Oxidative Cleavage of Alkenes by O2with a Non-Heme Manganese Catalyst

Article abstract of DOI:10.1021/jacs.1c05757

The oxidative cleavage of C═C double bonds with molecular oxygen to produce carbonyl compounds is an important transformation in chemical and pharmaceutical synthesis. In nature, enzymes containing the first-row transition metals, particularly heme and non-heme iron-dependent enzymes, readily activate O2 and oxidatively cleave C═C bonds with exquisite precision under ambient conditions. The reaction remains challenging for synthetic chemists, however. There are only a small number of known synthetic metal catalysts that allow for the oxidative cleavage of alkenes at an atmospheric pressure of O2, with very few known to catalyze the cleavage of nonactivated alkenes. In this work, we describe a light-driven, Mn-catalyzed protocol for the selective oxidation of alkenes to carbonyls under 1 atm of O2. For the first time, aromatic as well as various nonactivated aliphatic alkenes could be oxidized to afford ketones and aldehydes under clean, mild conditions with a first row, biorelevant metal catalyst. Moreover, the protocol shows a very good functional group tolerance. Mechanistic investigation suggests that Mn-oxo species, including an asymmetric, mixed-valent bis(μ-oxo)-Mn(III,IV) complex, are involved in the oxidation, and the solvent methanol participates in O2 activation that leads to the formation of the oxo species.

Full text of DOI:10.1021/jacs.1c05757

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Oxidative Cleavage of Alkenes by O2 with a Non-Heme Manganese
Catalyst
Zhiliang Huang, Renpeng Guan, Muralidharan Shanmugam, Elliot L. Bennett, Craig M. Robertson,
Adam Brookfield, Eric J. L. McInnes, and Jianliang Xiao*
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ABSTRACT: The oxidative cleavage of CC double bonds with
molecular oxygen to produce carbonyl compounds is an important
transformation in chemical and pharmaceutical synthesis. In nature,
enzymes containing the first-row transition metals, particularly heme
and non-heme iron-dependent enzymes, readily activate O2 and
oxidatively cleave CC bonds with exquisite precision under
ambient conditions. The reaction remains challenging for synthetic
chemists, however. There are only a small number of known
synthetic metal catalysts that allow for the oxidative cleavage of
alkenes at an atmospheric pressure of O2, with very few known to
catalyze the cleavage of nonactivated alkenes. In this work, we
describe a light-driven, Mn-catalyzed protocol for the selective
oxidation of alkenes to carbonyls under 1 atm of O2. For the first time, aromatic as well as various nonactivated aliphatic alkenes
could be oxidized to afford ketones and aldehydes under clean, mild conditions with a first row, biorelevant metal catalyst. Moreover,
the protocol shows a very good functional group tolerance. Mechanistic investigation suggests that Mn−oxo species, including an
asymmetric, mixed-valent bis(μ-oxo)-Mn(III,IV) complex, are involved in the oxidation, and the solvent methanol participates in O2
activation that leads to the formation of the oxo species.
numerous transition metal catalysts for oxidative cleavage of
alkenes (Scheme 1c,d).2c,6,7 More recently, organo- and
photocatalytic methods have been put forward.7a,8 Although
various mild oxidants have been examined, the use of O2
remains of utmost interest, as it is the most easily available,
least expensive, and cleanest oxidant. Pleasingly, a number of
the reported methods now allow O2 to be used as the oxidant
under various conditions.7a,9 Notwithstanding the progress
made, almost all the methods reported so far can only deal
with activated alkenes, such as styrene and derivatives. In
particular, until now, there appear to be no known catalysts that
can be used to cleave the more spread, nonactivated aliphatic
alkenes by using atmospheric O2, while showing a substrate scope
of potential for organic synthesis. To the best of our knowledge,
there are only three reports in the literature that describe the
oxidative cleavage of a few nonactivated aliphatic alkenes with
O2, two of which necessitated 3−5 equiv of reductant (Mn and
Co catalysts) while the third relied on a Pd catalyst with harsh
INTRODUCTION
■
Alkenes are one of the most important chemicals on which the
chemical industry is built. Apart from those that are derived
from oil and natural gas in immense quantities, alkenes are
widespread in drugs, natural products, polymers, and countless
organic chemicals.1 The CC double bonds thus provide a
ubiquitous functionality for accessing bespoke chemicals. In
this context, oxidative cleavage of CC double bonds to the
corresponding carbonyls is of particular interest, as ketones
and aldehydes are one of the few most often used
functionalities in organic synthesis.1a Indeed, oxidative cleavage
of alkenes has been practiced for over a century in research
laboratories and on various industrial scales.2 The standard
method for the direct oxidative cleavage of alkenes is
ozonolysis (Scheme 1a),3 which is widely performed by the
pharmaceutical and fine chemical industries.4 However, the use
of ozone as oxidant is associated with intrinsic safety issues, the
need for specialty equipment, and generation of over
stoichiometric amounts of waste.5 Alternative oxidants, such
as m-chloroperoxybenzoic acid, PhIO/HBF4, KMnO4,
CrO2Cl2, RuO4, and OsO4, are well-known to selectively
transform alkenes into carbonyls,2b,6 but they are expensive
and/or toxic, while creating waste (Scheme 1b).
