Diastereoselective anodic hetero- and homo-coupling of menthol-, 8-methylmenthol- and 8-phenylmenthol-2-alkylmalonates

Article abstract of DOI:10.3762/bjoc.13.5

Diastereoselective radical coupling was achieved with chiral auxiliaries. The radicals were generated by anodic decarboxylation of five malonic acid derivatives. These were prepared from benzyl malonates and four menthol auxiliaries. Coelectrolyses with 3,3-dimethylbutanoic acid in methanol at platinum electrodes in an undivided cell afforded hetero-coupling products in 22-69% yield with a diastereoselectivity ranging from 5 to 65% de. Electrolyses without a coacid led to diastereomeric homo-coupling products in 21-50% yield with ratios of diastereomers being 1.17:2.00:0.81 to 7.03:2.00. The stereochemistry of the new stereogenic centers was confirmed by X-ray structure analysis and ¹³C NMR data.

Full text of DOI:10.3762/bjoc.13.5

Diastereoselective anodic hetero- and homo-coupling of
menthol-, 8-methylmenthol- and 8-phenylmenthol-
2-alkylmalonates
Matthias C. Letzel, Hans J. Schäfer* and Roland Fröhlich§
Full Research Paper
Open Access
Address:
Beilstein J. Org. Chem. 2017, 13, 33–42.
Organisch-Chemisches Institut der Westfälischen Wilhelms-
Universität, Corrensstraße 40, D-48149 Münster, Germany
doi:10.3762/bjoc.13.5
Received: 11 October 2016
Accepted: 12 December 2016
Published: 05 January 2017
Email:
Hans J. Schäfer* - schafeh@uni-muenster.de
* Corresponding author
§ X-ray structure analysis
Associate Editor: J. A. Murphy
© 2017 Letzel et al.; licensee Beilstein-Institut.
License and terms: see end of document.
Keywords:
anodic decarboxylation; diastereoselectivity; Kolbe electrolysis;
radical hetero-coupling; radical homo-coupling
Abstract
Diastereoselective radical coupling was achieved with chiral auxiliaries. The radicals were generated by anodic decarboxylation of
five malonic acid derivatives. These were prepared from benzyl malonates and four menthol auxiliaries. Coelectrolyses with 3,3-
dimethylbutanoic acid in methanol at platinum electrodes in an undivided cell afforded hetero-coupling products in 22–69% yield
with a diastereoselectivity ranging from 5 to 65% de. Electrolyses without a coacid led to diastereomeric homo-coupling products
in 21–50% yield with ratios of diastereomers being 1.17:2.00:0.81 to 7.03:2.00. The stereochemistry of the new stereogenic centers
was confirmed by X-ray structure analysis and 13C NMR data.
Introduction
Intermolecular radical additions with high diastereoselectivity intermolecular coupling of radicals generated by anodic
have been described for a number of cases [1-9]. There are decarboxylation of carboxylic acids [15,16].
much fewer reports on intermolecular diastereoselective radical
coupling reactions [10-16]. There are some examples of high At the anode radicals can be generated by anodic decarboxyl-
diastereoselectivity in the coupling of radicals generated from ation of carboxylic acids in molar quantities, in a simple proce-
azo compounds [10,11], in intramolecular coupling of radicals, dure, unaffected by cage effects and in large diversity. For that
that are obtained by photochemical activation [12-14], and in reason, we were interested in exploring the structural influence
33

Beilstein J. Org. Chem. 2017, 13, 33–42.
Results and Discussion
Anodic hetero- and homo-coupling of
carboxylates
The carboxylic acids 13a/b–18a/b for the Kolbe electrolyses
were synthesized according to Scheme 1. The chiral auxiliary
1–4 is acylated with a benzylmalonyl chloride prepared from 5
and 6 and the benzyl group is subsequently removed by hydro-
genation to afford the free carboxylic acids 13a/b–18a/b for the
electrolyses.
of chiral auxiliaries (Figure 1) and the carboxylic acid on the
diastereoselectivity in the anodic coupling of carboxylic acids.
We report here on the diastereoselectivity found in the anodic
hetero- and homo-coupling of menthol- (1)-, 8-methylmenthol-
(2)-, 8-phenylmenthol- (3)-, and 8-p-anisylmenthol- (4)-2-alkyl-
malonates (Figure 1).
Benzyl 2-isopropylmalonate (5) was prepared in high yield,
using a method of Strating et al. [17], by deprotonation of the
benzyl ester 19 with lithium diisopropylamide and quenching
the enolate with carbon dioxide (Scheme 2a). Benzyl 2-tert-
butylmalonate (6) was prepared in good yield using a method of
Krapcho et al. [18], by double deprotonation of 3,3-dimethyl-
butyric acid (20) with LDA and quenching the dianion with
benzyl chloroformate (Scheme 2b).
