Aldehyde-catalyzed epoxidation of unactivated alkenes with aqueous hydrogen peroxide

Article abstract of DOI:10.1039/d1sc02360h

The organocatalytic epoxidation of unactivated alkenes using aqueous hydrogen peroxide provides various indispensable products and intermediates in a sustainable manner. While formyl functionalities typically undergo irreversible oxidations when activating an oxidant, an atropisomeric two-axis aldehyde capable of catalytic turnover was identified for high-yielding epoxidations of cyclic and acyclic alkenes. The relative configuration of the stereogenic axes of the catalyst and the resulting proximity of the aldehyde and backbone residues resulted in high catalytic efficiencies. Mechanistic studies support a non-radical alkene oxidation by an aldehyde-derived dioxirane intermediate generated from hydrogen peroxide through the Payne and Criegee intermediates.

Full text of DOI:10.1039/d1sc02360h

Chemical
Science
View Article Online
View Journal | View Issue
EDGE ARTICLE
Aldehyde-catalyzed epoxidation of unactivated
alkenes with aqueous hydrogen peroxide†
Cite this: Chem. Sci., 2021, 12, 10191
b
Ierasia Triandafillidi,ab Maroula G. Kokotou,a Dominik Lotter,b Christof Sparr
*
All publication charges for this article
have been paid for by the Royal Society
of Chemistry
a
*
and Christoforos G. Kokotos
The organocatalytic epoxidation of unactivated alkenes using aqueous hydrogen peroxide provides various
indispensable products and intermediates in a sustainable manner. While formyl functionalities typically
undergo irreversible oxidations when activating an oxidant, an atropisomeric two-axis aldehyde capable
of catalytic turnover was identified for high-yielding epoxidations of cyclic and acyclic alkenes. The
relative configuration of the stereogenic axes of the catalyst and the resulting proximity of the aldehyde
and backbone residues resulted in high catalytic efficiencies. Mechanistic studies support a non-radical
alkene oxidation by an aldehyde-derived dioxirane intermediate generated from hydrogen peroxide
through the Payne and Criegee intermediates.
Received 28th April 2021
Accepted 18th June 2021
DOI: 10.1039/d1sc02360h
rsc.li/chemical-science
alkenes. As one of the most common functionalities in organic
chemistry, a wide range of aldehydes are readily available and
have been employed as catalysts.14 However, one of the most
interesting characteristics is its auto-oxidation, where the
aldehyde reacts with molecular oxygen, leading to a variety of
activated intermediates.15 For instance, in the versatile
Mukaiyama epoxidation, overstoichiometric amounts of alde-
hydes have been employed as the mediators of the reaction
(Scheme 1, B).16–18 As a result, a particularly mild and selective
Introduction
Epoxides are versatile intermediates for the synthesis of
countless irreplaceable compounds.1 Since the introduction of
various versatile metal-catalyzed epoxidations pioneered by
Sharpless, Jacobsen, Katsuki and others,2 alkene epoxidation
has become one of the most studied reactions in organic
synthesis, both in industry and academia.2 Aer the successful
developments employing metal catalysts, much effort has been
devoted to the development of protocols where a more
sustainable metal-free catalyst is employed. The organocatalytic
epoxidation has ourished1a,1b,2 in particular with ketone,2
acid,3 nitrile4 or iminium salt2 catalysts (Scheme 1, A). Pioneered
by Adam,5 Curci,6 Yang,7 Denmark,8 Shi,9 Miller,10 Page11 and
others, a variety of oxidants, such as Oxone, tert-butyl hydro-
peroxide (TBHP) or less commonly hydrogen peroxide (H2O2)
were utilized to in situ generate the key dioxirane, peracid,
imidoperoxoic acid, or oxaziridine intermediates.
Over the last few years, the epoxidation of alkenes with
12
environmentally friendly aqueous H2O2 as the oxidant is
drawing increasing attention, since it is inexpensive, relatively
safe and affords water as byproduct. However, hydrogen
peroxide by itself is a poor oxidant for organic oxidations2,13 and
thus has to be activated by a catalyst to form a reactive inter-
mediate in order to enable the epoxidation of unactivated
aLaboratory of Organic Chemistry, Department of Chemistry, National and
Kapodistrian University of Athens, Panepistimiopolis 15771, Athens, Greece. E-mail:
ckokotos@chem.uoa.gr
bDepartment of Chemistry, University of Basel, St. Johanns-Ring 19, Basel 4056,
Switzerland. E-mail: christof.sparr@unibas.ch
† Electronic supplementary information (ESI) available: Experimental data,
optimisation studies, mechanistic and HRMS studies. See DOI:
10.1039/d1sc02360h
Scheme 1 Established epoxidations and conceptualization.
