Kinetic Resolution of Aziridines Enabled by N-Heterocyclic Carbene/Copper Cooperative Catalysis: Carbene Dose-Controlled Chemo-Switchability

Article abstract of DOI:10.1002/anie.202013679

Catalytic kinetic resolution (KR) and dynamic kinetic asymmetric transformation (DyKAT) are alternative and complementary avenues to access chiral stereoisomers of both starting materials and reaction products. The development of highly efficient chiral catalytic systems for kinetically controlled processes has therefore been one of the linchpins in asymmetric synthesis. N-heterocyclic carbene (NHC)/copper cooperative catalysis has enabled highly efficient KR and DyKAT of racemic N-tosylaziridines by [3+3] annulation with isatin-derived enals, leading to highly enantioenriched N-tosylaziridine derivatives (up to >99 % ee) and a large library of spirooxindole derivatives with high structural diversity and stereoselectivity (up to >95:5 d.r., >99 % ee). Mechanistic studies suggest that the NHC can bind reversibly to the copper catalyst without compromising its catalytic activity and regulate the catalytic activity of the copper complex to switch the chemoselection between KR and DyKAT.

Full text of DOI:10.1002/anie.202013679

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Accepted Article
Title: Kinetic Resolution of Aziridines Enabled by N-Heterocyclic Car-
bene/Copper Cooperative Catalysis: Carbene Dose-Controlled
Chemo-Switchability
Authors: Liuzhu Gong, Zi-Jing Zhang, Yu-Hua Wen, and Jin Song
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10.1002/anie.202013679
Angewandte Chemie International Edition
RESEARCH ARTICLE
Kinetic Resolution of Aziridines Enabled by N-Heterocyclic Car-
bene/Copper Cooperative Catalysis: Carbene Dose-Controlled
Chemo-Switchability
Zi-Jing Zhang, Yu-Hua Wen, Jin Song,* and Liu-Zhu Gong*
Abstract: Asymmetric methods that convert racemic starting
materials to enantioenriched products are inherently significant in
chemical synthesis. Catalytic kinetic resolution (KR) and dynamic
kinetic asymmetric transformation (DyKAT) are alternative and
complementary avenues to access chiral stereoisomers of both
starting materials and reaction products. The development of highly
efficient chiral catalytic systems for kinetically controlled processes
has therefore been one of the linchpins in asymmetric synthesis. N-
Heterocyclic carbene (NHC)/copper cooperative catalysis has
enabled highly efficient KR and DyKAT of racemic N-tosylaziridines
via [3 + 3] annulation with isatin-derived enals, leading to highly
enantioenriched N-tosylaziridine derivatives (up to >99% e.e.) and a
large library of spirooxindole derivatives with high structural diversity
and stereoselectivity (up to >95:5 d.r., >99% e.e.). Mechanistic
studies suggest that NHC can bind reversibly to the copper catalyst
without compromising its catalytic activity and regulate the catalytic
activity of the copper complex to switch the chemoselection between
KR and DyKAT.
between NHCs and metals (Figure 1b).[4d,6] Successful
cooperative catalysis of NHCs and hard Lewis acids,[7] such as
early transition metals, alkali and alkaline-earth metals, can be
achieved as a result of their weak interactions. On the other hand,
in the case of combining NHCs with late transition metals,[8] the
generation of NHC-ligated metal complexes ([M]∙NHC) is
unavoidable due to their strong interactions[4d] and would quench
the catalytic activity of the individual catalyst. As such, a
switchable interaction between NHCs and transition metals has
proven difficult to achieve, and active catalyst switching between
'on' and 'off' states through a ‘releasing/binding’ event between
NHCs and metals has rarely been realized.