Received: June 3, 2021
Published: June 23, 2021
In response to the mounting environmental and safety
issues, the past four decades have witnessed the study of
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and particularly, the use of benign and inexpensive O2 for
selective oxidation with the biologically relevant Mn remains “a
significant challenge for the synthetic chemist.”12b This may be
partly due to the different oxidation potentials required for
oxidizing a substrate versus activation of O2.
Scheme 1. Methods for the Oxidative Cleavage of Alkenes
and Schematic Showing of a Visible-Light-Driven Dioxygen-
Activation Strategy for the Reaction of O2 with a Metal
Catalyst
Photoirradiation has been explored to tune the redox
potential of metal catalysts.13 Bearing in mind the remarkable
property of a photoexcited catalyst being both more oxidizing
and more reducing than its ground state, we envisaged a
visible-light-driven dioxygen activation strategy for the
oxidative cleavage of alkenes with metal catalysts (Scheme
1). First, a molecular metal catalyst is excited by visible light to
alter its redox potential. The more reducing excited state could
then activate O2 to afford a more-oxidizing high-valent metal−
oxygen species, which could react with an alkene, leading to its
oxidation. In pioneering studies by Goldberg et al., light has
been shown to promote catalytic C−H oxidation with Mn(III)
complexes.12b,14
RESULTS AND DISCUSSION
■
Reaction Development. We set out to examine the
oxidation of an aliphatic alkene, N-methoxy-N,5-dimethylhex-
5-enamide (1a) (Scheme 2). To produce activated oxygen
Scheme 2. Optimized Conditions for the Oxidative
Cleavage of 1a by O2 and the X-ray Structure of
a
[Mn(dtbpy)2(OTf)2]
a
See the Supporting Information for details of optimization.
conditions (2% Pd, 8 atm O2, 100 °C, 24 h).10 In addition to
the chemical methods, enzymatic methods have been
explored;6b however, they are limited by substrate specificity
(Scheme 1e). Following on from our recent study of aerobic
cleavage of styrene derivatives with molecular iron and copper
catalysts,9a,11 herein, we report that the merger of a non-heme
Mn(II) catalyst with visible light enables the oxidative cleavage of
both aromatic and aliphatic alkenes under 1 atm of O2 at room
temperature (Scheme 1).
Being one of the most abundant, inexpensive, and
environmentally friendly metals on earth, manganese has
been extensively studied for biomimetic O2 activation in the
past four decades or so.12 The combination of a base metal
catalyst with O2 would provide an ideal “oxygenase-like”
synthetic protocol for oxidative cleavage of alkenes. However,
“despite O2 activation at Fe or Mn being a prominent target for
more than 40 years, there are still relatively few complexes that
activate O2 in a rationally designed and controlled manner”
species from O2 that can cleave the CC double bond, a
range of open-shell transition-metal complexes and metal salts
in combination with polydentate nitrogen ligands were
examined (Table S1 in the Supporting Information).
Delightfully, when the reaction was performed with Mn(OTf)2
and 2,2′-bipyridine type ligands under blue light irradiation
(470 nm, 9 W) in MeOH at 20 °C, the desired product 1,
resulting from the CC double bond cleavage, was obtained
(Table S1, entries 1−12). Screening of ligands revealed 4,4′-di-
tert-butyl-2,2′-dipyridine (dtbpy) to be most effective,
affording 1 in 32% yield (Table S1, entry 6). However, its
combination with other metal salts, such as Cu(OTf)2,
Fe(OTf)2, and CoCl2, was ineffective, affording no target
product (Table S1, entries 13−15). Notably, methanol as
solvent is critical; no conversion of 1a was observed when 1,2-
dichloroethane, tetrahydrofuran, benzene, ethanol, isopropa-
nol, or acetonitrile was utilized (Table S1, entries 16−21).
