Synthesis and Asymmetric Alkene Hydrogenation Activity of C2-Symmetric Enantioenriched Pyridine Dicarbene Iron Dialkyl Complexes

Article abstract of DOI:10.1021/acs.organomet.1c00046

Enantioenriched N-alkyl-imidazole-substituted pyridine dicarbene iron dialkyl complexes have been synthesized and characterized by 1H NMR and zero-field 57Fe M?ssbauer spectroscopies as well as single-crystal X-ray diffraction. In benzene-d6, reversible coordination of N2 was observed establishing an equilibrium between a five-coordinate, S = 1 iron dialkyl derivative and the corresponding six-coordinate, diamagnetic dinitrogen complex. A modest enantioselectivity of 45% enantiomeric excess (ee) was observed for the catalytic asymmetric hydrogenation of 1-isopropyl-1-phenyl ethylene at 4 atm of H2 using 10 mol % of an enantioenriched iron dialkyl precatalyst, (ACNC)Fe(CH2SiMe3)2 ((ACNC) = bis(alkylimidazol-2-ylidene)pyridine). Decreasing the H2 pressure to 1 atm increased the ee to 70%. Incubation experiments established that the reaction of the iron dialkyl precatalysts with H2 initiates a background reaction leading to the generation of a less selective catalyst; suppressing this pathway is crucial for obtaining high enantioselectivity. The attempted hydrogenation of methyl-2-acetamidoacrylate identified a deactivation pathway where N-H bond activation generated an iron alkyl κ2-amidate alkyl. For productive catalytic reactions, deuterium labeling studies are consistent with a pathway for hydrogenation involving fast, reversible [2,1]-alkene insertion and a slow, enantiodetermining [1,2]-insertion. Monitoring the catalytic alkene hydrogenation reaction by NMR spectroscopy supports a homogeneous active catalyst that also undergoes C-H activation of the ACNC ligand backbone as a competing reaction.

Full text of DOI:10.1021/acs.organomet.1c00046

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Synthesis and Asymmetric Alkene Hydrogenation Activity of
C2‑Symmetric Enantioenriched Pyridine Dicarbene Iron Dialkyl
Complexes
Peter Viereck, Stephan M. Rummelt, Natalia A. Soja, Tyler P. Pabst, and Paul J. Chirik*
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ABSTRACT: Enantioenriched N-alkyl-imidazole-substituted pyr-
idine dicarbene iron dialkyl complexes have been synthesized and
57
characterized by 1H NMR and zero-field Fe Mossbauer
̈
spectroscopies as well as single-crystal X-ray diffraction. In
benzene-d6, reversible coordination of N2 was observed establish-
ing an equilibrium between a five-coordinate, S = 1 iron dialkyl
derivative and the corresponding six-coordinate, diamagnetic
dinitrogen complex. A modest enantioselectivity of 45% enantio-
meric excess (ee) was observed for the catalytic asymmetric
hydrogenation of 1-isopropyl-1-phenyl ethylene at 4 atm of H2
using 10 mol % of an enantioenriched iron dialkyl precatalyst,
(ACNC)Fe(CH2SiMe3)2 ((ACNC) = bis(alkylimidazol-2-
ylidene)pyridine). Decreasing the H2 pressure to 1 atm increased
the ee to 70%. Incubation experiments established that the reaction of the iron dialkyl precatalysts with H2 initiates a background
reaction leading to the generation of a less selective catalyst; suppressing this pathway is crucial for obtaining high enantioselectivity.
The attempted hydrogenation of methyl-2-acetamidoacrylate identified a deactivation pathway where N−H bond activation
generated an iron alkyl κ2-amidate alkyl. For productive catalytic reactions, deuterium labeling studies are consistent with a pathway
for hydrogenation involving fast, reversible [2,1]-alkene insertion and a slow, enantiodetermining [1,2]-insertion. Monitoring the
catalytic alkene hydrogenation reaction by NMR spectroscopy supports a homogeneous active catalyst that also undergoes C−H
activation of the ACNC ligand backbone as a competing reaction.
feasible. Applying a ligand design pioneered by Bianchini in
olefin polymerization,9 our laboratory reported that C1-
symmetric pyridine(diimine) cobalt alkyl complexes promote
the asymmetric hydrogenation of minimally functionalized
alkenes including sterically hindered examples activated by
boron substituents.10 Deuterium labeling studies on a series of
indene derivatives identified a fast and reversible 2,1-insertion of
the substrate into a Co−H bond that accounted for the unusual
isotopic distribution of products and that 1,2-insertion was
turnover limiting en route to alkane formation.10b Related cobalt
catalysts have since been applied to the asymmetric hydro-
genation of vinyl silanes,11a diaryl ethenes,11b and sequential
hydrofunctionalization-hydrogenation11c−f reactions.
INTRODUCTION
■
Transition-metal catalyzed asymmetric hydrogenation is a
powerful method to generate enantioenriched products with
applications in the fragrance, pharmaceutical, and fine-chemical
industries.1 State-of-the-art catalysts for the asymmetric alkene
hydrogenation typically involve late, second, or third-row
transition metals in combination with chiral phosphine or
related ligands and are widely used due to their high activity,
enantioselectivity, and functional group tolerance (Scheme
1A).2 Additionally, the availability of metal precursors such as
[M(COD)Cl]2 (M = Rh, Ir; COD = 1,5-cyclooctadiene) and
reliable ligand substitution has enabled rapid and broad catalyst
discovery ultimately translating into commercial application-
s.1a,2f
The discovery of catalysts based on Earth-abundant rather
than precious metals has traditionally been motivated by
potential advantages in cost and sustainability,3 but as new
catalysts are discovered so are distinct types of reactivity4,5 and
unique mechanisms of action.6 Although titanocene7 and
zirconocene8 based complexes were among the first catalysts
for the asymmetric hydrogenation of minimally functionalized
olefins, cobalt catalysts have emerged as the most synthetically
Bis(phosphine)cobalt complexes exhibit a rich asymmetric
alkene hydrogenation reactivity. High-throughput experimenta-
Received: January 26, 2021
Published: April 5, 2021
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Recently iron(II) dialkyl derivatives, (ArCNC)Fe(CH2SiMe3)2
have been synthesized, obviating the need for alkali metal
reductants and the extreme air and moisture sensitivity of
dinitrogen derivatives.17c This synthetic approach has also
proven more versatile, being compatible with more chelate
variants than alkali metal reductions that form iron dinitrogen
compounds.
Scheme 1. Metal-Catalyzed Asymmetric Alkene
Hydrogenation2,16
Here we describe application of this method to the synthesis
and characterization of enantioenriched, C2-symmetric
(ACNC)Fe(CH2SiMe3)2 ((ACNC) = bis(alkylimidazol-2-
ylidene)pyridine) iron complexes and explore their utility for
the asymmetric hydrogenation of alkenes. Equilibria between
the five-coordinate, S = 1 iron dialkyl complexes and the
corresponding six-coordinate, S = 0 dinitrogen derivatives was
identified in solution. The enantioselectivity of the alkene
hydrogenation increased as the pressure of H2 was decreased.
