Asymmetric Epoxidation of Enones Promoted by Dinuclear Magnesium Catalyst

Article abstract of DOI:10.1002/adsc.202100482

Asymmetric synthesis with cheaper and non-toxic alkaline earth metal catalysts is becoming an important and sustainable alternative to conventional catalytic methodologies mostly relying on precious metals. In spite of some sustainable methods for enantioselective epoxidation of enones, the development of a well-defined and efficient catalyst based on magnesium complexes for these reactions is still a challenging task. In this perspective, we present the application of chiral dinuclear magnesium complexes for asymmetric epoxidation of a broad range of electron-deficient enones. We demonstrate that the in situ generated magnesium-ProPhenol complex affords enantioenriched oxiranes in high yields and with excellent enantioselectivities (up to 99% ee). Our extensive study verifies the literature data in this area and provides a step forward to better understand the factors controlling the oxygenation process. Elaborated catalyst offers mild reaction conditions and a truly wide substrate scope. (Figure presented.).

Full text of DOI:10.1002/adsc.202100482

RESEARCH ARTICLE
doi.org/10.1002/adsc.202100482
Asymmetric Epoxidation of Enones Promoted by Dinuclear
Magnesium Catalyst
Joanna A. Jaszczewska-Adamczaka and Jacek Mlynarskia,*
a
Institute of Organic Chemistry, Polish Academy of Sciences, Kasprzaka 44/52, 01-224 Warsaw, Poland
Fax: (+48)-22-632-66-81;
Phone: (+48)-22-632-2322
E-mail: jacek.mlynarski@gmail.com
Homepage: www.jacekmlynarski.pl
Manuscript received: April 20, 2021; Revised manuscript received: July 8, 2021;
Version of record online: ■■■, ■■■■
Supporting information for this article is available on the WWW under https://doi.org/10.1002/adsc.202100482
Abstract: Asymmetric synthesis with cheaper and non-toxic alkaline earth metal catalysts is becoming an
important and sustainable alternative to conventional catalytic methodologies mostly relying on precious
metals. In spite of some sustainable methods for enantioselective epoxidation of enones, the development of a
well-defined and efficient catalyst based on magnesium complexes for these reactions is still a challenging
task. In this perspective, we present the application of chiral dinuclear magnesium complexes for asymmetric
epoxidation of a broad range of electron-deficient enones. We demonstrate that the in situ generated
magnesium-ProPhenol complex affords enantioenriched oxiranes in high yields and with excellent
enantioselectivities (up to 99% ee). Our extensive study verifies the literature data in this area and provides a
step forward to better understand the factors controlling the oxygenation process. Elaborated catalyst offers
mild reaction conditions and a truly wide substrate scope.
Keywords: asymmetric epoxidation; magnesium; enones; ProPhenol; TBHP
Introduction
epoxidation of α,β-unsaturated carbonyl compounds,
the topic still seems to be relevant, and most research
A fundamental discovery done by Sharpless over 40[1] is moving toward the discovery of more sustainable
years ago regarding the possibility of asymmetric catalysts and reaction conditions nowadays. Particu-
epoxidation of allyl alcohols with a chiral titanium larly interesting seems to be the application of nontoxic
complex significantly prompted the practical applica- alkaline metals being demanded for the production of
tion of epoxides in the asymmetric synthesis. Optically active pharmaceutical ingredients (API).
pure oxirane derivatives can be further transformed
Magnesium driven transformations such as
into various more refined enantiomerically pure cycloaddition,[13] domino,[14] ring opening,[15] Michael
intermediates[2] or target molecules,[3] particularly natu- addition reactions[16] are just simply examples unre-
ral products,[4] pharmaceuticals[5] or drug candidates.[6] vealing the wide application of this metal in
This discovery, inspired a tremendous development of synthesis.[17] Magnesium complex offers also milder
new strategies in the field of asymmetric epoxidation, Lewis acidity compared to traditional transition metals.
not only restricted to metal catalysis,[7] but also This made magnesium peroxide very promising cata-
application
of
organocatalysts,[8]
bioinspired lysts for the epoxidation of electron-deficient olefins.
