Chiral-at-Iron Catalyst for Highly Enantioselective and Diastereoselective Hetero-Diels-Alder Reaction

Article abstract of DOI:10.1002/chem.202100703

This study demonstrates that chiral-at-iron complexes, in which all coordinated ligands are achiral and the overall chirality the consequence of a stereogenic iron center, are capable of catalyzing asymmetric transformations with very high enantioselectivities. The catalyst is based on a previously reported design (J. Am. Chem. Soc. 2017, 139, 4322), in which iron(II) is surrounded by two configurationally inert achiral bidentate N-(2-pyridyl)-substituted N-heterocyclic carbenes in a C₂-symmetric fashion and complemented by two labile acetonitriles. By replacing mesityl with more bulky 2,6-diisopropylphenyl substituents at the NHC ligands, the steric hindrance at the catalytic site was increased, thereby providing a markedly improved asymmetric induction. The new chiral-at-iron catalyst was applied to the inverse electron demand hetero-Diels-Alder reaction between β,γ-unsaturated α-ketoester and enol ethers provide 3,4-dihydro-2H-pyrans in high yields with excellent diastereoselectivities (up to 99 : 1 dr) and excellent enantioselectivities (up to 98 % ee). Other electron rich dienophiles are also suitable as demonstrated for a reaction with a vinyl azide.

Full text of DOI:10.1002/chem.202100703

Full Paper
doi.org/10.1002/chem.202100703
Chemistry—A European Journal
Chiral-at-Iron Catalyst for Highly Enantioselective and
Diastereoselective Hetero-Diels-Alder Reaction
[a]
[a]
[a]
[a]
[a]
Yubiao Hong, Tianjiao Cui, Sergei Ivlev, Xiulan Xie, and Eric Meggers*
Abstract: This study demonstrates that chiral-at-iron com-
plexes, in which all coordinated ligands are achiral and the
overall chirality the consequence of a stereogenic iron center,
are capable of catalyzing asymmetric transformations with
very high enantioselectivities. The catalyst is based on a
previously reported design (J. Am. Chem. Soc. 2017, 139,
2,6-diisopropylphenyl substituents at the NHC ligands, the
steric hindrance at the catalytic site was increased, thereby
providing a markedly improved asymmetric induction. The
new chiral-at-iron catalyst was applied to the inverse electron
demand hetero-Diels-Alder reaction between β,γ-unsaturated
α-ketoester and enol ethers provide 3,4-dihydro-2H-pyrans in
high yields with excellent diastereoselectivities (up to 99:1 dr)
and excellent enantioselectivities (up to 98% ee). Other
electron rich dienophiles are also suitable as demonstrated
for a reaction with a vinyl azide.
4
322), in which iron(II) is surrounded by two configurationally
inert achiral bidentate N-(2-pyridyl)-substituted N-heterocyclic
carbenes in a C -symmetric fashion and complemented by
2
two labile acetonitriles. By replacing mesityl with more bulky
Introduction
untapped opportunities for the design of novel chiral catalyst
[4]
architectures with potentially novel properties. In such chiral-
at-metal catalysts the required chirality is the consequence of
an asymmetric coordination of achiral ligands around the
central metal, thereby implementing a stereogenic metal center
with overall metal-centered chirality. Importantly, in this design
the metal serves both as the exclusive stereogenic center and
at the same time acts as the reactive center for catalysis. While
The development of homogeneous catalysts from earth-abun-
dant rather than noble metals is an important trend towards
the development of more sustainable chemistry. Much current
attention is focusing on the metal iron due to its high
abundance in the Earth’s crust combined with a low toxicity
[1]
profile. In fact, Nature makes use of iron as a catalytic or redox
center in a plethora of enzymes. With respect to asymmetric
iron catalysis, a significant variety of chiral iron complexes have
[5–8]
our initial work was focused on noble metals,
we recently
introduced the first example of a chiral-at-iron complex for
[2]
[9]
been developed to catalyze asymmetric transformations.