Deuterium labeling studies established that C−H activation of
the solvent is competitive with alkene hydrogenation.
RESULTS AND DISCUSSION
■
Our studies commenced with the preparation of a series of
ACNC18 ligands by a nucleophilic aromatic substitution of the
corresponding imidazoles to 2,6-dibromopyridine and subse-
quent deprotonation by KHMDS.17c Metalation of the ACNC
ligands was accomplished by addition of the free dicarbene of
the pincer to a pentane solution of freshly prepared py2Fe-
(CH2SiMe3)2 (py = pyridine; Scheme 2A).19 The resulting iron
tion (HTE) methods were applied to catalyst discovery and
combinations of cobalt(II) dialkyl, or combinations of cobalt-
(II) halides with zinc reductants generated highly active and
enantioselective catalysts for the hydrogenation of host of
functionalized alkenes.5a Notable examples include the
enantioselective synthesis of Levetiracetam on a 200-g scale in
methanol solution with performance superior to rhodium
catalysts as well as the hydrogenation of α,β-unsaturated
carboxylic acid derivatives including several drug precursors.5e
Attempts to translate the design principles from bis-
(phosphine)cobalt-catalyzed asymmetric alkene hydrogenation
of olefins to iron have been met with limited success. While
preparation of bis(phosphine)iron(II) dialkyl derivatives proved
relatively straightforward, treatment of these compounds with
dihydrogen in the presence of alkene resulted in rapid formation
of heterogeneous iron catalysts that promoted essentially
racemic hydrogenation reactions.12 These results suggested
that strong field tridentate pincer ligands, by virtue of their
higher affinity for the metal center, may result in more long-lived
and robust homogeneous hydrogenation catalysts. Indeed,
several examples of iron-catalyzed asymmetric alkene hydro-
functionalizations13 and iron-catalyzed asymmetric CX
reduction14 have been reported. However, the iron-catalyzed
asymmetric hydrogenation of alkenes with synthetically useful
enantioselectivity (>80% enantiomeric excess (ee)) remains
elusive.2
a
Scheme 2. (A) Preparation of (ACNC)Fe(CH2SiMe3)2 and
(B) Solid-State Structure of
(
(S)‑tBu,MeACNC)Fe(CH2SiMe3)2(N2) at 30% Probability
b
Ellipsoids
a
Reagents and conditions: (a) 2,6-dibromopyridine, 150 °C, 48 h. (b)
KHMDS, THF −110 °C to RT, 1 h. Hydrogen atoms attached to
b
stereogenic centers omitted for clarity.
Aryl-substituted, C2v-symmetric pyridine(diimine) iron dini-
trogen complexes provided early examples of catalysts for the
hydrogenation of alkenes, in some cases at part per million
loadings of iron.15 By replacing the imine donors of the
tridentate pincers with more donating N-heterocyclic carbenes
(NHC), Danopoulos and co-workers introduced a more
electron-rich iron dinitrogen complex, (iPrCNC)Fe(N2)2.16
Our laboratory later demonstrated that this class of complexes
was among the most active Earth abundant metal catalysts for
the hydrogenation of hindered, minimally functionalized
alkenes,17a and the active catalytic species were identified by
1H NMR spectroscopy and single-crystal X-ray diffraction.17b
dialkyl complexes precipitated from pentane as microcrystalline
red-brown or dark purple solids. A representative achiral
example, (iPrACNC)Fe(CH2SiMe3)2 was included in this
study for comparison.
Solution magnetic moments (Evans method) between 2.7
and 2.8 μB were measured for all three iron dialkyl complexes at
23 °C under vacuum, consistent with two unpaired electrons
and S = 1 ground states. Accordingly, all three compounds
exhibited paramagnetically broadened and shifted resonances in
the ambient temperature benzene-d6 NMR spectra. However,
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57
iPr
̈
Figure 1. Solid-state zero-field Fe Mossbauer spectra and infrared NN stretching frequencies of (A) ( ACNC)Fe(CH2SiMe3)2, (B)
(S)‑Cy,MeACNC)Fe(CH2SiMe3)2, (C) ((S)‑tBu,MeACNC)Fe(CH2SiMe3)2, (D) (S)‑tBu,MeACNC)Fe(CH2CMe3)2(N2), and (E) reversible N2-
coordination in (ACNC)Fe(CH2SiMe3)2.
for all three iron dialkyl derivatives, a strong NN band was
observed in the benzene solution infrared spectrum (Figure 1),
consistent with coordination of dinitrogen. The signals for
the identity of the alkyl ligand and the impact on dinitrogen
coordination is likely due to the decreased electron donating
ability of the neopentyl ligands which permit dinitrogen
(
(S)‑tBu,MeACNC)Fe(CH2SiMe3)2 under a nitrogen atmosphere
coordination.
57
̈
Zero-field Fe Mossbauer spectroscopy was used to further
study the electronic structures and dinitrogen coordination
behavior of the iron dialkyl complexes (Figure 1, Table 1). The
were significantly broadened such that assignment of the signals
was challenging. Freeze−pump−thawing the solution and
recording the 1H NMR spectrum under static vacuum
sharpened these signals, indicating a fast and reversible
coordination of N2 in benzene solution. Cooling a toluene-d8
solution of ((S)‑tBu,MeACNC)Fe(CH2SiMe3)2 to −80 °C under 1
atm of N2 produced signals consistent with a diamagnetic
compound, assigned to formation of a 6-coordinate, S = 0 iron
dinitrogen complex (Figure S27). This behavior contrasts
Table 1. Solid-State Zero-Field 57Fe Mossbauers of Alkyl-
̈
Substituted Pyridine Dicarbene Iron Complexes
[Fe]
δ (mm/s) |ΔEQ| (mm/s)
(
(
(
(
(
(
(
iPrACNC)Fe(CH2SiMe3)2 (78%)
0.11
0.19
0.13
0.15
0.14
0.13
0.10
2.56
1.20
2.46
1.61
2.43
1.53
1.55
iPrACNC)Fe(CH2SiMe3)2(N2)(22%)
(S)‑Cy,MeACNC)Fe(CH2SiMe3)2(59%)
(S)‑Cy,MeACNC)Fe(CH2SiMe3)2(N2)(41%)
(S)‑tBu,MeACNC)Fe(CH2SiMe3)2 (24%)
(S)‑tBu,MeACNC)Fe(CH2SiMe3)2(N2) (76%)
(S)‑tBu,MeACNC)Fe(CH2CMe3)2(N2) (>95%)
(
tBuACNC)Fe(CH2SiMe3)2, a previously reported diamagnetic
compound with an unusual square pyramidal geometry that
provided no evidence for N2 coordination in solution or the
solid state.17c
Single crystals of ((S)‑tBu,MeACNC)Fe(CH2SiMe3)2(N2) suit-
able for X-ray diffraction were obtained from a concentrated
Et2O−pentane solution stored at −30 °C. The solid-state
structure (Scheme 2B) confirmed the idealized octahedral
geometry with a dinitrogen ligand coordinated trans to the
pyridine of the pincer. This geometry is consistent with
previously reported (ArCNC)Fe(CH2SiMe3)2(N2) complex-
es.17c Unfortunately, attempts to obtain single crystals of the
five-coordinate dialkyl complexes have been unsuccessful.