Further optimization shows that a mixture of MeOH and 1,1,1-
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a
Scheme 3. Oxidation of 1,1-Disubstituted Alkenes
a
All the reactions were performed with alkene (0.5 mmol), [Mn(dtbpy)2(OTf)2] (2 mol %), in MeOH/TFE (1:1, 2 mL) with blue light irradiation
b
c
(9 W, 470 nm) at 20 °C under O2 (1 atm) for 12 h. Isolated yields are given. 1 mL of EtOAc was added. Starting material was fully recovered.
trifluoroethane (TFE) (1:1 volume) is optimal, boosting the
yield of 1 to 62% (Table S1, entry 22). Note that blue light is
essential for the oxidation, without which the chemistry could
not proceed even at 70 °C (Table S1, entries 25 and 26; also
see Figure S12).
The structure of the manganese complex [Mn-
(dtbpy)2(OTf)2], resulting from the reaction of Mn(OTf)2
with the dtbpy ligand, has been determined by X-ray
diffraction (Scheme 2 and Scheme S1). The complex shows
a somewhat distorted octahedral geometry with expected Mn−
N bond distances (Tables S7 and S8). It is worth noting that
the isolated [Mn(dtbpy)2(OTf)2] displayed a similar activity as
that prepared in situ (Table S1, entries 22 and 23), indicating
that it is formed in the in situ reaction. Our subsequent
investigation was centered around using [Mn(dtbpy)2(OTf)2]
(2 mol %) as catalyst and O2 (1 atm) as oxidant in MeOH/
TFE (1:1) with continuous blue light irradiation at room
temperature.
Scope of Reaction. To demonstrate the generality of this
photo-Mn catalytic system, we first examined a series of
nonactivated 1,1-disubstituted aliphatic alkenes. As is shown in
Scheme 3, a wide variety of such olefins were selectively
converted to the corresponding ketones. Thus, aliphatic
alkenes bearing amide, ester, or amino acid functionalities
are all suitable, affording the desired products in moderate
yields (1−10). Dipeptide, urea, or glucose-containing alkenes
could be oxidized selectively as well (11−13), showing
potential applications in bioconjugate chemistry. Olefins with
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a synthetically important carbonyl functionality could be
tolerated (14−17), and meanwhile, olefins without other
functional groups were also oxidatively cleaved to furnish
ketone products in good yields (18−21 and 23). However, 3-
fluoro-2-methyltridec-1-ene, in which the CC double is
deactivated by an adjacent electron-withdrawing fluorine
group, could not afford any cleavage product (22), highlighting
the sensitivity of the catalyst to substrate electronic effect. In
contrast, the electron-withdrawing, but well-separated, bro-
mide did not stop the formation of ketone 25. The presence of
halogen substituents in the oxidation products, such as
chloride in 24 and bromide in 25, makes the ketone products
more versatile in further applications. Still worth noting is that
the oxidation-susceptible benzylic C−H bond (viz. 23, 24 and
below) remained intact during the oxidation, showing the
protocol to be chemoselective. The catalysis thus makes 1,1-
disubstitued CC bonds an easily accessible latent carbonyl
functionality.
