Quinonediimines as redox-active organocatalysts for oxidative coupling of aryl- and alkenylmagnesium compounds under molecular oxygen

Article abstract of DOI:10.1039/c6cc03053j

It is revealed that N,N′-diphenyl-p-benzoquinonediimine works as a redox-active organocatalyst for the oxidative homo-coupling of aryl- and alkenylmagnesium compounds under molecular oxygen. The catalytic cycle was formally monitored by ¹H NMR experiments.

Full text of DOI:10.1039/c6cc03053j

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Quinonediimines as redox-active organocatalysts
for oxidative coupling of aryl- and
alkenylmagnesium compounds under molecular
oxygen†
Cite this:DOI: 10.1039/c6cc03053j
Received 12th April 2016,
Accepted 26th April 2016
Toru Amaya,* Riyo Suzuki and Toshikazu Hirao*‡
DOI: 10.1039/c6cc03053j
www.rsc.org/chemcomm
It is revealed that N,N0-diphenyl-p-benzoquinonediimine works as a
redox-active organocatalyst for the oxidative homo-coupling of
aryl- and alkenylmagnesium compounds under molecular oxygen.
The catalytic cycle was formally monitored by 1H NMR experiments.
Organocatalysis is now one of the most thriving areas in organic
synthesis.1 The reaction focused on here is organocatalytic
oxidative homo-coupling of aryl- and alkenylmagnesium com-
pounds under molecular oxygen (Scheme 1). However, such a
catalyst has been rarely developed before (only a few examples
have been reported as described later) despite the upsurge of
interest in organocatalysis.
The oxidative homo-coupling of aryl- and alkenylmagnesium
compounds (Scheme 1a) is one of the efficient methods for the
synthesis of symmetrical biaryls and bialkenyls. Stoichiometric
use of high-valent transition metal oxidants generally works
well for this reaction, which has been studied since about a
century ago.2 In the last decade, some catalytic systems using
transition metals have been constructed.3 Examples for the
combination of the catalyst and the terminal oxidant are shown
below: FeCl3 or MnCl2-1,2-dihaloethane,3a–c Li2CuCl4–CuBrꢀSMe2-
di-tert-butyldiaziridinone,3d FeCl3 or MnCl2 or Li2CuCl4 or
RuCl(C3S5)H2O(PPh3)2–O2,3e–h and FeCl3 or MnCl2–N2O.3i On
the other hand, the methodology employing organic oxidants is
Scheme 1 (a) Oxidative homo-coupling of aryl- and alkenylmagnesium
compounds. (b) Our previous study on the stoichiometric reaction. (c) This
work: organocatalytic oxidative homo-coupling using quinonediimine 1a
as a redox-active catalyst under molecular oxygen.
far more behind in this area, and the research studies have been oxidant for the coupling reaction.4c This finding should be a
quite limited.4 One of the reasons is the difficulty in making the milestone in this area from the viewpoint of metal-free coupling.
electron-transfer type reaction take place in preference to the The next challenge should be the construction of the organocatalytic
nucleophilic addition in a competitive situation, for example system under molecular oxygen, which is one of the desirable
employing stoichiometric 1,4-benzoquinone as an oxidant in terminal oxidants in the catalytic oxidation reactions from the
this case.4d In 2006, Mayr, Knochel and co-workers proved the viewpoint of sustainable chemistry. However, a possible side reac-
utility of 3,30,5,50-tetra-tert-butyldiphenoquinone with bulky tert- tion, that is reaction of the arylmagnesium compounds with
butyl groups in both sides of carbonyls as a stoichiometric molecular oxygen, makes this reaction more complicated. Only
two examples have been reported for the organocatalytic oxidative
Department of Applied Chemistry, Graduate School of Engineering,
coupling of aryl- and alkenylmagnesium compounds. One is a
Osaka University, Yamada-oka, Suita, Osaka 565-0871, Japan.
2,2,6,6-tetramethylpiperidine-N-oxyl (TEMPO) radical catalyzed reac-
E-mail: amaya@chem.eng.osaka-u.ac.jp, hirao@chem.eng.osaka-u.ac.jp
tion reported by Studer and co-workers.4e The other is a recently
† Electronic supplementary information (ESI) available. See DOI: 10.1039/c6cc03053j
reported 3,4,5-trifluoro-1,2-bis(perfluorophenyl)cyclopentadienyl
anion-catalyzed reaction by Korenaga and co-workers.4f In our
‡ Present address: The Institute of Scientific and Industrial Research, Osaka
University, Mihoga-oka, Ibaraki, Osaka 567-0047, Japan.
