Yuki
Yamamoto
a,
Daichi
Kurata
b and
Akiya
Ogawa
*c
aGraduate Faculty of Interdisciplinary Research, University of Yamanashi, 4-4-37 Takeda, Kofu, Yamanashi 400-8510, Japan
bDepartment of Applied Chemistry, Graduate School of Engineering, Osaka Prefecture University, 1-1 Gakuen-cho, Nakaku, Sakai, Osaka 599-8531, Japan
cOrganization for Research Promotion, Osaka Metropolitan University, 1-1 Gakuen-cho, Nakaku, Sakai, Osaka 599-8531, Japan. E-mail: ogawa@omu.ac.jp
First published on 13th November 2023
In this study, novel catalytic carbonylation of thiophenes and furans was successfully achieved by using a catalytic amount of Pd(OAc)2 (min. 1 mol%). The catalyst showed excellent catalytic performance under CO/CO2-binary conditions, and the use of p-benzoquinone (p-BQ) as a stoichiometric oxidant for the regeneration of high-valent palladium catalysts active for C–H bond activation of heteroaromatics successfully led to the corresponding carboxylic acids in up to quantitative yields. Conventional palladium-promoted direct carbonylation of heteroaromatics was difficult to conduct as a catalytic reaction due to the thermal decomposition of palladium active species. In sharp contrast, we found for the first time that the thermal decomposition of the catalyst could be suppressed by using a CO/CO2-binary system; thus, highly efficient conversion of thiophenes and furans to the corresponding carboxylic acids has been attained with only 1 mol% catalyst loading. In the catalytic reactions, CO is the carbonyl source. The control experiments clearly showed that pressurized CO2 suppresses the thermal decomposition of the active palladium species to inactive palladium black and improves the durability of the catalyst under reaction conditions. The direct and catalytic carbonylation via C–H bond activation has been considered one of the most challenging reactions; therefore, the method established in this study will lead to a novel, practical, and versatile transformation based on direct carbonylation.
Among the transition-metal-catalyzed transformations, catalytic carbonylation has emerged as one of the key fundamental reactions in industrial and pharmaceutical fields. Thus, the development of highly efficient and green carbonylation has been strongly demanded using abundant CO as a C1 source.2,3 Although there are many studies on transition-metal-catalyzed carbonylation, most of them have required the substrates pre-functionalized by halogen groups, directing groups, etc., limiting the scope and applications.4 From the background, direct carbonylation by C–H bond activation has attracted much attention in recent years.5,6 However, the development of direct/catalytic carbonylation of aromatic compounds is almost unprecedented. In the 1990s, pioneering studies for palladium-promoted direct carbonylation of aromatics were reported; in the systems, an excess amount of furan or thiophene was required under CO, resulting in the corresponding carboxylic acids in trace yields (Scheme 1a).7,8 Even today, direct, practical, and catalytic carbonylation of aromatics via C–H bond activation still remains as one of the unsolved problems in organic synthesis, and is now urgently needed for multi-functionalization directed to synthesis of functional molecules.
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Scheme 1 (a) Precedent work for Pd-promoted carbonylation of thiophene/furan. (b) Pd-catalyzed direct carbonylation of thiophenes/furans (this work). |
Herein, we report novel and direct catalytic oxidative carbonylation of thiophenes and furans using Pd(OAc)2 as the catalyst, which exhibited excellent catalytic ability (min. 1 mol%) under a CO/CO2-binary system to afford the corresponding carboxylic acids in up to quantitative yields (Scheme 1b).