Table 1. Oxidation of Mono-, Di-, Tri-, and Tetrasubstituted
Alkenes and Dialkenes
a
As maybe expected, this photo-Mn enabled protocol is well
suited for activated alkenes. Thus, as is seen in Scheme 3,
styrene and related derivatives were oxidatively cleaved to yield
carbonyl compounds in a highly selective manner and good to
excellent yields. Moreover, it shows an excellent functional
group compatibility, with halogen, nitro, ester, acid, cyclo-
propyl, alkynyl, pyridine, and boronic ester units all tolerated
(26−48). Both benzylic and tertiary C−H bonds, which are
prone to oxidation, were also tolerated during the oxidation
(42, 44−46), adding more support to the high chemo-
selectivity mentioned above. A gram-scale oxidative cleavage
was also demonstrated. Under the standard conditions but
with 0.01% mol (0.9 mg) of catalyst, α-methylstyrene (1.18 g,
10 mmol) was oxidized to ketone 26 with a turnover number
of 4000 in 12 h (Scheme S2). It is noted that this new strategy
allows for milder reaction conditions in comparison with the
previously reported Fe- and organo-catalytic methods,8b,d,9a,b
and shows improved compatibility with electron-withdrawing
groups in comparison with the photocatalytic method
developed by Wang et al.8c
a
The oxidation was then extended to monosubstituted,
internal disubstituted, trisubstituted, and tetrasubstituted
alkenes as well as dialkenes. As shown in Table 1, a diverse
range of such alkenes can be oxidized to afford the
corresponding carbonyls or their methanol-protected form,
dimethyl acetals. Thus, the unsaturated fatty acid derivative 49
was cleaved into an aldehyde, which was in situ converted into
the acetal 50. Cyclooctene 51 gave rise to two isolable,
valuable oxidation products 52 and 53 in 41% overall yield, the
former of which is likely to result from the oxidation of the
initially formed aldehyde. Worth noting is that the formation of
the epoxide 53 may indicate the involvement of a high valent
Mn−oxo species during the oxidation.15 The CC double
bonds of trisubstituted alkenes, such as those in 54, 56, and 58,
were all oxidized, affording carbonyl products and derivatives.
For instance, the cleavage of 58 led to benzophenone 38 and
the overoxidation product of benzaldehyde, methyl benzoate
57, in good yield (see the Supporting Information for details).
The viability of the protocol in oxidatively cleaving
tetrasubstituted alkenes is seen in the examples of 59, 61,
and 62, the isolated products being the ketones of higher
molecular weight in the case of 59 and 61. Note that the
cyclopentene 62 underwent ring-opening, affording the
diketone 16. Interestingly, dialkenes are also viable for this
transformation, with both the CC double bonds selectively
All the reactions were performed with alkene (0.5 mmol),
[Mn(dtbpy)2(OTf)2] (2 mol %), in MeOH/TFE (1:1, 2 mL) with
blue light (9 W, 470 nm) at 20 °C under O2 (1 atm) overnight.
b
Isolated yields are given. The yield was obtained by 1H NMR
analysis with mesitylene as internal standard.
oxidized to afford the corresponding dicarbonyl compounds in
good yields (63−65 and 67).
To further demonstrate the practical applicability of this
photo-Mn protocol in aerobic oxidation of CC double
bonds, we attempted the oxidative cleavage of a wide range of
natural products and their derivatives. As shown in Table 2,
terpenes could be selectively oxidized into terpenoids, which
are interesting chemical intermediates for fragrance (70 and
72). The nopinone 70, produced industrially from ozonolysis
of 69, has been used to synthesize Nabilone,16 a synthetic
cannabinoid used to treat nausea and vomiting during cancer
treatment, and the prostaglandin D2 (PGD2) receptor
antagonist S-5751.17 However, a detailed safety study of the
industrial ozonolysis has revealed the high risk of explosion and
a runaway reaction in this multistep process (−57, −27, 0, and
finally 25 °C).17 (+)-Nootkatone 73, a sesquiterpene ketone
from the heartwood of yellow cedar, was cleaved to afford the
corresponding methyl ketone in good yield. Interestingly,
although there are two CC double bonds in the structure of
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presence of DPA as a 1O2 trap, no endoperoxide was detected,
and importantly, the expected cleavage product acetophenone
26 was formed in 70% yield (Scheme S3). In addition, when
four well-known photosensitizers, eosin Y disodium salt,
[Ru(bpy)3·6H2O], [Ir(dFppy)3], and Rose Bengal, which are
Table 2. Oxidation of Natural Products or Their
Derivatives
a
1
all known to be capable of producing O2 under blue light
irradiation,21 were used individually as replacement catalyst for
the oxidative cleavage of 1a, none were found to catalyze the
reaction (Table S3). These observations indicate that the
photo-Mn promoted oxidative cleavage of alkenes does not
1
involve catalytic formation of O2.
Bearing in mind that the oxidative catalysis in question likely
involves high-valent Mn−oxygen species, we then followed the
photopromoted Mn activation of O2 by UV−vis spectroscopy.