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previous study, oxidation catalysts consisting of redox-active
poly- and oligoaniline derivatives were developed,5 including
catalysts for oxidative coupling of phenol derivatives using
molecular oxygen as a terminal oxidant.5c Recently, it was also
revealed that N,N0-diphenyl-p-benzoquinonediimine (1a) induces the
stoichiometric oxidative coupling of aryl- and alkenylmagnesium
compounds (Scheme 1b).6 Here, we report the catalytic version of the
reaction under molecular oxygen as a terminal oxidant (Scheme 1c).
The investigation began with the oxidative homo-coupling of
(1-phenylvinyl)magnesium bromide (2a) in the presence of a
catalytic amount of quinonediimine 1a under molecular oxygen.
The employed 1a was prepared by the oxidation of N,N0-diphenyl-
p-phenylenediamine with iodosylbenzene under metal free
conditions. The ICP-AES experiment of 1a certified that the
contamination of transition metals such as Cu, Fe, Mn and Pd is
negligibly small for this reaction (Cu, Fe and Mn: limit of quanti-
fication, Pd: 6 ꢁ 10ꢂ5 mol% to 2). A THF solution of 2a was added
Fig. 1 Profile of the yield for 3a with time.
Increasing the reaction temperature to 60 1C gave the product
to quinonediimine 1a in THF under molecular nitrogen at room 3a in 72% yield (Scheme 2). Bubbling of molecular oxygen instead
temperature. After 5 min, molecular oxygen was flowed through the
flask for 30 min. The desired coupling product 3a was formed in
64% yield, where the turnover number of 1a is 3.2 because 1a is a
two-electron oxidant (Scheme 2). Acetophenone was also formed in
8% as a side product. As a control experiment, the same reaction
was carried out in the absence of 1a. The yield of 3a was 6%.
of flowing did not induce an increase in the yield. The reaction
under dry air instead of molecular oxygen gave 3a in 68% yield.
Decreasing the amount of 1a to 5 mol% lowered the yield to 47%,
whereas the turnover number of 1a increased to 4.7.
Some quinonediimine derivatives 1b–d7 were also tested as
catalysts instead of 1a for this reaction. However, better results were
The reaction was monitored with time by sampling (Fig. 1). not obtained as compared to that with 1a (Table 1, entries 1–3).
First, the reaction took place under molecular nitrogen, where In the case of 1b, the reaction proceeded catalytically although
the red colour of 1a changed to pale yellow. Flowing molecular
oxygen (5–12 min) made the colour of the reaction mixture
change to green and then red. In this period, an increase in the
yield was observed. The red colour suggests the regeneration of 1a.
the efficiency was low (Table 1, entry 1). On the other hand,
there seems to be a problem in the regeneration step in the case
of 1c (Table 1, entry 2). Catalyst 1d did not give rise to the
oxidative coupling of 2a even in the stoichiometric reaction
After the colour of the reaction mixture turned red, an increase of (Table 1, entry 3).
the yield was almost stopped. This suggests that (1-phenylvinyl)-
magnesium bromide (2a) was almost consumed.
Table 1 Screening of catalysts for the oxidative coupling of 2a under
molecular oxygen
Entry
1
Catalyst
Yielda/%
38
2
12
3
1
a
Yield was calculated by the integral ratio of the peaks for 3a and 1,3,5-
trimethoxybenzene as an internal standard in the 1H NMR spectrum of
Scheme 2 1a-catalyzed oxidative coupling of 2a and its control experiment. the crude mixture.
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Table 2 shows the screening of the solvents for this reaction.
Communication
To gain information on the reaction path, the reaction was
The reaction was performed at room temperature. Use of Et2O, followed by 1H NMR spectroscopy (Fig. 2, and the enlarged figure is
CH2Cl2 and cyclopentyl methyl ether instead of THF was not shown in Fig. S1, ESI†). At first, 1a is dissolved in THF-d8, the
effective for this reaction (Table 2, entries 2–4). The mixed solution spectrum is shown in Fig. 2a. To the solution was added a
of THF/CH2Cl2 and THF/cyclopentyl methyl ether also did not give stoichiometric amount of 2a (200 mol%) under molecular nitrogen.
the better results than THF (Table 2, entries 5 and 6).