Figure 1: Menthol auxiliaries 1–4 used in the following anodic cou-
pling reactions.
Scheme 1: Synthesis of carboxylic acids 13a/b–18a/b.
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Beilstein J. Org. Chem. 2017, 13, 33–42.
coupling of the radicals. Coelectrolysis of two different
carboxylic acids affords unsymmetrical coupling products by
hetero-coupling. In the latter case three different coupling prod-
ucts are obtained: two symmetrical dimers and one unsymmetri-
cal coupling product, whose ratio is in most cases determined
by the statistical coupling of the intermediate radicals. An
excess of one coacid leads to mainly two products: the unsym-
metrical coupling product and the dimer of the coacid used in
excess.
The coelectrolysis (hetero-coupling) of carboxylic acids 13–17
with ten equivalents of 3,3-dimethylbutyric acid (20) afforded
the hetero-coupling products 21–25 in 22–69% yield of two dia-
stereomers, whereby one of the two diastereomers was formed
in 5–65% diastereomeric excess (Scheme 3).
Scheme 2: (a) Preparation of benzyl 2-isopropylmalonate (5) and
(b) preparation of benzyl 2-tert-butylmalonate (6).
The benzyl malonates 5 and 6 are converted to the correspond-
ing benzyl malonyl chlorides with thionyl chloride. To these at Because of the low diastereomeric excess for compounds 21
−40 °C the auxiliary menthol (1), 8-p-anisylmenthol (4) [19], and 22, the configuration of the major diastereomer was not de-
8-methylmenthol (2) [20] or 8-phenylmenthol (3) [21] was termined. The configurations for the major diastereomers of
added in the presence of triethylamine, whereby the menthyl 23–25 were obtained from crystal structure analyses and the
esters 7–12 were obtained in good yield after flash chromatog- correlation of the 13C NMR data.
raphy as a mixture of two diastereomers (Scheme 1).
According to an X-ray analysis the minor diastereomer 23b has
The benzyl menthyl malonates 7–12 were hydrogenated under the configuration (S) at the new formed stereogenic center
atmospheric pressure to afford the free carboxylic acids (Figure 2) [23].
13a/b–18a/b in high yield and purity (Scheme 1).
The configuration of the new stereogenic centers in compounds
Anodic hetero-coupling of carboxylates
24 and 25 were assigned on the basis of a characteristic down
Carboxylates of aliphatic carboxylic acids are oxidized to field shift in the 13C NMR of the carbonyl and the methine car-
carbonyloxy radicals at a platinum electrode at potentials being bon atom in the major diastereomer (Table 1).
generally higher than 2.0 V (vs NHE). The carbonyloxy radi-
cals undergo fast decarboxylation to alkyl radicals at or near the The higher diastereomeric excess in compounds 24 and 25 ob-
electrode surface [22]. The generation of radicals in a thin reac- tained with 8-phenylmenthol (3) as auxiliary is attributed to an
tion layer at the electrode surface leads to high radical concen- electronic interaction between the carbonyl and the phenyl
trations that favor bimolecular radical coupling. Electrolysis of group [24]. In order to enhance this interaction, the phenyl
equal carboxylic acids leads to a symmetrical dimer by homo- group was replaced for the more electron-rich anisyl group by
Scheme 3: Coelectrolysis (hetero-coupling) of carboxylic acids 13–17 with 3,3-dimethylbutyric acid (20).
35

Beilstein J. Org. Chem. 2017, 13, 33–42.
applying 8-anisylmenthol (4) as chiral auxiliary. However, with
acetic acid or 3,3-dimethylbutyric acid (20) as coacid no radical
hetero-coupling product of carboxylic acid 18 was found, but
polar compounds were obtained, whose structures were not de-
termined.
To explain this failure, it is assumed that under the electrolysis
conditions the electron-rich aromatic ring system is preferential-
ly oxidized. Cyclic voltammetry of the malonates 15a/b,
16a/b and 18a/b supports this assumption. The cyclic voltam-
mogram of 18a/b shows an oxidation peak at 1.75 V to 1.85 V
(Figure 3).
In the cyclic voltammogram of malonic acid derivative 16a/b a
peak appears at a potential of 2.4 V (Figure 3). The malonic
acid derivative 15a/b does not show any oxidation peak below
3 V (Figure 3). In this case the increase in current at 3 V is
caused by the oxidation of the solvent. These results clearly at-
tribute the peak at 1.75 to 1.85 V in carboxylic acid 18a/b to the
oxidation of the anisyl group. This is also in accord with oxida-
tion potentials from the literature [25], where the oxidation
potential for anisole and toluene was determined to be 1.15 V
and 1.35 V (vs Ag/Ag+), respectively.