The neopentyl analogue of ((S)‑tBu,MeACNC)Fe(CH2SiMe3)2
was prepared using an analogous procedure with freshly
prepared py2Fe(CH2CMe3)2.20 A red solid identified as
solid-state spectrum of (iPrACNC)Fe(CH2SiMe3)2 contained a
major component (78%) with an isomer shift of δ = 0.11 mm/s
and a quadrupole splitting of |ΔEQ| = 2.56 mm/s, assigned to the
5-coordinate, S = 1 iron dialkyl. These values were in agreement
with DFT calculations on full molecular models (δ = 0.12 mm/s,
ΔEQ = −2.43 mm/s, B3LYP). The minor component,
comprising 22% of the sample, exhibited an isomer shift of δ =
0.19 mm/s and a quadrupole splitting of |ΔEQ| = 1.20 mm/s
(calculated δ = 0.17 mm/s, ΔEQ = 1.65 mm/s, B3LYP), values
that compare to those reported previously for low-spin
(
(S)‑tBu,MeACNC)Fe(CH2CMe3)2(N2) was isolated in 66%
(
(
A rCNC)Fe(CH2 SiMe3 )2 (N2 ) compounds.17c For
(S)‑Cy,MeACNC)Fe(CH2SiMe3)2, the major component (59%)
1
yield and exhibited H and 13C NMR resonances consistent
with a diamagnetic compound (Scheme 3). Unlike the silicon-
containing congener, no color change was observed under
vacuum, and the N−N band at 2068 cm−1 persisted in the
benzene solution infrared spectrum. The subtle differences in
has an isomer shift of δ = 0.15 mm/s and a quadrupole splitting
of |ΔEQ| = 1.61 mm/s (calculated δ = 0.18 mm/s, ΔEQ = 1.62
mm/s, B3LYP), consistent with the six-coordinate, low-spin
iron(II) dinitrogen complex, while the parameters (δ = 0.13
mm/s; |ΔEQ| = 2.46 mm/s; calculated δ = 0.13 mm/s, ΔEQ =
−2.35 mm/s B3LYP) for the minor compound (41%)
correspond to the S = 1 five-coordinate iron dialkyl. For
Scheme 3. Preparation of
(
(S)‑tBu,MeACNC)Fe(CH2CMe3)2(N2)
(
(S)‑tBu,MeACNC)Fe(CH2SiMe3)2, the major component in the
solid state (76%) is the six-coordinate, iron(II) dinitrogen
complex (δ = 0.13 mm/s; |ΔEQ| = 1.53 mm/s; calculated δ =
0.19 mm/s, ΔEQ = 1.52 mm/s, B3LYP), while the minor
component (24%) corresponds to the five-coordinate S = 1 iron
dialkyl (δ = 0.14 mm/s; |ΔEQ| = 2.43 mm/s; calculated δ = 0.15
mm/s, ΔEQ = −2.40 mm/s, B3LYP). With the neopentyl
analogue, ((S)‑tBu,MeACNC)Fe(CH2CMe3)2(N2), only the six-
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coordinate dinitrogen complex was observed, with an isomer
shift of δ = 0.10 mm/s and a quadrupole splitting of |ΔEQ| = 1.55
mm/s was observed consistent with exclusive isolation of the
diamagnetic, six-coordinate complex.
Scheme 5. Evaluation of Enantioenriched (ACNC)Fe
Complexes for Asymmetric Alkene Hydrogenation
The behavior of (ACNC)Fe(CH2SiMe3)2 upon treatment
with strong L-type donors was explored. Exposure of aryl-
substituted (CNC)Fe(CH2SiMe3)2(N2) complexes to carbon
monoxide does not induce reductive elimination of the alkyl
ligands but instead results in ligand substitution to yield
(CNC)Fe(CH2SiMe3)2(CO).17c Likewise, exposure of a
benzene-d6 solution of ((S)‑tBu,MeACNC)Fe(CH2SiMe3)2 to 1
atm of CO generated ((S)‑tBu,MeACNC)Fe(CH2SiMe3)2(CO)
(Scheme 4A). A strong CO band centered at 1903 cm−1 was
Inspired by these observations, conditions favoring lowering
H2 pressures while maintaining an excess of dihydrogen were
explored. A series of hydrogenation reactions of 1a were
conducted in thick-walled glass vessels with 0.1, 0.5, 1, and 4 atm
of H2 using ((S)‑tBu,MeACNC)Fe(CH2SiMe3)2 as the precatalyst.
Decreasing enantiomeric excesses were observed with increasing
pressure, further confirming the inverse H2 pressure dependence
on enantioselectivity (Scheme 6). The highest enantioselectivity
Scheme 4. (A) Synthesis of
(
(S)‑tBu,MeACNC)Fe(CH2SiMe3)2(CO) and (B) Solid-
a
Structure of ((S)‑tBu,MeACNC)Fe(CH2SiMe3)2(CO)
Scheme 6. Effect of Hydrogen Pressure on Enantioselectivity
(70% ee) was observed when a J. Young NMR tube was used as
the reaction vessel and mixed only by vertical rotation. These
results demonstrate the impact of the mass transfer of hydrogen
on the levels of enantioselectivity.21 A variety of conditions were
evaluated including catalyst loading, solvent, and temperatures
(see the Supporting Information). In each case, however, no
improvement in enantioselectivity was observed.
a
Thermal ellipsoids at 30% probability. Hydrogen atoms attached to
stereogenic centers omitted for clarity.
observed in the benzene solution infrared spectrum. Single
crystals of ((S)‑tBu,MeACNC)Fe(CH2SiMe3)2(CO) were ob-
tained from a toluene−pentane mixture stored at −35 °C, and
the solid-state structure confirms an analogous idealized
octahedral geometry similar to (ACNC)Fe(CH2SiMe3)2(N2),
where CO occupies the site trans to the pyridine donor of the
ACNC pincer (Scheme 4B).
One plausible explanation for the observed inverse hydrogen
dependence is a competing, productive olefin isomerization
process which becomes more prominent at lower hydrogen
pressures. To rule out this hypothesis, the hydrogenation
reaction was conducted at substoichiometric quanitities of
hydrogen gas. One notable observation in the hydrogenation of
1a with ((S)‑tBu,MeACNC)Fe(CH2SiMe3)2 and 0.1 atm H2 gas is
that deuterium incorporation was observed in the methylene
position of the alkene (1a-d2, 31%) as well as in the benzylic
position (43%) and methyl groups (50%) of the resulting alkane
(Scheme 7A). Our laboratory has previously reported that
[(ArCNC)Fe] complexes are active for C(sp2)−H hydrogen
isotope exchange (HIE) using benzene-d6 as the deuterium
source.4d The C−D activation of the benzene-d6 solvent is
competitive with olefin insertion when the hydrogen pressure is
lowered, resulting in deuterium incorporation of the alkene. No
improvement of the enantioselectivity from the 1 atm conditions
was observed (64% ee). Deuteration of 1a with 1 atm of D2 gas at
23 °C in the presence of 10 mol % of ((S)‑tBu,MeACNC)Fe-
(CH2SiMe3)2 produced the alkane in 62% ee with near complete
deuteration of the benzylic and methyl positions (Scheme 7B).