Aziridines are featured in many biologically active molecules,
natural products, and pharmaceuticals[9] and have therefore
stimulated great interest in catalytic asymmetric synthesis.[10] Due
to their unique and strained core structure, aziridines can also
serve as versatile chiral building blocks for the construction of
synthetically
and
biologically
significant
nitrogenous
compounds.[11] In this context, the development of straightforward
methods that permit the conversion of racemic aziridines to
enantioenriched amine products is highly desirable.[12]
Regiodivergent KR,[13] reductive cross-coupling,[14] and DyKAT[15]
of racemic styrenyl aziridines via enantioselective ring-opening or
annulation with various nucleophiles have been extensively
investigated (Figure 1c). However, to date, NHC-bound
nucleophiles[16] have not been applied to stereoselectively open
the aziridine ring[17] for manufacturing enantiomerically enriched
N-heterocyclic compounds. We envisioned that an NHC-based
homoenolate[18] could associate with copper complex-activated
styrenyl aziridines[13g,15] to accomplish NHC/copper cooperatively
catalyzed[8b,8e,8g] asymmetric [3 + 3] annulation, leading to KR-
produced enantioenriched spirooxindolyl lactams[19] and
aziridines,[9] which have been both recognized as functional core
units in numerous natural products and biologically active
molecules (Figure 1d and 1e). Herein, we report highly
enantioselective KR of racemic aziridines via asymmetric [3 + 3]
annulation with enals enabled by copper/NHC cooperative
catalysis. In this case, the NHC not only is involved in the
organocatalytic cycle but also modulates the catalytic activity of
the copper complex as an additional ligand. More interestingly,
chemoselection between KR and DyKAT can be switched by
tuning the dose of NHC.
Introduction
Catalytic asymmetric synthesis of optically pure compounds is
increasingly in demand in the pharmaceutical, fine chemicals, and
agricultural industries.[1] Catalytic kinetic resolution (KR)[2] and
dynamic kinetic asymmetric transformation (DyKAT)[3] of racemic
mixtures are two alternative strategies to access enantioenriched
chiral molecules (Figure 1a). In the KR process, the chiral catalyst
preferentially accelerates the reaction of one enantiomeric
reagent (SR) over the other (SS), with a theoretical maximum 50%
yield of the desired product (PR) and the reserved enantiomer
(SS).[2] DyKAT involves a chiral catalyst-mediated racemization of
substrate enantiomers (SR and SS) and the catalytic
transformation of a racemic starting material into a single
enantioenriched product (PR), with 100% theoretical yield.[3] Thus,
the discovery of robust chiral catalyst systems for KR and DyKAT
to access enantiopure chiral adducts is of great importance in
terms of skeletal and stereochemical diversity.
N-Heterocyclic carbene (NHC) catalysis has been met with
great success in the past few decades.[4] The integration of metal
catalysis with NHC catalysis can achieve extra activation modes,
allowing unprecedented chemical reactions to ensue.[5] One of the
core issues of concern lies in the research on coordination events
Results and Discussion
[*]
Z.-J. Zhang, Y.-H. Wen, Dr. J. Song, Prof. L.-Z. Gong
Hefei National Laboratory for Physical Sciences at the Microscale,
Department of Chemistry, and Center for Excellence in Molecular
Synthesis of CAS, University of Science and Technology of China,
Hefei, 230026, China
On the basis of the synergistic catalysis design plan, we
investigated the KR of racemic 2-phenyl-N-tosyl aziridine 2a with
isatin-derived enal 1a, entailing both enantiomerically enriched
annulation products and aziridines at the same time (Table 1).
E-mail: jill@ustc.edu.cn; gonglz@ustc.edu.cn
Supporting information for this article is given via a link at the end of
the document.
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10.1002/anie.202013679
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RESEARCH ARTICLE
Figure 1. Design plan for the kinetic resolution (KR) and dynamic kinetic asymmetric transformation (DyKAT) of aziridines via NHC/Cu cooperative catalysis. a,
Schematic of the KR and DyKAT. Substrate enantiomers (SR, SS); product enantiomers (PR, PS); chiral catalyst (Cat*). b, Coordination events between NHCs and
metals in cooperative catalysis. c, Asymmetric ring-opening and annulation transformation of racemic styrenyl aziridines. d, Representative examples of naturally
occurring spirocyclic oxindole lactams and aziridines. e, This work: cooperative NHC/copper-catalyzed switchable KR and DyKAT.