transformations[9] and recently in the light-mediated
In 1997, Jackson and co-workers presented the for-
processes.[10] This resulted also in significant enlarging mation of optically pure epoxides from chalcones by
the range of substrates used from simple alkenes[11] to using a chiral magnesium complex with both enantio-
complex molecules that are functionalized at the last mers of ethyl tartarate (Scheme 1., 1a).[18] Conversion
stage of synthesis.[12]
of the corresponding E-chalcones to epoxy derivatives
Despite the enormous progress made in the devel- was reported with 81–94% ee and with moderate yields
opment of new methodologies for stereocontrolled 36–61% while the investigation were limited to only 5
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of Mg-based mononuclear alkoxide species as well as
its dimerization to the stable alkylperoxides where
each oxygen coordinate to two Mg atoms.[21] However,
despite specifying the correct catalyst structure, the
problem of enantioselectivity was not correctly ad-
dressed. The epoxidation carried out in the stoichio-
metric variant as well as in the catalytic variant
(10 mol% of the catalyst) resulted in the formation of a
product with quantitative yield in a short time but with
only low ee around 11%.
These research and insight into the correct structure
of magnesium complexes[23] prompted us to verify the
hypothesis of Jackson’s group and ultimately to design
magnesium-based highly enantioselective catalysts for
asymmetric epoxidation of a broad range of α,β-
unsaturated carbonyl compounds. Our idea was to put
two magnesium atoms in one catalyst molecule to
facilitate the formation of structures in which oxygen
atoms coordinate simultaneously to two metal centers.
In this paper, we show that the application of chiral
dinuclear magnesium catalyst based on the C2-symme-
try R,R-ProPhenol ligand performs better than previ-
ously published protocols in terms of enantioselectiv-
ity, while providing good to high reaction yields
(Scheme 1., 1c).
Scheme 1. Development of methods of asymmetric epoxidation
of E-chalcone S1 using chiral magnesium complexes.
examples. After 4 years, the same group published the
results of epoxidation of aliphatic enones. Initially,
epoxides have been formed with 40–54% yields and
Results and Discussion
67–82% ee by using 25% of the chiral complex Mg- Bearing in mind the divergent conclusions published
(+)-DET and TBHP as an oxidant.[19]
by the two research groups, we decided to address this
During further studies, the conditions were im- important topic thoroughly. To verify the hypothesis of
proved by replacing (+)-DET chiral ligand with its our both predecessors, we began by repeating the E-
tert-butyl derivative, which resulted in improvement chalcone S1 epoxidation by using the procedure from
both reaction yield (92–96%) and enantioselectivity 1997. After many attempts, as well as modifications to
(91–93% ee) by using 10 mol% of the catalyst. the original procedure, the results described by this
Although the tested substrate scope was narrow, it was group (Table 1, Supporting Information) could not be
shown that the epoxidation of 3-octen-2-one with the fully reproduced and the tested complexes turned out
addition of molecular sieves and 1 equiv. of water or to be capricious catalysts, unfortunately. Based on
with aqueous TBHP, the product was obtained with subsequent work, we assumed that the DET ligands
99–100% substrate conversion and the ee was in- does not offer a stable structure with two magnesium
creased to 97% with a reduction of the amount of atoms, which can lead to oxidation in many ways,
catalyst to 6 mol%.[20] Besides, they examined addition hence the repeatability of the reaction leaves much to
of ethanol instead of water in the epoxidation and be desired.
found that the amount of 0.48 equiv. EtOH affected the
Bearing in mind the formation of the dimeric
reaction results (conversion 94–99%, 91–96% ee). structure of magnesium alkoxide in this process, we
Interestingly, despite decades of extensive studies on chose ligands enabling the construction of such an
the reactivity of zinc- and magnesium alkyls towards architecture with two magnesium centers in one
O2,[21,22] the isolation and structural characterization of catalyst molecule. After many trials, we found that C2-
well-defined magnesium complexes still remained a symmetry Mg-R,R-ProPhenol (R,R-L1) complex
challenge at that time.
seems to be the catalyst of choice for asymmetric
After 10 years of Jackson’s research, Lewinski epoxidation of the basic E-chalcone S1. To compare
revised the topic of magnesium-promoted asymmetric the results by using both catalysts, two experiments
epoxidation of E-chalcone S1 with closer insight into were carried out parallelly (Table 4, Supporting in-
the structures of magnesium alkyl peroxides based on formation). Initially, we performed comparative experi-
β-diketiminate ligands (Scheme 1., 1b).[21] Lewinski ments on the epoxidation of S1 with Mg-(R,R)-
revealed also that the structures proposed by Jackson ProPhenol catalyst according to both Jackson’s and
are not correct and showed evidence of the formation Lewinski’s protocols. It quickly turned out that
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Table 1. Screening of solvents and temperature optimization in the enantioselective epoxidation of E-chalcone S1 under variant A
(without catalyst oxygenation) and variant B (with catalyst oxygenation).
