Cathodic hydrodimerization of nitroolefins

Article abstract of DOI:10.3762/bjoc.11.131

Nitroalkenes are easily accessible in high variety by condensation of aldehydes with aliphatic nitroalkanes. They belong to the group of activated alkenes that can be hydrodimerized by cathodic reduction. There are many olefins with different electron withdrawing groups used for cathodic hydrodimerization, but not much is known about the behaviour of the nitro group. Synthetic applications of this group could profit from the easy access to nitroolefins in large variety, the C-C bond formation with the introduction of two nitro groups in a 1,4-distance and the conversions of the nitro group by reduction to oximes and amines, the conversion into aldehydes and ketones via the Nef reaction and base catalyzed condensations at the acidic CH bond. Eight 1-aryl-2-nitro-1-propenes have been electrolyzed in an undivided electrolysis cell to afford 2,5-dinitro-3,4-diaryl hexanes in high yield. The 4-methoxy-, 4-trifluoromethyl-, 2-chloro- and 2,6-difluorophenyl group and furthermore the 2-furyl and 2-pyrrolyl group have been applied. The reaction is chemoselective as only the double bond but not the nitro group undergoes reaction, is regioselective as a β,β-coupling with regard to the nitro group and forms preferentially two out of six possible diastereomers as major products.

Full text of DOI:10.3762/bjoc.11.131

Cathodic hydrodimerization of nitroolefins
Michael Weßling and Hans J. Schäfer*
Full Research Paper
Open Access
Address:
Beilstein J. Org. Chem. 2015, 11, 1163–1174.
Organisch-Chemisches Institut der Westfälischen
Wilhelms-Universität, Correns-Straße 40, 48149 Münster, Germany
doi:10.3762/bjoc.11.131
Received: 17 April 2015
Accepted: 19 June 2015
Published: 14 July 2015
Email:
Hans J. Schäfer* - schafeh@uni-muenster.de
* Corresponding author
This article is part of the Thematic Series "Electrosynthesis".
Guest Editor: S. R. Waldvogel
Keywords:
cathodic hydrodimerization; C–C bond formation;
1,4-dinitrocompounds; electrosynthesis; nitroalkene
© 2015 Weßling and Schäfer; licensee Beilstein-Institut.
License and terms: see end of document.
Abstract
Nitroalkenes are easily accessible in high variety by condensation of aldehydes with aliphatic nitroalkanes. They belong to the
group of activated alkenes that can be hydrodimerized by cathodic reduction. There are many olefins with different electron with-
drawing groups used for cathodic hydrodimerization, but not much is known about the behaviour of the nitro group. Synthetic
applications of this group could profit from the easy access to nitroolefins in large variety, the C–C bond formation with the intro-
duction of two nitro groups in a 1,4-distance and the conversions of the nitro group by reduction to oximes and amines, the conver-
sion into aldehydes and ketones via the Nef reaction and base catalyzed condensations at the acidic CH bond. Eight 1-aryl-2-nitro-
1-propenes have been electrolyzed in an undivided electrolysis cell to afford 2,5-dinitro-3,4-diaryl hexanes in high yield. The
4-methoxy-, 4-trifluoromethyl-, 2-chloro- and 2,6-difluorophenyl group and furthermore the 2-furyl and 2-pyrrolyl group have been
applied. The reaction is chemoselective as only the double bond but not the nitro group undergoes reaction, is regioselective as a
ß,ß-coupling with regard to the nitro group and forms preferentially two out of six possible diastereomers as major products.