Figure 2: Crystal structure of the minor diastereomer 23b.
Table 1: 13C NMR data of compounds 23, 24 and 25.
13C NMR [ppm]
No.
major diastereomer
C=O CHCH2t-Bu
minor diastereomer
C=O CHCH2t-Bu
23 176.5 (23a) 52.4 (23a) 175.1 (23b) 51.5 (23b)
24 176.4 (24a) 47.3 (24a) 175.1 (24b) 46.5 (24b)
25 176.7 (25a) 51.7 (25a) 175.1 (25b) 50.9 (25b)
In the Kolbe electrolysis a critical potential of 1.9 to 2.2 V (vs
Ag/AgCl) has to be exceeded. At this potential the coverage of
Figure 3: Cyclic voltammograms of the malonic derivatives 15a/b, 16a/b and 18a/b (scan rate: 500 mA/s, solvent: acetonitrile, supporting electrolyte:
tetrabutylammonium perchlorate (TBAClO4), reference electrode: Ag/AgCl).
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Beilstein J. Org. Chem. 2017, 13, 33–42.
the electrode with carboxylate ions increases sharply, the
oxygen evolution is inhibited, solvent oxidation is retarded and
the Kolbe electrolysis is promoted [26].
Table 2: Facial selectivities for 26–29.
compound
re,re:re,si
re,si:si,si
26
27
28
29
1.17
1.39
5.14
7.03
1.23
1.49
If in the carboxylate an additional electrophore with a lower ox-
idation potential than the critical potential is present it is
oxidized instead of the carboxylate group. This is the case for
18a/b. Even in the case of 16a/b and 17a/b a significant portion
of polar products is found, indicating a partial oxidation of the
phenyl group.
4.76
not determinable
The absolute configuration of the major diastereomers 28a and
29a was determined by X-ray analysis (Figure 4 [23] and
Figure 5 [23], hydrogen atoms are left out, except those formed
Anodic homo-coupling of carboxylates
The carboxylic acids 13a/b–16a/b have also been subjected to at the new stereogenic centers). The new stereogenic centers in
homo-coupling and the diastereomers 26a/b/c–29a/b/c were both cases have (2’R,3’R)-configuration. For the diastereomers
afforded in 50–21% yield (Scheme 4).
26b, 27b, 28b and 29b a set of 1H and 13C NMR signals can be
observed for the protons and the carbon atoms of each half of
In the homo-coupling reaction two identical radicals combine the molecule. Based on this observation a (2’R,3’S)-configura-
to form two stereogenic centers. Three diastereomers can be tion was assigned to 26b, 27b, 28b and 29b. For the diastereo-
formed by re,re-, re,si- and si,si-coupling of the prostereogenic mers 26a/c, 27a/c, 28a and 29a only a single set of signals is
radical centers. Without facial selectivity they will be formed in obtained, because both halves of the molecule are chemically
a statistical ratio of 1:2:1. Facial selectivity is indicated by devi- equivalent due to its C2-symmetry.
ation from this statistical ratio. The selectivity for re,re-
coupling vs re,si-coupling is given by the ratio 2 (a:b), the In Figure 4 and Figure 5 the C2-symmetry can be easily seen.
selectivity for re,si- vs si,si-coupling by b:2c (Table 2).
From Figure 2, Figure 4 and Figure 5 the conformation of the
Scheme 4: Homo-coupling of carboxylic acids 13a/b–16a/b to diesters 26a/b/c–29a/b/c (n.d.: not determined).
37

Beilstein J. Org. Chem. 2017, 13, 33–42.
In first experiments using (−)-menthol (1) as a chiral auxiliary
we observed a low but nevertheless promising preference for
one diastereomer, depending on the substituent R (Scheme 3).
With the tert-butyl group in 22a/b a higher selectivity was ob-
served than with the isopropyl group in 21a/b.
Still higher discrimination between both diastereomeric faces
had been expected using a modified menthol with a phenyl
group in 8-position, which is 8-phenylmenthol (Figure 6).
Figure 4: Crystal structure of major diastereomer 28a.
Figure 6: Discrimination of diastereomeric faces in the menthol substi-
tuted radical A and in the 8-phenylmenthol substituted radical B.