Entry/Variant[b]
Solvent
Toluene
Temp. [ C]
Time [h]
Yield[h] [%]
ee[i] [%] (2R,3S)
°
1/A
0 to 10
0 to 10
0
0 to 10
0 to 10
0
0 to 10
0 to 10
0
24
24
96
24
24
144
24
24
144
24
24
24
24
144
20
144
144
144
96
56
20
60
79
79
35
83
80
88
83
18
30
55
73
76
70
93
61
88
94
74
95
94
78
81
88
69
79
91
37
78
81
86
85
86
92
88
19
85
90
78
84
84
90
93
87
72
96
92
83
2[c]/B
3[d]/B
4/A
Et2O
5/B
6/B
7/A
8/B
MTBE
9/B
DME
THF
1,4-dioxane
DCM
10/B
11[e]/B
12/B
13/B
14/B
15f/B
16/B
17/B
18[g]/B
19[g]/B
20[f]/B
21[f]/B
22/B
23/B
24/B
0 to 10
10 to 13
0 to 10
0 to 10
ACN
Toluene/ACN (1:1)
Toluene/MTBE (1:1)
Toluene/DME (1:1)
Toluene/Et2O (1:1)
Toluene/1,4-dioxane (1:1)
Toluene/1,4-dioxane (1:9)
Toluene/THF (1:1)
Toluene/THF (9:1)
Toluene/THF (1:9)
0
0
0
0
0
0
0
0
0
5
25
96
72
72
[a] Reactions were carried out by stirring the ligand 12 mol% R,R-L1 with 20 mol% n-Bu2Mg (0.5 M solution in n-heptane) in
solvent (1.84 mL) at room temperature for 1 h containing 2 eq. (0.8 mmol) of TBHP (4.0 M toluene solution), 1 eq. of chalcone
S1 (0.4 mmol) dissolved in 2.0 mL of appropriate solvent or its mixture unless otherwise stated.
[b]
°
Variant A – After synthesis of the chiral complex Mg-R,R-L1, the solution is cooled to À 10 C. Then 2 eq. (0.8 mmol) of TBHP
°
(4.0 M toluene solution) followed by 2.0 mL of chalcone S1 solution were added in one portion. The mixture is warmed to 0 C
and stirring is continued for the specified time; Variant B – After the synthesis of the chiral complex Mg-R,R-L1, the solution is
°
cooled to À 20 C and the Schlenk vessel is connected to the line with a desiccant and further to the oxygen balloon. Oxygen is
supplied for 1 hour at 625 rpm. Then 2 eq. (0.8 mmol) of TBHP (4.0 M toluene solution) followed by 2.0 mL of chalcone S1
solution were added in one portion. The mixture is warmed to a dedicated temperature and stirring is continued for the specified
time.
[c] Reactions were carried out with 10 mol% R,R-L1 and 10 mol% n-Bu2Mg (0.5 M solution in n-heptane).
[d] 0.8 eq. EtOH was added after chiral complex Mg-R,R-L1 synthesis and additionally stirred for 30 min.
[e]
°
O2 delivering at 10 C.
[f] Complete S1 conversion.
[g]
°
O2 delivering at 5 C.
[h] Isolated yield after silica gel chromatography.
[i] Determined by chiral HPLC analysis.
Lewinski’s conclusions were correct and this reaction
First, we attempted to careful optimization of the
protocol ensured higher enantiomeric excesses. It is reaction conditions. Initial experiments have been
important to emphasize that Lewinski’s thorough carried out for chalcone S1 with TBHP in various
research concerning the formation of an active solvents under the two protocols described in Table 1.
magnesium complex and the oxygenation of alkyl Variant A (Table 1) assumed conducting epoxidation
magnesium species are crucial for the course of the without catalyst oxygenation before TBHP and S1
reaction and greatly influenced our investigation.
addition to the reaction mixture, while Variant B
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(Table 1) assumed supplying oxygen to the catalyst for the influence of the ligand tuning on the reaction
°
1 hour at À 20 C before adding other reagents to the enantioselectivity. Knowing that the optimal reaction
reaction mixture. Conducting differential experiments parameters are crucial for enantioselectivity, we left
confirmed our earlier observations that oxygenation of this step unconventionally at the end to verify all
the catalyst solution is crucial for obtaining high ligands under the best conditions.
reaction yields and high asymmetric induction.