A similar deuterium incorporation pattern was observed when
the catalytic reaction was conducted at 4 atm of D2 but the ee
eroded to 50%. Importantly, no isomerized alkene was observed
during the course of the hydrogenation reactions. Consistent
Both ((S)‑Cy,MeACNC)Fe(CH2SiMe3)2 and ((S)‑tBu,MeACNC)-
Fe(CH2SiMe3)2 were evaluated for catalytic asymmetric alkene
hydrogenation. The 1,1-disubstituted alkene (1-isopropylvinyl)-
benzene (1a) was selected as a representative substrate due to its
previous use in asymmetric hydrogenation with related cobalt
catalysts.10a Initial conditions employed 10 mol % of the iron
dialkyl precatalyst with 4 atm of H2 in benzene-d6 solution. With
(
(S)‑Cy,MeACNC)Fe(CH2SiMe3)2, complete conversion to the
alkane was observed after 30 min. An enantiomeric excess of
40% was obtained favoring the (R)-isomer of the alkane product
(Scheme 5). Similar activity was observed with
(
(S)‑tBu,MeACNC)Fe(CH2SiMe3)2 and under identical catalytic
conditions, the ee increased to 45%. Decreasing the H2 pressure
with the latter iron precatalyst increased the ee to 70%. Curiously,
the related precatalyst, ((S)‑tBu,MeACNC)Fe(CH2CMe3)2(N2)
gave significantly lower enantioselectivity (48% ee), suggesting
that precatalyst activation may play a significant role in catalyst
performance (vide infra).
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(
(S)‑tBu,MeACNC)Fe(CH2SiMe3)2 produced a distinct color
Scheme 7. (A) Effect of Substoichiometric Quantities of
change from red to purple. The newly formed purple product
was independently synthesized and assigned as the iron MAA
complex, ((S)‑tBu,MeACNC)Fe(CH2SiMe3)(MAA), based on 1H
and 13C NMR spectroscopy and single-crystal X-ray diffraction
(Scheme 9). This complex arises from the protonation of one of
Hydrogen and (B) Deuterium Labeling Studies
Scheme 9. (A) Synthesis of
(S)‑tBu,MeACNC)Fe(CH2SiMe3)(MAA) and (B) Solid-State
Structure of ((S)‑tBu,MeACNC)Fe(CH2SiMe3)(MAA) at 30%
a
Probability Ellipsoids
with this observation, no deuterium was observed in the
homobenzylic methine position of alkane, demonstrating that
alkene isomerization is not the source of the higher ee observed
at lower pressures of H2. The observed positions of deuterium
incorporation demonstrate that the hydrogenation reaction
proceeds with fast and reversible 2,1-insertion and that 1,2-
insertion is likely turnover limiting and enantiodetermining.3d
A
stereochemical model rationalizing the moderate selectivity for
the (R)-enantiomer is presented in Figure S38. Additional
experimental and computational data are needed to support this
model. The origin of the inverse dependence between H2
pressure and enantioselectivity will be discussed below.
Other 1,1-disubstituted alkenes and trisubstituted alkenes
were evaluated for iron-catalyzed asymmetric alkene hydro-
genation (Scheme 8). With the goal of potentially slowing
a
Hydrogen atoms attached to stereogenic centers omitted for clarity.
Scheme 8. ((S)‑tBu,MeACNC)Fe(CH2SiMe3)2 as a Precatalyst
for the Asymmetric Hydrogenation of 1,1-Disubstituted and
Trisubstituted Alkenes
the neosilyl ligands of ((S)‑tBu,MeACNC)Fe(CH2SiMe3)2 and
coordination of the amidate. ((S)‑tBu,MeACNC)Fe(CH2SiMe3)-
(MAA) proved unreactive to H2 and HBPin even at elevated
temperatures (80 °C) and is air stable (∼5 h) in the solid state,
showing discoloration from a purple to a brown color after this
time. Utilizing ((S)‑tBu,MeACNC)Fe(CH2SiMe3)(MAA) as a
precatalyst for hydrogenation of 1a resulted in a slow reaction
along with poor (<5% ee) enantioselectivity. Thus this
protonation event is identified as a deactivation pathway, and
any hydrogenation reactivity may be the result of an unidentified
iron decomposition product.
Investigations into the catalyst speciation, specifically the iron
product formed following treatment of the iron dialkyl with H2,
were undertaken. Aryl-substituted [(CNC)Fe] compounds are
known to form the corresponding (CNC)Fe(H)2(η2-H2) and
(CNC)Fe(H)2(N2) derivatives upon exposure to dihydro-
gen.17b Treatment of a benzene solution of (S)‑tBu,MeACNC)Fe-
a
Average of two runs
(CH2SiMe3)2 with 1 atm of H2 followed by rapidly freezing and
57
̈
analysis by zero-field Fe Mossbauer spectroscopy revealed a
reactivity and increasing the overall enantioselectivity, alkene
1b, a more hindered analogue of 1a, was subjected to the
standard catalytic hydrogenation conditions. Slightly reduced
activity (70% conversion to alkane, 17 h) and lower ee (28%)
were observed. The less hindered 1,1-disubstituted alkene 1c
produced higher conversion (>95%, 30 min) but with negligible
enantioselectivity (∼5% ee). Trisubstituted alkenes 1d and 1e
also underwent hydrogenation with poor enantioselectivity
(13%, 16% ee, respectively), despite the slower reaction.
The hydrogenation of methyl-2-acetamidoacrylate (MAA, 1f)
was also studied to gain insight into to the functional group
tolerance of the iron catalysts and due to the previous success of
the activated alkenes in precious metal and cobalt-catalyzed
reactions.5a Addition of 1f to a benzene-d6 solution of
complex mixture of products (Figure S9).
Exposure of a benzene-d6 solution of (S)‑tBu,MeACNC)Fe-
(CH2SiMe3)2 to 1 atm of H2 at 23 °C immediately generated
SiMe4 with concomitant disappearance of all of the signals in the
1H NMR spectrum corresponding to the iron compound.