This hypothesis was proven to be accurate, obtaining an aston-
ishingly high diastereoselectivity of 65% de for 25a/b with
R = tert-butyl and 8-phenylmenthol (3) (Scheme 3). In the same
coupling reaction using 2,5-dimethylpyrrolidine as auxiliary the
analogous coupling product was obtained with a selectivity of
65% de as well [15]. The selectivity decreases to 38% de for
24a/b with R = isopropyl. When 8-methylmenthol (2) was used,
Figure 5: Crystal structure of major diastereomer 29a.
radicals that undergo the coupling reaction can be deduced. 23a/b was obtained with a moderate selectivity of 27% de, but a
Assuming a homolytic cleavage of the bond between C2’–C3’ good yield of 69%.
in compound 23b (Figure 2) and converting the sp3 hybridized
carbon atoms C2’ and C3’ into sp2 hybrids shows that the minor The facial selectivity for a single radical center can be calcu-
stereoisomer is formed by the shielding of the re-face through lated from the diastereomeric ratio obtained in the homo-cou-
the tert-butyl group. Hence the major diastereomer 23a is pling reactions, assuming that there is no simple diastereoselec-
formed by an attack via the less shielded si-face.
tivity favoring either the (2R,3R)/(2S,3S)- or the (2R,3S)-dia-
stereomers (Table 3). In coupling reactions without auxiliary
The same consideration for compound 28a (Figure 4) and com- control, no significant preference for either d, l or meso had
pound 29a (Figure 5) with a cleavage of the C2’–C3’ bond in been observed [35], proving this precondition to be legitimate.
the succinic acid derivatives shows that the major diastereomer
is formed via the si-face, which is less shielded by the tert-butyl Comparing the stereoselectivity in the homo- and hetero-cou-
or cumyl group.
pling reaction (Table 3), a slightly better selectivity is observed
for the homo-coupling reaction. This is probably due to the
bulkier coradical in the homo-coupling, compared with the 2,2-
Discussion
8-Phenylmenthol has been successfully used as a chiral auxil- dimethylpropyl radical in the hetero-coupling reaction.
iary [27] to control the stereochemistry in Diels–Alder reac-
tions [28], [2 + 2]- and [3 + 2]-cycloadditions and asymmetric With auxiliaries like 2,5-dimethylpyrrolidine, 2,5-dimethoxy-
ene reactions [29]; furthermore, it has been applied in 1,4- methylpyrrolidine or camphorsultam side products resulting
cuprate additions [30], Grignard additions [31], in supramolecu- from decarboxylation, disproportionation and further oxidation
lar chemistry [32] and in alkylation of malonic acid derivatives of the intermediate radical have been observed [35-37]. In
[33]. In the literature, there are only a few examples where contrast, hardly any side products of that kind were obtained
menthol auxiliaries have been used to control the stereochemis- using menthol related auxiliaries in anodic radical coupling
try in radical reactions [34].
reactions.
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Beilstein J. Org. Chem. 2017, 13, 33–42.
Table 3: Comparison of the diastereoselectivity in hetero- and homo-coupling reactions.
Electrolysis
Homo-coupling
Hetero-couplinga
of compound
facial diastereoselectivity
diastereomeric ratio
re:si
R:S
13a/b
14a/b
15a/b
16a/b
54.5:45.5b
59.0:41.0b
83.5:16.8
87.5:12.5
52.5:47.5b
55.0:45.0b
63.5:36.5
82.5:17.5
a3,3-Dimethylbutanoic acid was used as coacid in all cases. bThe absolute configuration of the major diastereomer has not been determined. There-
fore, the facial stereoselectivity is assumed to have the same preference as in the cases where the configuration is known.
Products analogous to these of the radical homo-coupling above
can be obtained by auxiliary controlled oxidative enolate cou-
pling in high yield with good stereocontrol [38-40]. With the
auxiliary controlled alkylation of enolates products being analo-
gous to radical hetero-coupling can be synthesized [41,42].
However, both methods require costlier reaction conditions as
inert gas, dry solvents and LDA as reagent, and are probably
harder to perform in a large scale as the Kolbe electrolysis.