Introduction
Olefins being activated by an electron withdrawing group can easily introduced by addition of a nitroalkyl anion to a carbonyl
be hydrodimerized by cathodic reduction [1,2]. Thereby, the group followed by elimination of water from the resulting
cathode serves as cheap, versatile, immobilized and mostly non- alcohol. The nitroolefin can be reduced at the nitro group, at the
polluting reagent providing economical and ecological advan- double bond and simultaneously at both groups. In acidic
tages compared to chemical reducing agents [3,4]. Alkenes with medium the nitro group is reduced between −0.25 V to −0.55 V
a large variety of electron withdrawing groups have been vs SCE to mixtures of syn/anti-oximes in 85% to 92% yield at a
explored in cathodic hydrodimerizations (Scheme 1) [1,2]. We mercury pool cathode and with slightly lower yields at a
were interested in the nitro group as a substituent. It can be graphite cathode [5-8]. The current controlled reduction of
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Scheme 1: Proposed mechanisms via pathways (I) to (III) for the cathodic hydrodimerization of olefins with electron attracting substituents.
alkyl- and aryl-substituted nitroalkenes in acidic medium [6-8]. There have been reports on the reductive dimerization of
affords mixtures of ketones and oximes in yields of 39% to 72% nitro alkenes prior to 1991. 1,4-Dinitro-2,3-diphenylbutane (3)
[9] and 55% to 91% [10], respectively.
has been obtained in less than 20% yield in the catalytic hydro-
genation of β-nitrostyrene (4) [11]. Hydrodimerization of 4 was
Conducting the reduction at the more negative potential of observed in enzymatic reduction [12]. Furthermore 3 was found
−1.1 V to −1.3 V vs SCE and otherwise comparable conditions in the reduction of 4 with TiCl3 [13,14]. High dimer yields are
amines are obtained in 60% to 69% yield [5]. Thereby, (E)-1- reported for the reduction of several nitro olefins with the
(3-cyclohexen-1-yl)-2-nitroethene can be chemoselectively dianion of cyclooctatetraene [15]. ß-Nitrostyrene (4) has been
reduced in 69% yield to 1-amino-2-(3-cyclohexen-1-yl)ethane reductively dimerized with organomanganese reagents to 3 in
without hydrogenating the C–C double bond.
low yield [16]. The electrochemical reduction of 1-nitroalkenes
was studied by cyclic voltammetry and controlled potential
The hydrodimerization of nitro olefins should lead to 1,4-di- coulometry. The reduction probably proceeds by initial forma-
nitroalkanes following the regioselectivity found in other tion of the radical anion, which subsequently dimerizes [17].
hydrodimerizations of activated olefins [1,2]. Thereby, the Later conditions were described to achieve selectively either a
proton concentration in the electrolyte should be not too high, cathodic ß,ß-coupling (cathodic hydrodimerization) or a α,ß-
as otherwise the reduction of the nitro group to oximes would coupling with aliphatic nitro alkenes having acidic α-protons.
be favoured. On the other side the electrolyte should not be ß,ß-Coupling can be achieved in good to high yield (41–95%) at
aprotic as protons are required for protonation of the intermedi- high current densities [18]. In the reduction of 3,3-dimethyl-1-
ate anions in the reductive dimerization (Scheme 1).
nitrobut-1-ene the intermediate radical anion has been identi-
fied by ESR. Nitroalkene 4 is reported to be converted quantita-
According to the proposed mechanism for the cathodic tively to the hydrodimer 3 with SmI2 [19]. A catalytic reductive
hydrodimerization the radical anion b formed by one electron β,β-carbon coupling of nitroalkenes catalyzed by a N-hetero-
reduction of the substrate a, has three pathways for dimeriza- cyclic carbene has been reported recently. Diastereomers are
tion [1,2]. In path (I) protonation followed by one-electron formed, whose dr (d,l- over meso-ratio) ranges between 66:34
reduction leads to anion c, which in a Michael addition with to 90:10. The interesting new reaction proceeds through a
substrate a forms the anion d, which is protonated to radical anion of the nitroalkene generated in a catalytic redox
hydrodimer f. In path (II) b undergoes a nucleophilic addition to process. For ß-isopropyl-nitroethylene the radical anion has
a forming a dimer radical anion that is reduced to e that is then been identified by ESR [20].
protonated to the dimer f. In path (III) the radical coupling of
Results and Discussion
two radical anions b leads to the dianion e, which is protonated
Investigation of the cathodic hydrodimeriza-
to the product.
tion of nitroalkene 1 to hydrodimer 2
We first checked the cathodic reduction of (E)-2-nitro-1-phen-
yl-1-propene (1) [for chemical formulas see Table 4] whether
the dimer 2,5-dinitro-3,4-diphenylhexane (2) can be obtained
and which would be the optimal conditions for a high selec-
tivity and yield. The optimization and subsequent hydrodimer-
ization of eight nitro olefins has been previously reported in
The cathodic hydrodimerization is performed in a divided elec-
trolysis cell by variation of the electrolyte (Table 1, Scheme 2).