Treatment of this product with excess carbon monoxide resulted
in rapid formation of a new, diamagnetic product in 82% yield
identified as ((S)‑tBu,MeACNC)Fe(CO)2-d3 in 82% NMR yield,
where complete deuteration at the 2, 4, and 6 positions of the
ligand backbone is observed (Scheme 10A). Diagnostic CO
bands were observed at 1907 and 1863 cm−1 in the benzene
solution infrared spectrum. To gain insight into the factors
affecting catalyst lifetime, this combined hydrogenolysis−
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drop in ee to 56% was observed (Scheme 10B, entry 4). By
comparison, pretreatment of the neopentyl variant,
Scheme 10. (A) Sequential Hydrogenation−Carbonylation
of ((S)‑tBu,MeACNC)Fe(CH2SiMe3)2 in the Absence of Alkene
Substrate and (B) Hydrogenation of 1a from H2 Pretreated
Iron Complexes
(
(S)‑tBu,MeACNC)Fe(CH2CMe3)2(N2) for 2 h produced lower
conversion (76%) and enantiomeric excess (40%), suggesting
that the decomposition products from background hydro-
genolysis of ((S)‑tBu,MeACNC)Fe(CH2SiMe3)2 and
(
(S)‑tBu,MeACNC)Fe(CH2CMe3)2(N2) are different or are
formed at different rates. These results account for the observed
inverse dependence of H2 pressure on enantioselectivity and also
explain why more hindered, slower to react alkenes are reduced
with lower selectivity; otherwise, decomposition of the active
catalyst results in reduced enantioselectivity.
Based on these results, the inverse dependence of
enantioselectivity is attributed to controlling the rate of
productive hydrogenation to catalyst decomposition to the ill-
defined unselective catalyst of unknown homogeneity
([Fe]decomp). An explanation of this effect is presented in
Scheme 11. At lower pressures of hydrogen, this decomposition
Scheme 11. Rationalization of Inverse H2 Pressure
Dependence on Enantioselectivity
carbonylation reaction was performed at a variety of hydrogen
treatment times and pressures, as the yield of ((S)‑tBu,MeACNC)-
Fe(CO)2-d3 after hydrogenolysis likely directly correlates to the
amount of homogeneous iron in solution. After 10 min of
reaction time, 1 and 4 atm of hydrogen produced 82% and 42%
NMR yield, respectively (Scheme 10A, entries 1 and 2),
demonstrating that increasing the concentration of hydrogen in
solution decreases the quantity of active catalyst. At 1 atm of H2
gas, at increasing reaction time, the yield of ((S)‑tBu,MeACNC)-
Fe(CO)2-d3 decreased from 82% to 54% (Scheme 10A, entries 1
and 3−5), confirming that the homogeneous iron species
decomposes under excess H2 gas. Performing the hydrogenation
reaction in cyclohexane-d12 also generated an NMR silent iron
rate is slowed resulting in a lower concentration of [Fe]decomp
compared to the desired enantioenriched catalyst ([Fe]enantio
)
and increased enantioselectivity is observed. This rationalization
is also consistent with lower levels of enantioselectivity on any
highly hindered or trisubstituted alkene. Unselective hydro-
genation with the decomposed catalyst is competitive with the
enantioselective catalyst, and thus the enantioselectivity is
eroded at higher pressures of H2.
CONCLUSION
■
In conclusion, enantioenriched (ACNC)Fe dialkyl complexes
have been prepared, structurally characterized and evaluated for
their activity in the catalytic asymmetric hydrogenation of
alkenes. The five-coordinate, S = 1 iron dialkyl complexes
undergo reversible coordination of N2 to form the correspond-
ing S = 0, idealized octahedral derivatives. Enantioselectivity as
high 70% ee was observed for the hydrogenation of 1a, and lower
pressures of H2 resulted in increased selectivity. In situ reaction
monitoring and deuterium labeling studies established that
alkene isomerization did not occur on a time scale competitive
with hydrogenation and was thereby eliminated as the origin of
the observed pressure effect. Addition of the enamide methyl-2-
acetamidoacrylate to a enantioenriched (ACNC)Fe dialkyl
complex resulted in a crystallographically characterized product
resistant to further reaction with H2. Additional studies
demonstrated that there is a dynamic, yet homogeneous
speciation; however, decomposition of the catalyst to a less
selective form may be the source of the modest levels of
enantioselectivity that were observed. These studies demon-
strate that maintaining well-defined catalyst speciation is critical
for enantioselective iron catalysis, and tridentate pincers, while
successful, still suffer from deleterious decomposition pathways.
Importantly, maintaining well-defined speciation guides the
development of next-generation iron catalysts for asymmetric
transformations.
1
product, and a complex mixture was observed by H NMR
spectroscopy after treatment with CO. Related aryl-substituted
pincer iron complexes, [(ArCNC)Fe] are known to form trans-
dihydride η2-dihydrogen complexes upon treatment of the
dinitrogen or dialkyl complexes with H2.17b It is likely that a
similar pathway is operative with the enantioenriched C2-
symmetric examples reported here; however, rapid C−H
activation and hydrogen isotope exchange processes with the
deuterated solvents complicate the spectroscopic character-
ization.
With the hydrogen-induced decomposition of
(
(S)‑tBu,MeACNC)Fe(CH2SiMe3)2 established, possible back-
ground catalytic reactions arising from these newly formed
iron products were evaluated. Benzene-d6 solutions of specific
iron compounds were pretreated with 4 atm of H2 for a
designated time followed by addition of 1a with subsequent
exposure to 1 atm of hydrogen and stirring at ambient
temperature for 30 min (Scheme 10B). With 10 min of
exposure of ((S)‑tBu,MeACNC)Fe(CH2SiMe3)2, complete con-
version of 1a was observed in the subsequent catalytic
hydrogenation and the resulting alkane was obtained in 75%
ee (Scheme 10B, entry 1). Increasing the incubation time to 2 h
resulted in a lower enantiomeric excess of 60% (Scheme 10B,
entry 2). With 48 h of pretreatment, an additional, albeit slight
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Asymmetric Hydrogenation of Olefins. Acc. Chem. Res. 2007, 40,
1402−1411. (c) Etayo, P.; Vidal-Ferran, A. Rhodium-Catalysed
Asymmetric Hydrogenation as a Valuable Synthetic Tool for the
Preparation of Chiral Drugs. Chem. Soc. Rev. 2013, 42, 728−754.
ASSOCIATED CONTENT
* Supporting Information
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.organomet.1c00046.
■
sı
̀
(d) Verendel, J. J.; Pamies, O.; Diéguez, M.; Andersson, P. G.
Complete experimental and computational details in-
cluding precatalyst optimization studies, optimized
structures, and characterization data for the deuterated
products (PDF)
Asymmetric Hydrogenation of Olefins Using Chiral Crabtree-Type
Catalysts: Scope and Limitations. Chem. Rev. 2014, 114, 2130−2169.
(e) Margarita, C.; Andersson, P. G. Evolution and Prospects of the
Asymmetric Hydrogenation of Unfunctionalized Olefins. J. Am. Chem.
Soc. 2017, 139, 1346−1356. (f) Shevlin, M. Practical High-Throughput
Experimentation for Chemists. ACS Med. Chem. Lett. 2017, 8, 601−
607.
Optimized structure of (iPrACNC)Fe(CH2SiMe3)2
(XYZ)
(3) (a) Chirik, P. J. Iron- and Cobalt-Catalyzed Alkene Hydro-
genation: Catalysis with Both Redox-Active and Strong Field Ligands.
Acc. Chem. Res. 2015, 48, 1687−1695. (b) Enthaler, S.; Junge, K.; Beller,
M. Sustainable Metal Catalysis with Iron: From Rust to a Rising Star?
Angew. Angew. Chem., Int. Ed. 2008, 47, 3317−3321. (c) Chen, J.; Lu,
Z. Asymmetric Hydrofunctionalization of Minimally Functionalized
Alkenes via Earth Abundant Transition Metal Catalysis. Org. Chem.