There is strong evidence that in the Kolbe electrolysis free radi-
cals are involved in the coupling reaction. Coupling of absorbed
radicals is ruled out by Eberson [43-45]. It was shown that the
product ratio of cyanoalkyl radicals, which can yield C–C or
C–N coupling products, does not differ in the Kolbe electroly-
Scheme 5: Reductive cleavage of 30a–c to 8-phenylmenthol (3) and
31a–c.
sis from the ratio obtained by the coupling of photochemically
produced cyanoalkyl radicals. Optically active carboxylates,
which have the asymmetric center at C2 racemize in mixed
Kolbe electrolyses [46,47]. This finding points to a free radical the oxidation of the intermediate radical and also lowers the dia-
or its reversible adsorption at the electrode. However, the latter stereoselectivity significantly (de 39%) compared to the bulkier
pathway was ruled out by experiments of Utley et al. [48,49], tert-butyl group with 65% de in 25a/b (Scheme 3) [51]. There-
when comparing the coupling of unsaturated and saturated fore, the tert-butyl group appears to be important for a higher
carboxylic acids and the effect of adsorption.
product yield and the diastereoselectivity of the coupling. On
the other side this bulky group prohibits the cleavage with the
Ester 30a has been cleaved with lithium aluminium hydride in so far successful reagents LiAlH4 and DIBAL. Therefore, in the
THF to 3 and 31a in 90% (Scheme 5) and with 30b (Scheme 5) future bulky chiral auxiliaries must be developed that can be
and DIBAL in toluene 92% of 31b were obtained [50]. 30c partially disassembled before their cleavage and slim cleavage
could be cleaved with lithium aluminium hydride in THF to reagents have to be found and explored.
83% 3 and 90% 31c [51]. However, to our great disappoint-
ment the successful cleavage with 30c could not be transferred Conclusion
to the structurally similar compounds 23a/b and 25a/b. Using We developed an efficient procedure for the synthesis of
the same reaction conditions as with 30a both with lithium alu- menthyl 2-tert-butyl and 2-isopropyl-4,4-dimethylpentanoates
minium hydride in THF and DIBAL in toluene with 23a/b and (21a/b–25a/b) with a chiral centre at C2 of the acid component.
25a/b the starting material was completely reisolated. Appar- For that purpose, malonic half-esters with substituted menthols
ently the carbonyl group is so much shielded by the tert-butyl as chiral auxiliaries were prepared. The half-esters were electro-
group and the auxiliary that the reducing agent is not able to chemically decarboxylated to alkyl radicals. In the presence of
reach the carbonyl group.
an excess of 3,3-dimethylbutylbutanoic acid that decarboxyl-
ated to a 2,2-dimethylpropyl radical preferentially the hetero-
However, the phenyl group at C2 of the ester 30c causes lower coupling products 21a/b–25a/b were obtained in up to 69%
yields (11%) of anodic coupling product, because it facilitates yield and diastereomeric ratios of up to 82.5:17.5 induced by
39

Beilstein J. Org. Chem. 2017, 13, 33–42.
the menthyl auxiliaries. However, the removal of the auxiliary a coolant of −25 °C. When the pH of the solution reached 8–9
in the esters is not yet resolved. Without a coacid succinic acid the electrolysis was stopped, the mixture was poured into
derivatives 26a/b/c–29a/b/c were obtained by dimerization of 30 mL of water and extracted with ether (5 × 20 mL). The
the half-ester radicals with yields of up to 50% and a facial dia- combined organic layers were washed with saturated sodium
stereoselectivity of up to 87.5:12.5.
hydrogen carbonate (2 × 20 mL) and dried over MgSO4. After
evaporation of the solvent in the vacuum the product was puri-
Products that are similar to these of the anodic coupling can be fied by flash chromatography.
obtained by auxiliary controlled oxidative enolate coupling.
However, this method often requires more expensive reagents, Homo-coupling reaction: 1.6 mmol of the auxiliary modified
functional groups are frequently more sensible to the used carboxylic acid was dissolved in 1.6 mL of a 0.1 N methanol
reagents and an up-scale is more difficult to perform.
solution of sodium methoxide (5% neutralization) and trans-
ferred into the micro-beaker-type cell. Dry methanol was added
On the other side anodic coupling of sodium carboxylates is to a total volume of 3 mL, which was electrolyzed maintaining
easy and simply to do. Methanol can be mostly used as solvent, a current density of 400 mA/cm2 and the temperature of the
the alkali salt of the carboxylic acid serves at the same time as solution in the range of 5–10 °C with a coolant of −25 °C. The
substrate and supporting electrolyte. The required equipment is further work-up follows the procedure given for the hetero-cou-
simple, inexpensive and readily available. An undivided beaker- pling reaction.
type cell is sufficient; electrolysis can be performed current-
controlled with a cheap power supply and an up-scale of the General procedure for the preparation of the menthol
reaction is mostly easy.
