Selective α,δ-hydrocarboxylation of conjugated dienes utilizing CO2and electrosynthesis

Article abstract of DOI:10.1039/d0sc03148h

To date the majority of diene carboxylation processes afford the α,δ-dicarboxylated product, the selective mono-carboxylation of dienes is a significant challenge and the major product reported under transition metal catalysis arises from carboxylation at the α-carbon. Herein we report a new electrosynthetic approach, that does not rely on a sacrificial electrode, the reported method allows unprecedented direct access to carboxylic acids derived from dienes at the δ-position. In addition, the α,δ-dicarboxylic acid or the α,δ-reduced alkene can be easily accessed by simple modification of the reaction conditions. This journal is

Full text of DOI:10.1039/d0sc03148h

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Selective a,d-hydrocarboxylation of conjugated
dienes utilizing CO2 and electrosynthesis†
Cite this: DOI: 10.1039/d0sc03148h
ab
All publication charges for this article
have been paid for by the Royal Society
of Chemistry
Ahmed M. Sheta,
Andrei V. Malkov
Mohammad A. Mashaly,b Samy B. Said,b Saad S. Elmorsy,c
a
a
*
and Benjamin R. Buckley
To date the majority of diene carboxylation processes afford the a,d-dicarboxylated product, the selective
mono-carboxylation of dienes is a significant challenge and the major product reported under transition
metal catalysis arises from carboxylation at the a-carbon. Herein we report a new electrosynthetic
approach, that does not rely on a sacrificial electrode, the reported method allows unprecedented direct
access to carboxylic acids derived from dienes at the d-position. In addition, the a,d-dicarboxylic acid or
the a,d-reduced alkene can be easily accessed by simple modification of the reaction conditions.
Received 5th June 2020
Accepted 13th July 2020
DOI: 10.1039/d0sc03148h
rsc.li/chemical-science
stoichiometric nickel dicarboxylation of 1,3-dienes and more
recently Martin has described a catalytic approach to the a,d-
dicarboxylation of diene feedstocks.11,12 However, hydro-
carboxylation of 1,3-dienes have scarcely been reported,
perhaps due to the inherent selectivity issues associated with
the site of carboxylation. Some selectivity has been observed for
mono-carboxylation at the a-carbon by Iwasawa but this tends
to depend on the substrate employed (Scheme 2a).13 Yu has
Introduction
Direct carboxylation of low value olen feedstocks utilising
carbon dioxide is regarded as a “dream reaction” owing to the
desire to utilise this low value, high volume waste gas.1–3
However, selectivity in these, and related carboxylation reac-
tions remains a signicant challenge (see for example Scheme
1). Electrochemical approaches to carboxylation have been
known for some time and recently Ackermann and others have
examined the electro–reductive transition metal carboxylation
of allyl chlorides with a sacricial electrode system and up to
9 : 1 regioselectivity being observed.4,5 Lu has described a sacri-
cial magnesium anode system in which the carboxylation of
a,b-unsaturated esters leads to a mixture of mono- and di-
carboxylic acids.6 Electrochemical approaches to a,d-dicarbox-
ylic acids from dienes have been known for some time, early
reports in the patent literature by Loveland describe the elec-
trolytic production of acyclic carboxylic acids from olens.7
However, several drawbacks to the system, such as the use of
a mercury electrode, prompted further research in this area.8
Dinjus reported the transition metal assisted electro-
carboxylation of 1,3-butadiene to afford predominantly the
straight chain dicarboxylic acid, again utilising a sacricial
reported
a
particularly impressive catalytic asymmetric
approach to a-hydroxymethylation of 1,3-dienes utilising CO2.14
magnesium anode.9 Dunach and Perichon later described
˜
a sacricial magnesium/nickel catalysed system with exclusive
dicarboxylic acid formation and good Z-olen selectivity.10 Aside
from the electrochemical literature Mori originally reported the
aDepartment of Chemistry Loughborough University, Ashby Road, Loughborough,
Leicestershire, LE11 3TU, UK. E-mail: b.r.buckley@lboro.ac.uk
bDepartment of Chemistry, Damietta University, Damietta El-Gadeeda City, Kafr Saad,
Damietta Governorate 34511, Egypt
cDepartment of Chemistry, Mansoura University, 25 El Gomhouria St, Dakahlia
Governorate 35516, Egypt
† Electronic supplementary information (ESI) available: Experimental procedures,
compound data and 1H, 13C and 19F NMR data. See DOI: 10.1039/d0sc03148h
Scheme 1 Representative attempts at selective electrocarboxylation.