The working potential was chosen from cyclic voltammetry and
current/voltage curves in the cell used for the preparative
conversion. The potential in the controlled potential electrol-
ysis was −0.9 V to −0.95 V vs SCE.
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Table 1: Hydrodimerization of 1 in dependence on the electrolyte composition.
Nr.
1
electrolyte
HOAca
(mmol)
T
(°C)
Q
yield (%)b
(mmol)
(F/mol)
2
5
1
1
2
3
4
5
3.06
3.06
5.09
7.50
6.13
DMF/H2O (9:1)
0.2 M TBABF4
0.2 M
–
20
20
30
30
30
1.95
1.25
1.08
1.5
24
c
20
–
–
DMF/H2O (25:1)
0.2 M TBABF4
–
DMF
0.2 M TBABF4
1 × 5.0
2 × 3.7
10 × 0.6
30
48
60
7
20
–
DMF
0.2 M TEA-pTos
4
DMF
1.01
–
–
0.2 M TEA-pTos
a0.2 M HOAc in electrolyte (Nr. 1); addition of corresponding fractions of an equivalent of the H+-donor at the start (Nr. 3, 4, 5) and after throughput of
the respective theoretical charge (Nr. 4, 5). bIsolated by flash chromatography. cProduct mixture, about 30% of 2.
Scheme 2: Cathodic reduction of nitroalkene 1 to hydrodimer 2 and oxime 5.
The results indicate: an increased acidity favours the formation
Table 2: Hydrodimerization of 1a in dependence of temperature,
of oxime 5 (Table 1, Nr. 1), whilst without a proton donor the
olefin presumably is polymerized to a large extent (Table 1,
Nr. 2). The addition of acetic acid in portions appears to be a
good choice as a too high proton concentration is avoided and
the necessary amount of protons is continuously provided in the
proper amount. TEA-pTos appears to be a better supporting
electrolyte than TBABF4: In the latter hydrogen bonds between
the fluorine atoms and water possibly increase the water
concentration in the double layer and this way reverse partially
the hydrophobic effect of the alkyl groups in the tetraethyl-
ammonium cation. The dimer yield should increase with
increasing radical concentration, which means that at the begin-
ning of the reaction the dimer yield should be higher than
towards the end. As olefin 1 and dimer 2 are expected to have a
higher oxidation potential than DMF due to the nitro group the
conversion and cell type.
Nr.
T (°C)
Q (F/mol)
Yield 2 (%)b
5c
6
30
50
−10
0
1.01
1.19
1.27
1.19
0.51
1.42
0.98
60
63
7
70
8
81
9
0
46 (83)d
44
10e
11f
30
0
88
a5.03 mmol 1 in 25 mL 0.2 M TEA-pTos/DMF. bIsolated yield. cNr. 5 in
Table 1 is shown for comparison. dYield in parenthesis based on
conversion; 45% reisolated 1. eUndivided cell, 0.25 equiv HOAc.
fUndivided cell without addition of acetic acid.
advantageous use of an undivided cell appears to be possible. is no higher yield at higher substrate concentration in the first
Taking the optimal conditions of electrolysis Nr. 5 in Table 1 half of the reaction compared to the second half. However, a
the influence of the parameters mentioned above was investi- remarkable increase of the yield is obtained in an undivided cell
gated (Table 2).
without addition of a proton donor. With a quantitative conver-
sion of 1 the dimer 2 is obtained in 88% material yield and 90%
The influence of the temperature is less significant than current yield. Presumably the protons are generated at the anode
expected. The increase of the temperature to 50 °C shows a by oxidation of residual water and/or the solvent DMF. A major
marginal increase of the yield, whilst a temperature decrease is source of residual water could be the very hygroscopic tosylate
more successful. Best results could be achieved at 0 °C. The as one of the reviewers suggested. The conditions of Nr. 11 in
yield after 50% charge consumption based on conversion is Table 2 should be suitable for the conversion of further
insignificantly higher (Table 2, Nr. 9). This indicates that there nitroalkenes.