esters: To a solution of 4.3 mmol of monobenzyl malonate 5 or
6 in 20 mL dry methylene chloride 0.8 mL thionyl chloride
(1.3 g, 10.8 mmol) were added and the mixture was refluxed for
3 h. After evaporation of the solvent and the unreacted thionyl
Experimental
General remarks
Optical rotations: Perkin-Elmer polarimeter 241, specific rota- chloride in vacuum, the remaining yellow oil was dissolved in
tions in grad·cm3·dm−1·g−1, c in g/100 mL. FTIR: Bruker IFS 20 mL methylene chloride without further purification and
28. 1H, 13C NMR: Bruker WM 300. X-ray structures: Data sets cooled to −40 °C. Under an argon atmosphere 2.81 mmol auxil-
were collected with an Enraf Nonius CAD4 diffractometer. iary, dissolved in 10 mL dry methylene chloride and 10 mL dry
Programs used: data reduction MolEN, structure solution triethylamine, were added slowly to the carboxylic acid chlo-
SHELXS-86, structure refinement SHELXL-93, graphics ride at −40 °C. After the complete addition, the mixture was
SCHAKAL-92. MS: Finnigan MAT, Varian Saturn II (ion trap) allowed to warm up to rt and stirred for 20 h. Then 20 mL of
with capillary column HP 5 (25 m, 0.2 mm i.d., 0.33 μm film); water were added and the mixture was extracted with methy-
DCI with ammonia as reactant gas. GLC: Hewlett-Packard HP lene chloride (4 × 20 mL). The combined organic layers were
5890 Series II, Shimadzu GC-14A, Carlo Erba 4200; quartz washed successively with 2 N HCl (3 × 20 mL), saturated sodi-
capillary columns: Macherey and Nagel FS-HP1 (25 m, um hydrogen carbonate (2 × 20 mL) and brine (20 mL) and
0.32 mm i.d., 0.25 μm film), AT 35 (2.5 m, 0.32 mm i.d., dried (MgSO4). After evaporation of the solvent the product
0.25 μm film). Preparative scale electrolyses: Undivided was purified by flash chromatography.
beaker-type glass cell, double walled for constant temperature
control, capacity: 3 mL (micro beaker-type cell). Platinum foils General procedure for the hydrogenation of the benzyl
serving as anode and cathode materials (platinum foils: esters: To a solution of 6.4 mmol benzyl ester in 100 mL of
1 × 1 cm). Convection was achieved by magnetic stirring. Cur- methanol 800 mg of the palladium catalyst (10% Pd on carbon)
rent source: Heinzinger galvanostat – potentiostat HN 600–600 were added. Hydrogenation was performed at atmospheric pres-
and TNs 300–1500.
sure until no further hydrogen was consumed. After filtration
through celite the solvent was evaporated in vacuum. The
residue was dissolved in a small amount of diethyl ether,
General procedure for the Kolbe electrolysis
Hetero-coupling reaction: 0.4 mmol of the auxiliary modified filtrated through celite and dried with MgSO4. After evapora-
carboxylic acid and 4 mmol of the coacid were dissolved in tion of the solvent the free carboxylic acid was obtained with
2.2 mL of a 0.1 N methanolic solution of sodium methanolate high purity as a sticky oil.
(5% neutralisation) and transferred into the micro-beaker-type
cell. Dry methanol was added to a total volume of 3 mL, which The preparation of compounds 5–29, their spectroscopic data
was electrolyzed maintaining a current density of 400 mA/cm2 and their elemental analyses are reported in Supporting Infor-
and the temperature of the solution in the range of 5–10 °C with mation File 1.
40

Beilstein J. Org. Chem. 2017, 13, 33–42.
17.Reiffers, S.; Wynberg, H.; Strating, J. Tetrahedron Lett. 1971, 32,
3001–3004. doi:10.1016/S0040-4039(01)97075-3
18.Krapcho, A. P.; Jahngen, E. G. E., Jr.; Kashdan, D. S.
Tetrahedron Lett. 1974, 15, 2721–2723.
Supporting Information
Supporting Information File 1
Experimental part.
doi:10.1016/S0040-4039(01)91723-X
19.8-p-Anisylmenthol (4) was synthesized following parts of the
procedures given in [20,21]. The diastereomeric menthols were
separated by HPLC.
[http://www.beilstein-journals.org/bjoc/content/
supplementary/1860-5397-13-5-S1.pdf]
20.Buschmann, H.; Scharf, H. D. Synthesis 1988, 827–830.
doi:10.1055/s-1988-27724
Acknowledgements
21.Červinka, O.; Svatoš, A.; Masojídková, M.
Dedicated to Professor Gerhard Erker, Westfälische Wilhelms-
Collect. Czech. Chem. Commun. 1990, 55, 491–498.
doi:10.1135/cccc19900491
Universität Münster, on the occasion of his 70th birthday.