Front. 2018, 5, 260−272. (d) Seo, C. S. G.; Morris, R. H. Catalytic
Homogeneous Asymmetric Hydrogenation: Successes and Oppor-
tunities. Organometallics 2019, 38, 47−65.
Accession Codes
CCDC 2048706−2048708 contain the supplementary crystallo-
graphic data for this paper. These data can be obtained free of
charge via www.ccdc.cam.ac.uk/data_request/cif, or by email-
ing data_request@ccdc.cam.ac.uk, or by contacting The Cam-
bridge Crystallographic Data Centre, 12 Union Road, Cam-
bridge CB2 1EZ, UK; fax: +44 1223 336033.
AUTHOR INFORMATION
Corresponding Author
Paul J. Chirik − Department of Chemistry, Princeton University,
Princeton, New Jersey 08544, United States; orcid.org/
0000-0001-8473-2898; Email: pchirik@princeton.edu
■
(4) (a) Pony Yu, R.; Hesk, D.; Rivera, N.; Pelczer, I.; Chirik, P. J. Iron-
Catalysed Tritiation of Pharmaceuticals. Nature 2016, 529, 195−199.
(b) Obligacion, J. V.; Bezdek, M. J.; Chirik, P. J. C(sp2)-H Borylation of
Fluorinated Arenes Using an Air-Stable Cobalt Precatalyst: Electroni-
cally Enhanced Site Selectivity Enables Synthetic Opportunities. J. Am.
Chem. Soc. 2017, 139, 2825−2832. (c) Pabst, T. P.; Obligacion, J. V.;
Authors
́
Peter Viereck − Department of Chemistry, Princeton University,
Princeton, New Jersey 08544, United States; orcid.org/
0000-0003-4691-8434
Stephan M. Rummelt − Department of Chemistry, Princeton
University, Princeton, New Jersey 08544, United States;
orcid.org/0000-0003-3996-0271
Natalia A. Soja − Department of Chemistry, Princeton
University, Princeton, New Jersey 08544, United States;
orcid.org/0000-0002-9635-748X
Tyler P. Pabst − Department of Chemistry, Princeton
University, Princeton, New Jersey 08544, United States;
orcid.org/0000-0003-4595-2833
Rochette, E.; Pappas, I.; Chirik, P. J. Cobalt-Catalyzed Borylation of
Fluorinated Arenes: Thermodynamic Control of C(sp2)-H Oxidative
Addition Results in Ortho-to-Fluorine Selectivity. J. Am. Chem. Soc.
2019, 141, 15378−15389. (d) Corpas, J.; Viereck, P.; Chirik, P. J.
C(Sp2)-H Activation with Pyridine Dicarbene Iron Dialkyl Complexes:
Hydrogen Isotope Exchange of Arenes Using Benzene-d6 as a
Deuterium Source. ACS Catal. 2020, 10, 8640−8647. (e) Pabst, T.
P.; Quach, L.; MacMillan, K. T.; Chirik, P. J. Mechanistic Origins of
Regioselectivity in Cobalt-Catalyzed C(sp2)-H Borylation of Benzoate
Esters and Arylboronate Esters. Chem. 2021, 7, 237−254.
(5) (a) Friedfeld, M. R.; Shevlin, M.; Hoyt, J. M.; Krska, S. W.; Tudge,
M. T.; Chirik, P. J. Cobalt Precursors for High-Throughput Discovery
of Base Metal Asymmetric Alkene Hydrogenation Catalysts. Science
2013, 342, 1076−1080. (b) Shevlin, M.; Friedfeld, M. R.; Sheng, H.;
Pierson, N. A.; Hoyt, J. M.; Campeau, L.-C.; Chirik, P. J. Nickel-
Catalyzed Asymmetric Alkene Hydrogenation of α,β-Unsaturated
Esters: High-Throughput Experimentation-Enabled Reaction Discov-
ery, Optimization, and Mechanistic Elucidation. J. Am. Chem. Soc. 2016,
138, 3562−3569. (c) Friedfeld, M. R.; Zhong, H.; Ruck, R. T.; Shevlin,
M.; Chirik, P. J. Cobalt-Catalyzed Asymmetric Hydrogenation of
Enamides Enabled by Single-Electron Reduction. Science 2018, 360,
888−893. (d) Zhong, H.; Friedfeld, M. R.; Chirik, P. J. Syntheses and
Catalytic Hydrogenation Performance of Cationic Bis(Phosphine)
Cobalt(I) Diene and Arene Compounds. Angew. Chem., Int. Ed. 2019,
58, 9194−9198. (e) Zhong, H.; Shevlin, M.; Chirik, P. J. Cobalt-
Catalyzed Asymmetric Hydrogenation of α,β-Unsaturated Carboxylic
Acids by Homolytic H2 Cleavage. J. Am. Chem. Soc. 2020, 142, 5272−
5281. (f) Zhong, H.; Beromi, M. M.; Chirik, P. J. Ligand Substitution
and Electronic Structure Studies of Bis(Phosphine)Cobalt Cyclo-
octadiene Precatalysts for Alkene Hydrogenation. Can. J. Chem. 2020,
99, 193−201.
Complete contact information is available at:
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Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
Financial support from a National Science Foundation (NSF)
Grant Opportunities of Academic Liaison with Industry
(GOALI) grant (Grant CHE-1855719) is acknowledged.
REFERENCES
■
(1) (a) Shultz, C. S.; Krska, S. W. Unlocking the Potential of
Asymmetric Hydrogenation at Merck. Acc. Chem. Res. 2007, 40, 1320−
1326. (b) Saudan, L. A. Hydrogenation Processes in the Synthesis of
Perfumery Ingredients. Acc. Chem. Res. 2007, 40, 1309−1319.
(c) Ohkuma, T.; Kitamura, M.; Noyori, R. Asymmetric Hydrogenation.
In Catalytic Asymmetric Synthesis; John Wiley & Sons, Ltd., 2005; pp 1−
110. (d) Asymmetric Catalysis on Industrial Scale: Challenges, Approaches
and Solutions, 2nd ed.; Blaser, H.-U., Federsel, H.-J., Eds.; Wiley-VCH,
(6) (a) Morello, G. R.; Zhong, H.; Chirik, P. J.; Hopmann, K. H.
Cobalt-Catalysed Alkene Hydrogenation: A Metallacycle Can Explain
the Hydroxyl Activating Effect and the Diastereoselectivity. Chem. Sci.
2018, 9, 4977−4982. (b) Hopmann, K. H. Cobalt-Bis(Imino)Pyridine-
Catalyzed Asymmetric Hydrogenation: Electronic Structure, Mecha-
nism, and Stereoselectivity. Organometallics 2013, 32, 6388−6399.