asymmetric catalysis (Figure 1a). In this catalyst, iron(II) is cis-
Despite impressive advancements over the past decade,
challenges remain with respect to catalytic performance, new
catalytic mechanisms, and the economic synthesis of the chiral
iron catalysts.
coordinated by two chelating N-(2-pyridyl)-substituted N-heter-
ocyclic carbene (PyNHC) ligands in a C -symmetric fashion and
2
the coordination sphere is further complemented with two
coordinating acetonitrile ligands. Depending on the helical
twist of the two PyNHC ligands, the metal center adopts either
a Λ or Δ absolute configuration. Importantly, the two PyNHC
ligands are configurationally inert while the two acetonitriles
are labile. This was accomplished by combining a strongly σ-
donating NHC moiety with a π-accepting pyridyl moiety in the
bidentate PyNHC which maximizes the ligand field stabilization
energy and at the same time labilizes the acetonitrile ligands
due to a kinetic trans-effect of the σ-donating NHC ligands. We
demonstrated that such a chiral-at-iron complex is capable of
catalyzing an enantioselective intramolecular Cannizzaro reac-
tion and an asymmetric Nazarov cyclization. However, enantio-
selectivities were only modest and we therefore fell short of
demonstrating the merit of this chiral-at-iron catalyst architec-
ture. Here, we report for the first time that such chiral-at-iron
catalysts can provide very high asymmetric inductions. We
achieved this by increasing the steric bulk of the substituent at
the NHC moieties from a previous 2,4,6-trimethylphenyl (Mes,
FeMes) to a 2,6-diisopropylphenyl (Dipp, FeDipp) moiety (Fig-
ure 1b). These moieties directly reach into the active site and
affect the asymmetric induction. We demonstrate in this work
Over the past 50 years, the development of chiral transition
metal catalysts has been centered predominately around the
careful design of tailored chiral metal-coordinating ligands.
[3]
However, since the seminal work of Alfred Werner it is already
established that chiral transition metal complexes do not need
to contain chiral ligands for achieving optical activity and we
have demonstrated over the past few years that chiral transition
metal catalysts composed solely of achiral ligands provide
[a] Y. Hong, T. Cui, Dr. S. Ivlev, Dr. X. Xie, Prof. Dr. E. Meggers
Fachbereich Chemie
Philipps-Universität Marburg
Hans-Meerwein-Strasse 4, 35043 Marburg (Germany)
E-mail: meggers@chemie.uni-marburg.de
Supporting information for this article is available on the WWW under
https://doi.org/10.1002/chem.202100703
©
2021 The Authors. Chemistry - A European Journal published by Wiley-
VCH GmbH. This is an open access article under the terms of the Creative
Commons Attribution Non-Commercial License, which permits use, dis-
tribution and reproduction in any medium, provided the original work is
properly cited and is not used for commercial purposes.
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close proximity to the site of catalysis, we aimed at increasing
the asymmetric induction by replacing the CF3 groups with
bulkier electron-withdrawing substituents, such as phthalimides
(
Λ-Fe1) and 3,5-bis(trifluoromethyl)phenyl moieties (Λ-Fe2).
However, when we evaluated the catalytic performance of
these new iron catalysts for the inverse electron demand
[10,11]
hetero-Diels-Alder reaction
of the β,γ-unsaturated α-ke-
toester 1, serving as a heterodiene, with the dienophile 2,3-
dihydrofuran (2) to generate the bicyclic compound 3, we
observed a decreased stereoselectivity. Whereas 3 mol% of Λ-
FeMes provided (3aS,4S,7aR)-3 with a dr of 98:2 and 91% ee
(
Table 1, entry 1), Λ-Fe1 and Λ-Fe2 displayed a slightly
diminished diastereoselectivity and only 88% ee (entries 2 and
). We therefore shifted our attention to the mesityl substituent
3
at the NHC ligand, which is involved in inter-ligand π-π-stacking
with the pyridyl moiety of the second PyNHC ligand and is
therefore in direct proximity of the catalytic site. Replacing the
mesityl group with a 2,6-dichloro-4-n-butyl group (Λ-Fe3)
provided the hetero-Diels-Alder product 3 with 98:2 dr and
9
1% ee (entry 4), identical to our previous catalyst Λ-FeMes.