The peaks for 1a disappeared and the peaks for the homo-coupling
product 3a appeared with the reduced quinonediimine compound
1a-red (Fig. 2b). The broad signals of 1a-red well-accorded with
those for the separately prepared one by the reaction of N,N0-
diphenyl-p-phenylenediamine with phenylmagnesium bromide
(see the supporting information of ref. 6). The broadening seems
to be due to aggregation. Introduction of molecular oxygen
clearly showed the regeneration of 1a (Fig. 2c). To the mixture
Table 2 Screening of solvents for the 1a-catalyzed oxidative coupling of
2a under molecular oxygen
Entry
Solvent
Yielda/%
1b
2
3
4
5
THF
Et2O
64
42
20
36
64
54
Table 3 Substrate scope for the 1a-catalyzed oxidative coupling of 2
under dry air
CH2Cl2
Cyclopentyl methyl ether
CH2Cl2/THF
6
Cyclopentyl methyl ether/THF
Yielda/%
71
a
Entry
1
Substrate
Product
Yield was calculated by the integral ratio of the peaks for 3a and 1,3,5-
trimethoxybenzene as an internal standard in the 1H NMR spectrum of
the crude mixture. This entry is the same as a result in Scheme 2.
b
2
3
4
79
74b
77
5
6
7
70
71
85
8c
70d
9c
61d
a
b
c
Isolated yield. Including a small amount of the impurity. 10 mol%
of 1a was used and the reaction was conducted under molecular oxygen.
d
Yield was calculated by the integral ratio of the peaks for 3a and 1,3,5-
Fig. 2 1H NMR experiment to follow the redox cycle of 1a in the oxidative
coupling of 2a and reoxidation under molecular oxygen.
trimethoxybenzene as an internal standard in the 1H NMR spectrum of
the crude mixture.
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was dropwise added at room temperature. After stirring for 5 min
at room temperature, the flask was put in a pre-warmed oil bath
(60 1C). Then, air dried through concentrated H2SO4 was flowed slowly
(8.3 mL minꢂ1) for 55 min. The reaction mixture was stirred at 60 1C in
this period, and then quenched with a mixed aqueous solution of
NaHCO3/Na2S2O3. To the mixture was added CH2Cl2. The aqueous layer
was filtered through filter paper and extracted with CH2Cl2 three times.
The combined organic layer was washed with brine and dried with
Na2SO4. After filtration, the mixture was concentrated in vacuo. The
residue was purified by silica-gel chromatography (0 to 10% CH2Cl2 in
hexane) to give 3h as a white flaky solid (108.5 mg, 0.43 mmol, 85%).
was added a stoichiometric amount of 2a (200 mol%), again
resulting in the complete consumption of 1a and the formation
of 3a and 1a-red (Fig. 2d). These experiments formally show the
catalytic cycle based on 1a and 1a-red with molecular oxygen as
a terminal oxidant.
Table 3 shows the substrate scope for the 1a-catalyzed
oxidative homo-coupling reaction.§ For the reaction of aryl-
magnesium compounds 2b–h, use of dry air instead of mole-
cular oxygen in the presence of 15 mol% of 1a gave the better
results (Table 3, entries 1–7). Substitution of the benzene ring
with p-MeO-, p-F-, p-Me- and o-Me was not a problem and gave
the corresponding homo-coupling products 3c–f in good yields
(70–79%, Table 3, entries 2–5). Bulky mesitylmagnesium bromide
(2g) also homo-coupled to give product 3g in 71% yield (Table 3,
entry 6). The coupling of 2-naphthylmagnesium bromide (2h)
showed the best yield (85%, Table 3, entry 7). The reaction of
(1-arylvinyl)magnesium bromides 2i–j took place under molecular
oxygen to provide the products 3i–j in moderate yields (Table 3,
entries 8 and 9).
In conclusion, it is revealed that quinonediimine 1a works as a
redox-active organocatalyst for the oxidative homo-coupling of
aryl- and alkenylmagnesium compounds under molecular oxygen.
The catalytic cycle was formally monitored by 1H NMR experi-
ments. It should be noted that this organocatalyst can catalyze the
oxidative carbon–carbon bond formation using molecular oxygen
as a terminal oxidant, which is one of the challenging topics in the
field of organocatalysts.
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This work was supported by a Grant-in-Aid for Scientific
Research on Innovative Areas ‘‘Advanced Molecular Trans-
formations by Organocatalysts’’ from The Ministry of Education,
Culture, Sports, Science and Technology, Japan (26105736).
Notes and references
§ A representative procedure: To a two-neck 10 mL dried flask with a
condenser was added 1a (39.4 mg, 0.15 mmol), and the atmosphere was
replaced by molecular nitrogen. Dry THF (1.0 mL) was added. A 0.50 M
THF solution of 2-naphthylmagnesium bromide (2h) (2.0 mL, 1.0 mmol)
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