Entry | CO (atm) | CO2 (atm) | Pd(OAc)2 (mol%) | Additive (equiv.) | Yield of 2a (%) |
---|---|---|---|---|---|
a Yields were determined by 1H NMR spectroscopy (isolated yield). b Reaction temperature: 70 °C. | |||||
1 | 20 | — | 10 | — | 9 |
2 | 20 | 1 | 10 | — | 12 |
3 | 20 | 1 | 10 | p-BQ (1.5) | 61 |
4 | 20 | 1 | 10 | p-BQ (3.0) | 75 |
5 | 20 | 1 | 10 | Chloranil (3.0) | Trace |
6 | 20 | 1 | 10 | Anthraquinone (3.0) | 10 |
7 | 50 | 1 | 10 | p-BQ (3.0) | 83 |
8 | 50 | 5 | 10 | p-BQ (3.0) | 92 |
9 | 30 | 5 | 1 | p-BQ (1.5) | ∼100 (86) |
10 | 10 | 5 | 3 | p-BQ (1.5) | 96 |
11b | 30 | 5 | 1 | p-BQ (1.5) | 67 |
12 | 30 | — | 1 | p-BQ (1.5) | 72 |
13 | — | 5 | 1 | p-BQ (1.5) | N. D. |
Under the optimal conditions (entry 9, Table 1), the scope of the Pd-catalyzed carbonylation of thiophenes was investigated (Table 2). A variety of thiophenes with ethyl, methyl, n-pentyl, 2-ethylhexyl, benzyl, BnOCH2–, phenyl, chloro, and bromo groups at the 2-positions were successfully transformed into the corresponding carboxylic acids in up to quantitative yields (2a–2i). Thiophene 1j was tolerable, and 2j was selectively obtained in 72% yield. Although the transformation of 1-benzothiophene did not proceed at all, the more electron-rich heterocyclic compound thieno[3,2-b]thiophene 1k successfully afforded the corresponding carboxylic acid 2k in 56% yield. For 3-substituted thiophenes, the corresponding carboxylic acids were obtained with good product selectivity and regioselectivity (2l–2p). It was noteworthy that the direct carbonylation could be conducted in gram-scale, and 10 mmol of 1a successfully converted to 2a in quantitative yield.
Among five-membered heterocycles, furans as well as thiophenes are one of the most important scaffolds for constructing functional materials. However, because furans are relatively unstable to heating, their reaction conditions are more restricted than those of thiophenes. Therefore, the construction of an efficient catalytic transformation has been required for the catalytic carbonylation of furans. In this study, the optimization of the reaction conditions for furans was also investigated in detail, and a variety of furans were successfully transformed into the corresponding carboxylic acids with excellent yields, as shown in Table 3 (see the ESI†). When furfuryl acetate 3a was used as the substrate, using 5 mol% of the Pd catalyst and 3.0 equiv. of p-BQ was effective to yield 4a in 92% yield under CO (30 atm)/CO2 (5 atm). It was noteworthy that 2-ethylfuran 3b, which has no directing group such as the AcO group of 3a, could be transformed into the corresponding carboxylic acid 4b in 78% isolated yield by increasing the loading of Pd(OAc)2 to 15 mol% and prolonging the reaction time to 48 h. Under the optimized conditions for direct carbonylation of furans, a variety of furans with n-propyl, n-butyl, methyl, phenyl, BnOCH2–, and bromo groups at the 2-positions were successfully transformed into the corresponding carboxylic acids in moderate to good yields, respectively (4c–4h). For the transformation of furan 3i, heating at 70 °C for 48 h using Pd(OAc)2 (15 mol%) and p-BQ (3.0 equiv.) successfully afforded 4i in 61% yield. Interestingly, when 3-bromofuran 3j was used as the substrate, 4j was regioselectively obtained as the sole product in 95% yield.9
a Yields were determined by 1H NMR spectroscopy (isolated yield). b Reaction conditions: Pd(OAc)2 (5 mol%), 20 h. c Reaction conditions: Pd(OAc)2 (15 mol%), 48 h. d Reaction temperature: 70 °C. | ||
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To gain insights into the reaction pathways, some mechanistic experiments were conducted. When Pd(OAc)2 (0.3 mmol) was heated under a CO atmosphere in AcOH (3.0 mL) at 50 °C for 15 min, a tetranuclear complex Pd4(CO)4(OAc)4 was formed. Pd4(CO)4(OAc)4 is a known compound, and the structure of the complex obtained by the reaction shown in eqn (1) was unambiguously determined by comparing its IR spectrum with that of the literature data (vCO = 1943 and 1972 cm−1, eqn (1) in Fig. 1).10 Interestingly, when Pd4(CO)4(OAc)4 (in situ generated) was heated at 100 °C for 15 min in AcOH under a CO2 atmosphere, new absorption bands attributed to the CO vibration (vCO = 1946, 1958 cm−1) were confirmed along with the acetate group vibration (v = 1400–1600 cm−1) by IR spectroscopy, indicating the formation of a novel Pd–CO complex Pdk(CO)l(OAc)mA (eqn (2) in Fig. 1). Since complex A was quite unstable, it was difficult to determine the structure of complex A by single crystal X-ray analysis, elemental analysis, and HRMS measurement.11
Heating the solution of Pd4(CO)4(OAc)4 in AcOH at 70 °C for 15 min under CO2 (5 atm) did not cause any transformation; thus, heating at 100 °C was necessary for the transformation of Pd4(CO)4(OAc)4 into complex A (eqn (3)). Furthermore, complex A was also obtained directly by heating the solution of Pd(OAc)2 in AcOH at 100 °C for 15 min under a CO atmosphere (1 atm) (eqn (4)). Besides, Pd4(CO)4(OAc)4 or complex A was not formed from Pd(OAc)2 under CO2 (5 atm) in the absence of CO even heating at 100 °C for 14 h (eqn (5)).