However, gratifyingly, when we introduced the bulkier Dipp
group (Λ-FeDipp), both catalytic activity and stereocontrol
improved markedly. Using 3 mol% of Λ-FeDipp, an almost full
conversion was observed after 4 hours at room temperature
and (3aS,4S,7aR)-3 was isolated in 98% yield with 97% ee and
9
1
9:1 dr (entry 5). The catalyst loading can be reduced to 2 or
mol% with only a slightly decreased performance (entries 6
and 7). We next tested some reaction parameters. Reducing the
reaction temperature from room temperature to 5°C did not
increase the stereoselectivity but markedly reduced the catalytic
activity. Executing the reaction under air instead of nitrogen
reduced somewhat the catalytic activity (93% conversion after
4
hours) and enantioselectivity (94% ee, Δ=À 3% ee) (entry 9).
More problematic is the presence of water: the addition of
.1% water reduced the enantioselectivity to 82% ee (Δ=
À 15% ee) (entry 10). The combination of air atmosphere and
.1% water is most deleterious. While catalytic activity and
0
Figure 1. Chiral-at-iron complexes for asymmetric catalysis. a.) Previously
developed chiral-at-iron catalyst scaffold. b.) Replacement of 2,4,6-trimeth-
ylphenyl (Mes) with 2,6-diisopropylphenyl (Dipp) substituents at the NHC
ligands increases steric hindrance at the catalytic site. c.) Application of the
sterically more demanding Dipp-functionalized chiral-at-iron catalyst to an
asymmetric hetero-Diels-Alder reaction. X=alkoxy or azide.
0
diastereoselectivity remained satisfactory, the enantioselectivity
dropped to just 63% ee (Δ=À 34% ee), which we rationalize
with a racemization of the catalyst during the reaction
(entry 11). Interestingly, when we added just one equivalent of
MeCN, the enantioselectivity recovered but the overall catalytic
activity suffered, most likely due to a competition between
ketoester substrate and MeCN for binding to the iron catalyst.
Figure 2 shows a crystal structure of the racemic FeDipp
complex. The Dipp substituents of the individual NHC ligands
stack against the pyridyl moieties of the neighboring bidentate
ligands with one isopropyl group of each Dipp moiety reaching
towards the catalytic site composed of the two labile
acetonitrile ligands. This steric hindrance of the Dipp group
leading to a more sterically crowded active site can explain the
improved asymmetric induction of Λ-FeDipp over Λ-FeMes for
the hetero-Diels-Alder reaction.
that the Λ-enantiomer of FeDipp catalyzes hetero-Diels-Alder
reactions with high diastereoselectivity and up to 98% enantio-
meric excess (ee) (Figure 1c).
Results and Discussion
We commenced our study by synthesizing a few modified
chiral-at-iron complexes (see Supporting Information for the
detailed synthesis) (Table 1). Our previously reported catalyst
[9]
FeMes contained a mesityl substituent at the NHC ligand and
Since configurational stability is a key requirement for
chiral-at-metal complexes devoid of any achiral ligands, we
evaluated the configurational stability of FeDipp. For this, Λ-
FeDipp (>99:1 er) was subjected to different conditions and
a CF group at the pyridine ligand. We found that the electron-
3
withdrawing CF3 group is beneficial for the configurational
stability of the chiral-at-iron complex. Since this substituent is in
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Table 1. Initial experiments and optimization.
