Iron(III) nitrate-induced aerobic and catalytic oxidative cleavage of olefins

Article abstract of DOI:10.1016/j.tetlet.2018.05.070

Microwave-assisted catalytic oxidative cleavage of olefins using Fe(NO₃)₃·9H₂O under O₂ is reported. This reaction system is particularly effective when 9-benzylidene-9H-fluorene derivatives are used as substrates even though they are tri- and tetra-substituted olefins.

Full text of DOI:10.1016/j.tetlet.2018.05.070

Accepted Manuscript
Iron(III) nitrate-induced aerobic and catalytic oxidative cleavage of olefins
Toru Amaya, Hayato Fujimoto
PII:
S0040-4039(18)30695-6
https://doi.org/10.1016/j.tetlet.2018.05.070
TETL 50017
DOI:
Reference:
Tetrahedron Letters
To appear in:
Received Date:
Revised Date:
Accepted Date:
24 April 2018
18 May 2018
24 May 2018
Please cite this article as: Amaya, T., Fujimoto, H., Iron(III) nitrate-induced aerobic and catalytic oxidative cleavage
of olefins, Tetrahedron Letters (2018), doi: https://doi.org/10.1016/j.tetlet.2018.05.070
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers
we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and
review of the resulting proof before it is published in its final form. Please note that during the production process
errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

Graphical Abstract
To create your abstract, type over the instructions in the template box below.
Fonts or abstract dimensions should not be changed or altered.
Iron(III) nitrate-induced aerobic and
catalytic oxidative cleavage of olefins
Leave this area blank for abstract info.
Toru Amaya*, Hayato Fujimoto

1
Tetrahedron Letters
Iron(III) nitrate-induced aerobic and catalytic oxidative cleavage of olefins
Toru Amaya a,*, Hayato Fujimoto a
aGraduate School of Engineering, Osaka University, Yamada-oka, Suita, Osaka 565-0871
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
Microwave-assisted catalytic oxidative cleavage of olefins using Fe(NO3)3∙9H2O under O2 is
reported. This reaction system is particularly effective when 9-benzylidene-9H-fluorene
derivatives are used as substrates even though they are tri- and tetra-substituted olefins.
2009 Elsevier Ltd. All rights reserved.
Available online
Keywords:
Oxidative cleavage of olefin
Nitrogen dioxide
Fe(NO3)3
Microwave
The oxidative cleavage of olefins to produce carbonyl-
containing compounds is a fundamental and important reaction in
organic synthesis (Scheme 1a). Harries ozonolysis2 represents
one of the most common methods1 for this conversion, although it
also includes issues regarding explosive properties, toxicity, and
the fact that it must be carried out the reaction at low
temperatures using special equipment. Therefore, more
convenient methods using easily available reagents are needed
for this conversion. Catalytic oxidative cleavage using O2 as a
terminal oxidant has attracted interest from the environmental
point of view and the fact that the reaction is more benign.3
Catalysts or activators that have been explored for this purpose
include NHPI,4 TEMPO,5 AIBN,6 t-BuONO,7 metal catalysts
such as Co,8 Mn,8c,9 Pd,10 Cu,11 Ni12 complexes,
polyoxometallates (POM)-M-NO2,13 Fe(III) bearing a pyridine
bisimidazoline ligand,14 Au nanoparticles,15 and CAN,16 and
photoredox catalysts or activators such as CBr4,17 I2,18 porphyrin
derivatives,19 AcrH+,20 eosin Y,21 and aromatic disulfides.22 It has
also been reported that biocatalyst23 undergoes oxidative
cleavage using O2 as a terminal oxidant. In most of these reports,
terminal or less-substituted olefins have been used as typical
substrates, but there are only limited examples of the aerobic and
catalytic oxidative cleavage of tri- and tetra-substituted olefins.
Among them, a catalytic system using POM-M-NO2 is of
interest,13 since the more substituents the starting material
contains, the more reactive it is. In this system, NO2 is thought to
play a key role. In this context, we hypothesized that metal
nitrates could be used in this reaction, because NO2 can be
generated from them by heating. Here, we report on the catalytic
oxidative cleavage of alkenes using Fe(NO3)3∙9H2O under an
atmosphere of O2 at a temperature of 150 °C (Scheme 1b).24
1.5 equivalents of a metal nitrate, 1 was reacted in CH2Cl2 at 150
°C (microwave irradiation) under air for 30 min. When
Zn(NO3)2∙6H2O and Cu(NO3)2∙3H2O were used, the
corresponding oxidatively cleaved ketone 2 was obtained in 7
and 46%, respectively (entries 3 and 5) although the use of
NaNO3, AgNO3, and Co(NO3)2∙6H2O did not afford 2 (entries 1,
2 and 4). In this screening, Fe(NO3)3∙9H2O was clearly the best
metal nitrate, with the product 2 being obtained in quantitative
yield (entry 6). Instead of microwave heating, a conventional
heating condition (oil bath) was performed using toluene as a
solvent in a sealed tube. Consequently, the reaction proceeded
without any problems to give 2 in 98% yield (entry 7). To check
the effect of water contained in Fe(NO3)3∙9H2O, the reaction was
carried out in the presence of MS4A. The yield decreased to 77%
(entry 8), where the nitrated products of 2 were observed in GC-
MS. Product 2 was not produced when other Fe salts such as
FeCl3 and Fe(OAc)2 were used (entries 12 and 13). These results
suggest that NO2 is involved in the reaction, because Fe(NO3)3,
when heated, is known to generate three molecules of NO2.25 In
fact, reducing the amount of Fe(NO3)3 to 0.5 equivalents did not
lower the yield (entry 9). On
An initial investigation was carried out using 9,9’-
bifluorenylidene (1) as a tetra-substituted olefin. Table 1 provides
information on the screening of metal nitrates. In the presence of