(c) Yu, R. P.; Darmon, J. M.; Milsmann, C.; Margulieux, G. W.; Stieber,
S. C. E.; DeBeer, S.; Chirik, P. J. Catalytic Hydrogenation Activity and
Electronic Structure Determination of Bis(arylimidazol-2-ylidene)-
̈
Morlenbach, Germany, 2010. (e) Knowles, W. S. Asymmetric
hydrogenations (Nobel lecture). Angew. Chem., Int. Ed. 2002, 41,
1998−2007.
(2) (a) Cui, X.; Burgess, K. Catalytic Homogeneous Asymmetric
Hydrogenations of Largely Unfunctionalized Alkenes. Chem. Rev. 2005,
105, 3272−3296. (b) Roseblade, S. J.; Pfaltz, A. Iridium-Catalyzed
1059
https://doi.org/10.1021/acs.organomet.1c00046
Organometallics 2021, 40, 1053−1061

Organometallics
pubs.acs.org/Organometallics
Article
pyridine Cobalt Alkyl and Hydride Complexes. J. Am. Chem. Soc. 2013,
135, 13168−13184.
(7) Broene, R. D.; Buchwald, S. L. Asymmetric Hydrogenation of
Unfunctionalized Trisubstituted Olefins with a Chiral Titanocene
Catalyst. J. Am. Chem. Soc. 1993, 115, 12569−12570.
M.; Cera, G. Recent Advances in Asymmetric Iron Catalysis. Molecules
2020, 25, 3889. (k) Liang, Q.; Song, D. Iron N-heterocyclic carbene
complexes in homogeneous catalysis. Chem. Soc. Rev. 2020, 49, 1209−
1232.
(14) (a) Morris, R. H. Asymmetric Hydrogenation, Transfer
Hydrogenation and Hydrosilylation of Ketones Catalyzed by Iron
Complexes. Chem. Soc. Rev. 2009, 38, 2282−2291. (b) Tondreau, A.
M.; Darmon, J. M.; Wile, B. M.; Floyd, S. K.; Lobkovsky, E.; Chirik, P. J.
Enantiopure Pyridine Bis(Oxazoline) “Pybox” and Bis(Oxazoline)
“Box” Iron Dialkyl Complexes: Comparison to Bis(Imi, no)Pyridine
Compounds and Application to Catalytic Hydrosilylation of Ketones.
Organometallics 2009, 28, 3928−3940. (c) Zuo, W.; Lough, A. J.; Li, Y.
F.; Morris, R. H. Amine(Imine)Diphosphine Iron Catalysts for
Asymmetric Transfer Hydrogenation of Ketones and Imines. Science
2013, 342, 1080−1083. (d) Li, Y.; Yu, S.; Wu, X.; Xiao, J.; Shen, W.;
Dong, Z.; Gao, J. Iron Catalyzed Asymmetric Hydrogenation of
Ketones. J. Am. Chem. Soc. 2014, 136, 4031−4039. (e) Bleith, T.;
Wadepohl, H.; Gade, L. H. Iron Achieves Noble Metal Reactivity and
Selectivity: Highly Reactive and Enantioselective Iron Complexes as
Catalysts in the Hydrosilylation of Ketones. J. Am. Chem. Soc. 2015,
137, 2456−2459. (f) Li, Y.-Y.; Yu, S.-L.; Shen, W.-Y.; Gao, J.-X. Iron-,
Cobalt-, and Nickel-Catalyzed Asymmetric Transfer Hydrogenation
and Asymmetric Hydrogenation of Ketones. Acc. Chem. Res. 2015, 48,
2587−2598. (g) Wei, D.; Darcel, C. Iron Catalysis in Reduction and
Hydrometalation Reactions. Chem. Rev. 2019, 119, 2550−2610.
(h) Huber, R.; Passera, A.; Mezzetti, A. Which Future for Stereogenic
Phosphorus? Lessons from P* Pincer Complexes of Iron(II). Chem.
Commun. 2019, 55, 9251−9266. (i) Seo, C. S. G.; Morris, R. H.
Catalytic Homogeneous Asymmetric Hydrogenation: Successes and
Opportunities. Organometallics 2019, 38, 47−65.
(15) (a) Bart, S. C.; Lobkovsky, E.; Chirik, P. J. Preparation and
Molecular and Electronic Structures of Iron(0) Dinitrogen and Silane
Complexes and Their Application to Catalytic Hydrogenation and
Hydrosilation. J. Am. Chem. Soc. 2004, 126, 13794−13807. (b) Archer,
A. M.; Bouwkamp, M. W.; Cortez, M.-P.; Lobkovsky, E.; Chirik, P. J.
Arene Coordination in Bis(Imino)Pyridine Iron Complexes: Identi-
fication of Catalyst Deactivation Pathways in Iron-Catalyzed Hydro-
genation and Hydrosilation. Organometallics 2006, 25, 4269−4278.
(c) Trovitch, R. J.; Lobkovsky, E.; Bill, E.; Chirik, P. J. Functional group
tolerance and substrate scope in bis(imino)pyridine iron catalyzed
alkene hydrogenation. Organometallics 2008, 27, 1470−1478.
(16) (a) Danopoulos, A. A.; Wright, J. A.; Motherwell, W. B.
Molecular N2 Complexes of Iron Stabilised by N-Heterocyclic ‘Pincer’
Dicarbene Ligands. Chem. Commun. 2005, No. 6, 784−786.
(b) Danopoulos, A. A.; Pugh, D.; Smith, H.; Saßmannshausen, J.
Structural and Reactivity Studies of “Pincer” Pyridine Dicarbene
Complexes of Fe0: Experimental and Computational Comparison of
the Phosphine and NHC Donors. Chem. - Eur. J. 2009, 15, 5491−5502.
(c) Pugh, D.; Wells, N. J.; Evans, D. J.; Danopoulos, A. A. Reactions of
‘Pincer’ Pyridine Dicarbene Complexes of Fe(0) with Silanes. Dalton
Trans. 2009, 7189−7195.
(8) Troutman, M. V.; Appella, D. H.; Buchwald, S. L. Asymmetric
hydrogenation of unfunctionalized tetrasubstituted olefins with a
cationic zirconocene catalyst. J. Am. Chem. Soc. 1999, 121, 4916−4917.
(9) Bianchini, C.; Mantovani, G.; Meli, A.; Migliacci, F.; Zanobini, F.;
Laschi, F.; Sommazzi, A. Oligomerisation of Ethylene to Linear α-
Olefins by New Cs- and C1-Symmetric [2,6-Bis(Imino)Pyridyl]Iron
and -Cobalt Dichloride Complexes. Eur. J. Inorg. Chem. 2003, 2003,
1620−1631.
(10) (a) Monfette, S.; Turner, Z. R.; Semproni, S. P.; Chirik, P. J.
Enantiopure C1-Symmetric Bis(Imino)Pyridine Cobalt Complexes for
Asymmetric Alkene Hydrogenation. J. Am. Chem. Soc. 2012, 134,
4561−4564. (b) Friedfeld, M. R.; Shevlin, M.; Margulieux, G. W.;
Campeau, L.-C.; Chirik, P. J. Cobalt-Catalyzed Enantioselective
Hydrogenation of Minimally Functionalized Alkenes: Isotopic Labeling
Provides Insight into the Origin of Stereoselectivity and Alkene
Insertion Preferences. J. Am. Chem. Soc. 2016, 138, 3314−3324.
