Oxidative Cleavage of Alkene C=C Bonds Using a Manganese Catalyzed Oxidation with H2O2 Combined with Periodate Oxidation

Article abstract of DOI:10.1002/ejoc.201901380

A one-pot multi-step method for the oxidative cleavage of alkenes to aldehydes/ketones under ambient conditions is described as an alternative to ozonolysis. The first step is a highly efficient manganese catalyzed epoxidation/cis-dihydroxylation of alkenes. This step is followed by an Fe(III) assisted ring opening of the epoxide (where necessary) to a 1,2-diol. Carbon–carbon bond cleavage is achieved by treatment of the diol with sodium periodate. The conditions used in each step are not only compatible with the subsequent step(s), but also provide for increased conversion compared to the equivalent reactions carried out on the isolated intermediate compounds. The described procedure allows for carbon–carbon bond cleavage in the presence of other alkenes, oxidation sensitive moieties and other functional groups; the mild conditions (r.t.) used in all three steps make this a viable general alternative to ozonolysis and especially for use under flow or continuous batch conditions.

Full text of DOI:10.1002/ejoc.201901380

A Journal of
Accepted Article
Title: Oxidative cleavage of alkene C=C bonds using a manganese
catalysed oxidation with H2O2 combined with periodate oxidation
Authors: Francesco Mecozzi, Jia Jia Dong, Davide Angelone, Wesley
R. Browne, and Niek Eisink
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To be cited as: Eur. J. Org. Chem. 10.1002/ejoc.201901380
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10.1002/ejoc.201901380
European Journal of Organic Chemistry
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Oxidative cleavage of alkene C=C bonds using a manganese
catalysed oxidation with H2O2 combined with periodate oxidation
Francesco Mecozzi,[a] Jia Jia Dong,[a] Davide Angelone,[a] Wesley R. Browne,[a]* Niek N. H. M. Eisink[b]*
Abstract A one-pot multi-step method for the oxidative cleavage of
alkenes to aldehydes/ketones under ambient conditions is described
as an alternative to ozonolysis. The first step is a highly efficient
manganese catalysed epoxidation/cis-dihydroxylation of alkenes.
This step is followed by an Fe(III) assisted ring opening of the
epoxide (where necessary) to a 1,2-diol. Carbon-carbon bond
cleavage is achieved by treatment of the diol with sodium periodate.
The conditions used in each step are not only compatible with the
subsequent step(s), but also provide for increased conversion
compared to the equivalent reactions carried out on the isolated
intermediate compounds. The described procedure allows for
carbon-carbon bond cleavage in presence of other alkenes,
oxidation sensitive moieties and other functional groups; the mild
conditions (r.t.) used in all three steps make this a viable general
alternative to ozonolysis and especially for use under flow or
continuous batch conditions.
Scheme 1. (a) Diol C-C bond cleavage with NaIO4, (b) C-C bond cleavage
in 3-carene oxide by Binder et al. [9] (c) The Lemieux-Johnson reaction.[10] (d)
3-step epoxidation-ring opening-cleavage strategy developed by Klein
Gebbink et al.[11] (Fe cat = [Fe(Otf)2(rac-BPBP)])
Introduction
Cleavage of the double bonds of alkenes to yield (di)carbonyl
compounds (ketones and aldehydes) is a key reaction in
synthetic organic chemistry and especially in total synthesis and
medicinal chemistry.[1] For example, ozonolysis, provides
access to wide range of products controlled largely by the
conditions used and the fate of the trioxolane intermediate.[2,3]
Its versatility is such that it is used widely, despite that alkene
ozonolysis creates hazards in the in situ generation of O3, and
the presence of ozonides and peroxides during concentration
steps. Flow chemistry[4] can reduce the steady state
concentrations of O3, however, the latter risks are not mitigated
by this approach. Furthermore, scale-up opportunities are
limited by the low temperatures, typically from – 78 to 0 °C[5–8]
and functional group intolerance, e.g., alkynes are converted to
carboxylic acids.