Under the cooperative catalysis of chiral NHC generated in situ
from 4a and a copper complex with BINAP (L1), the desired [3 +
3] annulation product 3aa was obtained in 22% yield with 94:6
diastereoselectivity (d.r.) and 94% enantiomeric excess (e.e.) at
room temperature (entry 1). Evaluation of chiral NHC precatalysts
(4a-4e, entries 1–5) revealed that improved results were obtained
with the use of 4c (entry 3). Then, a series of chiral diphosphine
ligands (L) were tested in combination with NHC precatalyst 4c
(see the Supporting Information for details), and the chiral
diphosphine ligand L2 was shown to be optimal (entry 6). The use
of an inorganic base such as Na2CO3 further improved the
reaction results, and the e.e. value of recovered 2a increased to
>99% (entry 7). Gratifyingly, the best results were obtained by
using half of the combined catalyst (entry 8), and a superefficient
KR process was identified. In the absence of either copper, chiral
diphosphine ligand, or NHC precatalyst, less than 5% yield of the
desired product was obtained, indicating that both the chiral
copper complex and NHC were required (entries 9–11). The
chirality of NHC 4c and chiral phosphine L2 was identified to be
matched for stereochemical control (entry 8 vs entries 12-15). The
combination of an achiral NHC precatalyst 4f and chiral copper
complex CuI(L2) enabled the reaction to give 3aa with moderate
enantioselectivity, indicating that NHC played a key role in the
stereochemical control (entry 12). The use of an achiral ligand L3
or rac-L1 dramatically eroded the reaction efficiency, further
verifying the superiority of synergistic catalysis in the KR process
(entries 13 and 14). Significantly, the diastereomer of 3aa was
obtained by simply taking the enantiomer of the diphosphine
ligand L2 in concert with the NHC precatalyst 4c; however, the
KR results were not satisfactory (entry 15). Additionally, a large-
scale experiment and the condition-based sensitivity screening[20]
were conducted under optimized conditions to further highlight the
robustness of this method (see the Supporting Information for
details).
With the optimized procedure, we proceeded to evaluate the
substrate scope of the KR reaction of racemic N-tosyl aziridines 2
with isatin-derived enals 1 (Figure 2). As expected, a broad range
of N-substituents (R1), including Me, Et, Bn, and Ph, were
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Table 1. Reaction optimization[a]
3aa
2a
entry
4
L
base
yield [%]
d.r.
94:6
-
e.e. [%]
yield [%]
e.e. [%]
1
2
4a
4b
4c
4d
4e
4c
4c
4c
4c
4c
-
L1
L1
NEt3
NEt3
22
<5
29
22
8
94
-
75
26
-
-
68
75
91
56
49
49(48)
-
3
L1
NEt3
95:5
68:32
88:12
>95:5
>95:5
>95:5
-
94
88
76
97
97
99
-
39
29
7
4
L1
NEt3
5
L1
NEt3
6
L2
NEt3
44
50
50(50)
-
75
>99
>99
-
7
L2
Na2CO3
Na2CO3
Na2CO3
Na2CO3
Na2CO3
Na2CO3
Na2CO3
Na2CO3
Na2CO3
8[b]
9[b,c]
10[b]
11[b]
12[b]
13[b]
14[b]
15[b]
L2
-
-
<5
-
-
-
-
-
L2
-
-
-
-
4f
L2
33
<5
15
25
93:7
-
87
-
64
-
48
-
4c
4c
4c
L3
rac-L1
ent-L2
89:11
40:60
70
92[d]
82
73
10
31[e]
[a] Reaction conditions: 1a (0.075 mmol), 2a (0.1 mmol), Cu(CH3CN)4PF6 (5 mol%), diphosphine ligand L (10 mol%), NHC precatalyst 4 (10 mol%),
and base (0.1 mmol) in toluene (1.0 mL) at 25 °C for 24 h under N2. The yield and diastereomeric ratio (d.r.) were determined by 1H NMR spectroscopy
(isolated yield in parentheses). The enantiomeric excess (e.e.) was determined by HPLC. [b] Cu(CH3CN)4PF6 (2.5 mol%), L2 (5 mol%), NHC precatalyst
4c (5 mol%), 30 h. [c] In the absence of Cu(CH3CN)4PF6. [d] e.e. value of the major diastereomer. [e] (S)-2a was obtained.
tolerated to give annulation products (3aa–3da) in good yields
and with excellent levels of stereoselectivity (>95:5 d.r. for all and
up to >99% e.e.) (Figure 2a). A wide variety of isatin-derived enals
containing either electron-withdrawing or electron-donating
substituents on the phenyl ring (R2) performed well and provided
the corresponding products 3ea–3la with excellent diastereo- and
enantioselectivities, accompanied by the recovered (R)-2a with
up to >99% e.e. (Figure 2a). The absolute configuration of product
3aa was determined by X-ray crystallography (see the Supporting
Information). We next investigated the scope of this cooperatively
catalyzed KR reaction with respect to racemic aziridines 2 (Figure
2b). The KR of aziridines 2b-2h with various substituents on the
benzene ring proceeded smoothly with almost 50% conversion
and delivered excellent KR results in all cases, irrespective of the
electronic nature and substitution pattern of the substituents. The
corresponding chiral spirooxindoles 3ab-3ah were all obtained in
good yields and with excellent stereoselectivities (up to >95:5 d.r.,
99% e.e.). 2-Naphthyl substituted aziridine 2i provided good
selectivity. Vinyl aziridines 2j and 2k also worked well to deliver
annulation products 3aj and 3ak with high levels of
stereoselectivity, while both unreacted enantiomeric aziridines
were recovered with >99% e.e. However, due to the unique effect
of the 2-(p-methoxy)phenyl (PMP) substituent of aziridine 2l, the
KR process gave unsatisfactory results for this substrate.