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would naturally be more desirable.16,17 We have recently re-
ported the selective hydrocarboxylation of substituted aromatic
alkenes utilising electrosynthesis and carbon dioxide.16 This
novel carbon–carbon bond forming process provides unprece-
dented access to all carbon quaternary centres through the
carboxylation of b,b-substituted olens. Unlike the majority of
previously reported transition metal catalysed approaches this
chemistry selectively affords the b-carboxylated product.
Herein, we present a new practical electrosynthetic approach to
highly regioselective 1,4-hydrocarboxylation of dienes (Scheme
2b, Table 1, entries 1 and 2).
Results and discussion
Investigations commenced by utilising our previously reported
conditions for alkene hydrocarboxylation, using carbon cathode
and anodes (Table 1, entry 3). Disappointingly this resulted in
the formation of almost a statistical mixture of the d-mono-
carboxylated alkene 2a, the a-monocarboxylated alkene 3, the
a,d-dicarboxylated alkene 4 and the a,d-reduced alkene 5.
Initially we screened a range of electrode pairs; Ni/C resulted in
selective formation of 5 with no sign of any carboxylation by GC/
MS analysis (Table 1, entry 4).18 Utilising Cu/C couple resulted
in higher selectivity towards the d-monocarboxylated alkene 2a
but signicant amounts of the reduced diene 5 were observed.
Switching to stainless steel (SS) and carbon provided a signi-
cant improvement in the selectivity towards 2a (Table 1, entry 6)
and further optimization through the addition of water (Table 1,
entries 8–10) provided our standard conditions in which the
side products 3, 4 and 5 have been signicantly reduced (Table
1, entry 1). Interestingly the use of stainless steel as cathode and
Scheme
2 Attempts at selective carboxylation of 1,3-dienes, (a)
transition metal catalysed and (b) this work.
Only one report of selective d-carboxylation, reported by
Walther and Schonecker in the early 1990's, utilizing stoichio-
metric nickel complexes on a steroidal substrate is known.15
The electrosynthesis of carboxylates from dienes, like those
from alkenes readily rely on the use of a sacricial electrode to
enable successful carboxylation and in some cases regiocontrol.
As we and others have expressed previously from a practical and
sustainability point of view, a non-sacricial metal system
Table 1 Optimization Studiesa
Ratiob
2a
Entry
Deviation from standard conditions
3
4
5
Conv. 1ac (%)
1
2
3
4
5
6
7
8
9
10
None
No TEOA
9
9
1.7
0
3.8
9
3.1
9
9
1
1
1
0
1
1
1
1
1
0
0.5
0.5
1
0
1
1
1
0.82
0.74
1
0.7
0.7
1
1
2
1
0
0.7
0.7
0
99 (57)
99
99
80
99
99
83
99
99
C (ꢀ), C (+), no H2O
Ni (ꢀ), C (+), no H2O
Cu (ꢀ), C (+), no H2O
SS (ꢀ), C (+), no H2O
SS (ꢀ), SS (+), no H2O
H2O (5.0 equiv.)
H2O (10.0 equiv.)
No TEOA or H2O
0
99
a
General conditions: CO2 (1 atm), stainless steel cathode, carbon anode, Et4NI (0.5 equiv.), TEOA (1.0 equiv.), DMF, single compartment cell, 10 V
(60–100 mA), 5 h rt. b Ratios determined by GC-MS analysis, all products displayed approximately a 3 : 1 E : Z ratio. c Conversion evaluated by GC-
MS analysis, numbers in parenthesis indicate isolated yield of 2a.
