Oxidation of alkenes with non-heme iron complexes: Suitability as an organic synthetic method

Article abstract of DOI:10.1016/j.tet.2014.10.037

In the course of a preliminary study to determine the preparative value and the synthetic applications of the non-heme iron(II) complexes Fe(bpmen)(OTf)₂ and Fe(tpa)(OTf)₂, in particular the oxidation of alkenes by using hydrogen peroxide as the terminal oxidant, we have found significant differences in catalyst behavior. After several attempts it was clear that the preparative relevance of the oxidation processes was linked to the concentration of the catalyst and optimal results were obtained when the concentration value was 5 mol %. At that concentration, the Fe(bpmen)(OTf)₂ catalyst mostly gave rise to mixtures of the epoxide and the trans-dihydroxylation products formed by water-assisted hydrolytic cleavage of the epoxides. Furthermore, the use of the tripodal ligand tpa led to cis dihydroxylation products. When deactivated olefins were used as substrates for the oxidation reaction, the cis-diols were obtained exclusively, although with modest conversions, regardless of the catalyst used.

Full text of DOI:10.1016/j.tet.2014.10.037

Tetrahedron 70 (2014) 9381e9386
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Oxidation of alkenes with non-heme iron complexes: suitability as
an organic synthetic method
David Clemente-Tejeda, Francisco A. Bermejo *
Departamento de Química Org aꢀ nica, Universidad de Salamanca, 37008 Salamanca, Spain
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 21 July 2014
Received in revised form 2 October 2014
Accepted 16 October 2014
Available online 22 October 2014
In the course of a preliminary study to determine the preparative value and the synthetic applications of
the non-heme iron(II) complexes Fe(bpmen)(OTf) and Fe(tpa)(OTf) , in particular the oxidation of al-
2 2
kenes by using hydrogen peroxide as the terminal oxidant, we have found significant differences in
catalyst behavior. After several attempts it was clear that the preparative relevance of the oxidation
processes was linked to the concentration of the catalyst and optimal results were obtained when the
2
concentration value was 5 mol %. At that concentration, the Fe(bpmen)(OTf) catalyst mostly gave rise to
Keywords:
Oxidation
Iron catalysis
cis-Dihydroxylation
cis-Jasmone
mixtures of the epoxide and the trans-dihydroxylation products formed by water-assisted hydrolytic
cleavage of the epoxides. Furthermore, the use of the tripodal ligand tpa led to cis dihydroxylation
products. When deactivated olefins were used as substrates for the oxidation reaction, the cis-diols were
obtained exclusively, although with modest conversions, regardless of the catalyst used.
Ó 2014 Elsevier Ltd. All rights reserved.
trans-Jasmone
1. Introduction
Current methodology to achieve the catalytic cis-dihydrox-
ylation of alkenes with preparative significance in organic synthesis
is mainly focused on osmium and ruthenium compounds. However,
some of the reagents used for this purpose are expensive, rather
volatile and toxic. Accordingly, the development of alternative
catalysts for the cis-1,2-dihydroxylation of alkenes is very
challenging.1
Inspired by the active site of iron oxidation enzymes, chemists
have designed a wide variety of complexes that could mimic these
metalloenzymes functionally, with the final goal of designing cat-
2
e16
17e33
alysts to achieve the oxidation of alkanes
and alkenes.
It
has been seen that the most effective non-heme iron catalysts are
those possessing nitrogen-based tripodal or linear tetradentate li-
gands, such that two cis labile sites available for coordination with
exogenous ligands become available (Fig. 1). During the last twenty
years, the preparation of a series of organic ligands that incorporate
the key features of the non-heme active iron site of the Rieske
dioxygenases, bacterial enzymes that perform the enantioselective
cis-dihydroxylation of arene and alkene double bonds, has led to
the characterization of several non-heme iron complexes and their
Fig. 1. Examples of the organic ligands used in the non-heme iron catalysis.
3
4e39
application to dihydroxylation processes.
However, most of
this effort has been developed by bioinorganic groups mainly in-
4
0
terested in understanding enzyme mechanisms.
In an investigation of the oxidation of alkenes by non-heme iron
enzyme mimics in the course of a preliminary study to determine
*
Corresponding author. Tel.: þ34 44 923 294481; e-mail address: fcobmjo@usal.
41
es (F.A. Bermejo).
http://dx.doi.org/10.1016/j.tet.2014.10.037
0
040-4020/Ó 2014 Elsevier Ltd. All rights reserved.

9382
D. Clemente-Tejeda, F.A. Bermejo / Tetrahedron 70 (2014) 9381e9386
the preparative value and synthetic applications of the non-heme
iron complexes derived from the above-mentioned linear
nitrogen-based tetradentate ligands, in particular the oxidation of
alkenes by using hydrogen peroxide as the terminal oxidant, we
focused our interest on bpmen iron(II) complexes and their ca-
pacity to oxidize steroids, monoterpenes and polycyclic aromatic
hydrocarbons.4
Nam to have high conversion efficiency; however, these authors
worked on substrates with a 0.12 mmol scale. Although some ep-
oxide was also generated, those complexes represented the first
3
8
examples of iron catalysts capable of olefin cis-hydroxylation.