As shown in Figure 1A, when the [Mn(dtbpy)2(OTf)2]
complex was exposed to O2 under the irradiation of blue light
for 1 h, a new absorption band at ∼537 nm appeared,
indicative of the formation of a new Mn−oxygen species.22 In
line with this conjecture, a color change from pale-yellow to
greenish-brown was observed. Notably, both blue light and O2
are essential for the formation of this species; in the absence of
either one, the complex remained unchanged. To help assign
the photoinduced absorption, a well-studied oxidant, PhIO,
was reacted with [Mn(dtbpy)2(OTf)2] in the dark under N2
(room temperature, MeOH solvent). Compared with the
oxidation using O2, the reaction with the stronger oxidant
PhIO was immediate, resulting in the same greenish-brown
solution. As can be seen, an identical absorption band at 537
nm was observed (Figure 1A, red line), suggesting that the two
conditions lead to the same Mn−oxygen species.
Delightfully, we were able to isolate the Mn−oxygen species
and determine its structure by X-ray diffraction. As is shown in
Figure 1B, it is a mixed-valent oxo-bridged binuclear
Mn(III,IV) complex, [Mn(dtbpy)2(μ-O)2Mn(dtbpy)-
(MeOH)2](OTf)3 (bis-μ-O2-Mn2). Unlike common bis-μ-
oxo Mn(III,IV) dimers, the complex features two asymmetric
metal centers in significantly different environments, with one
ligated by two dtbpy ligands while the other by only one. The
former is likely to be Mn(IV) and the latter Mn(III), judging
from the Mn−O and Mn−N bond distances.23 Most revealing
is that the isolated complex shows a clear UV−vis absorption
band at 537 nm (Figure 1A, black line), suggesting that the
same oxo-bridged species is formed when [Mn-
(dtbpy)2(OTf)2] is irradiated under O2 or reacted with
PhIO under N2, albeit with differing concentrations. HRMS
analysis also indicates that these two different reactions give
rise to the same Mn(III,IV) dimer (Figure S8). Figure 1C
shows the experimental and calculated mass spectrum of the
a
All the reactions were performed with alkene (0.5 mmol),
[Mn(dtbpy)2(OTf)2] (2 mol %), in MeOH/TFE (1:1, 2 mL) with
blue light (9 W, 470 nm) at 20 °C under O2 (1 atm) overnight.
Isolated yields are given.
(+)-Nootkatone, only the electron-rich exo double bond was
selectively oxidized. The α-cyperone derivative 75 and the 20-
methylpregna-4,20-diene-3,6-dione 77, which are active
pharmaceutical ingredients, underwent oxidative cleavage to
give the desired product 76 and 78 in a highly chemoselective
manner. Vitamin K1 could also be oxidized efficiently,
affording the valuable hexahydrofarnesyl acetone 80, a member
of sesquiterpenoids and used in jasmine compositions.18 These
reactions and those above are often accompanied by some side
products (for examples, see the Supporting Information).
Mechanistic Possibilities. While the detailed mechanism
of the oxidation remains largely unclear, we have performed a
range of experiments, aiming to shed light on possible reaction
pathways. As reactions between olefins and singlet oxygen
(1O2), which can be generated from O2, light, and a
photosensitizer, are well-known to give oxidative cleavage
products,19 we thought that it is important to first determine
−
molecular ion resulting from the loss of a HOTf and a OTf
fragment from the parent dimer.