Chem. Sci., 2021, 12, 10191–10196 | 10191
© 2021 The Author(s). Published by the Royal Society of Chemistry

View Article Online
Chemical Science
Edge Article
process allowed the epoxidation of an exceptionally broad range under otherwise identical conditions (2 eq. H2O2 : MeCN in t-
of alkenes at room temperature employing molecular oxygen as BuOH/aq. 0.6 M K2CO3; 4 ꢀ 10ꢁ5 M EDTA tetrasodium salt,
the terminal oxidant. The process can thereby be performed pH ¼ 11). When aldehyde 3a was employed as the catalyst, the
with16 or without transition metal catalysts17 or in the presence desired epoxide 2a was formed in 74% yield. Interestingly, the
of N-hydroxyphthalimide as the catalyst.18 The mechanisms of diastereomeric aldehyde 3b provided epoxide 2a in signicantly
these epoxidations were studied in great detail. Nonetheless, lower yield (34%), underscoring the prerequisite spatial posi-
the nature of the active oxygen species remains a subject of tioning of aryl and bromide moieties to augment catalyst
debate.16 Considering the broad utility of the Mukaiyama turnover. Furthermore, the diastereomeric catalysts 3c and 3d
epoxidation and the ideal attributes of aqueous H2O2 as oxidant with three stereogenic axes as well as the atropisomeric four-
for sustainable synthesis, we anticipated the development of an axis system 3e also gave considerably lower yields. While the
aldehyde-catalyzed epoxidation of unactivated alkenes by relative conguration of 3a notably impacts activity conclusively
accommodating the formyl functionality within a spatially well- by governing the conformation of catalytic intermediates, the
dened site of an atropisomeric multiaxis system. We describe enantioselectivity remained low for all cases (#10% ee). The
herein, that the atropisomeric two-axis aldehyde catalyst 3a that catalytic activity trends were also conrmed with the commer-
was identied as an efficient catalyst for the activation of cially available aldehydes without rotationally restricted axes
aqueous hydrogen peroxide, allows the synthesis of a broad (3f–i). Interestingly, an enhanced yield was also observed for
range of epoxides 2 from a variety of unactivated alkenes 1 with ortho-bromonaphthaldehyde (3i) as compared to parent 2-
notable turnover (Scheme 1, C).
naphthaldehyde (3h), supporting the notion that a bromide in
proximity to the active site is benecial for the reaction
outcome. Nonetheless, the atropisomeric two-axis aldehyde 3a
outperformed all other catalysts, highlighting the impact of
bromine and aryl groups in proximity to the active site to
improve the catalytic activity and turnover.
Having identied the unique characteristics of catalyst 3a,
we focused on optimizing the reaction conditions (Table 1).
With 5 mol% of 3a in the presence of 6 eq. H2O2 and aqueous
buffer in t-BuOH, the desired a-methyl styrene oxide (2a) was
formed in 98% yield (entry 2). Furthermore, control experi-
ments without catalyst, oxidant, buffer or MeCN conrmed that
all components are necessary for the epoxidation (Table 1, entry
3–6). In agreement with our previous ndings,20a,20b a lower pH
provided the desired product in compromised yield, validating
Results and discussion
We initiated our epoxidation studies using several atropiso-
meric two-, three- and four-axis systems 3a–3e, which were
recently prepared.19 To our delight, 5 mol% of catalyst 3a
provided excellent activity for the epoxidation of a-methyl-
styrene (1a) using H2O2 as the oxidant (Scheme 2), which is in
stark contrast to literature precedents where overstoichiometric
amounts of aldehyde were required.16–18 We next compared this
remarkable nding for the epoxidation of unactivated alkenes
with the other atropisomeric aldehydes comprising two to four
stereogenic axes, as well as commercially available aldehydes
Table 1 Optimization of the reaction conditionsa
3a
Entry
[mol%]
Solvent
Deviation
Yield (%)
1
2
3
4
5
6
7
8
5.0
5.0
0
t-BuOH
t-BuOH
t-BuOH
t-BuOH
t-BuOH
t-BuOH
t-BuOH
EtOAc
MeCN
CH2Cl2
CHCl3
MeOH
MeOH
—
74%
98%
9%
0%
0%
6 eq. H2O2
—
No H2O2
No buffer
5.0
5.0
5.0
5.0
5.0
5.0
5.0
5.0
5.0
1.0
No MeCN
0%
pH ¼ 10
41%
67%
82%
15%
12%
quant.