We chose the cis-jasmone 1 as a peculiar and interesting sub-
strate because its structure contains both a rich cis-alkene and
a cyclic deactivated double bond. The oxidation of 1 (0.5 mmol) in
the open air with hydrogen peroxide (1.2 equiv) in the presence of
2e44
In this work, we study the preparative significance of the cis-
dihydroxylation of alkenes by using the non-heme iron complexes
2 3
Fe(bpmen)(OTf) (5 mol %) in CH CN at room temperature proved
0
Fe(bpmen)(OTf)
amine) and Fe(tpa)(OTf)
fluoromethanesulphonate) (Fig. 1).
2
I (bpmen: bispicolyl-N,N -methylenthylenendi-
to be a regio- and stereoselective process. However, it afforded the
threo diol 2 as the only oxidation product with 80% yield and 94%
conversion (Table 1, entry 1). Furthermore, when the concentration
of the catalyst was decreased to 0.2 mol %, the conversion of the
oxidation reaction fell to 10% and, again, the diol 2 was obtained but
in only 6% yield (Table 1, entry 2). After several attempts, it was
clear that the preparative relevance of the process depended on the
catalyst concentration, and optimal results were obtained for cat-
alyst concentration values of 5 mol %. When the reaction was run
under an inert atmosphere (Ar), we did not observe any substantial
2
II (tpa: tripicolylamine. eOTf: tri-
2
. Results and discussion
Use of the bpmen system (I, Fig. 1) in epoxidation reactions for
2
2a
preparative purposes was first described by Jacobsen.
Later, the
oxidation of olefins to cis-diols by using tpa catalysts (II, Fig. 1)
under conditions of limiting substrate was described by Que and
Table 1
Iron (II) complex-catalyzed dihydroxylation of (Z)-Jasmone and (E)-Jasmone. Studies of the competition between dihydroxylation and epoxide hydrolytic cleavage
Entry
1
Substrate
Catalyst
Methoda
Conversion (%)b
Products (yield %)c
Fe(bpmen)(OTf)
2
2
2
2
A
94%
2
3
4
Fe(bpmen)(OTf)
Fe(bpmen)(OTf)
Fe(bpmen)(OTf)
D
10%
90%
Ad
A
100%
5
6
Fe(bpmen)(OTf)
2
2
A
C
100%
100%
Fe(bpmen)(OTf)
7
Fe(tpa)(OTf)
Fe(tpa)(OTf)
2
A
85%
8
2
A
75%
a
The different procedures (AeD) are described in Experimental section. Typical experiments were performed using 0.5 mmol of starting material. Additionally, most of the
tests were carried out at a scale of 2 mmol in order to test the preparative scale of the methodology.
b
c
1
Conversion was determined by GC or H NMR analysis of the crude product.
Isolated yield based on the starting substrate.
The reaction was carried under a nitrogen atmosphere.
d

D. Clemente-Tejeda, F.A. Bermejo / Tetrahedron 70 (2014) 9381e9386
9383
change in our primary results and hence autooxidation could be
ruled out (Table 1, entry 3). These results are different from those
afforded a mixture of the threo diol 2, and the epoxide diol 4, both
in 30% yield (Table 1, entry 6).
3
9
obtained previously by Costas and Beller with Me
2
PyTACN cata-
2
A change of catalyst to Fe(tpa)(OTf) allowed us to test the ox-
lysts (III, Fig. 1.) under conditions in which the olefin was not used
in large amounts (substrate 0.05 mmol scale) but instead was the
limiting reagent.
Working on a substrate at a scale of 0.5 mmol, we have pre-
viously reported the anomalous stereochemical outcome of this
oxidation reaction as being due either to the water-assisted hy-
drolytic cleavage of the epoxide precursor 3 or to the participation
of carbon-centered radical oxidized olefin species capable of fast
epimerization, leading to the most stable intermediate and hence
to the threo diol 2.43
idation of 1 when hydrogen peroxide (1.2 equiv) was used as the
terminal oxidant. The oxidation process afforded a mixture of
erythro (7) and threo (2) diols in a 2:1 ratio, respectively, with 85%
conversion and 70% yield (Table 1, entry 7). In this context, the use
of the tpa complex apparently increased the formation of the ex-
pected cis-dihydroxylation product, the erythro diol 7, and reduced
the formation of both the epoxide 3 and of its water-assisted
cleavage product 2 in comparison with previous results obtained
2
with Fe(bpmen)(OTf) . Under identical conditions, the trans-jas-
mone 6 led stereoselectively to the cis-dihydroxylation product, the
threo diol 2, with 75% conversion and 65% yield (Table 1, entry 8).
