RESEARCH
ciated cost (19). By contrast, nickel is nonprecious,
relatively cheap and abundant (~90,000 times
more than Ru), and capable of triggering double-
bond migration, albeit in varying E/Z ratios and
so-far limited generality (20). This reactivity has
been linked to Ni(II)-H as active species.
ORGANIC CHEMISTRY
E-Olefins through intramolecular
radical relocation
We envisioned that a simplified mechanistic
scenario that minimizes co-reagents and inter-
mediates may increase the likelihood for E/Z
control under nonprecious Ni catalysis in double-
bond migrations. Arguably, the simplest scenario
involves the direct delivery of a hydrogen from
position 1 to 3 in the allylic framework. Given
that radicals are not subject to the Woodward–
Hoffmann orbital symmetry restrictions, we hypo-
thesized that a radical-induced 1,3-H shift could
deliver a solution to the E/Z selection challenge.
The intermediacy of high-energy free organic
radicals would need to be avoided in this con-
text, as additional challenges, such as inter-
molecular H atom transfer events for radical
termination and chain propagation, would arise,
and these scenarios are known to deliver mod-
erate selectivities (see Fig. 1A). We envisioned
instead that if the substrate were coupled to a
nonprecious metalloradical complex, such as a
low-coordinate Ni(I) (21)—e.g., via p-coordination—
the resulting metalloradical-substrate complex
might have an inherent driving force for inter-
nal reorganization.
As part of our ongoing program in odd-
oxidation-state metal reactivity, we also studied
the propensity of dimeric metal complexes in
the +1 oxidation state to generate open-shell
monomers (22). Our findings suggest that for
certain complexes of suitable ligand environment,
such as the dinuclear N-heterocyclic carbene
(NHC)–derived Ni(I) dimer 1 (Fig. 2) (23), which
is readily accessible at low cost from commer-
cially available precursors, a double bond or solvent
could function as a trigger to generate an open-
shell metal complex.
Ajoy Kapat, Theresa Sperger, Sinem Guven, Franziska Schoenebeck*
Full control over the selectivity of carbon–carbon double-bond migrations would enable
access to stereochemically defined olefins that are central to the pharmaceutical, food,
fragrance, materials, and petrochemical arenas. The vast majority of double-bond
migrations investigated over the past 60 years capitalize on precious-metal hydrides that
are frequently associated with reversible equilibria, hydrogen scrambling, incomplete E/Z
stereoselection, and/or high cost. Here, we report a fundamentally different, radical-based
approach. We showcase a nonprecious, reductant-free, and atom-economical nickel
(Ni)(I)-catalyzed intramolecular 1,3-hydrogen atom relocation to yield E-olefins within
3 hours at room temperature. Remote installations of E-olefins over extended distances
are also demonstrated.
he carbon–carbon double bond in olefins
serves as a precursor to a rich array of
transformations and is a cornerstone in
the materials, pharmaceutical, agrochemical
arenas, and food industry (1, 2). Its con-
and generates stoichiometric amounts of waste.
Metal catalysis can potentially circumvent these
drawbacks (see below) and may also unleash the
possibility for remote functionalization. As such,
metal-catalyzed alkene isomerizations have had
major societal and industrial impact, e.g., in the
large-scale production of gasoline, nylon, deter-
gents, soaps, coatings, lubricants, food, cosmetics,
rubbers, and fragrances (2).
T
struction in a selective and stereochemically
defined manner—i.e., E versus Z olefin—is of
utmost importance, as the geometry is ulti-
mately coupled to function. Although numerous
strategies to construct olefins have become es-
tablished textbook knowledge, the E/Z selectivity
is frequently incomplete or comes at the expense
of valuable functionality in these classical ap-
proaches (e.g., Wittig, Julia, Peterson olefinations
or Birch reduction). Mixtures of E and Z isomers
are difficult to separate, however. More modern
catalytic strategies commonly achieve high se-
lectivity through semihydrogenations, requiring
an atmosphere of H2 or stoichiometric amounts
of acid or other H sources (3). Olefin metathesis
catalysts were developed to selectively access
Z-olefins, whereas the E-isomer is accessible in
high selectivity only with certain halogenated
or low-functionality compounds (4, 5). Ring-
opening strategies via C–C cleavage are ele-
gant alternatives to selectively install E-olefins
(6, 7).