83%
—
—
—
—
—
—
9
10
11
12
13
Scheme 2 Survey of aldehyde catalysts. aK2CO3/EDTA buffer (pH ¼
a
K2CO3/EDTA buffer (pH ¼ 11). Yield determined by 1H NMR using an
11). The yields were determined by 1H NMR using an internal standard.
internal standard.
10192 | Chem. Sci., 2021, 12, 10191–10196
© 2021 The Author(s). Published by the Royal Society of Chemistry

View Article Online
Edge Article
Chemical Science
that pH ¼ 11 is ideal for the generation of Payne's inter- catalyst loading to 1 mol% led to a reduced yield of 83% (entry
mediate20b,21 (peroxycarboximidic acid V from MeCN and H2O2, 13). Furthermore, aer performing the epoxidation (Table 1,
Table 1, entry 7 and mechanism in Scheme 5). The importance entry 12), the catalyst 3a was recovered intact (94% recovery by
of the generation of Payne's intermediate for the success of our 1H-NMR, 82% recovery aer column chromatography). To our
protocol is also highlighted by the fact that in the absence of knowledge, this is the rst example, where an aldehyde is
MeCN, no epoxidation is taking place (Table 1, entry 6). employed in substoichiometric amounts as the catalyst for an
However, Payne's intermediate alone cannot promote the epoxidation reaction (5 mol% versus usually 10–50 mol% of an
reaction to completion as can be extracted by the results of activated ketone in literature7–10 or 5–10 equivalents of
Table 1, entry 3. Using different solvents (entries 8–12), meth- pivaldehyde16–18).
anol was determined as the most effective medium for the
With the optimized reaction conditions dened, we set out
reaction, forming the desired a-methyl styrene oxide in quan- to explore the substrate scope of the aldehyde-catalysed epoxi-
titative yield (entry 12). On the other hand, a decrease of the dation of unactivated alkenes (Scheme 3). A variety of mono-
substituted styrenes were rst tested, providing excellent
isolated yields for the unfunctionalized and methoxy-
substituted styrenes (2b and 2c), but low yields for 2d and 2e
(in the case of 2e, 28% of the corresponding diol was also iso-
lated). In contrast to known procedures which lead to low
amounts of epoxide when terminal aliphatic alkenes are
employed, synthetically meaningful yields were obtained for
corresponding epoxides 2f and 2g. Gratifyingly, when studying
disubstituted alkenes, geminal and vicinal disubstituted olens
afforded an excellent outcome [2a, 2h (99 : 1 trans : cis from
99 : 1 trans : cis 1h) and 2i (only trans from only trans 2i)] and
also cyclic disubstituted alkenes provided epoxides in up to 97%
isolated yield (2j–2m). To explore the limitations of the method,
also trisubstituted unactivated alkene substrates were investi-
gated, leading to a 68% yield for a double epoxidation to
product 2n and an inferior performance for aryl-substituted 2o.
Unfortunately, tetrasubstituted alkenes or linear cis alkenes are
not viable substrates for this method, as in the former case, the
desired epoxide is not formed, while in the latter case, low yields
(around 16%) are observed.
Due to the novelty of aldehyde catalysis for epoxidations with
hydrogen peroxide, mechanistic studies to probe the reaction
pathway of this epoxidation were carried out (Scheme 4). In
agreement with analogous studies on the auto-oxidation of
aldehydes,15a,15b,15d,16i,18b control experiments for the epoxidation
of 1a to 2a support a mechanism involving an auto-oxidation of
aldehyde 3a. When the reaction was performed under an argon
Scheme 3 Substrate Scope. aK2CO3/EDTA buffer (pH ¼ 11). Yields of
products after isolation by column chromatography.