This transformation proved to be the method of choice to obtain the
threo-diol 2 from trans-jasmone 6 through a cis-dihydroxylation
process.
The use of electron-rich alkenes such as cis-3-hexen-1-ol piv-
alate 8 provides excellent stereoselectivity towards cis-dihydrox-
ylation. The oxidation of 8 with hydrogen peroxide (1.2 equiv) in
We were not very confident about our first proposal, since the
stereochemical outcome of the dihydroxylation process catalyzed
by these types of iron(II) complex is generally linked to an oxo-
hydroxy iron(V) species and its interaction with olefins through
V
a concerted [3þ2]-cycloaddition mechanism between Fe (bpme-
n)(O)(OH) and alkenes, which is strongly supported by DFT calcu-
lations.1 No previous references were found in the literature
regarding the isolation of trans-diols as major products under non-
heme iron-catalyzed reaction conditions; nevertheless, the in-
stability of the cis epoxide 3 may have been enhanced by the in-
creased concentration of the iron complex, mostly due to its Lewis-
acid character. Additionally, when the cis-epoxide 3 was allowed to
react under the same oxidizing reaction conditions (Table 1, entry
2
the presence of Fe(tpa)(OTf) (5 mol %) afforded the erythro-diol 9
stereoselectively, with 84% conversion and 80% yield (Table 2, entry
1). Good cis-dihydroxylation chemoselectivity has been obtained
with e-poor olefins at low substrate conversions, but not with an e-
3
8
rich olefin under preparative conditions. However, the use of
Fe(bpmen)(OTf) as catalyst under identical conditions afforded
2
4
), two products, 2 and 4, were obtained with 12% and 50% yields,
a mixture of the epoxide 10 and the threo-diol 11, with 24% and 53%
respectively. Both products exhibited the threo-diol functionality in
the open chain, which obviously helps to support the hydrolytic
cleavage of the epoxide 3 under the reaction conditions.
yield, respectively (Table 2, entry 2).
Table 2
In order to test the suitability of our second proposal, based on
the fast epimerization of a carbon-centered radical intermediate,43
we decided to perform the oxidation of trans-jasmone 6 with hy-
Oxidation of electron-rich and deactivated olefins by non-heme iron (II) complexes
Entry Substrate Catalyst
Methoda Conversion Products (yield %)c
b
(%)
drogen peroxide in the presence of Fe(bpmen)(OTf)
of 6 was achieved by applying a three-step reaction sequence with
0% overall yield (Scheme 1).
2
. The synthesis
1
2
3
4
5
6
7
8
9
1
1
8
8
Fe(tpa)(OTf)
Fe(bpmen)(OTf)
Fe(tpa)(OTf)
Fe(bpmen)(OTf)
Fe(tpa)(OTf)
Fe(bpmen)(OTf)
Fe(tpa)(OTf)
Fe(bpmen)(OTf)
2
A
A
A
A
A
A
A
A
A
A
A
84%
9 (81%)
2
2
2
2
100%
66%
100%
35%
78%
32%
40%
50%
75%
70%
10 (24%)þ11 (53%)
13 (7%)þ14 (50%)
13 (50%)þ15 (15%)
17 (20%)
18 (75%)
20 (30%)
6
12
12
16
16
19
19
21
21
24
2
2
2
20 (25%)
Fe(tpa)(OTf)
Fe(tpa)(OTf)
Fe(tpa)(OTf)
2
2
2
22 (10%)þ23 (18%)
22 (28%)þ23 (20%)
25 (5%)þ26 (8%)
þ27 (28%)
0
1
a
The different procedures are described in Experimental section. Typical exper-
iments were performed using 0.5 mmol of starting material. Most of the tests were
carried out at a scale of 2 mmol in order to test the preparative scale of the
methodology.
b
Conversion was determined by GC or 1H NMR analysis of the crude product.
Isolated yield based on the starting substrate.
c
Scheme 1. Synthesis of (E)-Jasmone using the CoreyeWinters method. a) Fe(bpme-
n)(OTf) (5 mol %), H (1.2 equiv), CH CN, 10 min at room temperature, (yield: 80%).
b) NeN -thiocarbonyldiimidazole (1.1 equiv), THF, 20 h at reflux, (yield: 100%). c)
P(OEt) , 20 h at reflux, (yield: 75%).
2
0
2
O
2
3
3
Again, the major product of the mixture was the water-assisted
cleavage product of the epoxide 10, the threo-diol 11.
0
Treatment of 2 with N,N -thiocarbonyldiimidazole in refluxing
THF led to the thiocarbonate 5 in quantitative yields. Finally, the
reaction of 5 with triethyl phosphite under reflux with the Corey-
Winter protocol47 afforded the trans-jasmone 6 with 75% yield.