A key challenge in non-ozone based methods for C=C bond
cleavage is to achieve the good atom economy and selectivity
that can be achieved with ozonolysis. In particular, the
avoidance of uncontrolled over oxidation of the products is
challenging. Stepwise approaches can provide increased
selectivity, as they allow greater control over the conditions in
each step. For instance, initial conversion of alkenes to vic-diols,
e.g. via epoxidation, can be followed by C-C bond cleavage with
NaIO4 or HIO4, with often high selectivity and typically full
conversion (Scheme 1),[12,13] which outweighs the ‘single step’
2- [14]
benefit of direct treatment of alkenes with ozone, Cr2O7
MnO4 .
or
- [15,16]
One pot methods[17] using catalytic RuCl3 or OsO4 in
combination with either OxoneTM, NaOCl, or NaIO4, directly
exploit the ability of the oxidant to cleave the oxidation products
formed by the catalytic first step.[18–20] Lemieux and Johnson’s
method (Scheme 1c) for alkene double bond cleavage employs
catalytic OsO4 to form the diol intermediate and NaIO4 both as
terminal oxidant to regenerate the osmium tetroxide and to
cleave the diol formed. This approach is used widely despite the
cost and toxicity of OsO4.[10,18,21–23] Later, RuCl3 was used in
combination with NaIO4 or Oxone, with various solvent
combinations, to give the similar transformations.[24,25]
[a]
[b]
Dr. F. Micozzi, Dr. J.J. Dong, Dr. D. Angelo, Prof. Dr. W.R. Browne
Molecular Inorganic Chemistry, Stratingh Institute for Chemistry,
Faculty of Science and Engineering, University of Groningen,
Nijenborgh 4 9747 AG Groningen, The Netherlands.
+31-503634428, w.r.browne@rug.nl
Recently alternative multistep approaches that replace 2nd
and 3rd row transition metal based catalysts have been
developed. Ochiai,[26] Lai[27] and co-workers have reported a
multi-step one-pot cleavage of alkenes with iodosyl benzene
and a manganese porphyrin catalyst, noting that epoxides were
formed as intermediates in the reaction. Binder et al.[9] reported
the cleavage of epoxides to carbonyl compounds with aqueous
Dr. N.N.H.M. Eisink
USSE, Faculty of Science and Engineering, University of Groningen,
Nijenborgh 4 9747 AG Groningen, The Netherlands.
+31-503636967 n.n.h.m.eisink@rug.nl
Supporting information for this article is given via a link at the end of
the document.
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10.1002/ejoc.201901380
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NaIO4 at room temperature. Klein Gebbink et al.[11] reported a
one-pot three step epoxidation-dihydroxylation-cleavage, which
is equivalent to cleavage with ozone. Epoxidation with an Fe(II)
catalyst and the terminal oxidant H2O2 was followed by sulphuric
acid catalysed ring opening and finally, cleavage of the trans-
diol with stoichiometric NaIO4 to yield the corresponding
(di)carbonyl compounds in good to excellent yields (43 to 99 %)
and selectivities (Scheme 1d). Despite limitations imposed by
epoxide ring opening with sulphuric acid, the epoxidation opens
up opportunities in regard to the regio- and chemo-selectivity of
the system.
The conditions used in the present study for the oxidation of
alkenes to their corresponding epoxide/diol was reported
earlier.[28,29] Briefly, alkene oxidation proceeds at room
temperature using a combination of a Mn(II) salt, pyridine-2-
carboxylic acid (PCA), (sub)stoichiometric butanedione and
H2O2 as terminal oxidant (Scheme 3). Electron rich and electron
poor alkenes are oxidised to their corresponding epoxides and
diols, respectively, in high yields and selectivities and with high
turnover frequencies (up to 40 s–1) and numbers (up to 300ꢀ000)
using this method. In the present report we show that these
conditions are not only compatible with the subsequent ring
opening/cleavage steps but also improve the reactions in
comparison to equivalent reactions with purified intermediate
products. With certain substrates, side products such as cis-diol
and α-hydroxy ketones are observed after epoxidation. However,
due to the subsequent ring opening and oxidation steps, most of
these side products are converted towards the desired
(di)carbonyls.