atmosphere (Scheme 4), only 11% product formation was
observed, emphasizing the involvement of oxygen in the reac-
tion in agreement with the epoxidation occurring through the
Payne intermediate (see Table 1, entry 3). In contrast, almost
quantitative yields were obtained by performing the reaction
under open air or a balloon of oxygen, verifying the notion that
oxygen is a constituent of the mechanism. According to liter-
ature,15a,15b,15d,16i,18b oxygen is required for the generation of the
Criegee intermediate IV.22 Indeed, adding 2 mol% of mCPBA in
the mechanistic experiment that was performed in the absence
of oxygen, the epoxidation reaction can be restored to a good
extent (42% yield, see below). Furthermore, if TEMPO or BHT
were added to the reaction as a radical trap, no epoxidation
product was formed, verifying the generation of radical inter-
mediates in the autooxidation of the catalyst. When the reaction
was performed in the dark, the yield of the desired epoxide 2a
remained constant, proving that the reaction mechanism does
Scheme 4 Mechanistic and radical clock experiments.
not follow a photochemical pathway. In order to exclude the
© 2021 The Author(s). Published by the Royal Society of Chemistry
Chem. Sci., 2021, 12, 10191–10196 | 10193

View Article Online
Chemical Science
Edge Article
transformation of intermediate IV and V, to form III and VII0,
which can also give rise to dioxirane VIII and acetamide. The
dioxirane intermediate VIII as the active oxidant then reacts
with unactivated alkene 1a to form epoxide 2a, regenerating
aldehyde 3a to close the catalytic cycle. The crucial role of the
buffer for the generation of intermediate V is highlighted in the
control experiments, as well as the inability of V alone to push
the reaction to completion. Oxygen from air is required for the
autooxidation of the aldehyde to form intermediate IV. A small
amount of peracid is necessary to promote the catalytic cycle via
the generation of IV and not to perform the epoxidation, as
highlighted by the recovery of 3a aer reaction completion and
the reinstatement of the epoxidation yield when catalytic
mCPBA was added to the control experiment under argon. A
nding consistent with the formation of dioxirane VIII is that 3a
under Shi-like conditions with Oxone as the oxidant, simulating
the formation of the dioxirane-intermediate, provided the
desired epoxide 2a in good yield (65%).24
Considering this mechanistic hypothesis, we examined the
possible pathways of the reaction by High Resolution Mass
Spectrometry (HRMS, see ESI† for details) and thereby detected
several of the intermediates of the proposed pathway. Adding
TEMPO as the radical scavenger to the reaction mixture, the
adducts of I and II (trapped with TEMPO) were identied,
supporting that the autoxidation step is occurring. The Criegee
intermediate IV and both intermediates V and VI were also
detected, corroborating the formation of the Payne interme-
diate, when using the appropriate aqueous buffer (pH ¼ 11).
Moreover, also the central alkene oxidant dioxirane VIII was
detected by HRMS. In order to rule out artifacts, the measure-
ments were also repeated using CD3CN or 2-bromobenzalde-
hyde (3g) to detect similar intermediates, such as the
corresponding Criegee intermediate and the dioxirane by
HRMS, thus further underpinning the proposed mechanism.24
Intermediate VII was observed in the case of 3g with CD3CN,
while VII0 was detected with 3a in the presence of TEMPO. In
accord with these ndings, both short-lived intermediates
provide exploratory support of an aldehyde-catalyzed epoxida-
tion by means of dioxirane formation.
Scheme 5 Proposed mechanism.
possibility that the epoxidation is promoted by an in situ
generated peracid, we substituted catalyst 3a by its acid or
alternatively by PhCOOH and observed a very low yield, which
again can be assigned to the reactivity of the Payne interme-
diate. This is in agreement with literature,10 where an acid in
combination with MeCN/H2O2 cannot promote the epoxidation
reaction. These results in combination with the almost quan-
titative recovery of 3a from the reaction mixture, verify that
a peracid is not responsible for the epoxidation, since in that
case, 3a could not have been recovered intact and should have
been oxidized to the corresponding acid,23 which is not capable
of performing the epoxidation. In order to test the nature of the
active intermediate that enables the epoxidation of the unac-
tivated alkenes, we performed the epoxidation with the radical
clock 1p. Epoxide 2p was observed in 19% yield, along with 19%
of diol 2p0 and 62% of unreacted 1p, without any ring-opened
product detected. This nding supports that the active
oxidant is of non-radical nature, and that the radical steps
during autooxidation of the aldehyde precede the epoxidation
step.