The oxidation of 6 with hydrogen peroxide (1.2 equiv) in the
2 2
By using either Fe(tpa)(OTf) or Fe(bpmen)(OTf) as catalysts
for the oxidation of cis-3-hexen-1-ol benzoate 12, we obtained
mixtures of the epoxide 13 (7%) and the erythro-diol 14 (50%) with
66% conversion in the first case, and a mixture of the epoxide 13
(50%) and the threo-diol 15 (15%) in the second case (Table 2, entries
3 and 4). With cis-4-hexen-1-ol benzoate 16, oxidation under
analogous conditions using the tpa ligand afforded the erythro
isomer 17 exclusively, with 20% yield (35% conversion), but led to
the isolation of epoxide 18 with 75% yield (78% conversion) with
the bpmen ligand.
48
presence of Fe(bpmen)(OTf)
perature led to the erythro diol 7 in 70% yield (Table 1, entry 5).
2 3
(5 mol %) in CH CN at room tem-
4
9
This experiment clearly demonstrated that the stereochemical
outcome of the oxidation reaction was due to the water-assisted
cleavage of the epoxide 3, since if the participation of an oxidized
olefin species capable of fast epimerization were correct, it would
have also afforded the threo diol 2, and this was not the case.
The use of oxone (1 equiv) as the terminal oxidant in the oxi-
dation of cis-jasmone 1 took place with 100% conversion and
Clearly, the tpa ligand appears to be the best choice to achieve
the cis-dihydroxylation of electron-rich alkenes (Table 2, entries 1, 3
and 5).

9384
D. Clemente-Tejeda, F.A. Bermejo / Tetrahedron 70 (2014) 9381e9386
In the case of electron-poor alkenes, the oxidation of diethyl
Biosystems QSTAR XL with ESI ionization. The GCeMS analysis of
the reaction mixtures was performed using a Agilent MS 220 gas
chromatograph and a GC7890A selective mass detector. A DB5
column was used (30 m long, 0.25 mm internal diameter and
maleate 19 with hydrogen peroxide (1.2 equiv) afforded the erythro
diol 20 exclusively, both with the tpa (30% yield, 32% conversion)
and the bpmen (25% yield, 40% conversion) ligands (Table 2, entries
7
and 8).
0.25
m
m layer thickness), with helium as the carrier gas. The sam-
ꢀ
In the case of 4,9(11)-androstadien-3,17-dione 21, oxidation
pling program started at 50 C as the initial temperature, and after
ꢀ
ꢀ
with hydrogen peroxide (1.2 equiv) in the presence of Fe(tpa)(OTf)
afforded a mixture of the epoxide 22 and the allylic alcohol 23 with
0% and 18% yields, respectively, with 50% conversion. Increasing
2
5 min the temperature was raised to 270 C with a gradient of 10 C/
min, and was held for an additional 5 min. The components of the
mixtures were identified by comparing their full mass spectra and
retention times with the corresponding data for reference com-
pounds at the National Institute of Standard Technologies database
(NIST 2011). The chemicals and solvents used were obtained from
commercial sources and used as received with the exception of
1
the concentration of the catalyst (15 mol %) and the terminal oxi-
dant hydrogen peroxide (3.6 equiv) led to the same mixture of
compounds 22 and 23 with 28% and 20% yields, respectively, with
7
5% conversion (Table 2, entries 9 and 10) (Fig. 2).
Fig. 2. Substrates and products from comparative studies between electron-poor and electron-rich olefins.
Finally, oxidation of the
epoxide 25 (5% yield), the enone 26 (8%) and cis diol 27 (28%) with
0% conversion (Table 2, entry 11). Structural assessment of cis-diol
7 was achieved through complete NMR analysis of the product
a
-ionone 24 afforded a mixture of the
tetrahydrofuran, which was distilled from sodium and benzophe-
none. H was titrated with KMnO previously normalized using
as a primary standard. Unless specified otherwise, the re-
ported yields are for chromatographically pure isolated products.
Preparation of the catalysts Fe(bpmen)(OTf) I and Fe(tpa)(OTf) II
was achieved as described in the literature. Protocols AeC are
described at a starting material scale of 0.5 mmol. No changes in the
yields or reaction products were observed when a starting material
scale of 2 mmol was tested.
2
O
2
4
7
2
2 2 4
K C O
and by comparison of the spectroscopic data with those described
2
2
5
0
45
for the same compound in the literature.
. Conclusions
3
The preparative relevance of the non-heme iron-catalyzed cis-
dihydroxylation of alkenes with hydrogen peroxide in the presence
of Fe(bpmen)(OTf) and Fe(tpa)(OTf) is linked to the catalyst
concentration, the optimal catalyst concentration being 5 mol %.