Furthermore, the methanol solutions of bis-μ-O2-Mn2 before
and after blue light irradiation were monitored by electron
paramagnetic resonance (EPR) spectroscopy. As shown in
Figure S13, the methanol solution of bis-μ-O2-Mn2 gives a
complex multiline spectrum, which is consistent with the S =
1/2 ground state of the antiferromagnetically coupled Mn(III/
IV) dimer.24 Notably, at room temperature, the Mn(III/IV)
dimer partially decomposes to Mn(II), which could be further
oxidized to the dimer by air under irradiation, and we see clear
signatures of Mn(III) in parallel mode EPR spectra (Figure
S14). Significantly, irradiating the MeOH-dissolved Mn(III/
IV) dimer with blue light increases the intensity of a signal in
the geff = 4 region, with a noticeable enhancement of hyperfine
1
whether O2 plays a role in the photo-Mn enabled oxidative
cleavage. The 1O2 trap 9,10-diphenylanthracene (DPA) is
1
known to react rapidly with O2 to give an endoperoxide
product (k ≈ 1.3 × 106 M−1 s−1).20 When α-methylstyrene was
subjected to the standard oxidation conditions but in the
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Figure 1. (A) UV−vis spectra of [Mn(dtbpy)2(OTf)2] with or without oxidants and of bis-μ-O2-Mn2 complex (0.25 mM, in MeOH). (B) X-ray
structure of the bis-μ-O2-Mn2 complex (for details, see Figure S7 and section 9.2 in the Supporting Information). (C) HRMS spectrum of the bis-
μ-O2-Mn2 complex formed in the in situ reaction of [Mn(dtbpy)2(OTf)2] with O2. (D) Kinetic behavior of the oxidation of α-methylstyrene
catalyzed by [Mn(dtbpy)2(OTf)2] and bis-μ-O2-Mn2. (E) Perpendicular mode, CW-EPR spectra of the bis-μ-O2-Mn2 dimer (black trace) dissolved
in cold (208 K) MeOH, followed by irradiation with blue light under air for 40 min (red trace), 5 min (blue), and 10 min (magenta) at the
specified temperatures. The left-hand panel shows the zoomed-in geff = 10 and geff = 4−6 regions of the spectra in the right-hand panel. Conditions:
MW power 10 dB, MA 5G, time constant 82 ms, conversion time 10 ms, sweep time 120 s, receiver gain 30 dB, average microwave frequency 9.385
GHz, temperature 20 K.
structure (ca. 90 G), along with the development of a
pronounced shoulder at ca. 1000 G, while the multiline
structure in the g = 2 region is lost (Figure 1E). This could be
consistent with generation of high-valent species from the
Mn(III/IV) dimer. We see clear evidence of Mn(III), and
although inconclusive, a Mn(IV) monomer (S = 3/2) with
large zero-field splitting would be expected to give signals in
the geff = 4−6 region: similar signals have previously been
assigned to Mn(IV).25
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The time course of the oxidation of a model substrate α-
methylstyrene 26a reveals additional insight. As shown in
Figure 1D, when the model reaction was performed by using
[Mn(dtbpy)2(OTf)2] under the standard conditions, a clear
induction period of ca. 40 min was observed (green line).
However, when the oxidation was performed with bis-μ-O2-
Mn2 as catalyst, the induction period disappeared, and a zero-
order kinetic profile on the substrate was observed at least up
to 60% conversion. Notably, when the Mn−oxygen species
generated from PhIO was employed as the catalyst, the
induction period largely disappeared as well (Figure S9). These
observations point to that under the catalytic conditions the
precatalyst [Mn(dtbpy)2(OTf)2] is first converted by O2 into
the bis-μ-O2-Mn2 complex in an induction period. We suspect
that the oxo dimer is, however, catalytically inactive;26 under
continuous irradiation, it may undergo rate-determining
photolysis to a monomeric Mn-oxo species that starts the
catalytic turnover,27 leading to the zero-order kinetics. Indeed,
when the bis-μ-O2-Mn2 complex was used as catalyst for the
aerobic oxidation of 26a, light was still required; in its
omission, the oxidation stalled (Scheme S4). This monomeric
oxo species could be the high-valent species detected by the
EPR.
Scheme 4. A Putative Mechanism for the Photo-Mn
Promoted Oxidative Cleavage of Alkenes
Because MeOH is critical for this aerobic oxidation reaction,
we suspected that it might be involved in the O2 activation that
leads to the formation of the bis-μ-O2-Mn2 complex. To gain
insight into the possible role of MeOH, the kinetic isotope
effect was examined in the oxidative cleavage of 26a. As is
shown in Figure S10, CH3OH and CH3OD gave the same
introduction period and same rate of 26a oxidation. On the
other hand, CD3OD afforded an induction period shorter by
ca. 10 min but a similar rate of oxidizing 26a. This somewhat
surprising inverse kinetic isotope effect indicates that, apart
from coordination to the metal center (Figure 1B), MeOH
participates in the photoassisted oxidation of [Mn-
(dtbpy)2(OTf)2] by O2 to give the dioxo−Mn(III,IV) dimer,
presumably by acting as an electron donor; however, the
cleavage of C−H and O−H bond of MeOH is not the rate-
determining step of its formation.