2
Tetrahedron
Scheme 1. (a) Oxidative cleavage of olefins and (b) This work.
A plausible reaction pathway is shown in the bottom half of
Scheme 3a. Two molecules of NO2 add to the olefin to give the
dinitrite compound 3. The elimination of NO together with
carbon-carbon bond cleavage then takes place to result in the
production of carbonyl compounds. Transformations of such
dinitrite compound to carbonyl compounds at high temperature
(260-280 °C) are reported in previous studies.27 In this scheme,
the involvement of an iron species cannot be excluded because
other metal nitrates in Table 1 also generate NO2 at the
conditions used. It appears that the reduced NO is re-oxidized
with a co-oxidant such as O2 to regenerate NO2 to complete the
catalytic cycle, as shown in Scheme 3. Actually, this mechanism
was confirmed by running the reaction in the presence of 10
mol% Fe(NO3)3 under O2, in which the product 3 was obtained in
97% yield (Scheme 3b).
the other hand, decreasing the temperature to 100 °C gave rise to
decreasing the yields (entries 10 and 11). These results suggest
the involvement of thermally generated NO2.
Table 1. Investigation of metal salts for the oxidative cleavage of
1.
Entry
1
Metal salts
NaNO3
Yield/ % a
0
0
2
AgNO3
3
Zn(NO3)2∙6H2O
7
4
Co(NO3)2∙6H2O
0
5
Cu(NO3)2∙3H2O
46
>99
98
77
>99
39
7
6
Fe(NO3)3∙9H2O
7
Fe(NO3)3∙9H2O (conventional heating)b
Fe(NO3)3∙9H2O with MS4A
Fe(NO3)3∙9H2O (0.5 equiv)
Fe(NO3)3∙9H2O (0.5 equiv), 120 °C
Fe(NO3)3∙9H2O (0.5 equiv), 100 °C
FeCl3
8
9
10
11
12
13
0
Fig. 1. Dependence of the yield of 2 on the amount of Fe(NO3)3
under a N2 atmosphere for oxidative cleavage.
Fe(OAc)2
0
a
1
Yield was determined by H NMR analysis of the reaction
mixture based on 1,3,5-tribromobenzene as an internal standard. b
Toluene was used as a solvent. The reaction was performed in a
sealed tube at 150 °C.
The generation of NO2 was qualitatively confirmed by
examining the reaction in the presence of 1,3,5-
trimethoxybenzene, which is known to react with even a trace
amounts of NO2 to produce a deep blue solution.13,26 In order to
confirm the involvement of NO2 in the oxidative cleavage, the
substrate 1 was treated with an excess of NO2 at room
temperature (Scheme 2). The product 2 was obtained in
quantitative yield, suggesting that NO2 is active species in this
reaction. The dependence of yield on the amount of Fe(NO3)3
used were investigated by running the reaction under an
atmosphere of N2 (Fig. 1). The relationship was linear, and the
use of 80 mol% Fe(NO3)3 was found to cause a complete
reaction. This amount of Fe(NO3)3 generates 2.4 equivalents of
NO2 to the substrate.
Scheme 3. (a) Plausible catalytic cycle. (b) Oxidative cleavage of
1 with a catalytic amount of Fe(NO3)3∙9H2O under O2 at 150 °C.
* Yield was determined by H NMR analysis of the reaction
1
mixture based on 1,3,5-tribromobenzene as an internal standard.
Scheme 2. Oxidative cleavage of 1 by NO2.
Table 2 provides information regarding the scope of this
catalytic system. Some 9-benzylidene-9H-fluorene derivatives