However, at these concentration values, the Fe(bpmen)(OTf) cat-
4.2. Protocol A (5 mol % of catalyst)
2
2
A 10 mL round-bottomed flask was loaded with 0.75 mL of
2
CH
1.0 equiv). The solution was stirred vigorously at room temperature.
A 0.13 M solution of H in CH CN (4 mL, 1.2 equiv) was added
3
CN, catalyst (0.025 mmol, 5 mol %), and substrate (0.5 mmol,
alyst mostly gave rise to mixtures of epoxides and the threo-diols
formed by water-assisted hydrolytic cleavage of the epoxides.
2
O
2
3
The Fe(tpa)(OTf)
2
complex always gave the cis-dihydroxylation
dropwise via a syringe. After the addition had been completed, the
reaction mixture was stirred for an additional 10 min. Then, a sat-
products as the major products in mixtures with the epoxides, and
in some cases (with e-rich (8) and deactivated (19) olefins) gave the
cis-dihydroxylation products (9 and 20) exclusively.
When deactivated olefins were used as substrates for the non-
heme iron-catalyzed oxidation of alkenes, cis-diols were obtained
exclusively, although with modest conversions, regardless of the
catalyst used in the transformations.
urated aqueous NaHCO
extracted with ethyl acetate. The combined organic layers were
dried over anhydrous Na SO , evaporated under reduced pressure,
3
solution was added and the mixture was
2
4
and purified by flash chromatography.
4.3. Iterative protocol B (15 mol % of catalyst)
A 50 mL round-bottomed flask was loaded with 0.75 mL of
4
4
. Experimental section
CH
1.0 equiv). The solution was stirred vigorously at room temperature.
A 0.13 M solution of H in CH CN (4 mL, 1.2 equiv) was added
dropwise via a syringe. After stirring for 10 min, 0.5 mL of CH CN
and catalyst (0.025 mmol, 5 mol %) was added. This was followed by
dropwise addition of H (30 wt %, 68 L, 0.6 mmol, 1.2 equiv) in
CH CN (4 mL, 0.13 M). A third addition was performed for a total of
15 mol % catalyst and 3.6 equiv of H . After the last 10 min of
3
CN, catalyst (0.025 mmol, 5 mol %), and substrate (0.5 mmol,
.1. General experimental methods
2
O
2
3
1H NMR spectra were measured at either 200 or 400 MHz and
C NMR were measured at 50 or 100 MHz in CDCl3 and referenced
3
13
1
13
to TMS ( H) or solvent ( C) except where indicated otherwise.
HRMS determinations were recorded at the Mass Spectrometry
Service of the University of Salamanca, Spain, on an Applied
2
O
2
m
3
2 2
O

D. Clemente-Tejeda, F.A. Bermejo / Tetrahedron 70 (2014) 9381e9386
9385
stirring, NaHCO
mixture was extracted with ethyl acetate. The combined organic
layers were dried over anhydrous Na SO , evaporated under re-
duced pressure, and purified by flash chromatography.
3
-saturated aqueous solution was added and the
4.11. 2-[(2SR,3RS)-3-Ethyloxiran-2-yl]ethyl benzoate (±)13
1H NMR (CDCl
): d
¼1.05 (t, J¼8 Hz, 3H), 1.56 (m, 2H), 1.98 (m,
¼4 Hz, 1H), 3.12 (dt, J ¼6 Hz, J ¼5 Hz, 1H),
¼7 Hz, J ¼5 Hz, 2H), 7.57 (d, J¼5 Hz,
H), 8.06 (d, J¼7 Hz, 2H) ppm. C NMR (CDCl ): ¼10.8 (q), 21.3 (t),
7.8 (t), 54.6 (d), 58.3 (d), 62.6 (t), 128.6 (d, 2C), 129.8 (d, 2C), 130.3
2
4
3
2H), 2.92 (dt, J ¼7 Hz, J
1
2
1
2
4
1
2
.50 (t, J¼7 Hz, 2H), 7.43 (dd, J
1
2
1
3
3
d
4
.4. Protocol C
(
s), 133.2 (d), 166.7 (s) ppm. ESI-HRMS (MþNa): calculated for
A 50 mL round-bottomed flask was loaded with substrate
(
(
0.5 mmol, 1.0 equiv), 7.5 mL of CH
3
CN, 5.0 mL of H
2
O, Oxone
C H O Na: 243.0991, experimental: 243.0987.
13 16 3
0.5 mmol, 1.0 equiv) and catalyst (0.025 mmol, 5 mol %). The so-
ꢀ
4.12. (3SR,4RS)-3,4-Dihydroxyhexyl benzoate (±)14
lution was stirred and heated at 80 C for 6 h. Then, the solution was
filtered and the filtrate was extracted with ethyl acetate. The
1H NMR (CDCl
H), 3.58 (m, 1H), 3.74 (m, 1H), 4.46 (m, 2H), 7.39 (dd, J
¼0.95 (t, J¼7 Hz, 3H), 1.46 (m, 2H), 1.90 (m,
¼7 Hz,
combined organic layers were dried over anhydrous Na
2
SO
4
,
3
): d
2
J
(
(
(
1
evaporated under reduced pressure, and purified by flash
chromatography.