[a]
[b]
[c]
[d]
Entry
Catalyst
Conditions
Conversion (%)
dr
ee (%)
1
2
3
4
5
6
7
8
9
Λ-FeMes
Λ-Fe1
Λ-Fe2
standard
standard
standard
standard
standard
50
60
64
77
98:2
93:7
94:6
98:2
99:1
99:1
99:1
99:1
99:1
99:1
99:1
99:1
91
88
88
91
97
96
95.5
97
94
82
63
Λ-Fe3
[
e]
Λ-FeDipp
Λ-FeDipp
Λ-FeDipp
Λ-FeDipp
Λ-FeDipp
Λ-FeDipp
Λ-FeDipp
Λ-FeDipp
99 (98)
2 mol% Λ-FeDipp
1 mol% Λ-FeDipp
5°C instead of r.t.
99
[
f]
89
32
93
99
97
under air
10
11
12
2
added H O (0.1%)
air, H
air, H
2
O (0.1%)
O (0.1%), MeCN
[
g]
[h]
[h]
2
19 (92)
97 (86)
[
a] Standard condition: 1 (0.1 mmol), 2 (0.15 mmol), catalyst (0.003 mmol, 3 mol%) in distilled CH
2
Cl
2
(2.0 mL) stirred at r.t. for 4 h under nitrogen. Deviations
CHCHCl as internal standard. [c] Diastereomeric ratios
1
from these standard conditions are shown. [b] Determined by H-NMR of crude products using Cl
determined by H-NMR. [d] Determined with the purified products by HPLC on chiral stationary phase. [e] Isolated yield. [f] Reaction time of 8 h. [g] 1
equivalent of MeCN added. [h] Results in brackets are for extended reaction time of 24 h.
2
2
1
afterwards coordinated to (R)-α-methoxyphenylacetate, ((R)-
Aux1, 99% ee). Racemization leads to the formation of a
diastereomeric mixture of Δ-(R)-Fe4 and Λ-(R)-Fe4, which can
(Figure 3). In non-coordinating solvents such as CH Cl water
2 2
and air must be omitted which is consistent with results shown
in Table 1 (entries 9–11). It is worth noting that Λ- and Δ-
FeDipp are configurationally stable in the solid state under air
for at least several weeks. Analogous racemization experiments
with Λ-FeMes provided almost identical results (see Supporting
Information), revealing that the higher steric crowding of
FeDipp compared to FeMes does not affect its configurational
stability.
With an improved chiral-at-iron catalyst for the hetero-Diels-
Alder reaction in hand, we next performed a substrate scope
(Figure 4). We started with the reaction of modified methyl (E)-
2-oxo-4-phenyl-3-butenoate (1) with the dienophile 2,3-dihy-
drofuran. Replacing the methyl ester of 1 with an ethyl ester
provided the bicyclic product 4 in 96% yield with 96% ee as a
single diastereomer (99:1 dr). An allyl ester afforded the bicyclic
product 5 in 96% yield with 97% ee and 98:2 dr. Substituents
in the phenyl moiety were also well tolerated. For example, a
para-, meta- or ortho-methyl in the phenyl ring as well as an
ortho-bromine, para-fluorine, or a para-trifluoromethyl group
provided the bicyclic products 6–11 (96–99% yield, 98:1–99:1
dr, 96–98% ee) with equally high yields and stereoselectivities.
1
be analyzed by H-NMR, allowing a calculation of the degree of
racemization. Note, all racemization experiments were per-
formed in the presence of a 5-fold excess of α-ketoester 1
which improved reproducibility for reasons that are not
completely clear yet. Nevertheless, since α-ketoester is present
in large excess at the beginning of the catalytic reaction, these
conditions are representative for the catalytic conditions.