species to re-form the oxo dimer. A similar mechanistic
pathway is seen in the work of Bruice on oxidative cleavage of
CC double bonds by a Mn(IV)O porphyrin complex.15c
Additional support for the mechanism is found in the
16O2−18O2 tracer experiments. As shown in Scheme S6, when
the alkene 62 was oxidized with pure 16O2 or 18O2, only 16O-
or 18O-labeled cleavage product was observed; however, when
a mixture of 16O2−18O2 was used, all statistically possible
products were formed. The formation of the statistical mixture
is consistent with what is expected from the mechanism; that
is, the two oxygen atoms in the product 16 originate from two
different O2 molecules, while ruling out a pathway where the
cleavage product results from an dioxetane intermediate.9a
Based on the above results and literature precedents, a
putative mechanism for the oxidative cleavage is tentatively
suggested (Scheme 4). As illustrated for a 1,1-disubstituted
alkene, the Mn(II) catalyst is first excited by blue light to afford
a more active Mn(II) intermediate A, which reacts with O2 to
form a Mn(III)−superoxo species B.12b,28 Hydrogen abstrac-
tion by B from methanol, presumably coordinated to Mn(III),
gives rise to an intermediate C, which then transfers to the
Mn(IV)−oxo D with release of formaldehyde (was detected by
GC-MS, see Figure S17) and water.28c While catalytically
active, the monomeric D may easily transfer to the more stable,
observable bis-μ-O2-Mn2 complex. Under the blue light
irradiation, the oxo dimer dissociates, presumably reversibly,
to D and a Mn(III) species. Having a radical character, D adds
to the alkene to produce a new radical species E, which would
be active toward O2, forming a six-membered metal−peroxo
species F. The unstable species F would rapidly decompose to
form the ketone product and formaldehyde while regenerating
D. In the whole catalytic reaction, bis-μ-O2-Mn2 is an off-cycle
species. Its formation via C and D involves the participation of
methanol as an electron and hydrogen donor, and the inverse
kinetic isotope effect when using CD3OD may have several
origins.29 Continuous irradiation is necessary, as the active
species D could undergo dimerization with off-cycle Mn(III)
CONCLUSIONS
■
In summary, a non-heme Mn(II)-catalyzed aerobic cleavage of
activated as well as nonactivated CC double bonds has been
established for the first time. Both aliphatic and aromatic
alkenes could be oxidized with this “oxygenase-like” protocol,
affording synthetically versatile carbonyl compounds from
widespread olefins. The oxidation proceeds under an
atmospheric O2 pressure at room temperature, providing an
atom-economic, environment- and user-friendly approach for
oxidative cleavage of alkenes. Mechanistic investigations
indicate that an asymmetric, mixed-valent bis(μ-oxo)-
dimanganese(III,IV) complex is formed as a key but off-cycle
intermediate in the catalysis. Notably, blue light irradiation of
the precatalyst and participation of MeOH are all key elements
in the activation of O2 and formation of the oxo dimer, and
light is necessary to generate the active Mn(IV)O species
and sustain catalytic turnover.
ASSOCIATED CONTENT
* Supporting Information
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/jacs.1c05757.
■
sı
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https://doi.org/10.1021/jacs.1c05757
J. Am. Chem. Soc. 2021, 143, 10005−10013

Journal of the American Chemical Society
pubs.acs.org/JACS
Article
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Experimental details and procedures, optimization
studies, mechanistic experiments, crystallographic data,
and spectral data for all compounds (PDF)
Accession Codes
CCDC 1997610 and 2050295 contain the supplementary
crystallographic data for this paper. These data can be obtained
free of charge via www.ccdc.cam.ac.uk/data_request/cif, or by
emailing data_request@ccdc.cam.ac.uk, or by contacting The
Cambridge Crystallographic Data Centre, 12 Union Road,
Cambridge CB2 1EZ, UK; fax: +44 1223 336033.
AUTHOR INFORMATION
Corresponding Author
Jianliang Xiao − Department of Chemistry, University of
Liverpool, Liverpool L69 7ZD, U.K.; orcid.org/0000-
0003-2010-247X; Email: j.xiao@liverpool.ac.uk
■
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Authors
Zhiliang Huang − Department of Chemistry, University of
Liverpool, Liverpool L69 7ZD, U.K.
Renpeng Guan − Department of Chemistry, University of
Liverpool, Liverpool L69 7ZD, U.K.
