SHORT COMMUNICATION
with either 0, 0.015, or 50 equiv. of MeCOOH added at the start;
reactions were performed for 10, 20, 70, or 90 min and either
1.0 equiv. or 1.2 equiv. H2O2 was used. The carvone epoxide was
isolated in order to obtain an authentic sample for comparison and
quantification purposes. The isolation was performed in a similar
procedure but without MeCOOH, and with a tenfold increase of
the amount of the substrate (7.2 mmol) and 1.5 h reaction time.
ondary allyl alcohols are also tolerated under our reaction
conditions (Table 4, entries 6 and 7): perillic acid is prefer-
entially cleaved at the exocyclic double bond, yielding 59%
of the corresponding ketone at 82% conversion. The sec-
ondary alcohol 1,5-hexadien-3-ol is transformed selectively
into 3-hydroxy-pent-4-enal (43% at 55% conversion). Un-
fortunately, apart from the successful conversion of 1,3-cy-
clohexadiene, other conjugated dienes or trienes gave only
little or no identified aldehyde product.
Oxidative Cleavage Protocol, Method B: The epoxidation protocol
described above for the monoalkenes (method A) was also applied
for the oxidative cleavage method B. At the end of the reaction of
method A (i.e. after 10 min), the reaction mixture was warmed up
to 50 °C, and H2SO4 (0.5 equiv.) in H2O (75 equiv.) was added,
after which the mixture was stirred for 0.5 h. Then, NaHCO3
(1 equiv.), NaIO4 (1.5 equiv.), and H2O (600 equiv.) were added to
the reaction mixture, which was stirred for an additional 0.5 h. Sub-
sequently, CD3CN (1 mL), and nitrobenzene (1 equiv.) in MeCN
(1 mL) were added, after which a sample was analyzed with 1H
NMR spectroscopy. For accurate determination of the conversion,
after analysis with NMR spectroscopy, diethyl ether (20 mL) was
added, and a sample was subjected to GC analysis. The reactions
with cis-cyclooctene, citronellol, and citronellyl acetate were run on
threefold larger scale (2.16 mmol), and isolated yields were deter-
mined by extraction with diethyl ether (3ϫ 20 mL), drying over
MgSO4, filtration, and concentration in vacuo. For the reaction
with perillic acid, after concentration, the crude mixture was fur-
ther purified by column chromatography to provide the pure prod-
uct. The reactions with 1-dodecene and 2-methyl-undecene were
additionally analyzed by GC for accurate determination of the con-
version. For the reaction with dienes, a protocol similar to method
B was used, the only difference being that 1.0 equiv. instead of
1.5 equiv. of H2O2 were utilized. For the reaction with carvone,
1.1 equiv. of H2O2 was used. Furthermore, at the end of the reac-
tion, diethyl ether (20 mL) was added, followed by nitrobenzene
(1 equiv.) in MeCN, and a sample was subjected to GC analysis.
Conclusions
A regioselective Fe-based oxidative cleavage protocol was
developed for the conversion of electron-rich internal and
terminal olefins to the corresponding carbonyl compounds
with low oxidant loadings and short reaction times. The
protocol shows a unique electronic preference for the cleav-
age of electron-rich alkenes over less electron-rich alkenes
and for internal alkenes over external alkenes. The observed
selectivity is based on electronic rather than steric factors,
as also less accessible electron-rich double bonds are
cleaved. The selective oxidation of geraniol, perillic acid,
and 1,5-hexadien-3-ol furthermore shows the functional
group tolerance of the protocol. The low catalyst loading,
short reaction time, and functional group tolerance of the
system compare favorably with other regioselective sys-
tems.[16,26] The system is the first regioselective cleavage sys-
tem of internal double bonds reported for multiple types of
dienes. The method also outperforms protocols using Ru,
Os, and W oxides in the sense that these generally cannot
discriminate between the double bonds in polyenes or over-
oxidize the initial aldehyde product to the carboxylic acid
level.[23,32,33] Overall, this Fe-based cleavage protocol pro-
vides a practical and mild procedure that allows for the (re-
gio)selective formation of aldehydes and ketones, without
significant over-oxidation.