A proposed mechanism consistent with the ndings conse-
quently involves the initial autooxidation of a fraction of the
aldehyde 3a under aerobic conditions, forming radical inter-
mediate I (Scheme 5).15a,15b,15d,16i,18b The peroxy-radical interme-
diate II and peracid III is subsequently formed with oxygen.15
The addition of peracid III to aldehyde 3a provides the Criegee
intermediate IV.15b,22 At pH ¼ 11, the Payne intermediate V is
generated,4,20b,21 which is in equilibrium with VI from a reaction
with peracid III. The Criegee and Payne intermediates (IV + V)
result in a postulated species VII, which breaks up to form the
key dioxirane intermediate VIII, the acetamide byproduct and
regenerates peracid III. Another plausible pathway is the
Conclusions
In conclusion, we have developed a sustainable and efficient
method for the epoxidation of unactivated alkenes utilizing an
atropisomeric multiaxis aldehyde as the catalyst in combination
with hydrogen peroxide as the oxidant. This study reveals the
feasibility of aldehyde-catalyzed epoxidations and the mecha-
nistic studies shed rst light on this unique reactivity. To our
knowledge this is the rst example of an epoxidation reaction
that employs an aldehyde in catalytic amounts. Ongoing studies
aim to rationalize the individual requirements for catalyst
design to further increase catalytic efficiency and to accomplish
stereoselectivity.
Data availability
Experimental data are available from the authors upon request.
10194 | Chem. Sci., 2021, 12, 10191–10196
© 2021 The Author(s). Published by the Royal Society of Chemistry

View Article Online
Edge Article
Chemical Science
Am. Chem. Soc., 1996, 118, 491; (b) D. Yang, M.-K. Wong,
Y.-C. Yip, X.-C. Wang, M.-W. Tang, J.-H. Zheng and
K.-K. Cheng, J. Am. Chem. Soc., 1998, 120, 5943.
8 For selected examples, see: (a) S. E. Denmark, Z. Wu,
C. M. Crudden and H. Matsuhashi, J. Org. Chem., 1997, 62,
8288; (b) S. E. Denmark and H. Matsuhashi, J. Org. Chem.,
2002, 67, 3479.
Author contributions
I. T., C. S. and C. G. K. conceived the study, designed the
experiments, and analyzed the data. I. T. performed the exper-
iments and M. G. K. the HRMS studies. D. L. provided catalysts
3b–3e. The manuscript was written through contributions of all
authors.
9 For selected examples, see: (a) Y. Tu, Z.-X. Wang and Y. Shi, J.
Am. Chem. Soc., 1996, 118, 9806; (b) Z.-X. Wang, Y. Tu,
M. Frohn, J.-R. Zhang and Y. Shi, J. Am. Chem. Soc., 1997,
119, 11224; (c) C. P. Burke and Y. Shi, J. Org. Chem., 2007,
72, 4093; (d) N. Nieto, I. J. Munslow, H. Fernadez-Perez and
A. Vidal-Ferran, Synlett, 2008, 18, 2856.
10 For selected examples, see: (a) G. Peris, C. E. Jakobsche and
S. J. Miller, J. Am. Chem. Soc., 2007, 129, 8710; (b)
C. E. Jakobsche, G. Peris and S. J. Miller, Angew. Chem., Int.
Ed., 2008, 47, 6707; (c) P. A. Lichtor and S. J. Miller, Nat.
Chem., 2012, 4, 990.
Conflicts of interest
There are no conicts to declare.
Acknowledgements
C. G. K., I. T. and M. G. K. gratefully acknowledge the Hellenic
Foundation for Research and Innovation (HFRI) for nancial
support through a grant, which is nanced by 1st Call for H. F.
R. I. Research Projects to Support Faculty Members
&
11 For selected examples, see: (a) P. C. B. Page, G. A. Rassias,
D. Bethell and M. B. Schilling, J. Org. Chem., 1998, 63,
2774; (b) P. C. B. Page, M. M. Farah, B. R. Buckley and
A. J. Blacker, J. Org. Chem., 2007, 72, 4424.
12 The environmental impact of H2O2 is a matter of debate: (a)
Hydrogen Peroxide, Toxicological Overview, Public Health
England, 2009, https://assets.publishing.service.gov.uk/
government/uploads/system/uploads/attachment_data/le/
337708/
Researchers and the procurement of high-cost research equip-
ment grant (grant number 655). I. T. and M. G. K. would like to
thank State Scholarships Foundation (IKY) for nancial support
through a post-doctoral research scholarship funded by the
“Supporting Post-Doctoral Researchers-Call B” (MIS 5033021),
action of the Operational Programme “Human Resources
Development, Education and Lifelong Learning” and co-funded
by the European Social Fund (ESF) and Greek National
Resources. The COST Action C–H Activation in Organic
Synthesis CA15106 is acknowledged for supporting the Short-
Term Scientic Mission of I. T. to the University of Basel and
Dr D. Kaldre for helpful discussions. The Swiss National Science
Foundation is gratefully acknowledged for nancial support (C.