In a stepwise approach the selectivity towards the C=C
bonds to be oxidized is governed by the epoxidation step, and
hence a multistep oxidation protocol allows regioselectivity
between several alkene motifs to be achieved (Scheme 2). A
further point with regard to selectivity lies at the ring opening
step, which has been largely neglected to date.
A stepwise approach to the oxidative cleavage of alkene
C=C bonds faces three main challenges; 1) generating the
epoxide, 2) selective ring open to the diol and 3) selective
oxidation of the diol. Furthermore,
a “one-pot” reaction
sequence necessitates compatibility between the products
formed in each step and the reagents used in subsequent steps.
Scheme 3. Oxidation of methylcyclohexene reported by Saisaha et al.[28,29]
Results and Discussion
Two-step oxidative cleavage of alkenes.
C-C bond cleavage of epoxides with aqueous NaIO4 was
reported earlier,[9] and hence a relatively simple approach to
alkene oxidative cleavage is to add NaIO4 after the epoxidation
step. With cyclic alkenes, e.g., 3-carene or methylcyclohexene
(Scheme 4), epoxidation proceeded with full conversion as
reported earlier.[28] Addition of solid NaIO4 to the reaction mixture
did not result in conversion of the epoxide, in part due to poor
solubility of NaIO4. However, dilution with water, after
epoxidation, prior to adding solid NaIO4, provided the desired
scission products as the major product (Scheme 4).
Scheme 2. One pot multistep strategy allows for the regioselectivity of the
reaction to be controlled during the epoxidation and/or the epoxide ring
opening steps.
Here, we report a general method based on a Mn based
catalyst for the oxidation of alkenes together with oxidative diol
cleavage with periodate to (di)carbonyl compounds. The
two/three step one-pot C=C bond cleavage reaction starts with
an in situ Mn/PCA (pyridine-2-carboxylic acid) catalysed
epoxidation/cis-dihydroxylation with H2O2 as terminal oxidant.
The diol is directly obtained in the oxidation with electron
deficient alkenes or by the Fe(ClO4)3 mediated hydrolysis of the
epoxides obtained from the oxidation of electron rich alkenes.
The obtained diols are thereafter cleaved with stoichiometric
NaIO4, yielding the corresponding (di)carbonyl compounds in
high yields and selectivity. Furthermore, the regio- and chemo-
selectivity in the oxidation of the various classes of alkenes is
explored through the oxidation of compounds bearing multiple
C=C bonds.
Scheme 4. One-pot two-step oxidation of 3-carene and methyl cyclohexene
to the corresponding scission products via epoxides. Reaction conditions: i:
Mn(ClO4)3 (0.02 mol %), PCA (0.2 mol %), butanedione (1.0 equiv.), H2O2 (3
equiv.) CH3CN (0.25 M), 0 °C – r.t. 1 h ii: NaIO4 (4.0 equiv.), CH3CN/H2O (2:1,
0.17M), r.t. 18 h iii: Mn(ClO4)3 (0.01 mol %), PCA (0.1 mol %), butanedione
(0.5 equiv.), H2O2 (1.5 equiv.) CH3CN (0.5 M), 0 °C – r.t. 1 h iv: NaIO4 (2.0
equiv.), CH3CN/H2O (2:1, 0.33M), r.t. 18 h
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In acetonitrile/water, the 3-carene epoxide was converted
Ring opening of epoxides with Fe(ClO4)3
cleanly to the desired cleavage product with 4.0 equivalents of
NaIO4 over 18 h. This result clearly indicates that the reaction
conditions introduced by the first step does not hinder the
subsequent oxidative cleavage. To test the influence of these
reaction conditions on the oxidative cleavage of careen oxide,
both in situ generate epoxide as isolated epoxide were
subjected to the oxidative cleavage (1.0 equivalent of NaIO4 in
The epoxide ring opening is typically accelerated using hard
acids such as H2SO4 or BF3 etherate, however these are not
desirable in regard to achieving a broad functional group
tolerance. Iron(III) salts were considered as a viable alternative
to these hard acids, as they have been shown earlier to catalyse
the ring opening of epoxides in the presence of various
nucleophiles;[30–33] in particular in alcohols.[34,35] First attempts
to catalyse the ring opening of the epoxide product formed in
acetonitrile with Fe(ClO4)3 were unsuccessful, possibly due to
formation of the stable complex [Fe(CH3CN)6]2+.