Accordingly, dissolving Δ-FeDipp in dry CH Cl for 4 hours
2
2
under nitrogen atmosphere demonstrated configurational inert-
ness of Δ-FeDipp under these conditions (Δ:Λ=99:1). How-
ever, the same conditions but under an atmosphere of air
resulted in a significant racemization (Δ:Λ=81:19). The
presence of 0.1% water under an inert atmosphere resulted in
Δ:Λ=60:40, while the combination of 0.1% water and air
atmosphere led to a complete racemization. However, when we
added just 0.1% MeCN to the conditions in the presence of
0
.1% water under air atmosphere, racemization was completely
suppressed (Δ:Λ=99:1). These experiments demonstrate that
FeDipp is configurationally robust in the presence of MeCN
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Figure 2. X-ray crystal structure of racemic FeDipp. Only one enantiomer is shown. Only one disordered species of the CF groups is shown. The
hexafluorophosphate anions, the acetonitrile solvent molecule and the hydrogen atoms are omitted. Displacement ellipsoids are shown at 50% probability
level at 100 K.
Figure 3. Racemization study. Conditions: All experiments were performed with Δ-FeDipp (>99:1 er) in dry CH
equivalents). After an incubation time under conditions described below, (R)-Aux1 (0.01 M in CH Cl , 1.0 equivalent) was added followed by triethylamine
0.01 M in CH Cl , 1.2 equivalents). The resulting mixture was concentrated to dryness, redissolved in CD
reaction conditions for the initial incubation: 1) Under nitrogen atmosphere. 2) Under air atmosphere instead. 3) Under nitrogen atmosphere and addition of
.1% H O. 4) Under air atmosphere and addition of 0.1% H O. 5) Under air atmosphere, addition of 0.1% H O, and addition of 0.1% MeCN.
2 2
Cl for 4 h in the presence of α-ketoester 1 (5
2
2
1
(
2
2
2 2
Cl and analyzed by H-NMR spectroscopy. Different
0
2
2
2
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Figure 4. Substrate scope. Reaction conditions: ketoester (0.10 mmol), dienophile (0.15 mmol) and Λ-FeDipp (0.003 mmol, 3.0 mol%) in distilled CH
(
(
2
Cl
2.0 mL) stirred at r.t. for 4 h under nitrogen. [a] Performed with 2 equivalents of dienophile (0.20 mmol). [b] Performed with 5 equivalents of dienophile
0.50 mmol). [c] Reaction time increased to 24 h and scale doubled (0.20 mmol ketoester).
2
The phenyl moiety can also be replaced with a naphthyl moiety,
an indole, and a furane (products 12–14, 92–99% yield, 95:5–
ethyl vinyl ether afforded the Diels-Alder product 24 in 95%
yield with 88:12 dr and 91% ee. Using instead 2-meth-
oxypropene as the dienophile provided the dihydropyrane
product 25 with 98% yield but a reduce diastereoselectivity of
70:30 dr and a modest enantioselectivity of 88% ee. 1-Meth-
oxyvinylbenzene is not a suitable dienophile and provided the
dihydropyrane 26 in only 40% yield and with 83:17 dr and
65% ee after an elongated reaction time of 24 hours. 1-
Azidoethenylbenzene can also be used as the dienophile and
the reaction with ketoester 1 afforded the azidopyrane product
27 with 95:5 dr and 95% ee but only a modest yield of 42%.
Finally, it is worth noting that the chiral-at-iron catalyzed
inverse electron demand hetero-Diels-Alder reaction can be
9
9:1 dr, 96–98% ee). Likewise, bicyclic products with alkenyl,
cyclohexyl, and a variety of different alkynyl groups in 4-
position are also accessible with very high yields and high
stereoselectivities (products 15–22, 80–98% yield, 95:5–98:2
dr, 90–97% ee). A crystal structure of 22 confirmed the
preference for the endo stereochemistry (see Supporting
Information). We also tested other dienophiles. Accordingly, the
reaction of 3,4-dihydro-2H-pyran with ketoester 1 afforded the
bicyclic product 23 in 83% yield with 94:6 dr and 96% ee. For
optimal results, two equivalents of the dienophile were used.
The reaction of ketoester 1 with 5 equivalents of the dienophile
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scaled up without any loss in performance: using just 1 mol% of
Λ-FeDipp, ketoester ester 1 at a scale of 1 mmol reacted with
2
9
,3-dihydrofuran to furnish bicyclic 3,4-dihydro-2H-pyran 6 in
9% yield with 99:1 dr and 97% ee.