In contrast to the elegant chiral diphosphine-copper(I)-
catalyzed DyKATs of electron-rich aryl-substituted aziridines
reported by Chai and coworkers,[15] the KR resolution of these
substrates has remained unexplored. The great challenge in
obtaining access to the KR mainly resulted from the rapid copper-
catalyzed substrate racemization. NHCs can form a relatively
stable complex with copper salts,[8b,8g] which would impact the
catalytic performance of the copper-diphosphine complex. Thus,
we hypothesized that fine-tuning the proportions of copper,
diphosphine ligand, and NHC would be able to leverage the
racemization rate of electron-rich aryl-substituted aziridines so
that either the KR or DyKAT of electron-rich aryl-substituted
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10.1002/anie.202013679
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aziridines could be accessed (Figure 3). Indeed, the ratio of
ternary catalysts had a considerable effect on the success of the
KR, and premixing Cu(CH3CN)4PF6, diphosphine L2, and NHC 4a
in
a ratio of 1:2:2 enabled the generation of a hybrid
Figure 2. Substrate scope for the kinetic resolution of racemic N-tosyl aziridines via NHC/Cu cooperative catalysis. Reaction conditions: 1 (0.075 mmol), 2 (0.1
mmol), Cu(CH3CN)4PF6 (2.5 mol%), diphosphine ligand L2 (5 mol%), NHC precatalyst 4c (5 mol%), and Na2CO3 (0.1 mmol) in toluene (1.0 mL) at 25 °C for 30 h
under N2. The diastereomeric ratio (d.r.) was determined by 1H NMR spectroscopy. Isolated yields. The enantiomeric excess (e.e.) was determined by HPLC.
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NHC/diphosphine Cu(I) complex[21] and consumed the active Cu(I) was highly efficient, as excellent enantioselectivities were
diphosphine species responsible for the racemization of
aziridines,[15] thereby enabling KR (Figure 3a). As anticipated, in
the presence of such an in situ-generated hybrid copper complex,
the KR of 2-PMP-substituted aziridine 2l with enal 1a successfully
afforded desired product 3al in 48% yield, >95:5 d.r., 94% e.e.,
accompanied by the recovery of 2l in 47% yield with 96% e.e.
Consequently, this KR of electron-rich aryl-substituted aziridines
obtained for both desired products 3am-3ao (93–95% e.e.) and
the recovered aziridines 2m–2o (92–>99% e.e.). Since tuning the
ratio of NHC to the copper complex can alter the racemization rate
of electron-rich aryl-substituted aziridines 2, we next turned our
attention to establishing the DyKATs of these substrates (Figure
3b). The presence of 2.5 mol% NHC 4c, 5 mol% Cu(CH3CN)4PF6
and 10 mol% diphosphine L2 was identified as the best combined
Figure 3. Substrate scope for the kinetic resolution and dynamic kinetic asymmetric transformation of electron-rich aryl-substituted aziridines via NHC/Cu
cooperative catalysis. [a] Kinetic resolution. Reaction conditions: Cu(CH3CN)4PF6 (2.5 mol%), diphosphine ligand L2 (5 mol%), NHC precatalyst 4c (5 mol%), and
Na2CO3 (0.1 mmol) were stirred in toluene (1.0 mL) at 25 °C for 1 h; then, 1a (0.06 mmol), 2 (0.1 mmol), and toluene (1.0 mL) were added to the reaction mixture
and stirred for 12 h under N2. After completion of the reaction, 50 μL of NEt3 was added. The diastereomeric ratio (d.r.) was determined by 1H NMR spectroscopy.
Isolated yields. The enantiomeric excess (e.e.) was determined by HPLC. [b] Dynamic kinetic asymmetric transformation. Reaction conditions: 1 (0.12 mmol), 2
(0.1 mmol), Cu(CH3CN)4PF6 (5 mol%), diphosphine ligand L2 (10 mol%), NHC precatalyst 4c (2.5 mol%), and Na2CO3 (0.1 mmol) in toluene (1.0 mL) at 25 °C
under N2. [c] Cu(CH3CN)4PF6 (2.5 mol%), diphosphine ligand L2 (2.5 mol%), NHC precatalyst 4c (5 mol%). [d] With 1a (0.075 mmol), 60 h. [e] Cu(CH3CN)4PF6 (5
mol%), diphosphine ligand L2 (5 mol%), NHC precatalyst 4c (2.5 mol%).