22.Schäfer, H. J. Top. Curr. Chem. 1990, 152, 92–151.
23.Crystallographic data (excluding structure factors) for the structures
reported in this paper have been deposited with the Cambridge
Crystallographic Data Centre as supplementary publication no.
CCDC-101327. Copies of the data can be obtained free of charge on
application to The Director, CCDC, 12 Union Road, Cambridge CB2
1EZ, UK [fax: int. code +44(1223)336-033, e-mail:
deposit@ccdc.cam.ac.uk].
References
1. Porter, N. A.; Giese, B.; Curran, D. P. Acc. Chem. Res. 1991, 24,
296–304. doi:10.1021/ar00010a003
2. Smadja, W. Synlett 1994, 1–26. doi:10.1055/s-1994-22728
3. Curran, D. P.; Porter, N. A.; Giese, B. Stereochemistry of Radical
Reactions; VCH: Weinheim, 1996.
4. Sibi, M. P.; Porter, N. A. Acc. Chem. Res. 1999, 32, 163–171.
doi:10.1021/ar9600547
24.Johnes, G. B.; Chapman, B. J. Synthesis 1995, 475–497.
doi:10.1055/s-1995-3957
5. Sibi, M. P.; Manyem, S.; Zimmerman, J. Chem. Rev. 2003, 103,
3263–3296. doi:10.1021/cr020044l
25.Effenberger, F.; Kottmann, K. Tetrahedron 1985, 41, 4171–4182.
doi:10.1016/S0040-4020(01)97192-3
6. Srikanth, G. S. C.; Castle, S. L. Tetrahedron 2005, 61, 10377–10441.
doi:10.1016/j.tet.2005.07.077
26.Dickinson, T.; Wynne-Jones, W. F. K. Trans. Faraday Soc. 1962, 58,
382–387. doi:10.1039/TF9625800382
7. Subramanian, H.; Landais, Y.; Sibi, M. P. Radical Addition Reactions.
In Comprehensive Organic Synthesis, 2nd ed.; Knochel, P.;
Molander, G. A., Eds.; Elsevier, 2014; Vol. 4, pp 699–741.
8. Yang, Y.-H.; Sibi, M. P. Stereoselective Radical Reactions. In
Encyclopedia of Radicals in Chemistry, Biology and Materials;
Chatgilialoglu, C.; Studer, A., Eds.; John Wiley and Sons, 2012; Vol. 2,
pp 655–691.
27.Kipphardt, H.; Enders, D. Kontakte (Darmstadt) 1985, 2, 37–45.
28.Bednarski, M.; Danishefsky, S. J. Am. Chem. Soc. 1986, 108,
7060–7067. doi:10.1021/ja00282a035
29.Whitesell, J. K.; Bhattacharya, A.; Buchanan, C. M.; Chen, H. H.;
Deyo, D.; James, D.; Liu, C.-L.; Minton, M. A. Tetrahedron 1986, 42,
2993–3001. doi:10.1016/S0040-4020(01)90590-3
30.Oppolzer, W.; Löhner, H. J. Helv. Chim. Acta 1981, 64, 2808–2811.
doi:10.1002/hlca.19810640842
9. Guindon, Y.; Godin, F.; Mochirian, P. A.; Prevost, M. Selected
diastereoselective reactions: free radical additions and cyclizations. In
Comprehensive Chirality; Carreira, E. M.; Yamamoto, H., Eds.;
Elsevier, 2012; Vol. 2, pp 472–503.
31.Comins, D. L.; Guerra-Weltzien, L. Tetrahedron Lett. 1996, 37,
3807–3810. doi:10.1016/0040-4039(96)00709-5
32.Siering, C.; Grimme, S.; Waldvogel, S. R. Chem. – Eur. J. 2005, 11,
1877–1888. doi:10.1002/chem.200401002
doi:10.1016/B978-0-08-095167-6.00215-9
10.Eichin, K.-H.; Beckhaus, H.-D.; Hellmann, S.; Fritz, H.; Peters, E.-M.;
Peters, K.; von Schnering, H.-G.; Rüchardt, C. Chem. Ber. 1983, 116,
1787–1821. doi:10.1002/cber.19831160509
33.Ihara, M.; Takahashi, M.; Taniguchi, N.; Yagui, K.; Niitsuma, H.;
Fukumoto, K. J. Chem. Soc., Perkin Trans. 1 1991, 525–535.
doi:10.1039/P19910000525
11.Peyman, A.; Beckhaus, H.-D.; Kramer, D.; Peters, K.;
von Schnering, H.-G.; Rüchardt, C. Chem. Ber. 1991, 124, 1989–1996.
doi:10.1002/cber.19911240918
34.Zhang, A.; Mohan, R. M.; Cook, L.; Kazanis, S.; Peisach, D.;
Foxman, B. M.; Snider, B. B. J. Org. Chem. 1993, 58, 7640–7651.
doi:10.1021/jo00079a006
12.Wessig, P.; Wettstein, P.; Giese, B.; Neuburger, M.; Zehnder, M.