Scheme 2 summarizes comparison of results ob-
The initial studies towards the development of tained for various chiral ProPhenol ligands (R,R-L2–
efficient conditions began with the evaluation of R,R-L14). The data collected during these experiments
various solvents (Table 1). With R,R-L1,as a ligand in indicate that a slight change in the structure of the
°
toluene at 0 C, the transformation reached completion R,R-L ligand had a significant influence on the
within 96 h, affording the chiral epoxide P1with high enantioselectivity and yield of the reaction. Evolution
enantioselectivity (entry 3). High level of enantioselec- of the ligands with substituents on the aryl ring showed
tivity (85%) and good yield have been also maintained that any substituents decrease enantioselectivity, re-
in MTBE (entry 8) while the reaction carried out in gardless of their electronic nature. This effect was
THF was highly enantioselective yet not efficient most evident for the bulky tert-butyl substituents in
(entry 10). However, the best results in terms of R,R-L5. Interestingly, high enantioselectivity of 97%
enantioselective formation of epoxide P1 (96% ee) ee was maintained for the ligand R,R-L9 with the 2-
were recorded in the toluene/THF (1:9) mixture
(Table 1, Entry 22). Prolonged reaction time (96 h) at
°
0 C resulted in the formation of P1 with 78% yield.
Slightly lower enantioselectivities (91–93% ee) and
similar 74% yields were observed for toluene/1,4-
dioxane mixture (Table 1, entry 19). Notably, decreas-
°
ing the temperature to À 20 C had a negative effect on
the epoxidation process. The product P1 was isolated
with only 26% yield, while providing lower enantiose-
lectivities up to 52% ee. We also carried out experi-
ments with different oxidizing agents like cumyl
hydrperoxide (CHP), H2O2 (30%, aq.) and oxygen
(Table 6, Supporting Information). In case of CHP we
obtained product P1 with 21% yields and 44% ee,
while using hydrogen peroxide (30% aq.) was not
promising due to water contamination that resulted in
the catalyst decomposition. Also, the use of oxygen,
without any other oxidants did not cause the epoxide
formation. After this careful analysis, the reaction
°
carried out in toluene/THF mixture (1:9) at 0 C has
been selected for further stages of research.
Concerning the reaction protocol, the optimal
scenario assumed the oxygenation of the 2.0 mL
volume of the catalyst n-BuMg-R,R-L1 and the
addition of S1 in a solution which would also be
confirmed in the previous optimization studies related
to the selection of the solvent. Detailed optimisation is
collected in Supporting Information material (Table 7).
Finally, we investigated the influence of Mg/R,R-L1
molar ratio on the reaction enantioselectivity. Results
ultimately proved that the assumed metal-to-ligand
structures (2:1) build up the most efficient and
enantioselective catalysts. The slight excess of R,R-L1
used in relation was beneficial for longer (72 h)
epoxidation and reduced the influence of slow degra-
dation of ProPhenol ligand. The addition of chalcone
S1 in solution instead of the solid substrate proved also
to be optimal.
After confirming the effectiveness of R,R-L1 ligand
in asymmetric epoxidation, we also checked carefully
Scheme 2. Structures of tested R,R-L-ProPhenol ligands.
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thiophenyl group. These studies have also shown that position (59–68%) can be noticed. A similar selectivity
the coordination of magnesium to phenolic -OH is in G2 group was obtained for the fused aromatic ring
essential for high catalyst efficiency and enantioselec- substituents as in the G1 group. The selectivity of the
tivity. Thus, ligands R,R-13, and 14 turned out S28 epoxidation with the 1-naphthyl substituent
inefficient. However, the para-substitution of the reaches 77% ee (P28) compared to 52% ee for the S12
phenol ring did not change the catalyst efficiency counterpart, however the efficiency remains low at
significantly. The same level of asymmetric induction 38%, while for the S29 substrate the results are very
was observed for R,R-L11 with the Cl-substituent at good and in practice match those for S13. The case of
the para position of the central phenol backbone. The heterocyclic substituents is also much better. Epoxida-
R,R-L10 ligand was definitely the most favorable in tion products were obtained for all five tested
terms of reaction efficiency (95%), but with a slightly substrates S30–S34.
