Investigating radical cation chain processes in the electrocatalytic Diels-Alder reaction

Article abstract of DOI:10.3762/bjoc.14.51

Single electron transfer (SET)-triggered radical ion-based reactions have proven to be powerful options in synthetic organic chemistry. Although unique chain processes have been proposed in various photo- and electrochemical radical ion-based transformati

Full text of DOI:10.3762/bjoc.14.51

Investigating radical cation chain processes in the
electrocatalytic Diels–Alder reaction
Yasushi Imada1, Yohei Okada2 and Kazuhiro Chiba*1
Letter
Open Access
Address:
Beilstein J. Org. Chem. 2018, 14, 642–647.
1Department of Applied Biological Science, Tokyo University of
Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu, Tokyo
183-8509, Japan and 2Department of Chemical Engineering, Tokyo
University of Agriculture and Technology, 2-24-16 Naka-cho, Koganei,
Tokyo 184-8588, Japan
doi:10.3762/bjoc.14.51
Received: 29 December 2017
Accepted: 27 February 2018
Published: 16 March 2018
Email:
This article is part of the Thematic Series "Electrosynthesis II".
Guest Editor: S. R. Waldvogel
Kazuhiro Chiba* - chiba@cc.tuat.ac.jp
* Corresponding author
© 2018 Imada et al.; licensee Beilstein-Institut.
License and terms: see end of document.
Keywords:
chain process; Diels–Alder reaction; electrocatalytic; radical cation;
single electron transfer
Abstract
Single electron transfer (SET)-triggered radical ion-based reactions have proven to be powerful options in synthetic organic chem-
istry. Although unique chain processes have been proposed in various photo- and electrochemical radical ion-based transformat-
ions, the turnover number, also referred to as catalytic efficiency, remains unclear in most cases. Herein, we disclose our investiga-
tions of radical cation chain processes in the electrocatalytic Diels–Alder reaction, leading to a scalable synthesis. A gram-scale
synthesis was achieved with high current efficiency of up to 8000%. The reaction monitoring profiles showed sigmoidal curves
with induction periods, suggesting the involvement of intermediate(s) in the rate determining step.
Introduction
Recently, radical ion reactivity has received great attention in tive catalytic transformations. Although understanding the chain
the field of synthetic organic chemistry. The single electron mechanism is a prerequisite to the rational design of new radical
transfer (SET) strategy is the key to generating radical ions, ion-based reactions, it remains unclear in most cases. In particu-
which provide powerful intermediates for bond formations. lar, only a handful of reports have mentioned the “length,” also
Photo- [1-6] and electrochemistry [7-12] are the most straight- referred to as catalytic efficiency, of such radical ion chain pro-
forward approaches to induce SET processes. Since the cesses. As an early example, Bauld estimated the chain lengths
pioneering work by Ledwith [13-17], a chain process involving of cyclodimerizations of cyclohexadiene and trans-anethole (1)
radical ions has constituted a unique mechanism for this class of [18]. More recently, Yoon has established a straightforward
reactions, which also has the potential for contributing to effec- method to estimate the chain length of photoredox processes
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Beilstein J. Org. Chem. 2018, 14, 642–647.
using the combination of quantum yield and luminescence found to go to completion with a catalytic amount of electricity.
quenching experiments [19]. With such an understanding in The desired Diels–Alder adduct 3 was obtained in 98% yield
hand, radical ion chain processes could be further optimized to with less than 0.1 F/mol of electricity, suggesting that the cur-
realize greener transformations.
rent efficiency was up to 980%. The key step in the chain
process should be the bulk SET between the starting trans-anet-
We have been developing anodic cycloadditions [20-25] hole (1) and the aromatic radical cation (3·+), triggering the cat-
enabled by lithium perchlorate/nitromethane electrolyte solu- alytic cycle (Figure 1). The concentration of substrates must be
tion [26], some of which were achieved with a catalytic amount balanced to lengthen the chain process, since a higher concen-
of electricity. Such electrocatalytic cycloadditions should tration of trans-anethole (1) is effective for the bulk SET, but it
involve radical cation chain processes, meaning that the reac- can also cause undesired self-dimerization. We intentionally
tion is not only triggered by an oxidative SET at the surface of stopped the reaction at 0.01 F/mol in order to highlight the
the electrode but also by an intermolecular SET process in bulk difference between the concentrations used and then optimize
solution. We assumed that the catalytic efficiency of the reac- them (Table 1).
tion would be further improved through optimizing and/or
tuning the conditions in order to facilitate the bulk SET pro-
cesses. As recently demonstrated by Baran [27,28] and Wald-
vogel [29,30], electrochemical synthesis has also proven to be
highly scalable as well as sustainable. The longer chain length,
also referred to as a higher “current efficiency” in this context,
would enhance such advantages of the electrochemical synthe-
sis. It should also be noted that the mechanism of electrochemi-
Scheme 1: SET-triggered Diels–Alder reaction of trans-anethole (1)
and isoprene (2).
cal reactions can easily be studied since the amount of elec-
tricity passed can be precisely controlled in a switchable