S. and D. L.).
Hydrogen_Peroxide_Toxicological_Overview_phe_v1.pdf; (b)
T. Mahaseth and A. Kuzminov, Mutat. Res., 2017, 773, 274; (c)
S. Fukuzumi, Y. -M. Lee and W. Nam, Chin. J. Catal., 2021,
42, 1241; (d) Y. Xue, Y. Wang, Z. Pan and K. Sayama,
Angew. Chem., Int. Ed., 2021, 60, 10469.
13 (a) G. Goor, J. Glenneberg and S. Jacobi, Hydrogen Peroxide,
Wiley-VCH, Weinheim, 2012. For reviews see: (b)
G. Grigoropoulou, J. H. Clark and J. A. Elings, Green Chem.,
2003, 5, 1; (c) G. De Faveri, G. Ilyashenko and
M. Watkinson, Chem. Soc. Rev., 2011, 40, 1722.
Notes and references
1 For selected reviews, see: (a) O. A. Wong and Y. Shi, Chem.
Rev., 2008, 108, 3958; (b) Y. Zhu, Q. Wang, R. G. Cornwall
and Y. Shi, Chem. Rev., 2014, 114, 8199; For books, see: (c) 14 For a recent review, see: Q. Wang, Q. Gu and S. You, Angew.
A. K. Yudin, Aziridines and Epoxides in Organic Synthesis, Chem., Int. Ed., 2019, 58, 6818.
Wiley-VCH, Weinheim, 2006; (d) G. Centi, S. Perathoner 15 For selected examples, see: (a) J. R. McNesby and C. A. Heller
and S. Abate, Modern Heterogeneous Oxidation Catalysis:
Design, Reactions and Characterization, Wiley-VCH,
Weinheim, 2009.
2 For a recent review, see: I. Triandallidi, D. I. Tzaras and
C. G. Kokotos, ChemCatChem, 2018, 10, 2521.
3 For the initial introduction of m-CBPA: N. Prileschajew, Ber.
Dtsch. Chem. Ges., 1909, 42, 4811.
Jr, Chem. Rev., 1954, 54, 325; (b) L. Vanoye, A. Favre-
´
Reguillon, A. Aloui, R. Philippe and C. de Bellefon, RSC
Adv., 2013, 3, 18931; (c) K. Miyamoto, J. Yamashita,
S. Narita, Y. Sakai, K. Hirano, T. Saito, C. Wang, M. Ochiai
and M. Uchiyama, Chem. Commun., 2017, 53, 9781; (d)
A. Maity, S.-M. Hyun and D. C. Powers, Nat. Chem., 2018,
10, 200.
4 G. B. Payne, P. H. Deming and P. H. Williams, J. Org. Chem., 16 (a) T. Yamada, T. Takai, O. Rhode and T. Mukaiyama, Chem.
1961, 26, 659.
Lett., 1991, 20, 1; (b) T. Yamada, T. Takai, O. Rhode and
T. Mukaiyama, Bull. Chem. Soc. Jpn., 1991, 64, 2109; (c)
W. W. Nam, H. J. Kim, S. H. Kim, R. Y. N. Ho and
J. S. Valentine, Inorg. Chem., 1996, 35, 1045; (d)
B. B. Wentzel, P. A. Gosling, M. C. Feiters and
R. J. M. Nolte, J. Chem. Soc., Dalton Trans., 1998, 2241; (e)
B. B. Wentzel, P. L. Alsters, M. C. Feiters and
R. J. M. Nolte, J. Org. Chem., 2004, 69, 3453; (f) A. C. Serra
and A. Gonsalves, Tetrahedron Lett., 2011, 52, 3489; (g)
5 For selected examples, see: (a) W. Adam, R. Curci and
J. O. Edwards, Acc. Chem. Res., 1989, 22, 205; (b) W. Adam,
P. B. Rao, H.-G. Degen, A. Levai, T. Patonay and C. R. Saha-
Moller, J. Org. Chem., 2002, 67, 259.