lower asymmetric induction (94% ee). Finally, ring
size reduction in the amino alcohol moiety in the R,R- 98% ee) for the P30–P34 products as well as good to
L12 ligand was unsuccessful. high yields (77–97%). Interestingly, higher enantio-
The enantioselectivity results are very high (93–
To demonstrate the wide applicability of the meric excess values were obtained for epoxidation of
developed methodology, we have carried out the the S35 substrate with a branched aliphatic substituent
reaction of over sixty alkenes. While the SI material (18%, 95% ee) than for the structural isomer S19, but
contains information about all experiments, Scheme 3 the reaction did not occur at all for substrate S57 with
summarizes the most promising results obtained with longer aliphatic carbon chain on the carbonyl side. In
the use of the dinuclear magnesium catalyst. Although the case of fluorinated substrates S37 and S38, the
we observed excellent yields and enantioselectivity for enantiomeric excess and yield are at a very good level
most substrates, the epoxidation efficiency varied (73–81%, 91–94% ee), while p-NO2- groups affected
depending on the chalcone structure, and particularly the overall yields and enantioselectivities (29–74%,
the location of the substituents on the benzene ring of 52–90% ee). Due to the poor solubility of the S40 and
substrates P1–P11 as follows: para- (76–95%, 79– S41 substrates, in these specific cases, the epoxidation
97% ee)>meta- (68–95%, 78–85% ee)>ortho- (0– procedure was modified and instead of using 2.0 mL
32%, 18–55% ee).
of the solvent mixture, these substrates were trans-
In the case of chalcones containing ortho and para- ferred to the reaction mixture as a suspension in
methoxy substituents, only traces of the product were 4.0 mL of dedicated solvent. It can also be seen that
observed, while the substrate with the o-Me substituent the para-NO2-group on the ketone side adversely
turned to be unreactive.
affects the selectivity of epoxidation if combined in
The study also revealed a significant decrease in addition to the presence of electron-donating substitu-
selectivity for the 1-naphthyl substituent (P12: 38%, ents or the general absence of substituents on the
52% ee), and an increase in selectivity for 2-naphthyl benzene ring at the double bond, similar to the P27
(P13: 86%, 96% ee). Such large differences may case (56%, 48% ee), for P39 we have 52% ee and 29%
indicate the existing steric hindrance and difficulties in yields. For the commercially available aliphatic linear
proper S12 arrangement at the catalyst reaction center. enone S44 the product was obtained with good
It was also the very first time to obtain epoxidation enantioselectivity and good yield (88%>70% ee)
products P14 and P15 (Scheme 3) with excellent when the reaction was scaled up. The reactivity study
selectivity>97–99% ee and very good yields 83–86%. of cyclic enones S45–S47 resulted in obtaining
Additionally, excellent enantioselectivity (> 98–99% products with moderate yields and enantioselectivity.
ee) were obtained for the substrates with the con-
We also managed to recover the R,R-L1 catalyst in
jugated bond system for (2E, 4E)-1,5-diphenylpenta- 70–85% yield from the reaction mixture during
2,4-dien-1-one (S16) and (2E, 4E)-1-phenylhexa-2,4- product column chromatography by elution with a
dien-1-one (S17), where the γ-σ double bond is in the more polar eluent.
acyclic system.
On the basis of the previously postulated mecha-
Epoxidation of S16, S17 with condensed double nisms[21] and based on the absolute configuration of
bonds occurred at the α,β-position and resulted in the epoxides, we proposed a tentative catalytic cycle for
formation of the product with high yield and stereo- enantioselective epoxidation of enones (S) mediated by
selectivity. However, the epoxidation of S18 (2-(cyclo- chiral magnesium peroxide and TBHP (Scheme 4). It
hex-2-en-1-ylidene)-1-phenylethanone), occurred on is important to notice, that based on our observation
the external γ,δ-double bound albeit with only 14% and previous experiments oxygenation step with O2 is
yield probably due to sterically reason. At first glance, crucial for preformation of the catalyst (II) that is
the substituents on the benzene ring in the chalcones further regenerated with TBHP in catalytic cycle. We
S22–S27 have a smaller effect on the enantioselectivity postulate that treating the chiral magnesium complex
results (48–93% ee), however, a decrease in the yield with O2 leads to the inclusion of molecular oxygen
for the products P22, P24 with substituents in the ortho between the magnesium-carbon bond of the Mg-n-Bu
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Scheme 3. Scope of the reaction.
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epoxidation of electron-poor alkenes will enable the
rational development of new, efficient and environ-
mentally harmless catalysts that can be successfully
used in science and industry.