Jørgensen et al. and Evans et al. independently set the
[12]
[13]
gold standard for asymmetric inverse demand hetero-Diels-
Alder reactions between β,γ-unsaturated α-ketoester and
electron-rich dienophiles using readily available copper(II)-bis
(oxazoline) catalysts, leading to valuable substituted 3,4-dihy-
dro-2H-pyrans. Jørgensen and Evans established the preference
of an endo transition state. DFT calculations by Houk and
coworkers confirmed the preference for the endo diastereose-
lectivity due to secondary orbital interactions between the
oxadiene and a lone pair of the heteroatom at the dienophile
[14]
(
see transition state in Figure 1c). Xu recently demonstrated
that copper(II)-bis(oxazoline) catalysts can also be applied to
[15]
the reaction of β,γ-unsaturated α-ketoester with vinyl azides.
Feng and coworkers introduced chiral N,N’-dioxide/erbium(III)
catalyst erbium(III)-N,N’dioxide catalysts for the asymmetric
[16]
reaction of β,γ-unsaturated α-ketoester with enol ether, while
X.-W. Wang, Xia, and Z. Wang recently reported a copper(II)-bis
[17]
(
oxalamide) catalyst for this transformation. However, to the
best of our knowledge, our work marks the first example of
iron-catalyzed asymmetric hetero-Diels-Alder cycloadditions
between β,γ-unsaturated α-ketoester and enol ether, including
one example with vinylazide as the dienophile.
Finally, after having established the utility of the new chiral-
at-iron catalyst, we improved the synthesis of enantiomerically
pure Λ- and Δ-FeDipp (Figure 5). Accordingly, starting with the
pyridylimidazolium salt LDipp, which can be synthesized in a
single step from 2,6-diisopropylaniline and 2-bromo-5-
trifluoromethylpyridine, conversion to its silver carbene com-
plex followed by electrolysis in MeCN with an iron plate as the
sacrificial anode provided the racemic complex rac-FeDipp in
[18]
5
6% yield.
Reaction of the racemic mixture with the
Figure 5. Optimized synthesis of enantiomerically pure Λ- and Δ-FeDipp.
salicyloxazoline auxiliary (S)-Aux2 in the presence of Et N
3
afforded the complex Λ-(S)-Fe5 in 46% yield as a single
diastereomer. Interestingly, no Δ-(S)-Fe5 is formed in this
procedure so that Δ-FeDipp can be isolated in 44% yield with
acetonitriles. By introducing bulky 2,6-diisopropylphenyl sub-
stituents at the NHC ligands, the steric hindrance at the catalytic
site was increased, thus providing a markedly improved
asymmetric induction. The new chiral-at-iron catalyst was
applied to the inverse electron demand hetero-Diels-Alder
reaction between β,γ-unsaturated α-ketoester and enol ethers
provide 3,4-dihydro-2H-pyrans in high yields with excellent
diastereoselectivities (up to 99:1 dr) and excellent enantiose-
lectivities (up to 98% ee). Other electron rich dienophiles are
also suitable as demonstrated for a reaction with a vinyl azide.
Chiral 3,4-dihydro-2H-pyrans and their corresponding tetrahy-
dropyrans are frequent motifs in natural products and other
9
4:6 er. Reaction of this enantiomerically enriched Δ-FeDipp
with the matched auxiliary (R)-Aux2 then provided Δ-(R)-Fe5 as
a single diastereomer. Treatment of the individual enantiomeric
auxiliary complexes Λ-(S)-Fe5 and Δ-(R)-Fe5 with NH PF in
4
6
MeCN at 30°C provided the enantiomerically pure catalysts Λ-
FeDipp (92% yield, >99:1 er) and Δ-FeDipp (77% yield over 2
steps, >99:1 er).