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anode eliminated the reduced product 5 but showed no several challenging aliphatic dienes: for reasons which are
improvement in selectivity towards 2a (Table 1, entry 7). In the unclear 1k and 1l did not incorporate CO2 under our optimised
absence of TEOA we observed little change in the selectivity of conditions.
the reaction, but more unidentiable by-products (by GCMS)
In order to form low yields of 2l we had to employ the non-
were observed (unlike the corresponding reaction carried out aqueous conditions from Table 1 (entry 6). However, cyclo-
with alkenes16), however, in the absence of a suitable proton hexadiene 1m did react under our optimised conditions to
source (e.g. both TEOA and water) the dicarboxylic acid 4 was afford a mixture of alkenes from direct and conjugate addition
the sole product in up to 50% unoptimised isolated yield (Table in excellent yield (80%).
1, entry 10).
An examination of the aryl substituent (1a–e) reveals that
With the optimized conditions in hand, initial examination selectivity of the hydrocarboxylation (2 vs. 3) is in some way
of the scope of the reaction was carried out with a variety of aryl related to the electron density of the aryl ring. Electron with-
and aliphatic dienes (1a–m, Table 2), good selectivity of the 1,4- drawing groups (4-F, CF3) resulted in a slightly poorer ratio
hydrocarboxylated products were obtained and, in some cases when compared to more electron rich aryl substituents (4-H,
(2f–h), the d-substituted carboxylic acid was obtained exclu- Me, OMe). Initial Hammett correlation using s, or the modied
sively. The thiophene substrate 1g resulted in exclusive forma- s+ or sꢀ values revealed no obvious correlation. However, when
tion of 2g. Interestingly substitution of the diene in the 4- we plotted the regioselectivity of (2a–d/3a–d) over the modied
position with a methyl group 1h also afforded exclusive Swain–Lupton parameters (sS–L
)
19 a correlation (r2 ¼ 0.992) was
formation of the 4-substituted acid 2h. The symmetrical diene observed (Fig. 1).20 Addition of the intermediate radical anion to
1f afforded 2f in good yield, however, for reasons which are CO2 is accompanied by decrease in negative charge. Electronic
unclear at present, its isomer 1i did not incorporate carbon effects of aryl substituents should inuence benzylic radical to
dioxide and the corresponding reduced alkene 5i was the only a lesser extent compared to benzylic anion. Therefore, a modest
detectable product by GC-MS analysis. Anthracene 1j proved to slope of the line (r ¼ ꢀ0.55) with F (eld-inductive constant)
be a good substrate and the corresponding mono-carboxylate 2j dominant over R (resonance constant) appears to be in line with
was isolated in 65% yield. We then turned our attention to the preferential formation of linear isomer 2. The 4-F
Table 2 Substrate Scopea,b
a
General conditions: CO2 (1 atm), stainless steel cathode, carbon anode, Et4NI (0.5 equiv.), TEOA (1.0 equiv.), DMF, single compartment cell, 10 V
(60–100 mA), 5 h rt. Products were isolated as the corresponding methyl esters and 2/3 ratios determined aer hydrogenation of the double bond.
b
c
d
Products 2/3a–e and 2/3g & h displayed approximately a 3 : 1 E : Z ratio. Ratios determined by GC-MS analysis. Isolated as the alkene. The
e
reduced diene was the major product by GC-MS analysis. Conditions from Table 1, entry 6 employed.
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adsorbed radical anion of the diene, subsequent carboxylation
and further electron transfer and protonation from water
affords the nal a,d-monocarboxylated product. The reaction at
the counter electrode has been eloquently described by Chang
and co-workers in their study of deuteration reactions employ-
ing electrosynthesis and D2O.21 In the absence of water the
Fig. 1 Swain–Lupton correlation of regioselectivity of carboxylation
for the 4-aryl substituted 1,3-dienes (2/3).
substituted 1,3-diene 1c produces 2/3 with lower regioselectivity
vs. 4-H, OMe and CF3 due to its increased ability to inductively
destabilise the formation of positive character at the benzylic
position. In addition, this provides further evidence that in
these particular cases reduction of the diene occurs in prefer-
ence to that of CO2, thus route b shown in Scheme 3a likely
dominates.