manner. Described herein is a demonstration of excellent cur-
rent efficiency and high productivity for the electrocatalytic When a relatively lower concentration was used, the current
Diels–Alder reaction.
efficiency was measured at 1300% (Table 1, entry 1). The
termination of the radical cation chain process would be a re-
ductive SET of the radical cations (1·+, 3·+) at the cathode.
Results and Discussion
The present work began by optimizing the SET-triggered Therefore, we tested higher concentrations of the substrates to
Diels–Alder reaction of trans-anethole (1) and isoprene (2) as facilitate the bulk SET processes. Gratifyingly, we were able to
models (Scheme 1), which was first reported by Bauld [31] and achieve increased current efficiencies when 100 mM and
was elegantly revisited by Yoon [32]. We also reported the 300 mM concentrations of trans-anethole (1) were used
electrochemical variation of the reaction [21,22], which was (Table 1, entries 2 and 3). However, some dimerization of
Figure 1: Plausible mechanism for the electrocatalytic Diels–Alder reaction. Adapted from [22].
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Beilstein J. Org. Chem. 2018, 14, 642–647.
Table 1: Optimization of the electrocatalytic Diels–Alder reaction.
Entrya
Conditions
Yield (%)b, current efficiency (%)
1
2
3
4
X = 16, Y = 48
13, 1300
58, 5800
62, 6200
80, 8000
X = 100, Y = 300
X = 300, Y = 900
X = 300, Y = 3000
aAll reactions were carried out in 10 mL of CH3NO2 at rt. bYields were determined by 1H NMR analysis using benzaldehyde as an internal standard.
trans-anethole (1) via the trapping of the radical cation (1·+) by follow pseudo-first order reaction kinetics. However, the ob-
neutral trans-anethole was also detected in both cases served induction period indicated that this was not the case and
(Scheme 2). Since the undesired dimerization can decrease the an intermediate(s) was involved in the rate determining step.
current efficiency, we raised the amount of isoprene (2) from 3 This mechanism could be rationalized on the basis of a radical
to 10 equivalents in order to suppress it (Table 1, entry 4). As a cation chain process since the concentrations of both starting
result, the current efficiency reached up to 8000%, meaning trans-anethole (1) and the aromatic radical cation (3·+) would
that one electron was able to produce 80 molecules of the impact the overall reaction rate. Indeed, when the monitoring
Diels–Alder adduct 3.
was carried out with a lower concentration of trans-anethole
(1), no induction period was observed and the reaction required
With the optimized conditions (Table 1, entry 4) in hand, we nearly a stoichiometric amount of electricity to complete
monitored the reaction by gas chromatography mass spectrome- (Figure 3).
try (GC–MS, Figure 2). Surprisingly, we found that only
0.015 F/mol was sufficient to complete the reaction and the We finally turned our attention to the scalability of the reaction.
Diels–Alder adduct 3 was obtained in 98% yield, suggesting On the basis of the above discussed radical cation chain mecha-
that the current efficiency was up to 6533%. To the best of our nism, even higher concentrations of the substrates would still be
knowledge, this is one of the highest current efficiencies in effective (Table 2). To our delight, a high current efficiency of
electrochemical synthesis in that one electron can run the around 5000% was maintained even at 1.0 M and 2.0 M con-
radical cation chain process up to 65 times.
centrations of trans-anethole (1, Table 2, entries 1 and 2). How-
ever, 5.0 M was too concentrated and caused precipitation of
GC–MS monitoring showed a sigmoidal curve with an induc- the supporting electrolyte (Table 2, entry 3). To our satisfaction,
tion period. The monitoring was carried out in the presence of a up to 4.15 g of the Diels–Alder adduct (3) was isolated with
large excess (10 equivalents) of isoprene (2), which might 0.03 F/mol, giving a current efficiency of 3167% (Table 2,
Scheme 2: Undesired dimerization of trans-anethole (1).
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Beilstein J. Org. Chem. 2018, 14, 642–647.
Figure 2: GC–MS monitoring of the electrocatalytic Diels–Alder reaction (1: 300 mM; 2: 3000 mM).
Figure 3: GC–MS monitoring of the electrocatalytic Diels–Alder reaction (1: 1 mM; 2: 2000 mM).
Table 2: Optimization of the electrocatalytic Diels–Alder reaction.
Entrya
Conditions
Yield (%)b, current efficiency (%)
1
2
3
4
X = 1, Y = 3
X = 2, Y = 6
X = 5, Y = 15
X = 2, Y = 6
55, 5500
49, 4900
2, 200
95, 3167c, 4.15 g
aAll reactions were carried out in 10 mL of CH3NO2 at rt. bYields were determined by 1H NMR analysis using benzaldehyde as an internal standard.
c0.03 F/mol was used.
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Beilstein J. Org. Chem. 2018, 14, 642–647.
Figure 4: GC–MS monitoring of the electrocatalytic Diels–Alder reaction (1: 2 M; 2: 6 M). Blue dots show the dimer 4.
entry 4). Under these conditions, the undesired dimerization of Acknowledgements
trans-anethole (1) took place to give the dimer 4. However, we This work was partially supported by JSPS KAKENHI Grant
found that the electrochemical radical cation Diels–Alder reac- Numbers 15H04494, 17K19222 (to K. C.), 16H06193, and
tion was also possible from the dimer, whose photochemical 17K19221 (to Y. O.).
version was reported by Yoon [33]. The reaction was moni-
ORCID® iDs
Yohei Okada - https://orcid.org/0000-0002-4353-1595
tored by GC–MS and also showed a sigmoidal curve (Figure 4).
Conclusion
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