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Beilstein J. Org. Chem. 2015, 11, 1163–1174.
The cyclovoltammogram (CV) of 1 shows two irreversible For work-up unreacted aldehyde was removed by way of the
reduction peaks at −1.08 V and −1.8 V vs SCE. The second bisulfite adduct, this facilitated the crystallization and impro-
peak can be attributed to the reduction of hydrodimer 2, as for ved the yields. The preparation of the nitroalkenes 1, 4, 8, 9 is
isolated 2 the reduction peak is found at this potential. The first described in [25]; the IR, 1H NMR, and MS data are provided in
peak can be assigned to the reduction of 1 forming the radical the experimental part (Supporting Information File 1). From a
anion. Addition of acetic acid shows no potential shift but a comparison of the experimental δ value for the vinylic proton
slight increase of the peak current. This could indicate that the with this from an increment calculation the cis position of the
radical anion is fast protonated and the resulting radical is hydrogen atom to the nitro group can be assigned for the
further reduced. Proton addition, however, could also favour the nitroalkenes 1, 8, 9, which is the E-configuration.
reduction of the nitro group to the oxime, which consumes four
electrons. Decreasing hydrodimer yields with increasing As the trifluoromethyl compound 10 is not accessible by the
temperature could be due to the existence of chemical side reac- method A or B it is prepared in two steps from aldehyde 6c via
tions of the radical anion, such as oligomerization or protona- the n-butylazomethine [24]. Particularly difficult was the syn-
tion, which are more accelerated at higher temperatures thesis of 12, where a product mixture is formed; additionally 12
compared to the radical dimerization. It should be mentioned decomposes partly during purification by fractional crystalliza-
that at the cathode deep red species are formed that become tion, furthermore it is air sensitive. All that leads to low yields
colorless upon addition of acetic acid. In an undivided cell and of 12. The dinitrodiene 16 was prepared from 1,4-dinitrobutane
an unstirred electrolyte, which allows diffusion between the and two equivalents of benzaldehyde with 1,2-diaminoethane as
electrodes, a red colour appears at the cathode, which disap- catalyst in 59% yield [26]; 1,4-dinitrobutane was prepared from
pears at the anode. This indicates the formation of coloured 1,4-dibromobutane [27]. The structures of the prepared com-
nitroalkyl anions and their decolourization by protonation.
pounds were secured by comparing the melting points with
these from the literature [24-27] and their spectroscopic data.
The nitroalkenes were obtained by condensation of aldehydes The nitroolefins 10–15 exhibit the same spectroscopic features
with nitroalkanes (Scheme 3, Table 3) [21,22].
as these of 1, 4, 8, 9. The C,H,N and C,H,F,N analyses addition-
ally confirm the structures. From the 1H NMR spectra for all
nitro olefins the E-configuration of the double bond can be
derived.
Cyclic voltammetry
The reduction potentials (Ep,c) of the nitroalkenes were deter-
mined by cyclic voltammetry. The values, ordered by
decreasing potentials, are shown in Scheme 4.
The reduction potentials Ep,c are determined by the con-
Scheme 3: Preparation of the 1-aryl-2-nitroalkenes 1, 4, 8–15.
