Stepwise radical cation Diels-Alder reaction via multiple pathways

Article abstract of DOI:10.3762/bjoc.14.59

Herein we disclose the radical cation Diels-Alder reaction of aryl vinyl ethers by electrocatalysis, which is triggered by an oxidative SET process. The reaction clearly proceeds in a stepwise fashion, which is a rare mechanism in this class. We also found that two distinctive pathways, including direct and indirect , are possible to construct the Diels-Alder adduct.

Full text of DOI:10.3762/bjoc.14.59

Stepwise radical cation Diels–Alder reaction
via multiple pathways
Ryo Shimizu1, Yohei Okada2 and Kazuhiro Chiba*1
Letter
Open Access
Address:
Beilstein J. Org. Chem. 2018, 14, 704–708.
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.14.59
Received: 30 December 2017
Accepted: 09 March 2018
Published: 27 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 Shimizu et al.; licensee Beilstein-Institut.
License and terms: see end of document.
Keywords:
Diels–Alder reaction; radical cation; rearrangement; single electron
transfer; stepwise
Abstract
Herein we disclose the radical cation Diels–Alder reaction of aryl vinyl ethers by electrocatalysis, which is triggered by an oxida-
tive SET process. The reaction clearly proceeds in a stepwise fashion, which is a rare mechanism in this class. We also found that
two distinctive pathways, including “direct” and “indirect”, are possible to construct the Diels–Alder adduct.
Introduction
Umpolung, also known as polarity inversion, is a powerful ap- this class and thus have been widely used in synthetic organic
proach in synthetic organic chemistry to trigger reactions that chemistry [13-15].
are otherwise difficult or impossible. In an umpolung reaction,
the normal reactivity of the molecules being studied is reversed, The Diels–Alder reaction is a classic reaction, and one of the
e.g., electrophilicity is generated from a nucleophile. The single most powerful methods to construct six-membered ring
electron transfer (SET) process has been recognized as the most systems. A “normal” Diels–Alder reaction must consider an
straightforward way to induce umpolung, which has recently electronic matching of the substrates, with an electron-rich
been carried out by means of photo- [1-6] and electrochemical diene and electron-deficient dienophile as the general combina-
[7-12] approaches. A typical example involves an oxidative tion. Although having both an electron-rich diene and dieno-
SET of an electron-rich and thus nucleophilic C–C double bond. phile is a less- or non-effective combination, oxidative SET has
The oxidative SET produces a radical cation species, which proven to be able to overcome this mismatch and such a
offers electrophilic reactivity for subsequent transformations. strategy is well-known as a radical cation Diels–Alder reaction.
Enol ether radical cations are among the simplest members of The use of trans-anethole as a model electron-rich dienophile is
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Beilstein J. Org. Chem. 2018, 14, 704–708.
the representative example in this class. It was first reported by chlorate/nitromethane electrolyte solution [33]. The reactions
Bauld in 1986 [16] and was elegantly revisited by Yoon in 2011 involve a radical cation chain process and are complete using a
[17] in the field of photoredox catalysis (Scheme 1). The reac- catalytic amount of electricity. During the course of our study,
tion was further studied by Ferreira and Shores [18], followed we discovered that radical cation Diels–Alder reactions are also
by a unique mechanistic investigation by Rappé [19]. Although possible by electrocatalysis, however, the scope was limited to
most recent examples of the radical cation Diels–Alder reaction styrenes [34]. Described herein is a stepwise radical cation
have employed styrenes, the scope is not limited to such elec- Diels–Alder reaction of enol ethers by electrocatalysis, which
tron-rich dienophiles. Bauld and Yoon demonstrated that aryl proceeds via multiple unique pathways.
vinyl ethers, enol ether equivalents, and aryl vinyl sulfides are
also promising dienophiles for the reactions (Scheme 2) [17,20- Results and Discussion
25].
The present work began with the synthesis of the aryl vinyl
ether 1 from p-propylphenol in 2 steps (Scheme S1 and Figure
S1 in Supporting Information File 1). Both E- and Z-forms were
readily purified by silica gel column chromatography. When the
anodic oxidation of the Z-form 1Z was carried out in the pres-
ence of 2,3-dimethyl-1,3-butadiene (2), the corresponding
Diels–Alder adduct 3 was obtained in excellent yield
(Scheme 3). The reaction was completed using a catalytic
amount of electricity and therefore should involve a radical
cation chain process. Since Diels–Alder adduct 3 was an
approximately cis/trans = 1:2 mixture, the reaction must
proceed in a stepwise fashion. This stereochemistry was con-
firmed when the E-form 1E also gave the same synthetic
outcome. Namely, the Diels–Alder adduct 3 was obtained as an
approximately cis/trans = 1:2 mixture, indicating that the reac-
tion was indeed stepwise.
Scheme 1: Radical cation Diels–Alder reaction of trans-anethole [17].
When the reaction was carefully monitored by gas chromatogra-
phy–mass spectrometry (GC–MS), we found that an adduct was
generated in the early stage that was not the Diels–Alder prod-
uct 3. Therefore, we intentionally stopped the reaction after
0.1 F/mol of electricity had passed and attempted to identify the
adduct. We found that it was a vinylcyclobutane 4, whose for-
