coupling, we speculate
that a radical mechanism of the type shown in Scheme 1 may be
operative under catalytic conditions. There are two noteworthy
features of the proposed mechanism which we find attractive. First,
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potential of 3 is close to that of samarium diiodide, which is a
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