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catalyst system for the DyKAT. The dynamic kinetic annulation
reaction of enal 1a with aziridine (rac)-2l proceeded cleanly and
generated desired spirooxindole product 3al in 91% yield, >95:5
d.r. and >99% e.e. Variations in the substituent and substitution
pattern of enals 1 were tolerated with 2-PMP-substituted aziridine
2l and its analogs (2m-2o), and the corresponding products (3al-
3ml) were obtained in good yield (70-93%) and with excellent
diastereoselectivity and enantioselectivity (up to >95:5 d.r., >99%
e.e.).
Both spirooxindole and aziridine can be transformed into
synthetically significant compounds by subjecting them to facile
reaction conditions, as shown in Figure 4. Under the action of
SmI2 at room temperature, the tosyl group (Ts) of 3aa could be
easily removed to give compound 5 without loss of enantiopurity.
The reduction of 3aa with LiAlH4 successfully generated
spiroindolinepiperidine 6. In addition, hydrogenation of 3ak over
Pd/C led to spirooxindole 7 in 97% yield with maintained
enantiopurity. The enantioenriched aziridine (R)-2a obtained from
the KR is synthetically useful because of its propensity to undergo
ring opening reactions to give a series of functionalized molecules.
Chiral diamine 8 was obtained in 93% yield and >99% e.e. from
the treatment of anilines with (R)-2a. In the presence of catalytic
Pd(PhCN)2Cl2, the addition of excess 1,3,5-trimethoxybenzene to
(R)-2a afforded amide 9 with almost complete retention of the
stereochemical integrity.[22]
superior ability to promote rapid racemization; thus, optically pure
(R)-2l became racemic within 4 h (Figure 5a, conditions 1 and 2).
In particular, the 1:1 complexation of copper and L2 enabled a
faster racemization process (Figure 5a, condition 1 vs 2). In
contrast, the racemization of (R)-2l promoted by the 1:1 copper-
L2 complex slowed with increasing amounts of NHC 4c (Figure
5a, conditions 3 and 4) and was completely inhibited by the
addition of 10 mol% 4c (Figure 5a, conditions 5 and 6). To identify
the copper complex species existing under these conditions and
to determine which one altered the reaction pathway, 31P NMR
studies were carried out (Figure 5b). The standard 31P NMR
spectra of L2, CuI(L2) and CuI(L2)(4c) complexes were collected
and are shown in b1-b3 (Figure 5b). The 31P NMR spectrum of
the catalyst system of Cu(CH3CN)4PF6, L2, and 4c in a ratio of
1:1:2 found that a considerable amount of the CuI(L2)(4c)
complex formed, as indicated by a signal (δ -1.17 ppm) similar to
that observed in the standard spectrum of the CuI(L2)(4c)
complex, but the CuI(L2) complex existed in trace amounts
(Figure 5b, b4). Considering that racemization is difficult in the
presence of such a catalyst system (Figure 5a, conditions 5 and
6), we can conclude that the CuI(L2)(4c) complex shows no
catalytic activity for racemization. In contrast, in the 31P NMR
spectrum of the catalyst mixture of Cu(CH3CN)4PF6, L2, and 4c
in a ratio of 1:1:0.5, two signals assigned to the CuI(L2)(4c)
complex (δ -1.17 ppm) and the CuI(L2) complex (δ -1.42 ppm),
respectively, were found by comparison with the standard spectra
in b2 and b3, showing that L2 was almost completely consumed
in the reaction (Figure 5b, b5). The existence of the CuI(L2)
complex may account for the racemization in the presence of this
1:1:0.5 catalyst system (Figure 5a, condition 3). Even more
interestingly, the signal for the CuI(L2) complex appeared again
with the addition of enal 1a to the catalyst mixture (1:1:2) (Figure
5b, b6), presumably arising from the formation of the homoenolate
that consumes some NHC 4c. The addition of aziridine 2l caused
the signal for the CuI(L2) complex to disappear again, together
with the release of L2 (Figure 5b, b7). These observations
suggest that NHC can be released from the CuI(L2)(4c)
complex[8g] along with the addition of enal 1a and can continue
acting as an organocatalyst to activate the enal. In addition, the
absence or presence of the CuI(L2) complex governs the reaction
pathway toward the enantioselective KR or DyKAT of 2l.