(c) Viereck, P.; Krautwald, S.; Pabst, T. P.; Chirik, P. J. A Boron
Activating Effect Enables Cobalt-Catalyzed Asymmetric Hydrogena-
tion of Sterically Hindered Alkenes. J. Am. Chem. Soc. 2020, 142, 3923−
3930.
(11) (a) Chen, J.; Chen, C.; Ji, C.; Lu, Z. Cobalt-Catalyzed
Asymmetric Hydrogenation of 1,1-Diarylethenes. Org. Lett. 2016, 18,
1594−1597. (b) Zuo, Z.; Xu, S.; Zhang, L.; Gan, L.; Fang, H.; Liu, G.;
Huang, Z. Cobalt-Catalyzed Asymmetric Hydrogenation of Vinyl-
silanes with a Phosphine-Pyridine-Oxazoline Ligand: Synthesis of
Optically Active Organosilanes and Silacycles. Organometallics 2019,
38, 3906−3911. (c) Guo, J.; Shen, X.; Lu, Z. Regio- and
Enantioselective Cobalt-Catalyzed Sequential Hydrosilylation/Hydro-
genation of Terminal Alkynes. Angew. Chem., Int. Ed. 2017, 56, 615−
618. (d) Chen, J.; Lu, Z. Asymmetric Hydrofunctionalization of
Minimally Functionalized Alkenes via Earth Abundant Transition
Metal Catalysis. Org. Chem. Front. 2018, 5, 260−272. (e) Cheng, Z.;
Guo, J.; Lu, Z. Recent Advances in Metal-Catalysed Asymmetric
Sequential Double Hydrofunctionalization of Alkynes. Chem. Commun.
2020, 56, 2229−2239. (f) Chen, J.; Shen, X.; Lu, Z. Cobalt-Catalyzed
Markovnikov Selective Sequential Hydrogenation/Hydrohydrazida-
tion of Aliphatic Terminal Alkynes. J. Am. Chem. Soc. 2020, 142,
14455−14460.
(12) Hoyt, J. M.; Shevlin, M.; Margulieux, G. W.; Krska, S. W.; Tudge,
M. T.; Chirik, P. J. Synthesis and Hydrogenation Activity of Iron Dialkyl
Complexes with Chiral Bidentate Phosphines. Organometallics 2014,
33, 5781−5790.
(13) (a) Gopalaiah, K. Chiral Iron Catalysts for Asymmetric
Synthesis. Chem. Rev. 2013, 113, 3248−3296. (b) Chen, J.; Xi, T.;
Lu, Z. Iminopyridine Oxazoline Iron Catalyst for Asymmetric
Hydroboration of 1,1-Disubtituted Aryl Alkenes. Org. Lett. 2014, 16,
6452−6455. (c) Chen, J.; Cheng, B.; Cao, M.; Lu, Z. Iron-Catalyzed
Asymmetric Hydrosilylation of 1,1-Disubstituted Alkenes. Angew.
Chem., Int. Ed. 2015, 54, 4661−4664. (d) Chen, J.; Lu, Z. Asymmetric
Hydrofunctionalization of Minimally Functionalized Alkenes via Earth
Abundant Transition Metal Catalysis. Org. Chem. Front. 2018, 5, 260−
272. (e) Cheng, B.; Liu, W.; Lu, Z. Iron-Catalyzed Highly
Enantioselective Hydrosilylation of Unactivated Terminal Alkenes. J.
Am. Chem. Soc. 2018, 140, 5014−5017. (f) Chen, J.; Lu, Z. Asymmetric
Hydrofunctionalization of Minimally Functionalized Alkenes via Earth
Abundant Transition Metal Catalysis. Org. Chem. Front. 2018, 5, 260−
272. (g) Pellissier, H. Recent Developments in Enantioselective Iron-
Catalyzed Transformations. Coord. Chem. Rev. 2019, 386, 1−31.
(h) Wen, H.; Liu, G.; Huang, Z. Recent Advances in Tridentate Iron
and Cobalt Complexes for Alkene and Alkyne Hydrofunctionalizations.
Coord. Chem. Rev. 2019, 386, 138−153. (i) Chen, C.; Wang, H.; Sun,
Y.; Cui, J.; Xie, J.; Shi, Y.; Yu, S.; Hong, X.; Lu, Z. Iron-Catalyzed
Asymmetric Hydrosilylation of Vinylcyclopropanes via Stereospecific
C-C Bond Cleavage. iScience 2020, 23, 100985. (j) Casnati, A.; Lanzi,
(17) (a) Yu, R. P.; Darmon, J. M.; Hoyt, J. M.; Margulieux, G. W.;
Turner, Z. R.; Chirik, P. J. High-Activity Iron Catalysts for the
Hydrogenation of Hindered, Unfunctionalized Alkenes. ACS Catal.
2012, 2, 1760−1764. (b) Yu, R. P.; Darmon, J. M.; Semproni, S. P.;
Turner, Z. R.; Chirik, P. J. Synthesis of Iron Hydride Complexes
Relevant to Hydrogen Isotope Exchange in Pharmaceuticals. Organo-
metallics 2017, 36, 4341−4343. (c) Rummelt, S. M.; Darmon, J. M.; Yu,
R. P.; Viereck, P.; Pabst, T. P.; Turner, Z. R.; Margulieux, G. W.; Gu, S.;
Chirik, P. J. Synthesis, Structure, and Hydrogenolysis of Pyridine
Dicarbene Iron Dialkyl Complexes. Organometallics 2019, 38, 3159−
3168.
(18) The “A” designator before the CNC abbreviation signifies an
alkyl rather than aryl N-imidazole substituent.
́
(19) Cámpora, J.; Naz, A. M.; Palma, P.; Alvarez, E.; Reyes, M. L. 2,6-
Diiminopyridine Iron(II) Dialkyl Complexes. Interaction with
Aluminum Alkyls and Ethylene Polymerization Catalysis. Organo-
metallics 2005, 24, 4878−4881.
1060
https://doi.org/10.1021/acs.organomet.1c00046
Organometallics 2021, 40, 1053−1061

Organometallics
pubs.acs.org/Organometallics
Article
(20) Fernández, I.; Trovitch, R. J.; Lobkovsky, E.; Chirik, P. J.
Synthesis of Bis(Imino)Pyridine Iron Di- and Monoalkyl Complexes:
Stability Differences between FeCH2SiMe3 and FeCH2CMe3
Derivatives. Organometallics 2008, 27, 109−118.
(21) Sun, Y.; Landau, R. N.; Wang, J.; LeBlond, C.; Blackmond, D. G.
A Re-Examination of Pressure Effects on Enantioselectivity in
Asymmetric Catalytic Hydrogenation. J. Am. Chem. Soc. 1996, 118,
1348−1353.
1061
https://doi.org/10.1021/acs.organomet.1c00046
Organometallics 2021, 40, 1053−1061