Table 3: Preparation of 1-aryl-2-nitroalkenes.
formation of the aryl group, the electron density at the double
Aldehyde
Nitroalkane
Method
Nitroalkenea
Yield (%)b
c
6a, R: phenyl
7a, R1: H
4
50c
54
6a, R: phenyl
7b, R1: Me
7c, R1: Et
7b, R1: Me
7b, R1: Me
7b, R1: Me
7b, R1: Me
7b, R1: Me
7b, R1: Me
7b, R1: Me
A
A
1
6a, R: phenyl
8
62
6b, R: 4-methoxyphenyl
6c, R: 4-trifluoromethylphenyl
6d, R: 2-furyl
B
d
9
44
10
11
12
13
14
15
42d
75
A
A
A
B
A
6e, R: 2-pyrrolyl
10e
58
6f, R: 2-chlorophenyl
6g: 2,6-dichlorophenyl
6h: 2,6-difluorophenyl
36
62
aFor the structures of the nitroalkenes see Scheme 4. bIsolated, not optimized yield. cRef. [23]. dRef. [24]. eCrude yield higher, product decomposes
slowly during recrystallization.
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Scheme 4: Reduction potentials (Ep,c in Volt) of nitroolefins. Conditions: amalgamated gold wire, v = 0.1 V/s, 0.2 M TEA-pTos in DMF, accuracy of
Ep,c = +/− 0.02V vs SCE, measured against the Marple electrode and converted to SCE.
bond and the nitro group, the energy of the radical anion and the In the CV of all nitroolefins a second reduction peak appears at
reactivity of the radical anion. We have not determined these a potential being 600–800 mV more cathodic compared to the
values, but have concentrated ourselves on the preparative first one. Possibly this is the reduction of the hydrodimer as the
aspects of the cathodic hydrodimerization. Certain influences of CV of the hydrodimer of nitroolefin 1 indicates. This is
substituents on the reduction potentials of the nitroolefins can different for the nitroolefins 14 and 15, which are o,o’-disubsti-
be qualitatively seen. Aryl substituents shift the potentials to tuted at the phenyl ring (Figure 1).
more negative values according to their Hammett σ values [28]:
10 (4-CF3, σp = 0.53) > 1 (4-H, σp = 0) > 9 (4-CH3O, In the CV of 14 and 15 (Figure 1a) already at low scan rates
σp = −0.12). With a Hammett equation for an electrochemical (0.1 V/s) an anodic peak (Ep,a = −0.95 V for 14 and
reaction and using the Ep values as E0-values one obtains from Ep,a = −0.92 V for 15) appears in the reverse scan. Reversing
these three values a Hammett reaction constant ρ = 5.34. This is the scan after the first peak leads for 15 at a scan rate of 10 V/s
similar to the reaction constant ρ = 6.37 obtained from the to a CV peak with Ep,c = −1.084 V, Ep,a = −0.904 V and
Hammett plot for the one-electron reduction of substituted ip,c/ip,a = 1. For 14 higher scan rates were necessary to achieve a
benzo- and naphthoquinones in DMF [29], which have an elec- similar effect, but there the curve became strongly distorted
trophore being similar to this of the nitroolefins. For the other possibly due an increasing capacitive current and iR-drop. This
substituents no σ-values are available to apply the Hammett indicates, that most probably due to the o,o-substituents in 15
equation. They are ordered according to decreasing Ep-values in the follow-up reaction of the radical anion is slowed down for
three groups: 11 (2-furyl) > 9 (4-CH3O) > 12 (2-pyrrolyl); 14 steric reasons. For 14 no dimer was found (see below). Further
(two o-Cl) ≈ 13 (one o-Cl) > 15 (two o-F); another correlation electroanalytic investigations were omitted in favour of the
concerns the vinyl substituents at C2 of the double bond: 4 preparative scale hydrodimerizations of the nitroolefins.
(2-H) > 1 (2-CH3) ≈ 8 (2-C2H5) > 17 (no aryl group, methylene
Preparative scale electrolyses at the Hg
groups only). These orders are compatible with the electron
donating abilities of the substituents, being derived from their cathode
σm values [28]. The more positive potential of 16 compared to 1 The preparative scale electrolyses were performed using the
could be due to intramolecular interactions of the nitro groups following conditions: Hg cathode, undivided cell, 0.2 M TEA-
with the non-conjugated double bonds. The Ep,c of 1 and 4 pTos in DMF at 0 °C, cathode potential of −0.90 V to −0.95 V
measured at an amalgamated gold-wire electrode in DMF are vs SCE. These conditions were optimal for the potential
somewhat more positive than those measured at a Pt-disc in controlled conversion of nitroolefin 1 into dimer 2. The conver-
ACN [17].
sions shown in Table 4 consumed one charge equivalent
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Beilstein J. Org. Chem. 2015, 11, 1163–1174.