Conclusion
[19,20]
We have here demonstrated for the first time that chiral-at-iron
complexes, in which all coordinated ligands are achiral and the
overall chirality is exclusively due to a stereogenic iron center,
are capable of catalyzing asymmetric transformations with very
high enantioselectivities. The octahedral chiral-at-iron catalyst
contains two configurationally inert achiral bidentate N-(2-
pyridyl)-substituted N-heterocyclic carbenes and two labile
bioactive molecules.
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Experimental Section
Detailed experimental procedures, analytical data, NMR spectra, CD
spectra, and HPLC traces are provided in the Supporting Informa-
tion.
[3] A. Werner, Ber. Dtsch. Chem. Ges. 1911, 44, 1887–1898.
[
4] a) L. Zhang, E. Meggers, Acc. Chem. Res. 2017, 50, 320–330; b) X. Huang,
E. Meggers, Acc. Chem. Res. 2019, 52, 833–847.
[5] Our first work on reactive chiral-at-iridium catalysts: H. Huo, C. Fu, K.
Harms, E. Meggers, J. Am. Chem. Soc. 2014, 136, 2990–2993.
[
6] Our first work on chiral-at-rhodium catalysts: C. Wang, L.-A. Chen, H.
Huo, X. Shen, K. Harms, L. Gong, E. Meggers, Chem. Sci. 2015, 6, 1094–
1100.
Deposition numbers 2064430 (for FeDipp) and 2064431 (for 22)
contain the supplementary crystallographic data for this paper.
These data are provided free of charge by the joint Cambridge
Crystallographic Data Centre and Fachinformationszentrum Karls-
ruhe Access Structures service www.ccdc.cam.ac.uk/structures.
[
7] Our first work on chiral-at-ruthenium catalysts: Y. Zheng, Y. Tan, K.
Harms, M. Marsch, R. Riedel, L. Zhang, E. Meggers, J. Am. Chem. Soc.
2
017, 139, 4322–4325.
[
8] Our first work on chiral-at-osmium catalysts: G. Wang, Z. Zhou, X. Shen,
S. Ivlev, E. Meggers, Chem. Commun. 2020, 56, 7714–7717.
[
9] Our first work on chiral-at-iron catalysts: Y. Hong, L. Jarrige, K. Harms, E.
Meggers, J. Am. Chem. Soc. 2019, 141, 4569–4572.
Acknowledgements
[
[
[
This project has received funding from the European Research
Council (ERC) under the European Union’s Horizon 2020
research and innovation programme (grant agreement No
[
8
83212). Open access funding enabled and organized by
Projekt DEAL.
1
649.
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15] N. Thirupathi, F. Wei, C.-H. Tung, Z. Xu, Nat. Commun. 2019, 10, 3158.
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[
1
Conflict of Interest
[
[
2
011, 17, 8202–8208.
The authors declare no conflict of interest.
[
[
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Keywords: asymmetric catalysis · chiral-at-metal · hetero-Diels-
Alder · iron · stereogenic metal
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Manuscript received: February 25, 2021
Accepted manuscript online: April 15, 2021
Version of record online: ■■■, ■■■■
Chem. Eur. J. 2021, 27, 1–8
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FULL PAPER
A chiral-at-iron complex, in which all
coordinated ligands are achiral and
the overall chirality is exclusively due
to a stereogenic iron center, catalyzes
hetero-Diels-Alder reactions with high
diastereoselectivities (up to 99:1 dr)
and enantioselectivities (up to 98%
ee). Key for this excellent stereocon-
trol are bulky 2,6-diisopropylphenyl
substituents at the N-heterocyclic
carbene ligands which increase the
steric hindrance at the catalytic site.
Y. Hong, T. Cui, Dr. S. Ivlev, Dr. X. Xie,
Prof. Dr. E. Meggers*
1
– 8
Chiral-at-Iron Catalyst for Highly
Enantioselective and Diastereoselec-
tive Hetero-Diels-Alder Reaction