The role of water in the reaction was conrmed through
deuterium labelling studies of anthracene 1j employing D2O
which resulted in formation of [D]2j or in the absence of CO2 [D]
5j both with ꢁ80% D incorporation (Scheme 3b). This leads us
to propose the mechanism highlighted [Scheme 3a, route (b)] in Fig. 2 Overall processes at both the anode and cathode.
which electron transfer to the diene proceeds to form the
Scheme 3 Postulated mechanism (a) and deuterium labelling studies Scheme 4 Summary of the versatility of the electrosynthetic condi-
(b).
tions to selectively afford 3 different products.
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dicarboxylated product dominates and in the absence of CO2
the a,d-reduction of the diene occurs (Fig. 2).
H. Neumann, R. Franke, R. Jackstell and M. Beller,
Science, 2019, 366, 1514–1517.
Probing the substrates a little further revealed that selec-
tive carboxylation of non-conjugated alkenes, such as 6, is
possible under the reaction conditions affording the a,b-
hydrocarboxylated product 7 (Scheme 4a), thus demon-
strating that conjugation of the diene is essential for
successful carboxylation to occur, in a similar fashion to the
reported styrene hydrocarboxylation.16 The methodology
could also be extended to trienes such as 8 with the a,f-
hydrocarboxylated product 9a predominating when using the
conditions employed for dienes in Table 2 (Scheme 4b). In
addition, depending on the reaction conditions employed
one can choose the product distribution required (Scheme
4c); addition of H2O to reaction provides the a,d-mono-
carboxylated product; removal of any proton source affords
the solely the a,d-dicarboxylated product and switching the
electrode system results in a,d-reduction of the diene.
3 (a) Q. Liu, L. Wu, R. Jackstell and M. Beller, Nat. Commun.,
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Conclusions
In summary, a highly regioselective hydrocarboxylation process
that enables the direct formation of carboxylic acids from
dienes giving access to a,d-hydrocarboxylation products has
been reported. A wide variety of substrates have been tolerated
under these electrosynthetic conditions; Thus, this approach is
complimentary to the current literature in which a-addition and
dicraboxylation dominates. Preliminary mechanistic studies
suggest that eld inductive effects are dominant over resonance
effects in the transition state. Thus lower regioselectivties of 2
vs. 3 are observed when the 4-substituent is inductively with-
drawing. The current process goes beyond these state-of-the-art
systems enabling the selective mono-carboxylation of 1,3-
dienes, non-conjugated dienes and trienes.
6 H. Wang, Y.-F. Du, M.-Y. Lin, Z. Kai and J.-X. Lu, Chin. J.
Chem., 2008, 26, 1745–1748.
7 J. W. Loveland, Electrolytic production of acyclic carboxylic
acids from hydrocarbons, US Pat., 3032489, May 1, 1962.
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D. E. De Vos, ChemElectroChem, 2014, 2, 73–76.
9 J. Bringmann and E. Dinjus, Appl. Organomet. Chem., 2001,
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Conflicts of interest
˜
10 S. Derien, J. C. Clinet, E. Dunach and J. Perichon,
There are no conicts to declare.
Tetrahedron, 1992, 48, 5235–5248.
11 M. Takimoto and M. Mori, J. Am. Chem. Soc., 2001, 123,
2895–2896.
12 A. Tortajada, R. Ninokata and R. Martin, J. Am. Chem. Soc.,
2018, 140, 2050–2053.
Acknowledgements
We thank the Egyptian cultural affairs and missions sectors for
a visiting fellowship to AMS, the EPSRC (EP/P030599/1) and 13 J. Takaya, K. Sasano and N. Iwasawa, Org. Lett., 2011, 13,
Loughborough University for additional funding. Anas Alkayal,
1698–1701.
and Volodymr Tabas for initial substrate screening and Sophie 14 (a) Y.-Y. Gui, N. Hu, X.-W. Chen, L. L. Liao, T. Ju, J.-H. Ye,
Ezeilo for assistance in the preparation of compounds 6 and 7.
Z. Zhang, J. Li and D.-G. Yu, J. Am. Chem. Soc., 2017, 139,
17011–17014; (b) X.-W. Chen, L. Zhu, Y.-Y. Gui, K. Jing,
Y.-X. Jiang, Z.-Y. Bo, Y. Lan, J. Li and D.-G. Yu, J. Am.
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