mation was only observed in the early stage of the reaction and
Scheme 2: Radical cation Diels–Alder reactions of aryl vinyl ether and
sulfides [17,25].
We have been developing oxidative SET-triggered cycloaddi- was completely consumed after 0.7 F/mol of electricity was
tions of enol ethers by electrocatalysis [26-32] in lithium per- passed (Scheme 4 and Figure 1). Vinylcyclobutanes are known
Scheme 3: Radical cation Diels–Alder reaction of aryl vinyl ether (1). Conditions: 1.0 M LiClO4/CH3NO2, carbon felt electrodes, 1.2 V vs Ag/AgCl,
0.7 F/mol.
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Beilstein J. Org. Chem. 2018, 14, 704–708.
Scheme 4: Oxidative SET-triggered reaction of aryl vinyl ether 1c. Conditions: 1.0 M LiClO4/CH3NO2, carbon felt electrodes, 1.2 V vs Ag/AgCl,
0.1 F/mol.
Figure 1: GC–MS Monitoring of the oxidative SET-triggered reaction of aryl vinyl ether 1c.
to rearrange to cyclohexenes via thermal and/or photochemical
processes and therefore, we carried out the anodic oxidation of
vinylcyclobutane 4 in the absence of 2,3-dimethyl-1,3-buta-
diene (2, Scheme 5 and Supporting Information File 1, Figure
S2). Interestingly, the rearrangement took place effectively to
give Diels–Alder adduct 3 as an approximately cis/trans = 1:4
mixture, a significant difference from the synthetic outcome
mentioned above (Scheme 3). Notably, no rearrangement was
observed without electricity and the vinyl substituent was found
to be essential for the transformation since no cyclohexane 6
was obtained from the cyclobutane 5 (Scheme 6). We also
Scheme 5: Oxidative SET-triggered rearrangement of vinyl cyclo-
butane 4. Conditions: 1.0 M LiClO4/CH3NO2, carbon felt electrodes,
1.2 V vs Ag/AgCl, 0.5 F/mol.
found that the Diels–Alder adduct 3 with an approximately (Scheme 7). On the basis of the oxidation potentials, oxidative
cis/trans = 1:1 mixture was obtained in the early stage of the SET would selectively take place from the aryl vinyl ether 1
reaction (Supporting Information File 1, Figure S3).
even in the presence of 2,3-dimethyl-1,3-butadiene (2) to
generate the radical cation 1·+, in which the stereochemistry
Taken together, we can now propose a mechanism for the derived from the starting material is lost. Indeed, the anodic oxi-
radical cation Diels–Alder reaction of the aryl vinyl ether 1 dation of either the Z- (1Z) or the E-form (1E) in the absence of
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Beilstein J. Org. Chem. 2018, 14, 704–708.
ture. However, since the oxidative SET-triggered rearrange-
ment of the vinylcyclobutane 4 gives the Diels–Alder adduct 3
as an approximately cis/trans = 1:4 mixture, this should proceed
via a different intermediate from the acyclic radical cation inter-
mediate (A·+). Here, we propose the cyclic radical cation inter-
mediate B·+ for the rearrangement, imparting stereoselectivity
for the six-membered ring closure. The anodic oxidation of the
Diels–Alder adduct 3 does not give either the retro-reaction
product 1 or the vinylcyclobutane 4 and therefore, it seems that
the overall transformation involves irreversible steps. Thus, the
radical cation Diels–Alder reaction of aryl vinyl ether 1 effec-
tively proceeds either via “direct” or “indirect” pathways,
affording the corresponding adduct 3 in excellent yield.
Conclusion
In conclusion, we have demonstrated that the radical cation
Diels–Alder reaction initiated by electrocatalysis in lithium per-
chlorate/nitromethane electrolyte solution is not limited to
Scheme 6: Unsuccessful rearrangement of cyclobutanes. Conditions:
1.0 M LiClO4/CH3NO2, carbon felt electrodes, a) no electricity, b)1.2 V
vs Ag/AgCl, 0.1 F/mol.
2,3-dimethyl-1,3-butadiene (2) led to isomerization. In other styrenes but was also effective for the aryl vinyl ether. While
words, inversion of the configuration of the radical cation 1·+ the mechanism is still controversial, most reported radical
proceeds readily, leading to a loss in stereoselectivity. The cation Diels–Alder reactions are highly stereoselective, even in-
radical cation 1·+ is then trapped by 2,3-dimethyl-1,3-butadiene cluding stereospecific concerted examples. On the other hand,
(2) to construct the acyclic radical cation intermediate A·+, our current results clearly indicate that a stepwise mechanism is
which is potentially converted into the aromatic radical cation also effective for this class. Furthermore, the radical cation
with a six-membered ring (3·+) or a four-membered ring (4·+) Diels–Alder reaction of the aryl vinyl ether is found to proceed
via rapid intramolecular SET processes. It can be rationalized via multiple unique pathways, including direct and indirect
that the six-membered ring closure of the acyclic radical cation manners. Our findings described herein are beneficial to design
intermediate (A·+) would be a stepwise process, leading to the novel SET-triggered cycloadditions, which are under develop-
Diels–Alder adduct 3 as an approximately cis/trans = 1:1 mix- ment in our laboratory.
Scheme 7: Proposed mechanism for the radical cation Diels–Alder reaction of aryl vinyl ether 1.
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Supporting Information
Supporting Information File 1
Additional scheme and figures, general remarks, synthesis
and characterization data, including copies of 1H and
13C NMR spectra.
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Acknowledgements
This work was partially supported by JSPS KAKENHI Grant
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