Helv. Chim. Acta 1994, 77, 829–837. doi:10.1002/hlca.19940770322
13.Wessig, P.; Lindemann, U.; Neuburger, M.; Zehnder, M. J. Inf. Rec.
1996, 23, 19–21.
35.Klotz-Berendes, B. Studien zur diastereoselektiven Kupplung anodisch
erzeugter Radikale. Ph.D. Thesis, Universität Münster, 1994.
36.Letzel, M., Auxiliarkontrollierte dimeriserung von
2-tert-butylmalonsäureamid zu 2,3-di-tert-butylbernsteinsäurederivaten
durch Kolbe elektrolyse. Master Thesis, Universität Münster, 1994.
37.Letzel, M. Studien zur diastereoselektiven Kupplung anodisch
erzeugter Radikale in Hetero- und Homokupplungen. Ph.D. Thesis,
Universität Münster, 1997.
14.Lomölder, R.; Schäfer, H. J. Angew. Chem. 1987, 99, 1282–1283.
doi:10.1002/ange.19870991211
Angew. Chem., Int. Ed. Engl. 1987, 26, 1253–1254.
doi:10.1002/anie.198712531
15.Klotz-Berendes, B.; Schäfer, H. J.; Grehl, M.; Fröhlich, R.
Angew. Chem. 1995, 107, 218–220. doi:10.1002/ange.19951070217
Angew. Chem., Int. Ed. Engl. 1995, 34, 189–191.
doi:10.1002/anie.199501891
38.Porter, N. A.; Su, Q.; Harp, J. J.; Rosenstein, I. J.; McPhail, A. T.
Tetrahedron Lett. 1993, 34, 4457–4460.
doi:10.1016/0040-4039(93)88058-Q
39.Langer, T.; Illich, M.; Helmchen, G. Synlett 1996, 1137–1139.
doi:10.1055/s-1996-5668
16.Schäfer, H. J. In Electroorganic Chemistry, 5th ed.; Hammerich, O.;
Speiser, B., Eds.; CRC Press, 2016; pp 705–773.
40.Langer, T.; Illich, M.; Helmchen, G. Tetrahedron Lett. 1995, 36,
4409–4412. doi:10.1016/0040-4039(95)00786-C
41

Beilstein J. Org. Chem. 2017, 13, 33–42.
41.Evans, D. A.; Takacs, J. M. Tetrahedron Lett. 1980, 21, 4233–4236.
doi:10.1016/S0040-4039(00)92870-3
42.Evans, D. A.; Ennis, M. D.; Mathre, D. J. J. Am. Chem. Soc. 1982, 104,
1737–1739. doi:10.1021/ja00370a050
43.Eberson, L. Electrochim. Acta 1967, 12, 1473–1478.
doi:10.1016/0013-4686(67)80061-6
44.Eberson, L.; Gränse, S.; Olofsson, B. Acta Chem. Scand. 1968, 22,
2462–2470. doi:10.3891/acta.chem.scand.22-2462
45.Eberson, L. Acta Chem. Scand. 1963, 17, 2004–2018.
doi:10.3891/acta.chem.scand.17-2004
46.Eberson, L.; Ryde-Petterson, G. Acta Chem. Scand. 1973, 27,
1159–1161. doi:10.3891/acta.chem.scand.27-1159
47.Eberson, L.; Nyberg, K.; Servin, R. Acta Chem. Scand., Ser. B 1976,
30, 906–907. doi:10.3891/acta.chem.scand.30b-0906
48.Hawkes, G. E.; Utley, J. H. P.; Yates, G. B.
J. Chem. Soc., Perkin Trans. 2 1976, 1709–1716.
doi:10.1039/p29760001709
49.Utley, J. H. P.; Yates, G. B. J. Chem. Soc., Perkin Trans. 2 1978,
395–400. doi:10.1039/p29780000395
50.Solladié-Cavallo, A.; Csaky, A. G.; Gantz, I.; Suffert, J. J. Org. Chem.
1994, 59, 5343–5346. doi:10.1021/jo00097a041
51.Nguyen, P. Q., Master Thesis, University of Münster, 1998, p. 39. The
experimental procedure for the conversion of 30c into 31c and 3 is
given in Supporting Information File 1.
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