The flexibility of the Mn(II)/PCA system in terms of solvent,
opens up opportunities to achieve the ring opening step in
acetone.[28] Epoxidation of 3-carene in acetone proceeded in full
conversion within 10 min (determined by 1H-NMR spectroscopy).
Addition of solid Fe(ClO4)3 to solutions lead to only limited
conversion towards the desired diol (Scheme 7). Since in the
current protocol, NaIO4 is added with water, addition of aqueous
Fe(ClO4)3 to perform ring opening was explored and indeed, with
water, the diol products were obtained within 3 h at room
temperature. 1.0 mol % Fe(ClO4)3 in a 2:1 acetone:water ratio
proved to be optimal for both achieving high conversion and
maintaining a homogenous solution.
1
acetonitrile/water 2 : 1, 0.16M for 18 h). Analysis by H NMR
spectroscopy after 18 h proved that the in situ prepared carene
epoxide formed 2.5 x more product then the isolated epoxide.
This indicates that the that the reaction conditions from the first
step, most likely the acetic acid formed from butanedione, is
highly advantageous in regard to the subsequent periodate
oxidation. The conditions are not only compatible but also are
complementary to each other
In the examples described thus far, the epoxidation step
takes place under mildly acidic (acetic acid) conditions, however,
the addition of periodate and water does not result in rapid
epoxide ring opening. A competition reaction between 3-carene
-oxide and diol with equimolar amounts of NaIO4 illustrates that
ring opening is the rate limiting step (Scheme 5). The vic-diol
was oxidized rapidly and preferentially leaving the epoxide
untouched. These data confirm that direct oxidation of the
epoxide by periodate is not kinetically competent and the
difference in reactivity opens opportunities for selectivity in
cleavage between epoxides.
Scheme 5. Selective oxidation of the 3-carene diol in the presence of the 3-
carene oxide. Reaction conditions: NaIO4 (0.5 equiv.), r.t. CH3CN:H2O (2:1,
0.5 M), 18 h
Scheme 7. Summary of ring opening reactions. Reaction conditions:
Epoxidation: Mn(ClO4)3 (0.02 mol %), PCA (0.2 mol %), butanedione (1.0
equiv.), H2O2 (3 equiv.) CH3CN (0.25 M), 0 °C – r.t. 1 h Fe(ClO4)3: Fe(ClO4)3
(1.0 mol %.), in CH3CN (0.25 M) or CH3CN/H2O (2:1, 0.17M), r.t. 18 h
This kinetically determined selectivity is exemplified in the
kinetic attrition of a mixture of cyclohexene and 3-carene
epoxides. Treating this mixture with 0.5 equivalent of NaIO4 left
the 3-carene oxide relatively untouched while the cyclohexene
was nearly fully consumed (Scheme 6) indicating that indeed the
more readily opened epoxide is not only selectively opened but
also subsequently cleaved to the dicarbonyl product.
The compatibility of the reagents used and by-products
formed (e.g., acetic acid) was examined using a one-pot three-
step reaction. Epoxidation of 2,3-dimethyl-2-butene in (CD3)2CO
(Scheme 8) was followed by ring opening to the corresponding
diol with Fe(ClO4)3 in H2O and subsequent cleavage to acetone
with 1.0 equiv. of NaIO4. The reaction was monitored by Raman
spectroscopy and 1H-NMR and all three steps went to
completion with high selectivity within 1 h at room temperature.
The reaction proceeds with full conversion and selectivity to the
expected product (acetone).
Scheme 6. Selective oxidation of cyclohexene oxide in the presence of 3-
carene oxide. Reaction conditions: NaIO4 (0.5 equiv.), r.t. CH3CN:H2O (1:1,
0.5 M), 18 h
The same reactions were attempted on aryl-alkenes
considering that reactivity of aryl-alkenes is often distinctly
different to aliphatic alkenes, especially in regard to the stability
of their epoxide products. Addition of periodate in water to the
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10.1002/ejoc.201901380
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formed styrene epoxide, resulted in only 20% conversion,
Scheme 9a. In contrast, the one-pot three step approach in
which the epoxidation of styrene with H2O2 was followed by ring
opening and oxidation periodate provided the desired product
within 1 h at room temperature.