1
3
2
¼5 Hz, 2H), 7.49 (d, J¼5 Hz,1H), 8.00 (d, J¼7 Hz, 2H) ppm. C NMR
CDCl ):
¼10.6 (q), 24.9 (t), 30.5 (t), 62.6 (t), 71.2 (d), 76.3 (d), 128.6
d, 2C), 129.8 (d, 2C), 130.3 (s), 133.3 (d), 167.2 (s) ppm. ESI-HRMS
Na: 261.1097, experimental:
3
d
4
.5. Protocol D
MþNa): calculated for
13 18 4
C H O
2
61.1088.
In order to perform this experiment we followed the method of
4
6
Que et al. JACS, 2003, 125, 9912e9913.
4.13. (3RS,4RS)-3,4-Dihydroxyhexyl benzoate (±)15
Compounds (ꢁ)2 and 4 (as a mixture of diastereoisomers) are
ꢀ
described in reference n 43.
ꢀ
1H NMR (CDCl
H), 3.58 (m, 1H), 3.74 (m, 1H), 4.46 (m, 2H), 7.39 (dd, J
3
):
d
¼0.95 (t, J¼7 Hz, 3H), 1.46 (m, 2H), 1.90 (m,
¼7 Hz,
Compounds 22, 23, and 25 are described in reference n 42.
2
1
1
3
J
(
2
¼5 Hz, 2H), 7.49 (d, J¼5 Hz,1H), 8.00 (d, J¼7 Hz, 2H) ppm. C NMR
4
.6. Trans-jasmone 6
CDCl ):
3
d
¼10.1 (q), 26.6 (t), 29.9 (t), 62.2 (t), 71.0 (d), 76.0 (d), 128.6
1H NMR (CDCl
(d, 2C), 129.8 (d, 2C), 130.2 (s), 133.3 (d), 167.3 (s) ppm. ESI-HRMS
MþNa): calculated for Na: 261.1097, experimental:
261.1084.
3
):
d
¼0.92 (t, J
1
¼7 Hz, 3H), 1.27 (m, 2H), 1.95 (m,
¼4 Hz, 1H), 2.49 (m, 1H), 2.86
(
13 18 4
C H O
2
(
(
H), 2.04 (s, 3H), 2.35 (dd, J
¼6 Hz, 2H), 5.36 (m, 2H) ppm. C NMR (CDCl
q), 25.6 (t), 26.2 (t), 31.8 (t), 34.5 (t), 125.1 (d), 133.1 (d), 139.1 (s),
1
¼5 Hz, J
2
1
3
d, J
1
3
):
d
¼13.9 (q),17.4
4.14. (4S,5R)-4,5-Dihydroxyhexyl benzoate (±)17
1
C
71.1 (s), 209.3 (s) ppm. ESI-HRMS (MþNa): calculated for
11
H
16ONa: 187.1093, experimental: 187.1094.
1H NMR (CDCl
3
):
d
¼1.17 (t, J¼6.2 Hz, 3H), 1.49e2.06 (m, 4H),
2
.44 (br s, 2H), 3.64 (m, 1H), 3.80 (m, 1H), 4.36 (t, J¼6.6 Hz, 2H), 7.40
¼7 Hz, J ¼5 Hz, 2H), 7.55 (d, J¼5 Hz, 1H), 8.02 (d, J¼7 Hz, 2H)
ppm. C NMR (CDCl ):
¼17.0 (q), 25.7 (t), 28.3 (t), 65.1 (t), 70.7 (d),
4.7 (d), 128.6 (d, 2C), 129.7 (d, 2C), 130.4 (s), 133.2 (d), 167.0 (s)
4
.7. 2-[(2SR,3RS)-2,3-Dihydroxypentyl]-3-methylcyclopent-2-
(
dd, J
1
2
enone (±)7
13
3
d
7
1H NMR (CDCl
):
d
¼0.92 (t, J¼7 Hz, 3H),1.48 (m, 2H), 2.11 (s, 3H),
13
3
ppm. ESI-HRMS (MþNa): calculated for C13
18 4
H O Na: 261.1097, ex-
2
d
.53 (m, 4H), 3.38 (m, 2H), 3.58 (m, 2H) ppm. C NMR (CDCl
¼10.4 (q), 17.8 (q), 25.6 (t), 26.3 (t), 32.5 (t), 34.3 (t), 74.0 (d), 75.0
d), 138.0 (s), 174.9 (s), 212.8 (s) ppm. ESI-HRMS (MþNa): calculated
for C11 Na: 221.1148, experimental: 221.1147.
3
):
perimental: 261.1101.