Experimental Section
General Procedure for Enantioselective Epoxida-
tion of Substrates S1–S66
A 25 mL Schlenk vessel with a magnetic stir bar inside was
heat-gun dried for 5 min under vacuum. (R,R)-ProPhenol ligand
R,R-L1 (0.12 eq.) was added to the Schlenk vessel and the
system was placed under vacuum for additional 15 min. After
the drying step, a freshly prepared mixture of dry solvents
Toluene/THF (1:9) 1.84 mL was added to the vessel under an
atmosphere of argon, followed by addition of (0.2 eq.) n-Bu2Mg
(0.5 M solution in n-heptane) and continued stirring at room
temperature for 1 hour. After synthesis of the chiral complex,
Scheme 4. Proposed Catalytic Cycle.
°
the solution is cooled to À 20 C and the Schlenk vessel is
connected on one side to the vacuum/argon line and on the
other side to the oxygen balloon via a glass connector. The
vessel was briefly evacuated and backfilled with oxygen
(repeated for three times). Oxygen is supplied for 1.5 hour at
725 rpm. Then 2 eq. (0.8 mmol) of TBHP (4.0 M toluene
solution) followed by 2.0 mL of enone S (1.0 eq.; 0.4 mmol)
solution were added in one portion under argon flow. After the
moiety and this results in a catalytic formation of a
reactive chiral peroxide (II, n-Bu at this stage), which
is the proper catalyst. This chiral peroxide, also having
a Lewis acid center, coordinates the carbonyl oxygen
of the enone to give complex (III) followed by a
nucleophilic oxygen attack from the re-face to the
activated enone as described by the transition structure
(IV), resulting in an epoxide (P) with the assigned
configuration (for investigated enones mainly 2R,3S)
°
addition of the enone S solution, the mixture is warmed to 0 C
and stirring is continued at this temperature for the 72 h. The
reaction was quenched with the mixture (1:1; 4 mL) of saturated
and a chiral magnesium alkoxide (V) which completes NH4Cl(aq) and saturated Na2SO3(aq) and stirred for additional
15 min. (650 rpm) or quenched with water (in case of enones
S45–S48) without additional stirring. Quenched reaction mix-
ture was transferred to the separatory funnel and washed with
AcOEt (2×15.0 mL) or Et2O (2×35.0–40.0 mL in case of
enones S44–S48). The combined organic extracts were washed
with H2O (1×15 mL; in case of enones S45–S48 washed 2×
50.0 mL H2O) and brine (2×50.0 mL), dried over Na2SO4, and
the solvent was removed under reduced pressure. After the
removal of solvents, the crude mixture was subjected to silica
column chromatography to yield the epoxide product P.
the reaction cycle. The next step which the new cycle
gets started is the regeneration of peroxide (II) from
chiral magnesium alkoxide (V) using TBHP. Based on
the previous study,[21] we can assume that regeneration
of the catalysts (V into II) occurs with the formation of
magnesium tert-butoxide species as the result of the
alkoxide ligand exchange by TBHP. Overall, oxygen is
needed to initiate the catalytic cycle by forming the
proper catalyst (II), but its regeneration is possible
with the TBHP oxidant only.
Acknowledgements
Conclusion
Financial support from the Polish National Science Centre
(OPUS Grant No. NCN 2017/27/B/ST5/01111) is gratefully
acknowledged. We would like to thank O. Popik and K.
Michalak for their fruitful discussions about epoxidation under
development.
In conclusion, we have developed the most effective
strategy to date to obtain enantiomerically pure
epoxides derived from chalcones by using magnesium-
based catalysis and readily available C2-symmetry
ProPhenol ligands. The catalytic system developed by
us allowed to obtain a wide range of epoxides with
high efficiency and very good enantioselectivity for
both chalcones and more complex enones. By examin-
ing an extremely diverse group of electron-poor
alkenes, we could also learn about the limitations of
the proposed methodology. Chiral epoxides are versa-
tile scaffolds and can be used for further functionaliza-
tion, e.g., in the synthesis of biologically active
compounds or pharmaceutical drugs. We believe that
the results of our research on the asymmetric
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These are not the final page numbers!

RESEARCH ARTICLE
Asymmetric Epoxidation of Enones Promoted by Dinuclear
Magnesium Catalyst
Adv. Synth. Catal. 2021, 363, 1–10
J. A. Jaszczewska-Adamczak, J. Mlynarski*