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coupling of (iodomethyl)cyclopropane with 1.1 equivalents of
PhMgBr catalyzed by 5 mol% 2 resulted in a 79% yield of 4-
phenyl-1-butene, the product resulting from rearrangement of
the (cyclopropyl)methyl radical (Table 1, entry 11). This
result suggests that a radical intermediate results from
reduction of the alkyl halide, as shown in the proposed
mechanism of Scheme 2. No unrearranged product was
observed, and no coupling products of any kind were
observed in the absence of 2.
The last step in the catalytic cycle, the reduction of 1 by 4,
to form 2 and 3, was demonstrated by addition of one
equivalent of 1 to the NnBu4+ salt of 4 (4a)[7a] in THF, which
resulted in an immediate color change from dark green to
dark gray/black. As a consequence of extensive paramagnetic
broadening of signals corresponding to the paramagnetic
species 1, 2, and 4 in [D8]THF solutions, it was not possible to
accurately measure the equilibrium constant by 1H NMR
spectroscopy. However, all four species 1–4 were detected and
the NnBu4+ salt of 3 was isolated from the other Ni-containing
species in 29% yield (1H NMR spectroscopy in [D8]THF
versus an internal standard; see the Supporting Information),
consistent with the equilibrium mixture predicted by the
observed redox potentials.
observed to participate in catalytically competent reaction
steps. These results lend substantial support to proposed
mechanisms for nickel-mediated cross-coupling reactions that
feature one-electron redox events for the nickel species,[4d]
and especially corroborate the bimetallic oxidative addition
mechanism (featuring comparable but inner-sphere redox
events) suggested by Breitenfeld, Hu et al.[6a] This study also
provides experimental mechanistic evidence for the roles of
nickel(I) and nickel(III) intermediates in this catalysis. Of
particular interest is the demonstration of a function for the
nickel(III)–alkyl complex (1), especially given previous spec-
ulation about such species in cross-coupling reactions. In
catalysis initiated by the bis(amido) complex 2, the neutral
nickel(III)–alkyl species appear to participate only in redox
reactions, and not directly in any of the key bond-forming or
bond-breaking steps. This nickel(III) species is formed as
À
a by-product of the C X bond activation, and plays a key role
in oxidizing nickel(I) in the catalytic mixture back to
nickel(II). The latter redox process not only provides the
nickel(II) species required for the coupling steps, but removes
nickel(I), which is active for the nonproductive homocoupling
of the halide substrate.
A somewhat more speculative aspect of this reaction
mechanism concerns detail regarding the reaction of the
radical species with the anionic nickel(II) complex. This step
may involve attack of the radical on the nickel center, to
generate the nickel(III) complex 5’ (Scheme 2), from which
the product is formed by reductive elimination. Alternatively,
the organic radical might directly attack the alkyl or aryl
ligand of 3’ to give 4 and the coupled product. The pathway
involving 5’ is currently assumed, given spectroscopic obser-
vation of related intermediates by Vicic and co-workers[11] as
well as the observation of reductive elimination from NiIII–
alkyl species by the research groups of Kochi[12] and Mirica.[7d]
Also, the two-electron NiI/NiIII reductive elimination from 5’
seems reasonable given that the reverse process, a two-
electron NiI/NiIII oxidative addition, has been experimentally
demonstrated in the independent synthesis of 1 (Scheme 1).
This catalytic system is noteworthy as one of the few
examples of an intact two-coordinate metal complex that
competently catalyzes an organic transformation. Previously,
[Fe{N(SiMe3)2}2] has been described as an active precatalyst
for the hydrosilylation of organic carbonyl groups,[13] and 2
catalyzes the hydrosilylation of alkenes.[8] The catalytic
mechanism of Scheme 2 is unusual in several respects that
appear to leverage the very low coordination number of 2.
Direct alkylation of 2 by the Grignard reagent without
halogen displacement exploits the inherent electron defi-
ciency of two-coordination to stabilize a strongly reducing,
anionic intermediate (3). The various redox processes of the
mechanism proceed without ligand exchange, which is
facilitated by the ability of this stable two-coordinate frame-
work to support multiple oxidation states. These results
suggest that two-coordinate complexes are a promising new
class of potential catalysts whose unique chemical properties
enable novel metal-mediated transformations.
This redox equilibrium step plays an important role in
determining the efficiency of catalysis. This is indicated, for
example, by stoichiometric reactions of 3 with 1-iodonaph-
thalene. This reaction produces a low yield of cross-coupled
product (13%); however, addition of one equivalent of
MeMgBr to the reaction mixture led to a substantially better
yield (77%). This is attributed to the effect of the Grignard
reagent on the redox equilibrium step of the cycle (Scheme 2).
Apparently, the rapid reaction of MeMgBr with 2 to form 3
drives the redox equilibrium to the right (to 2 and 3 and,
ultimately, to only 3). Consistently, the addition of one
equivalent of MeMgBr to an equilibrium mixture of 1–4
(produced by the reaction of 4a with 1) resulted in an
immediate color change from dark gray/black to the charac-
teristic blue color of 3. Analysis of the resulting products by
1H NMR spectroscopy indicated that all Ni-containing species
had been converted into 3. By shifting the equilibrium in this
way, the Grignard reagent ensures efficient recycling of 1 and
4 to 3, such that every radical in the cycle has a coupling
partner. In the absence of the Grignard reagent, 3 is
consumed in the reduction of the aryl halide, and because
the redox reaction produces an equilibrium mixture, the Ni
by-products are not efficiently recycled. Additionally, 4 was
found to react with aryl halides to produce undesired
homocoupling products: the reaction of 4 with 1-iodonaph-
thalene in THF over 1 h produced 1,1’-binaphthalene in 80%
yield. This unproductive process is also prevented by the
effect of the Grignard reagent on the equilibrium. Notably,
this reaction of 4 with aryl halide is substantially slower than
the oxidation of 4 by 1, a result predicted by Breitenfeld, Hu
et al. for an analogous nickel(I) intermediate in their sys-
tem.[6a]
The stoichiometric reactions described above provide
compelling support for the proposed mechanism of Scheme 2.
Significantly, this mechanism involves several intermediates
(1–4) that have been isolated, completely characterized, and
À
In conclusion, a well-defined catalytic system for the C C
coupling of aryl halides with Grignard reagents catalyzed by
a two-coordinate nickel complex has been identified and
4
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Angew. Chem. Int. Ed. 2014, 53, 1 – 6
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