Muralidharan Shanmugam − Department of Chemistry and
Photon Science Institute, The University of Manchester,
Manchester M13 9PL, U.K.; orcid.org/0000-0003-3818-
1401
Elliot L. Bennett − Department of Chemistry, University of
Liverpool, Liverpool L69 7ZD, U.K.; orcid.org/0000-
0003-3798-4296
Craig M. Robertson − Department of Chemistry, University of
Liverpool, Liverpool L69 7ZD, U.K.; orcid.org/0000-
0002-4789-7607
Adam Brookfield − Department of Chemistry and Photon
Science Institute, The University of Manchester, Manchester
M13 9PL, U.K.
Eric J. L. McInnes − Department of Chemistry and Photon
Science Institute, The University of Manchester, Manchester
M13 9PL, U.K.; orcid.org/0000-0002-4090-7040
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Aerobic Cleavage of Alkenes and Alkynes into Carbonyl and Carboxyl
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Albrecht, M. Donor-Flexible Bis(pyridylidene amide) Ligands for
Highly Efficient Ruthenium-Catalyzed Olefin Oxidation. Angew.
Chem., Int. Ed. 2020, 59, 8932. (c) Cousin, T.; Chatel, G.; Kardos,
N.; Andrioletti, B.; Draye, M. Recent Trends in the Development of
Sustainable Catalytic Systems for the Oxidative Cleavage of
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5256. (d) Song, T.; Ma, Z.; Ren, P.; Yuan, Y.; Xiao, J.; Yang, Y. A
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(e) Daw, P.; Petakamsetty, R.; Sarbajna, A.; Laha, S.; Ramapanicker,
R.; Bera, J. K. A Highly Efficient Catalyst for Selective Oxidative
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(f) Lippincott, D. J.; Trejo-Soto, P. J.; Gallou, F.; Lipshutz, B. H.
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Z.; Qi, X.; Lee, J.-F.; Lei, A. Revealing the Structure and Reactivity of
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Complete contact information is available at:
https://pubs.acs.org/10.1021/jacs.1c05757
Notes
(8) (a) Wan, J.-P.; Gao, Y.; Wei, L. Recent Advances in Transition-
Metal-Free Oxygenation of Alkene CC Double Bonds for Carbonyl
Generation. Chem. - Asian J. 2016, 11, 2092. (b) Wang, T.; Jiao, N.
TEMPO-catalyzed Aerobic Oxygenation and Nitrogenation of Olefins
via CC Double-Bond Cleavage. J. Am. Chem. Soc. 2013, 135,
11692. (c) Deng, Y.; Wei, X.-J.; Wang, H.; Sun, Y.; Noël, T.; Wang, X.
Disulfide-Catalyzed Visible-Light-Mediated Oxidative Cleavage of
CC Bonds and Evidence of an Olefin−Disulfide Charge-Transfer
Complex. Angew. Chem., Int. Ed. 2017, 56, 832. (d) Cheng, Z.; Jin,
W.; Liu, C. B2pin2-Catalyzed Oxidative Cleavage of a CC Double
Bond with Molecular Oxygen. Org. Chem. Front. 2019, 6, 841.
(9) (a) Gonzalez-de-Castro, A.; Xiao, J. Green and Efficient: Iron-
Catalyzed Selective Oxidation of Olefins to Carbonyls with O2. J. Am.
Chem. Soc. 2015, 137, 8206. (b) Xiong, B.; Zeng, X.; Geng, S.; Chen,
S.; He, Y.; Feng, Z. Thiyl Radical Promoted Chemo- and
Regioselective Oxidation of CC Bonds Using Molecular Oxygen
via Iron Catalysis. Green Chem. 2018, 20, 4521. (c) Bhowmik, A.;
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The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We are grateful to the EPSRC (EP/R009694/1) for funding,
including the EPR National Facility at Manchester (EP/
V035231/1 and EP/S033181/1), the China Scholarship
Council and University of Liverpool for a PhD studentship
(RPG), and the Analytical Services of the Department of
Chemistry of the University of Liverpool for product analysis.
We also thank Dr. Huayan Yang (Department of Applied
Physics, University of Geneva), Dr. Laurence Kershaw Cook
(Department of Chemistry, University of Liverpool), and Dr.
Gaia Neri (Stephenson Institute for Renewable Energy,
University of Liverpool) for technical assistance.
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