(
4
.15. 3-(3-Methyloxiran-2-yl)propyl benzoate (±)18
18 3
H O
1H NMR (CDCl
): d
¼3.02 (m, 2H), 4.36 (t, J¼6.8 Hz, 2H), 7.41 (dd,
3
4
.8. (3SR,4RS)-3,4-Dihydroxyhexyl pivalate (±)9
1H NMR (CDCl
J
2
5
1
¼7.2 Hz, J ¼6.4 Hz, 2H), 7.50 (d, J¼6.4 Hz, 1H), 8.02 (d, J¼7.2 Hz,
2
1
3
H) ppm. C NMR (CDCl ):
3
d¼24.0 (q), 25.9 (t), 28.8 (t), 53.1 (d),
3
):
d
¼0.96 (t, J¼8 Hz, 3H), 1.16 (s, 9H), 1.45 (m, 2H),
6.9 (d), 64.7 (t), 128.6 (d, 2C), 129.7 (d, 2C), 130.3 (s), 133.2 (d),
: 221.1172,
13
1
.73 (m, 2H), 3.58 (m, 1H), 4.20 (m, 2H), 4.31 (m, 1H) ppm. C NMR
CDCl ):
¼10.5 (q), 25.0 (t), 27.4 (q, 3C), 30.3 (t), 39.0 (s), 61.9 (t),
1.1 (d), 76.1 (d), 179.3 (s) ppm. ESI-HRMS (MþNa): calculated for
1
66.9 (s) ppm. ESI-HRMS (MþH): calculated for C13
17 3
H O
(
7
C
3
d
experimental: 221.1181.
11 22 4
H O Na: 241.1410, experimental: 241.1405.
4
.16. (2RS,3SR)-Diethyl 2,3-dihydroxysuccinate 20
1
4
.9. 2-[(2SR,3RS)-3-Ethyloxiran-2-yl]ethyl pivalate (±)10
1H NMR (CDCl
H NMR (CDCl ):
d
¼1.30 (t, J ¼7 Hz, 3H), 3.20 (br s, 1H), 4.26 (m,
13
3
1
2
H), 4.55 (s, 1H) ppm. C NMR (CDCl
3
):
d
¼14.3 (q), 62.5 (t), 73.1 (d),
3
):
d
¼1.05 (t, J¼7 Hz, 3H), 1.18 (s, 9H), 1.58 (m, 2H),
171.3 (s) ppm. ESI-HRMS (MþNa): calculated for C H O Na:
8
14
6
13
1
.87 (m, 2H), 2.92 (m,1H), 3.00 (m,1H), 4.22 (t, J¼7 Hz, 2H) ppm.
NMR (CDCl ):
¼10.8 (q), 21.3 (t), 27.2 (q, 3C), 27.6 (t), 38.9 (s), 54.4
d), 58.2 (d), 62.1 (t), 178.7 (s) ppm. ESI-HRMS (MþNa): calculated
for C11 : 201.1485, experimental: 201.1480.
C
229.0682, experimental: 229.0681.
3
d
(
4
.17. (E)-3,5,5-Trimethyl-4-(3-oxobut-1-en-1-yl)cyclohex-2-
enone 26
21 3
H O
4
.10. (3RS,4RS)-3,4-Dihydroxyhexyl pivalate (±)11
1H NMR (CDCl
1H NMR (CDCl
3
):
d
¼0.99 (s, 3H), 1.06 (s, 3H), 1.88 (s, 3H), 2.12 (d,
J¼16.8 Hz,1H), 2.26 (s, 3H), 2.35 (d, J¼16.8 Hz,1H), 2.69 (d, J¼9.4 Hz,
3
):
d
¼0.99 (t, J¼7 Hz, 3H),1.20 (s, 9H),1.45 (m, 2H),
1H), 5.97 (s, 1H), 6.17 (d, J¼15.6 Hz, 1H), 6.65 (dd, J
1
¼9.4 Hz, J
¼23.7 (q), 27.5 (q), 27.8 (q), 28.1 (q),
36.9 (s), 47.5 (t), 55.6 (t),127.1 (d),133.9 (d),143.8 (d),159.4 (s),197.8
2
¼15.6,
13
13
1
.73 (m, 2H), 3.39 (m, 1H), 3.50 (m, 1H), 4.20 (m, 2H) ppm. C NMR
CDCl ):
¼10.0 (q), 26.5 (t), 27.4 (q, 3C), 33.2 (t), 39.0 (s), 61.6 (t),
0.9 (d), 75.9 (d), 179.3 (s) ppm. ESI-HRMS (MþNa): calculated for
Na: 241.1410, experimental: 241.1403.
3
1H) ppm. C NMR (CDCl ): d
(
7
C
3
d
(s), 198.6 (s) ppm. ESI-HRMS (MþNa): calculated for C13
18 2
H O Na:
11
22
H O
4
229.1199, experimental: 229.1201.