Scheme 8. One-pot three step oxidation of the 2,3-dimethyl-2-butene at room
temperature. 1) Mn(ClO4)2.6H2O 0.01 mol %, PCA 0.5 mol %, NaOAc 1.0
mol %, butanedione 0.5 equiv., H2O2 1.5 equiv., (CD3)2CO, 0.5 M substrate,
15 min; 2) Fe(ClO4)3 1.0 mol %, (CD3)2CO /H2O (2:1, v/v), 5 min; 3) 1 equiv.
NaIO4, (CD3)2CO /H2O (2:1, v/v), 15 min.
Figure 1. In-line monitoring of the ring opening of styrene oxide by Raman
spectroscopy showing complete ring opening within 20 min. Top: decay of
Raman band of epoxide at 1254 cm-1, bottom: Raman spectra before and after
ring opening.
Indeed, the epoxidation was complete within a few minutes and
the subsequent iron(III) catalysed ring opening of the epoxide
was complete within 20 min (Figure 1 and Scheme 9). The
subsequent oxidative C-C bond cleavage with periodate/water
was complete within 1 h. The short reaction time required for the
Lewis acid catalysed ring-opening of the styrene oxide opened
a facile pathway for the C-C bond cleavage of aromatic
substrates and new possibilities for the chemoselectivity of the
system.
The compatibility of the reaction conditions for epoxidation with
the ring opening step is exemplified by subjecting isolated
styrene oxide to the Fe(ClO4)3 catalysed ring opening. The ring
opening was proceeded in 75% conversion after 15 min while
the in situ generated epoxide was fully converted within the
same time.
Functional group tolerance of the system
The limits to the selectivity that could be achieved with the one
pot three step reaction were explored in the partial epoxidation
of both citral and citronellol. Partial epoxidation allowed for the
sensitivity of the unreacted alkene to the conditions of the
subsequent steps to be evaluated. Oxidation with 2.0 equiv. of
NaIO4 (with 50 % water by volume) resulted in selective
conversion of the epoxide to the desired aldehyde, with full
recovery of remaining starting material (Scheme 10). These
data confirm that neither terminal alcohols, trisubstituted, nor
-unsaturated alkenes are sensitive to the cleavage
conditions of the final step. Furthermore, it demonstrates that
double bond selectivity in the epoxidation step can be used to
control the overall selectivity of C=C bond cleavage.
Scheme 9. (a) Two step cleavage of styrene oxide. (b) 3 step one pot
oxidation of styrene. Epoxidation: Mn(ClO4)2.6H2O 0.01 mol %, PCA 0.5
mol %, NaOAc 1.0 mol %, butanedione 0.5 equiv., H2O2 1.5 equiv., acetone,
0.5 M substrate,30 min; Fe(ClO4)3: Fe(ClO4)3 1.0 mol %, acetone /H2O (2:1,
v/v), 15 min; Cleavage: 1 equiv. NaIO4, acetone /H2O (2:1, v/v), 30 min.
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note that the epoxidation step proceeded with 71 % conversion,
indicating that the subsequent two steps were essentially
quantitative and selective towards formation of the desired
product. (Scheme 12).
Scheme 12. 3 step one-pot C=C bond cleavage of α-methyl styrene.
Epoxidation: Mn(ClO4)2.6H2O 0.01 mol %, PCA 0.5 mol %, NaOAc 1.0 mol %,
butanedione 0.5 equiv., H2O2 1.5 equiv., acetonitrile, 0.5 M substrate,30 min;
Fe(ClO4)3: Fe(ClO4)3 1.0 mol %, acetone /H2O (2:1, v/v), 30 min; Cleavage: 1
equiv. NaIO4, acetonitrile /H2O (2:1, v/v), 1h.
Scheme 10. One-pot two step C=C bond cleavage of citral and citronellol.
Epoxidation: Mn(ClO4)2.6H2O 0.01 mol %, PCA 0.5 mol %, NaOAc 1.0 mol %,
butanedione 0.5 equiv., H2O2 1.5 equiv., acetonitrile, 0.5 M substrate,30 min;
Cleavage: 2 equiv. NaIO4, acetonitrile /H2O (2:1, v/v), 3h.