3
4a-g were initially investigated. The oxidative cleavage of the
employed 7 derivatives 4a-g proceeded to give fluorenone (2) in
high yields (89-99%, entries 1-7). However, the yield of the
stilbene (4k and 4l), 5a was produced in 32% and 30%,
respectively (entries 3 and 6). When 1,1-diphenylethene (4m)
was used, the yield of 5i was 34% (entry 7). The use of 4-
methoxystyrene (4n) gave only trace amounts of the
corresponding aldehyde 5e (entry 8). In the above series,
rearranged carbonyl compounds 7 were observed (entries 1-8). A
similar rearrangement was observed previously, as exemplified
by the reaction of benzhydrylideneadamantane with NO2
(Scheme S1). In this reaction, an epoxide is first formed, which
then undergoes ring opening, followed by the migration of
phenyl group to give the rearranged spiroketone (Scheme S1).30 It
is consistent with the results of entries 4 and 5, which are
comparing the effect of epoxide. Therefore, such an epoxidation
reaction would be expected to compete with the desired oxidative
cleavage. In the case of less-hindered fluorenylidene derivatives
due to their planar structures, the formation of the dinitrite
compound 3 may be dominant rather than epoxidation. Other
typical by-products were found to be non-rearranged oxidized
products 8 and nitrated products 9 (entries 2-5). These side
reactions all result in the yield of the main reaction being low.
simultaneously produced corresponding aldehyde
5
was
moderate (5a: 50%, 5b: 63%, 5c: 78%, 5d: 79%, 5e: 78%, and
5f: 86%, entries 1-6) due to overoxidation.28 The yield of 1-
naphthaldehyde 5g was particularly low (entry 7). Only a trace
amount of the oxidatively cleaved products was obtained from
the reaction of diphenyl substituted derivative 4a’ (entry 8).
Interestingly, our recently reported macrocycle 4h29 bearing four
olefin moieties also reacted completely to give the corresponding
ketoaldehyde 5h in 75% yield (Scheme 4).
Table 2. Substrate scope for 9-benzylidene-9H-fluorene
derivatives 4
Table 3. Substrate scope for phenyl-substituted ethylene
compounds 4i-n
Entry
Ar, R 4
Yields/ %
2
5a-g
50a
1
2
3
4
5
6
7
8
Ph, H 4a
4-MePh, H 4b
4-ClPh, H 4c
4-BrPh, H 4d
4-MeOPh, H 4e
4-CF3Ph, H 4f
1-naphthyl, H 4g
Ph, Ph 4a’
89a
96b
95b
99b
97b
97b
98a
63b
78b
79b
78b
86b
19a
Entry
Substrate Yields/ %a
Observed by-productsb
1
2
trace
trace
a
Yields were determined by GC-MS analysis of the reaction
mixture based on 1,3,5-tribromobenzene as an internal standard. b
Yields were determined by H NMR analysis of the reaction
3
1
mixture based on 1,3,5-tribromobenzene as an internal standard.
4c
5c
6
Scheme 4. Oxidative cleavage of macrocycle 4h.
7
Phenyl-substituted
ethylene
compounds
were
next
investigated (Table 3). Because these derivatives showed a lower
reactivity compared to 9-benzylidene-9H-fluorene derivatives, 30
mol% of Fe(NO3)3∙9H2O was used in these reactions. The use of
tetraphenylethene (4i) as a tetra-substituted substrate gave only
trace amounts of the benzophenone (5i) (entry 1). On the other
hand, the tri-substituted triphenylethene (4j) reacted to give the
corresponding product 5i and benzaldehyde (5a) in 68% and 10%
yields, respectively (entry 2). In the case of trans- and cis-
8
a Yields were determined by H NMR analysis of the reaction
mixture based on 1,3,5-tribromobenzene as an internal standard. b
These compounds were suggested in 1H NMR and GC-MS
analyses. c 10 mol% of Fe(NO3)3∙9H2O was used.
1