Figure 1: (a) CV of 15; v = 0.1 V/s, (b) CV of 15; v = 10 V/s.
Table 4: Preparative hydrodimerization of nitroalkenes.
Nitroalkene
Hydrodimera
Yield (%)b
88
1
4
8
2
3
71c
84
18
75
9
19
68
10
20
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Table 4: Preparative hydrodimerization of nitroalkenes. (continued)
85
11
12
21
22
73d
83
13
23
aProducts are mixtures of diastereomers (see chapter: Structure of the hydrodimers). bIsolated yield; material yield corresponds to 95–100% of the
current yield. cSee text following Table 4. dReduction in divided cell, as product is sensitive to anodic oxidation; yield in undivided cell: 60%.
(Q = 1 F mol−1) for completion, then the electrolysis current anion in the reduction of 15, which allows the formation of 40%
had decreased to nearly 0 mA. In the work-up following the of the dimer 29 and leads to less oxime and nitro alcohol as side
electrolysis the products in general can be extracted by nonpolar products (Scheme 5b).
petroleum ether/diethyl ether mixtures from the aqueous emul-
The dimers 2 and 18–23 could be identified by 1H, 13C NMR,
MS and elemental analyses (see Structures of the hydrodimers
and Experimental part in Supporting Information File 1). Dimer
3 is insoluble in common solvents at rt, thus no 1H and
13C NMR could be obtained. It has a correct elemental analysis
and the IR spectrum is similar to this of 2 and the other dimers
with regard to the NO2 group. It melts at 238–242 °C with
decomposition, which is similar to the product obtained by
hydrogenating dimerization of olefin 4 in [11]. The insolubility
and the melting point disagree, however, with compound 3
(n = 1) described in [20]. From the laser desorption ionization
(LDI) mass spectrum of 3 it could be presumed that 3 is mainly
sions or suspensions, respectively. The insoluble dimer 3 was
isolated by filtration and washing the solid with petroleum
ether/diethyl ether. The products are obtained after purification
by flash chromatography as colourless oils, which are mixtures
of diastereomers. They crystallize partially or completely after
some time and are in general not sensitive against air and light.
An exception is the pyrrole derivative 22, in the air its light
colour deepens quickly to brown. The electrolyses proceed
uniformly. The current reaches after a short induction period
(1–3 min) depending on the substrate a maximal current of
250–450 mA, which then decreases exponentially to zero.
The dichloro derivative 14 deviates from this behaviour. a trimer (3, n = 2). The trimer could arise by a Michael addition
Applying the usual electrolysis conditions no dimer 26 but only of the intermediate dimer radical anion or dimer dianion of 4 to
the oxime 24 (37%) and the nitro alcohol 25 (31%) are formed olefin 4. Indications to greater portions of 3 (n = 1) and 3
(Scheme 5a). As already indicated in the CV of 14 the dimeriza- (n = 3) were not found in the LDI–MS. Support for this assump-
tion of the intermediate radical anion of 14 is apparently tion comes from coulometry for 4 in [17], which indicates
hindered for steric reasons, which can explain the absence of oligomerization. Oligomerization does not occur if the
the dimer. This can favour the further reaction of the radical substituent α to the nitro group is an alkyl group as in olefin 1,
anion of 14 to the oxime 24 and the Michael addition of possibly due to steric hindrance.
hydroxy ions to form the nitro alcohol 25.
The dinitrodiene 16 is intramolecularly coupled at the Hg
The smaller space filling of the fluorine atom compared to the cathode to form the dinitrocyclohexane 30 (Scheme 6a), it also
chlorine atom should lead to a sterically less hindered radical does not show the usual behaviour found in the preceding elec-
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Beilstein J. Org. Chem. 2015, 11, 1163–1174.