These insights motivated us to investigate the catalytic performance of A (in situ generated) in catalytic carbonylation in the presence/absence of CO and CO2 (Table 4). When the reaction was conducted under CO (30 atm), 2a was obtained in 66% yield (entry 1). On the other hand, the reaction under CO (30 atm)/CO2 (5 atm) resulted in the formation of 2a in 93% yield (entry 2). In contrast, the reaction under CO2 (5 atm) did not afford the product 2a (entry 3).
Entry | CO (atm) | CO2 (atm) | Yield of 2a (%) |
---|---|---|---|
a Yields were determined by 1H NMR spectroscopy. | |||
1 | 30 | — | 66 |
2 | 30 | 5 | 93 |
3 | — | 5 | N. D. |
It has been reported that heating Pd4(CO)4(OAc)4 above 100 °C led to the insertion of CO into the Pd–acetate bond, and the thermal decomposition proceeded irreversibly via the reductive elimination of the formed unstable palladium species along with the release of CO2, resulting in the formation of inactive palladium black.12,13 On the other hand, the developed catalytic reactions in this study proceeded well under the CO/CO2-binary system, suggesting that CO2 pressurization suppressed the above thermal decomposition and improved the stability and thermal durability of complex A (Scheme 2).
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Scheme 2 Proposed reversible reactions that could account for the thermal stability of A under CO/CO2. |
To clarify the effect of CO2 on the reactions, we next attempted to synthesize A from Pd(OAc)2 under pressurized CO conditions in AcOH. When the solution of Pd(OAc)2 in AcOH was heated at 100 °C for 15 min under CO (10 atm), an insoluble black solid (palladium black) was formed and complex A was obtained in trace amounts (eqn (6) in Fig. 2).14 On the other hand, the reaction under CO (10 atm)/CO2 (5 atm) in AcOH successfully led to the formation of A, which was confirmed by IR spectroscopy (eqn (7) in Fig. 2). Thus, it was clearly demonstrated that pressurized CO2 suppressed the thermal decomposition of A to inactive palladium black and improved the durability of A under reaction conditions.
Based on these insights and previous studies, a possible reaction pathway for Pd-catalyzed direct carbonylation of thiophenes and furans is proposed, as indicated in Scheme 3. Initially, Pd(OAc)2 reacts with CO to form Pd4(CO)4(OAc)4. Then, the following partial thermal decomposition of Pd4(CO)4(OAc)4 occurs and complex A is generated, which is stabilized by pressurized CO2. Subsequently, the C–H bond activation of thiophenes or furans by A leads to arylpalladium(II) species Bvia concerted metalation–deprotonation processes, in which the C–Pd bond formation proceeds along with the generation of AcOH.15–18 Insertion of CO into the C–Pd bond of B forms C, and the following reductive elimination affords D with Pd0. Finally, the protonation/deacetylation of D in AcOH gives the corresponding carboxylic acids. Pd0 could be oxidized by p-BQ in AcOH under CO/CO2-binary conditions, and the catalytically active species A could be regenerated.
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Scheme 3 A possible reaction pathway for Pd-catalyzed carbonylation of thiophenes and furans under CO/CO2-binary conditions. |
Footnotes |
† Electronic supplementary information (ESI) available. See DOI: https://doi.org/10.1039/d3cy01379k |
‡ This work is dedicated to Prof. Dennis P. Curran (University of Pittsburgh) on the occasion of his 70th birthday. |
This journal is © The Royal Society of Chemistry 2023 |