In the case of the epoxidation of diphenyl ethylene initially low
conversion was observed under the standard reaction
conditions. This was overcome[36] by
a
reducing the
Similar results were obtained with 3-vinyl benzaldehyde.
In a one-pot 2-step reaction (i.e. without deliberate ring opening
of the epoxide product) epoxidation of the alkene was allowed
to proceed up to ~70% conversion. Subsequent partial oxidation
of the resulting epoxide to 1,3-benzene-dialdehyde was then
performed. Both reactions were done without complete
conversion to monitor the stability of the various functional
groups to the reaction conditions. It can be concluded that the
aldehyde functionality was preserved in both steps, i.e. the
aldehyde did not react in the oxidation of the alkene nor with
NaIO4. Furthermore, the alkene moiety was unaffected by the
subsequent periodate oxidation. (scheme 11).
concentration of the starting material to 0.25 M (Scheme 13).
Scheme 13. 3 step one-pot C=C bond cleavage of diphenyl ethylene.1)
Mn(ClO4)2.6H2O 0.02 mol %, PCA 1.0 mol %, NaOAc 2.0 mol %, butanedione
1.0 equiv., H2O2 3.0 equiv., acetone, substrate 0.25 M, r.t., 15 min; 2)
Fe(ClO4)3 1.0 mol %, acetone/H2O (2:1 v/v), r.t., 5 min; 3) NaIO4 1.2 equiv.,
acetone/H2O (2:1, v/v), r.t., 3 h.
Subsequent ring opening was rapid (< 1 h), while the C-C bond
cleavage step was complete using a slight excess of NaIO4 (3
h). A basic workup yielded the desired product in almost
quantitative yield and high selectivity (Figure 2).
Scheme 11. Partial conversion of the 3-vinyl benzaldehyde to its epoxide and
subsequently dialdehyde. Epoxidation: Mn(ClO4)2.6H2O 0.01 mol %, PCA 0.5
mol %, NaOAc 1.0 mol %, butanedione 0.5 equiv., H2O2 1.5 equiv., acetonitrile,
0.5 M substrate,60 min; Cleavage: 2 equiv. NaIO4, acetonitrile /H2O (2:1, v/v),
3h.
Scope of the reaction
α-Methyl styrene was converted to acetophenone under the
same reaction conditions as used for the oxidation of styrene
and isolated by column chromatography in 65 % yield, with an
overall reaction time of 2 h, for the three steps. It is important to
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10.1002/ejoc.201901380
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alkenes is desirable. The epoxidation step was performed in-
flow using a syringe pump and simple HPLC tubing and mixer:
the substrate and the reagents, in one syringe, were mixed
continuously with a solution of H2O2. The addition of the reaction
mixture to aqueous Fe(III)(ClO4)3 yielded the corresponding diol
quantitatively, and subsequent addition of sodium periodate
achieved bond cleavage. Using this approach, styrene was
converted to benzaldehyde (vide supra) at 5 mmol scale also.
Conclusions
We report an alternative protocol to ozonolysis that overcomes
several of the limitations imposed by ozonolysis in the cleavage
of C=C bonds to ketone and aldehydes. All steps are carried
under ambient conditions with off-the-shelf reagents in the
presence of water and air in contrast to the “classic” ozonolysis
conditions (e.g., -78 °C) and avoids the formation of potentially
hazardous intermediates such as trioxolane intermediates. The
approach provides for useful selectivity both between double
bonds and with regard to other functional group. For instance,
the lack of reactivity of alkynes, primary alcohols and aldehydes
reported earlier for the Mn/PCA catalysed oxidation with H2O2
opens up application of this C=C bond cleavage approach to
alkenes bearing these functional groups. The selectivity of the
present method comes from both the first oxidation step: The
Mn/PCA based epoxidation/syn-dihydroxylation is both selective
and specific towards electron rich double bonds over -
unsaturated double bonds; and the epoxide ring opening step.