On the basis of these experimental results, a plausible catalytic
cycle is proposed for the KR of aziridines (Figure 6). Initially, the
NHC/diphosphine Cu(I) complex catalyst, [CuI(L2)(4c)], is formed
from the coordination reaction of Cu(CH3CN)4PF6, L2, and NHC
precatalyst 4c under basic conditions and has been identified in
the standard reaction by ESI-MS (see the Supporting Information).
The addition of isatin-based enal 1a to NHC 4c generates Breslow
intermediate I, which represents azolium homoenolate species II
in mesomeric form, and concurrently releases some catalytically
active CuI(L2) species via the dissociation of NHC 4c from the
Figure 4. Synthetic transformations.
CuI(L2)(4c) complex. Principally,
a catalyst resting state
To understand the NHC-controlled switchable reaction pathway
between the KR and DyKAT of aziridines, a series of kinetic
studies were conducted (Figure 5). The racemization profile of
(R)-2l (99% e.e.) was first investigated with different catalyst
systems (Figure 5a). The combination of 5 mol% Cu(CH3CN)4PF6
with either 5 mol% or 10 mol% chiral phosphine L2 showed a
[CuI(L2)(4c)][21,23] might exist, which, after the loss of NHC 4c, can
participate in the catalytic cycle (left cycle, copper catalysis) as an
active species.[13g,15] The N atom of the aziridine and one of the O
atoms of the Ts group coordinate to the copper center to deliver
electrophilic intermediates III and IV. Thereafter, complexes III
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Figure 5. Mechanistic studies. a, Racemization profile of (R)-2l with different catalyst systems. (R)-2l was added after prestirring the combined catalyst and base
for 1 h. b, 31P NMR studies on the coordination effect between a copper complex of diphosphine ligand L2 and NHC catalyst 4c.
and IV can undergo SN2-type substitution with NHC-bound
nucleophile II at the 2-position of the aziridines at different rates.
Since the diastereomeric complex [(S)-2[Cu]*] (IV) is more
reactive and undergoes a much faster reaction than [(R)-2[Cu]*]
(III) does, intermediate V is primarily generated, and (R)-2
remains with high enantiopurity. Finally, the N-acylation
cyclization of intermediate V furnishes final product 3 and
regenerates the organocatalyst NHC-4c and the copper complex
CuI(L2) or CuI(L2)(4c).
In summary, highly efficient KR and DyKAT of racemic N-
tosylaziridines with isatin-derived enals have been achieved by
the cooperative catalysis of chiral NHCs and copper complexes,
leading to highly enantioenriched N-tosylaziridines and
spirooxindole derivatives with high structural diversity. The NHC
catalyst not only serves as a Lewis base organocatalyst but also
acts as a ligand coordinating to the copper complex of
diphosphine to regulate the catalytic activity. The chemoselection
between the KR and DyKAT is switchable by tuning the dose of
the chiral NHC, and the absence or presence of the Cu complex
of diphosphine governs the reaction pathway. This interplay of
NHC between ligand and organocatalyst is highly beneficial for
Conclusion
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We are grateful to the National Natural Science Foundation of China
(grant nos. 21831007 and 21702199), Chinese Academy of Science
(grant no. XDB20000000), the Anhui Provincial Natural Science
Foundation (grant no. 1808085QB30), and the Fundamental
Research Funds for the Central Universities (WK2060190083).
Keywords: N-heterocyclic carbene • copper • cooperative
catalysis • kinetic resolution • dynamic kinetic asymmetric
transformation
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under the catalysis of CuIL* (see ref. 13g, 13i, and 15), all failed to deliver
desired products under the catalysis of Cu(CH3CN)4PF6, L2, and 4c in a
ratio of 1: 2: 2.
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Zi-Jing Zhang, Yu-Hua Wen, Jin Song,*
and Liu-Zhu Gong*
Page No. – Page No.
Kinetic Resolution of Aziridines
Enabled by N-Heterocyclic Car-
bene/Copper Cooperative Catalysis:
Carbene Dose-Controlled Chemo-
Switchability
Highly efficient KR and DyKAT of racemic N-tosylaziridines with isatin-derived
enals have been achieved by the cooperative catalysis of chiral NHCs and copper
complexes, leading to highly enantioenriched N-tosylaziridines and spirooxindole
derivatives with high structural diversity.
This article is protected by copyright. All rights reserved.