4
Tetrahedron
26. Gowenlock, B. G.; King, B.; Pfab, J. J. Chem. Res. Synop. 2000,
276-277.
27. Kuhn, L. P.; DeAngelis, L. J. Am. Chem. Soc. 1954, 76, 328-329.
28. The corresponding overoxidized acid was isolated in entry 1.
There is a report of the oxidation of aldehyde to the carboxylic
acid in the presence of Fe(NO3)3∙9H2O under O2, see Tanaka, S.;
Kon, Y.; Uesaka, Y.; Morioka, R.; Tamura, M.; Sato, K. Chem.
Lett. 2016, 45, 188-190.
In conclusion, the catalytic oxidative cleavage of alkenes
using Fe(NO3)3∙9H2O under O2 was developed. This reaction
system is particularly effective when 9-benzylidene-9H-fluorene
derivatives are used as substrates even though they are tri- and
tetra-substituted olefins.
29. Amaya, T.; Fujimoto, H.; Tanaka, T.; Moriuchi, T. Org. Lett.
2018, 20, 2055-2058.
30. Bosch, E.; Kochi, J. K. J. Am. Chem. Soc. 1996, 118, 1319-1329.
Acknowledgments
We wish to thank Prof. Toshiyuki Moriuchi for the useful
discussions, and Ms. Miharu Kamitani for the support of the
experiments.
Supplementary Material
Supplementary data (Scheme S1 and experimental details
associated with this article can be found, in the online version, at
https://doi.org/xxx.
References and notes
1. For reviews: (a) Rajagopalan, A.; Lara, M.; Kroutil, W. Adv.
Synth. Catal. 2013, 355, 3321-3335. (b) Wan, J.-P.; Gao, Y.; Wei,
L. Chem. Asian J. 2016, 11, 2092-2102.
2. (a) Harries, C. Ann. 1905, 343, 311-344. (b) For a review: Bailey,
P. S. Chem. Rev. 1958, 58, 925-1010.
3. Urgoitia, G.; SanMartin, R.; Herrero, M. T.; Domínguez, E. ACS
Catal. 2017, 7, 3050-3060.
4. Lin, R.; Chen, F.; Jiao, N. Org. Lett. 2012, 14, 4158-4161.
5. Wang, T.; Jiao, N. J. Am. Chem. Soc. 2013, 135, 11692-11695.
6. Wang, G.-Z.; Li, X.-L; Dai, J.-J.; Xu, H.-J. J. Org. Chem. 2014,
79, 7220-7225.
7. Miao, C.-X.; Yu, B.; He, L.-N. Green Chem. 2011, 13, 541-544.
8. (a) Ganeshpure, P. A.; Satish, S. Tetrahedron Lett. 1988, 29,
6629-6632. (b) Reetz, M. T.; Töllner, K. Tetrahedron Lett. 1995,
36, 9461-9464. (c) Chen, H.; Ji, H.; Zhou, X.; Xu, J.; Wang, L.
Catal. Commun. 2009, 10, 828-832.
9. Varkey, S. P.; Ratnasamy, C.; Ratnasamy, P. J. Mol. Catal. A:
Chem. 1998, 135, 295-306.
10. (a) Wang, J.-Q.; Cai, F.; Wang, E.; He, L.-N. Green Chem. 2007,
9, 882-887. (b) Feng, B.; Hou, Z.; Wang, X.; Hu, Y.; Li, H.; Qiao,