The past 60 years of research focused pri-
marily on two mechanisms for double-bond
transposition (11): The vast majority of trans-
formations proceed via metal hydrides. Whereas
the precious-metal hydrides deliver an external
H through closed-shell polar mechanisms (9, 11),
less-precious metal hydrides, such as Co, have
been shown to engage in reversible hydrogen
atom transfer via biradical pairs (Fig. 1A) (12, 13).
These processes make use of external H (that is
present as co-reagent). Because of the revers-
ible nature of these reactions, scrambling of
hydrogens may occur, and control of E/Z se-
lectivity is challenging. The E-selectivity is gen-
erally much higher for the precious-metal hydride
processes that proceed through 1,2-addition,
followed by b-hydride elimination (Fig. 1A) (9). The
latest advance in this area is from Skrydstrup’s
laboratory employing in situ–generated Pd-H at
elevated temperatures (14). The possibility for
hydride-free binuclear Pd-catalyzed isomeri-
zation was recently also reported (15). An al-
ternative mechanistic scenario involves the less
well-described p-allyl mechanism (Fig. 1B) that
proceeds by means of 1,3-addition (11). Examples
include isomerizations involving zirconocenes
(Bu2ZrCp2) (16) and Grotjahn’s highly active Ru
catalyst that delivers E-olefins with excellent
selectivities via a hemilabile ligand that acts
as a base (17).
When we subjected [Ni(m-Cl)IPr]2 dimer 1 to
4-methoxyallylbenzene 2, selective generation
of the corresponding isomerized E-alkene 3 was
observed. After evaluating different reaction pa-
rameters, we found that E-olefin 3 was gen-
erated quantitatively and exclusively (24) within
3 hours at room temperature in chlorobenzene
(Fig. 2A).
Double-bond shifts of allyl precursors con-
stitute a potentially powerful alternative strat-
egy, as the allyl group can be installed readily,
and the desired E-geometry may subsequently
be set in a catalytic and atom-economical trans-
formation (8, 9, 10). This goal cannot be reached
through classical synthetic approaches, as direct
sigmatropic hydrogen shifts are geometrically
inaccessible in the required antarafacial sense.
Although base may be used to mediate double-
bond migration [at ~200°C, as used on an in-
dustrial scale (9)], the E/Z ratios of the resulting
double bonds are modest (~80:20), and the pro-
cess is incompatible with sensitive functionality
To gain further insight, we subjected Ni(I)
catalyst 1 to a mixture of substrate 4 and the
deuterium-labeled 5-d1 (containing >98% deu-
terium enrichment). We did not observe isotopic
scrambling and instead formed 6 and 7-d1 as
the exclusive products, regardless of whether the
reaction was run in deuterated or nondeuterated
solvent (Fig. 2B and fig. S11 to S14). These data
provide strong support that the solvent does not
act as a source of hydrogen/deuterium and that
the 1,3-H shift proceeds exclusively intramolecu-
larly. Our further investigation of the catalytic
reaction with paramagnetic proton nuclear mag-
netic resonance (NMR) and electron paramag-
netic resonance (EPR) spectroscopic analyses
showed clear indications of radicals being
present (see figs. S19 to S22 for details). We
In light of the ever-increasing demands for
greater sustainability, particularly for processes
of societal and industrial relevance, a key chal-
lenge in this arena is to overcome the need for
precious-metal catalysts and/or stoichiometric
additives (and waste) (9, 18). Ru has an Earth
abundance of only 10−7% and a considerable asso-
Institute of Organic Chemistry, RWTH Aachen University,
Landoltweg 1, 52074 Aachen, Germany.
*Corresponding author. Email: franziska.schoenebeck@rwth-aachen.de
Kapat et al., Science 363, 391–396 (2019)
25 January 2019
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