The C-C bond cleavage can be performed directly on the
epoxide with between 2 and 4 equiv. of periodate, however, if
the epoxidation is carried out in acetone, facile ring opening to
the diol with Fe(ClO4)3 proceeds relatively quickly (depending on
substrate) and can be followed by cleavage with only one equiv.
of NaIO4, with overall reaction times of less than 4 h.
Figure 2. 1H-NMR spectra of (A) 1,1-diphenyl-ethene, and crude products
after (B) epoxidation (incomplete conversion, 0.5 M), (C) epoxidation
(complete conversion, 0.25 M), (D) ring opening and (E) cleavage reactions,
(respectively).
Although relatively insoluble, bisfluorene was also submitted
to the three step procedure. Oxidation took place under the
same conditions but with an 8-fold decrease in substrate
concentration compared with that used typically, with ca. 75% of
the ketone product together with the pinnacol rearranged
product (ca. 25 %) (Scheme 14). Notably, analysis after the first
(epoxidation) step revealed that the desired scission product
(fluorenone) was already present. Epoxidation of the highly
strained alkene present in bisfluorene, is likely to be followed by
ring opening to the diol and, in the presence of excess peroxide,
to further oxidation leading to cleavage. Indeed, the outcome of
the first step is not changed by the subsequent steps. To the
best of our knowledge, the epoxide is not described in the
literature and the diol has been shown to undergo
photochemical rearrangements to the ketone and rearranged
product in similar ratios to that observed here.[37,38] We surmise
that the reaction either proceeds via a carbocation intermediate
or formation of the diol.
Importantly, the regioselectivity can be controlled through
the ring opening step also, as different epoxides show markedly
different reactivity towards the conditions used for ring opening
with iron(III) perchlorate or direct oxidation with NaIO4.
Furthermore, not only are all described steps compatible
with each other, but they complement each other also. When
performing the reaction steps in consecutively in a one-pot
manner, higher conversions are obtained compared to the
isolated counter parts.
Experimental Section
Scheme 14. Direct C=C bond cleavage of bisfluorene. 1) Mn(ClO4)2.6H2O
0.08 mol %, PCA 4.0 mol %, NaOAc 8.0 mol %, butanedione 4.0 equiv., H2O2
12.0 equiv., acetone 0.0625 M, r.t., 30 min;
See the Supporting Information for experimental details
regarding reaction details and and characterisation.
General Procedure for Substrate Oxidation
Epoxidation.
Although providing for facile epoxide ring opening with Fe(III)
salts, the use of acetone in combination with H2O2, raises a
safety issue, due to the possible formation of explosive organic
peroxides. For larger scale reactions, the use of an in-flow
epoxidation-ring opening arrangement for the oxidation of the
The substrate (1 mmol) was added to a 0.5 mL solution of
Mn(ClO4)2·6H2O (0.2 mM in either acetonitrile or acetone, 0.1
µmol, 0.01 mol %) and 0.5 mL solution of picolinic acid (10 mM
in either acetonitrile or acetone, 5 µmol, 0.5 mol %). 17 µL
NaOAc (0.6 M in H2O, 10 µmol, 1 mol %), 43.5 µL butanedione
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(0.5 mmol, 0.5 equiv.) and either acetonitrile or acetone were
added to give a final volume of 2 mL and a final concentration of
the substrate of 0.5 M (for less reactive substrates the amount
of starting material is reduced by half to give a final
concentration of 0.25 M). The solution was stirred in an ice/water
bath before addition of 85 µL H2O2 (50 wt%, 1.5 mmol, 1.5
equiv.). Conversion was monitored either directly by Raman
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Entry for the Table of Contents
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Alkene cleavage
Francesco Mecozzi, Jia Jia Dong,
Davide Angelone, Wesley R. Browne,*
Niek N. H. M. Eisink*
Page No. – Page No.
A
one-pot multi-step method for the oxidative cleavage of alkenes to
Oxidative cleavage of alkene C=C
bonds using a manganese catalysed
oxidation with H2O2 combined with
periodate oxidation
aldehydes/ketones under ambient conditions is reported. Combining a highly
efficient manganese catalysed epoxidation/cis-dihydroxylation with Fe(III)(ClO4)3
assisted ring opening is followed by periodiate cleavage of the resulting diol.
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