Scheme 5: Hydrodimerization of nitroalkene 14 and 15.
trolyses. A significant decrease of the current is only found after nitroolefin 1 could be hydrodimerized to the dimer 2. With 60%
a current consumption of 2.96 F/mol. Except for benzaldehyde the yield is lower than in the reduction at the Hg cathode, where
no further side products were detected. 30 is formed as mixture 88% of the dimer were obtained. Possibly higher yields can be
of diastereomers, which could not be separated by flash chro- obtained with other graphite varieties or other nontoxic cathode
matography.
materials. But in principle the mercury cathode can be replaced
by a graphite cathode.
Structure of the hydrodimers
All products show for the nitro group characteristic asymmet-
rical and symmetrical vibrations at 1530–1560 cm−1 and
1350–1360 cm−1, which, compared to the educts, are shifted to
shorter wavelengths.
The hydrodimers show in the upper masses of the mass spectra
few fragments and these have a low intensity. The base peak in
all hydrodimers results from breaking of the dibenzyl bond and
loss of NO2 affording the mass = (M+/2 − 46).
The C–C bond formation can lead to α,α-, α,β- and ß,ß-coupled
products. The 1H NMR spectra and MS data support in all cases
a ß,ß-coupling. A α,β- or a α,α-coupling would lead to the
occurrence of methyl singlets or non-coupled benzylic protons.
Such signals were not observed in the spectra of the hydro-
Scheme 6: (a) Intramolecular hydrocoupling of dinitrodiene 16 and
(b) hydrodimerization of 1-nitrocyclohexene (17).
The aliphatic nitroalkene 17 could be hydrodimerized in 68% dimers.
yield to the hydrodimer 31, which is a mixture of diastereomers.
Partial separation by flash chromatography and 1H NMR spec- The stereochemistry of the hydrodimer results from a β,ß-C–C
troscopy of the fractions indicates four diastereomers in a ratio bond formation and from a α,δ-diprotonation, which creates a
of about 38:9:14:1.
dimer with four stereocenters with the exception of dimer 3,
which has only two stereocenters. This means 23 diastereomers
It is possible to substitute the cathode material mercury against can be formed, which are decreased to six diastereomers due to
the environmentally benign graphite. At a graphite cathode the the identity of two pairs of enantiomers as shown in Scheme 7.
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Beilstein J. Org. Chem. 2015, 11, 1163–1174.
The numbering (determining C-1) is arbitrary, but the
remaining positions follow unequivocally from the coupling
constants (for example in 2b: J1,2 = 6.64 Hz, J5,6 = 6.51 Hz).
The diastereomers show remarkable differences in the chemical
shifts. This also holds for significant differences in the chem-
ical shifts for formally identical protons in 2b/e. The consider-
able differences probably result from the anisotropy effect of
the aromatic ring and the nitro group. For the nitro group a
similar anisotropic cone as for the carbonyl group is assumed
[30]. Due to the presence of two nitro and two phenyl groups
conformations are possible, where protons are in shielded and
unshielded areas. Also phenyl protons appear as broad, high
field shifted signals. For 18c a ratio of high field and normal
Scheme 7: Possible stereoisomers and their mirror images for the
hydrodimers 2 and 18–23; R and S are the configurations at the
stereogenic centers.
Configurations could not be assigned, as data for comparison signals of 4:6 was found. With decoupling experiments they can
are not available in the literature and crystals for X-ray diffrac- be clearly assigned to be phenyl protons. Comparable results, as
tion could not be obtained.
shown for 2, were found for the mixtures of diastereomers of
the other hydrodimers. Besides decoupling experiments also
The dimers are obtained as mixtures of diastereomers; as they 1H NMR simulations give valuable support to assign the com-
do not differ significantly in their MS and IR spectra the com- plex coupling pattern. This is shown for 18b where the
pounds had to be characterized by their 1H NMR data. For that complexity of the spectrum is strongly increased by the
purpose the diastereomers were purified as good as possible by diastereotopic methylene protons (Figure 2).