Acknowledgments
Utrecht University and the financial support through its “Focus en
Massa” program are acknowledged. J. C. is grateful to the China
Scholarship Council (CSC) for a doctoral scholarship.
[1] A. Corma, S. Iborra, A. Velty, Chem. Rev. 2007, 107, 2411–
2502.
[2] U. Biermann, W. Friedt, S. Lang, W. Lühs, G. Machmüller,
J. O. Metzger, M. R. Klaas, H. J. Schäfer, M. P. Schneider, An-
gew. Chem. Int. Ed. 2000, 39, 2206–2224; Angew. Chem. 2000,
112, 2292–2310.
[3] U. Biermann, U. Bornscheuer, M. A. R. Meier, J. O. Metzger,
H. J. Schäfer, Angew. Chem. Int. Ed. 2011, 50, 3854–3871; An-
gew. Chem. 2011, 123, 3938–3956.
[4] Ozonolysis on industrial scale is performed by Novasep.
[5] D. Yang, C. Zhang, J. Org. Chem. 2001, 66, 4814–4818.
[6] C. M. Ho, W. Y. Yu, C. M. Che, Angew. Chem. Int. Ed. 2004,
43, 3303–3307; Angew. Chem. 2004, 116, 3365–3369.
[7] W. Yu, Y. Mei, Y. Kang, Z. Hua, Z. Jin, Org. Lett. 2004, 6,
3217–3219.
Experimental Section
Monoalkene Epoxidation, Method A: Alkene substrate (0.72 mmol),
active [Fe(OTf)2(mix-BPBP)] (1) {0.5%; containing 3.6 μmol of
combined [Fe(OTf)2(S,S-BPBP)] and [Fe(OTf)2(R,R-BPBP)], in a
batch commonly containing inactive [Fe(OTf)2(R,S-BPBP)] (0.9–
1.2 μmol)},[27] MeCOOH (0.015 equiv.), and MeCN (3 mL) were
mixed at 0 °C. H2O2 (1.0 equiv.) in MeCN (0.5 mL) was added
dropwise by hand, and the mixture was stirred for 10 min prior
to addition of diethyl ether (20 mL) and nitrobenzene (1.0 equiv.,
internal standard) in MeCN (1 mL), and subjected to GC analysis
to determine the conversion for cis-4-octene, trans-4-octene, 1-de-
cene, 2-methyl-1-undecene, 2-cyclohexen-1-one, and 3,4-epoxy-1-
cyclohexene (Table S2). With other substrates, instead of addition
of diethyl ether, CD3CN (1 mL) and nitrobenzene (1 equiv., in-
ternal standard) in MeCN (1 mL) were added, and the sample was
subjected to NMR spectroscopic analysis (referred to as “yields
determined by NMR”). The two analysis methods were compared
for cis-4-octene: both procedures gave the same results. With 2-
cyclohexen-1-one and dimethyl fumarate, the conversion was deter-
mined by GC analysis and the epoxide yield by NMR spectroscopic
analysis. For the epoxidation of carvone, method A was applied,
[8] A. Haimov, H. Cohen, R. Neumann, J. Am. Chem. Soc. 2004,
126, 11762–11763.
[9] P. Spannring, P. C. A. Bruijnincx, B. M. Weckhuysen, R. J. M.
Klein Gebbink, Catal. Sci. Technol. 2014, 4, 2182–2209.
[10] H. Mimoun, L. Saussine, E. Daire, M. Postel, J. Fischer, R.
Weiss, J. Am. Chem. Soc. 1983, 105, 3101–3110.
[11] B. M. Choudary, P. N. Reddy, J. Mol. Catal. A 1995, 103, L1.
[12] P. A. Ganeshpure, S. Satish, Tetrahedron Lett. 1988, 29, 6629–
6632.
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