9386
D. Clemente-Tejeda, F.A. Bermejo / Tetrahedron 70 (2014) 9381e9386
4
.18. (E)-4-((2R,3S)-2,3-Dihydroxy-2,6,6-trimethylcyclohexyl)
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J.; Nam, W. J. Inorg. Biochem. 2006, 100, 627e633.
8. Lane, B. S.; Burgess, K. Chem. Rev. 2003, 103, 2457e2474.
but-3-en-2-one 27
1
1
9. (a) Ono, M.; Okura, I. J. Mol. Catal. 1990, 61, 113e122; (b) Burger, R. M. Chem. Rev.
1998, 98, 1153e1170.
1H NMR (CDCl
J¼10.6 Hz, 1H), 2.30 (s, 3H), 3.58 (d, J¼3.2 Hz, 1H), 6.08 (d,
):
d
¼0.78 (s, 3H), 1.05 (s, 3H), 1.14 (s, 3H), 2.10 (d,
3
2
0. Nam, W.; Ho, R.; Valentine, J. S. J. Am. Chem. Soc. 1991, 113, 7052e7054.
1. Guajardo, R. J.; Hudson, S. E.; Brown, S. J.; Mascharak, P. K. J. Am. Chem. Soc. 1993,
15, 7971e7977.
22. (a) White, M. C.; Doyle, A. G.; Jacobsen, E. J. Am. Chem. Soc. 2001, 123,
194e7195; (b) Chen, M. S.; White, C. Science 2007, 318, 783e787; (c) Ver-
2
1
3
J¼16.0 Hz, 1H), 6.96 (dd, J
1
¼10.6 Hz, J
¼22.4 (q), 25.4 (t), 27.2 (q), 28.3 (q), 32.4 (q), 33.8 (t), 34.1
s), 53.4 (d), 73.6 (s), 74.6 (d), 135.0 (d), 146.9 (d), 198.9 (s) ppm. ESI-
Na: 249.1461, experimental:
2
¼16.0, 1H) ppm. C NMR
1
(
3
CDCl ): d
7
(
meulen, N. A.; Chen, M. S.; White, C. Tetrahedron 2009, 65, 3078e3084; (d)
Chen, M. S.; White, C. Science 2010, 327, 566e567; (e) Bigi, M. A.; Reed, S.;
White, C. Nat. Chem. 2011, 3, 216e222; (f) Bigi, M. A.; Reed, S.; White, C. J. Am.
Chem. Soc. 2012, 134, 9721e9726.
HRMS (MþNa): calculated for C13
49.1468.
22 3
H O
2
2
2
2
2
2
3. Duban, E. A.; Bryliakov, K. P.; Talsi. Eur. J. Inorg. Chem. 2007, 852e857.
4. Fujita, M.; Que, L. Adv. Synth. Catal. 2004, 346, 190e194.
5. Dubois, G.; Murphy, A.; Stack, T. D. P. Org. Lett. 2003, 5, 2469e2472.
6. Quinonero, D.; Musaev, D. G.; Morokuma, K. Inorg. Chem. 2003, 42, 8449e8455.
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Acknowledgements
We are grateful to Takasago International Chemicals (Europe)
SA, El Palmar, Murcia, Spain for the generous gift of cis-jasmone.
Also, D.C.T. wishes to thank the F.S.E. and the Consejería de Edu-
caci oꢀ n de la Junta de Castilla y Le oꢀ n for a predoctoral grant.
7489e7500.
28. Bukowski, M. R.; Comba, P.; Lienke, A.; Limberg, C.; Lopez de Laorden, C.; Mas-
Ballest
eꢀ , R.; Merz, M.; Que, L. Angew. Chem., Int. Ed. 2006, 45, 3446e3449.
2
9. Taktak, S.; Ye, W.; Herrera, A. M.; Rybak-Akimova, E. V. Inorg. Chem. 2007, 46,
929e2942.
0. Gosiewska, S.; Lutz, M.; Spek, A. L.; Klein Gebbink, R. J. M. Inorg. Chim. Acta
007, 360, 405e417.
1. Bitterlich, B.; Anilkumar, G.; Gelalcha, F. G.; Spilker, B.; Grotevendt, A.; Jackstell,
2
Supplementary data
3
2
3
Supplementary data related to this article can be found at http://
dx.doi.org/10.1016/j.tet.2014.10.037.
R.; Tse, M. K.; Beller, M. Chem.dAsian J. 2007, 2, 521e529.
2. Anilkumar, G.; Bitterlich, B.; Gelalcha, F. G.; Tse, M. K.; Beller, M. Chem. Commun.
2
3
3
007, 289e291.
3. Gelalcha, F. G.; Bitterlich, B.; Tse, M. K.; Beller, M. Angew. Chem., Int. Ed. 2007, 46,
293e7296.
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ꢀ
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1