flash chromatography and/or HPLC. Single diastereomers are
denoted alphanumerically (e.g., 2a, 2b). The same letter means The ratios of diastereomers for the products 2 and 18–23 are
for two diastereomers of different hydrodimers that they have summarized in Table 6.
similar NMR spectra with regard to chemical shift and multi-
plicity. This corresponds to a similar rate of elution in chroma- The main part of the mixture consists usually of the isomers a
tography.
and b. Dimer 22 is an exception being possibly caused by the
NH groups of the pyrroles. Their hydrogen bonds could influ-
ence the relative energies of the transition states leading to the
1H NMR spectra
For the hydrodimers 2 and 18–23 five different diastereomers diastereomers. One of the two meso-configurations can be
a–e can be identified. In Table 5 the 1H NMR data of the five assigned to isomer 22a because of the missing coupling
diastereomers 2a–e are assembled.
between the benzylic methine protons.
Table 5: δ-Values and multiplicities of the alkyl protons in 2a–e.
Isomer
δ (ppm) and multiplicity for H-atom at carbon-atom Nr.:
1
6
2
5
3
4
2a
2b
2c
2d
2e
1.25, d
4.85, dq
3.44, d
1.28, d
1.90, d
4.91, dq
4.79, dq
3.36 and 3.71, 2 dd
3.64, dd
1.74, d
1.29, d
5.21/5.22, 2 dqa
4.47–4.56, m
4.13–4.15, m
1.25, d
1.30, d
4.44, dq
4.62, dq
4.59, dd
3.33, dd
aCoupling pattern of the α-nitro protons is verified by NMR-simulation.
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Beilstein J. Org. Chem. 2015, 11, 1163–1174.
Figure 2: 1H NMR spectrum of 18b (without aromatic H); below experimental spectrum, above: simulated signals for 2-H to 7-H.
correlate very well with the results of the proton resonance
experiments. The measured values agree quite well with incre-
ment calculations (Table 7) [31].
Table 6: Ratioa of the diastereomers a–e from the dimers 2 and
18−23.
Dimer
a
b
c
d
e
Elemental analyses
2
10
11
12
7
14
17
20
14
16
3.2
2
2
1
1
1
1
1
1
3
The structures could be secured additionally by elemental
analyses and in the case of dimer 20 by high resolution MS.
They were obtained from the mixtures of isomers taking into
account all elements (C, H, N, halogen).
18
19
20
21
22
23
4
3
6
6
3
2
11
1.7
2
3
2
1.7
5.5
Σ 1(for c, d, e)
Conclusion
aDetermined by comparing the intensities in the 1H NMR spectra of
different mixtures; average values from different electrolyses.
The potential controlled cathodic hydrodimerization of
1-nitroalkenes affords a one step electrochemical C–C bond
formation to 1,4-dinitro compounds. Applying optimized
conditions the hydrodimers are obtained in good to very good
The 1H NMR data obtained for 29–31 are compatible with the yields. Besides mercury also graphite can be used as cathode
shown structures.
material. The scope of the reaction is demonstrated in ten
nitroalkenes with different 1-aryl and mostly 2-methyl
substituents. Likewise the cathodic cyclization of a dinitrodiene
13C NMR spectra
The proposed structures were confirmed by their 13C NMR could be realized.
spectra. Nearly all diastereomers can be characterized via their
13C signals. The regioselective ß,ß-linkage follows clearly from The dimerization is chemoselective: the fairly easy reduction of
the multiplicities of the carbon atom resonances. Signals of ali- the nitro group can be suppressed and aryl C–Cl and aryl C–F
phatic quaternary carbon atoms were not detected. The differ- bonds are not cleaved. Additionally a good regioselectivity is
ences between the signals of single diastereomers of a dimer obtained, among the possible three coupling products only the
Table 7: Calculated and experimental 13C shifts for 18.
Carbon atoms
C-1/-8
C-2/-7
C-3/-6
C-4/-5
δ (ppm) calculated
δ (ppm) found
15.0
22.0
90.4
54.4
9.80–10.81
20.98–26.00
88.92–91.70
48.73–51.31
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Beilstein J. Org. Chem. 2015, 11, 1163–1174.
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