6 For selected examples, see: R. Mello, M. Fiorentino,
O. Sciacovelli and R. Curci, J. Org. Chem., 1988, 53, 3890.
7 For selected examples, see: (a) D. Yang, Y.-C. Yip,
M.-W. Tang, M.-K. Wong, J.-H. Zheng and K.-K. Cheng, J.
© 2021 The Author(s). Published by the Royal Society of Chemistry
Chem. Sci., 2021, 12, 10191–10196 | 10195

View Article Online
Chemical Science
Edge Article
Y. Li, X. T. Zhou, S. Y. Chen, R. C. Luo, J. Jiang, Z. X. Liang
and H. B. Ji, RSC Adv., 2015, 5, 30014; (h) J. Wang,
M. Yang, W. Dong, Z. Jin, J. Tang, S. Fan, Y. Lu and
G. Wang, Catal. Sci. Technol., 2016, 6, 161; (i) W. Zhou,
J. Zhou, Y. Chen, A. Cui, F. Sun, M. He, Z. Xu and Q. Chen,
Appl. Catal., A, 2017, 542, 191.
C. G. Kokotos, Green Chem., 2017, 19, 1291; (c) D. Limnios
and C. G. Kokotos, ACS Catal., 2013, 3, 2239; For examples
on the use of triuoromethyl ketones for oxidation
reaction from other groups, see: (d) Q.-Q. Cheng, Z. Zhou,
¨
H. Jiang, J. H. Siitonen, D. H. Ess, X. Zhang and L. Kurti,
Nat. Catal., 2020, 3, 386; (e) M. Cai, K. Xu, Y. Li, Z. Nie,
L. Zhang and S. Luo, J. Am. Chem. Soc., 2021, 143, 1078.
17 (a) K. Kaneda, S. Haruna, T. Imanaka, M. Hamamoto,
Y. Nishiyama and Y. Ishii, Tetrahedron Lett., 1992, 33, 21 (a) G. B. Payne and P. H. Williams, J. Org. Chem., 1961, 26,
6827; (b) K. R. Lassila, F. J. Waller, S. E. Werkheiser and
A. L. Wressell, Tetrahedron Lett., 1994, 35, 8077; (c)
C. Lehtinen and G. Brunow, Org. Process Res. Dev., 1999, 3,
651; (b) L. A. Arias, S. Adkins, C. J. Nagel and R. D. Bach, J.
Org. Chem., 1983, 48, 888; (c) S. Ye, J. J. Hu and D. Yang,
Angew. Chem., Int. Ed., 2018, 57, 10173.
101; (d) F. Loeker and W. Leitner, Chem.–Eur. J., 2000, 6, 22 (a) J. Criegee, Justus Liebigs Ann. Chem., 1948, 560, 127. This
2011.
Criegee intermediate is not to be confused with the Criegee
18 (a) F. Minisci, C. Gambarotti, M. Pierini, O. Porta, C. Punta,
F. Recupero, M. Lucarini and V. Mugnaini, Tetrahedron Lett.,
2006, 47, 1421; (b) R. Spaccini, L. Liguori, C. Punta and
H. R. Bjorsvik, ChemSusChem, 2012, 5, 261.
19 D. Lotter, A. Castrogiovanni, M. Neuburger and C. Sparr, ACS
Cent. Sci., 2018, 4, 656.
zwitterion formed in alkene ozonolysis. (b) Z. Hassan,
¨
M. Stahlberger, N. Rosenbaum and S. Brase, Angew. Chem.,
Int. Ed., 2021, DOI: 10.1002/anie.202014974.
23 (a) N. Shapiro and A. Vigalok, Angew. Chem., Int. Ed., 2008,
47, 2849; (b) Z. E. Hamami, L. Vanoye, P. Fongarland,
C. de Bellefon and A. Favre-Reguillon, J. Flow Chem., 2016,
6, 206.
20 (a) D. Limnios and C. G. Kokotos, J. Org. Chem., 2014, 79,
4270; (b) E. Voutyritsa, A. Theodorou, M. G. Kokotou and 24 For detailed mechanistic studies and results, see ESI.†
10196 | Chem. Sci., 2021, 12, 10191–10196
© 2021 The Author(s). Published by the Royal Society of Chemistry