Y. Green Chem. 2009, 11, 1446-1452.
11. (a) Hossain, M. M.; Shyu, S.-G. Tetrahedron 2014, 70, 251-255.
(b) Liu, Y.; Xue, D.; Li, C.; Xiao, J.; Wang, C. Catal. Sci. Tech.
2017, 7, 5510-5514.
12. Urgoitia, G.; SanMartin, R.; Herrero, M. T.; Domínguez, E. Adv.
Synth. Catal. 2016, 358, 1150-1156.
13. Rubinstein, A.; -Lozanao, P.; , J. J.; Poblet, J. M.;
Neumann, R. J. Am. Chem. Soc. 2014, 136, 10941-10948.
14. Gonzalez-de-Castro, A.; Xiao, J. J. Am. Chem. Soc. 2015, 137,
8206-8218.
15. Turner, M.; Golovko, V. B.; Vaughan, O. P. H.; Abdulkin, P.;
Berenguer-Murcia, A.; Tikhov, M. S.; Johnson, B. F. G.; Lambert,
R. M. Nature 2008, 454, 981-984.
16. Dhakshinamoorthy, A.; Pitchumani, K. Catal. Commun. 2009, 10,
872-878.
17. Hirashima, S.-I.; Kudo, Y.; Nobuta, T.; Tada, N.; Itoh, A.
Tetrahedron Lett. 2009, 50, 4328-4330.
18. Fujiya, A.; Kariya, A.; Nobuta, T.; Tada, N.; Miura, T.; Itoh, A.
Synlett 2014, 25, 884-888.
19. Murthy, R. S.; Bio, M.; You, Y. Tetrahedron Lett. 2009, 50, 1041-
1044.
20. Suga, K.; Ohkubo, K.; Fukuzumi, S. J. Phys. Chem. A 2003, 107,
4339-4346.
21. Singh, A. K.; Chawla, R.; Yadav, L. D. S. Tetrahedron Lett. 2015,
56, 653-656.
22. (a) Baucherel, X.; Uziel, J.; Jugé, S. J. Org. Chem. 2001. 66,
4504-4510. (b) Deng, Y.; Wei, X.-J.; Wang, H.; Sun, Y.; Noël, T.;
Wang, X. Angew. Chem. Int. Ed. 2017, 56, 832-836.
23. Lara, M.; Mutti, F. G.; Glueck, S. M.; Kroutil, W. Eur. J. Org.
Chem. 2008, 3668-3672.
24. There is one report (see below) of the oxidative cleavage of
olefins using a Fe(NO3)3∙9H2O/O2 system at 80 °C. However, only
one substrate was examined in this study. Furthermore, the
proposed mechanism is different from ours. Presumably, this is
because temperature was too low to permit the generation of NO2.
Pillai, U. R.; Sahle-Demessie, E.; Namboodiri, V. V.; Varma, R.
S. Green Chem. 2002, 4, 495-497.
25. Hill, W. D. Jr. Inorg. Chim. Acta 1986, 121, L33.

5
Iron(III) nitrate-induced aerobic and catalytic
oxidative cleavage of olefins
Toru Amaya*1 and Hayato Fujimoto1
1
Graduate School of Engineering, Osaka University,
Yamada-oka, Suita, Osaka 565-0871
Highlight
• Catalytic oxidative cleavage of olefins under O2
• Use of inexpensive Fe(NO3)3∙9H2O
• Environmental benign method
• P t cul ly ff ct v wh 9-benzylidene-9H-
fluorene derivatives are used as a substrate