Aminophosphine Palladium Pincer-Catalyzed Carbonylative

This is an open access article published under an ACS AuthorChoice License, which permits copying and redistribution of the article or any adaptations for non-commercial purposes.

Article Cite This: ACS Omega 2019, 4, 1560−1574

http://pubs.acs.org/journal/acsodf

Aminophosphine Palladium Pincer-Catalyzed Carbonylative Sonogashira and Suzuki−Miyaura Cross-Coupling with High Catalytic Turnovers Prashant Gautam, Neelam J. Tiwari, and Bhalchandra M. Bhanage* Department of Chemistry, Institute of Chemical Technology, N.P. Marg, Matunga, 400019 Mumbai, India

ACS Omega 2019.4:1560-1574. Downloaded from pubs.acs.org by 212.115.51.187 on 01/18/19. For personal use only.

S Supporting Information *

ABSTRACT: This work documents the first palladium pincer complex-catalyzed carbonylative Sonogashira (CS) and carbonylative Suzuki−Miyaura (CSM) cross-coupling. Compared to previous protocols, which employ hazardous and toxic solvents, the aminophosphine pincer complex {[C6H32,6-(NHP{piperidinyl}2)2]Pd(Cl)} (III) catalyzes both the cross-coupling reactions in propylene carbonate, an ecofriendly and sustainable polar aprotic solvent. Advantageously, employing III allows the CS cross-coupling to be carried out at a palladium loading of 10−4 mol % and the CSM crosscoupling to be carried out at 10−6 mol %, thus resulting in catalytic turnovers of 105 and 107, respectively. Relative comparison of the pincer complex with conventional palladium precursors Pd(OAc)2 and PdCl2(PPh3)2 shows the efficiency and robustness of the pincer complex in effecting higher catalytic activity at low palladium loadings.

■

INTRODUCTION

large amounts of waste, thus resulting in poor atom economy. The lack of regioselectivity in accessing ortho and para isomers, their separation, synthesis of biaryl ketones with meta substitution, and electron-withdrawing functionalities are additional drawbacks associated with the Friedel−Crafts acylation. Ynones are conventionally synthesized by reacting acid chlorides with alkynyl organometallic reagents3−7 or by the transition-metal-catalyzed cross-coupling between terminal alkynes and acid chlorides.8−11 Given the reactive nature of acid chlorides, these protocols suffer from poor functional group tolerance and poor atom economy. The palladium-catalyzed three-component carbonylative cross-coupling between aryl halide and aryl boronic acid12,13 [carbonylative Suzuki−Miyaura (CSM)] or terminal alkyne14,15 [carbonylative Sonogashira (CS)] using carbon monoxide as a C1 source is a straightforward and convenient strategy for synthesizing biaryl ketones and ynones, respectively. Both these reaction protocols are atomeconomic and have wide functional group tolerance. The fact that alkynes and aryl boronic acids are nontoxic and air-, moisture-, and thermally stable is an added advantage (Scheme 1). The synthesis of biaryl ketones and ynones from aryl halides and pseudohalides through the CSM and CS cross-coupling using a range of homogenous and heterogeneous palladium catalysts is well documented.13,16−33,15,34−49 However, to drive a

The development of protocols for the synthesis of biaryl ketones and ynones (α,β-acetylenic ketones) is extremely significant in synthetic organic chemistry.1 Biaryl ketones represent key structural motifs present in pharmaceutical drugs, sunscreen agents, and natural products. Ynones, on the other hand, are central building blocks present in biologically active molecules and are key intermediates in the synthesis of different heterocyclic functionalities and natural products (Figure 1). Traditionally, biaryl ketones are synthesized through the Friedel−Crafts acylation, which is driven by utilizing stoichiometric amount of Lewis acid.2 The presence of Lewis acid causes compatibility issues with functional groups and generation of

Received: October 20, 2018 Accepted: January 10, 2019 Published: January 17, 2019

Figure 1. Representative examples of important molecules containing the biaryl ketone and ynone functionality. © 2019 American Chemical Society

1560

DOI: 10.1021/acsomega.8b02886 ACS Omega 2019, 4, 1560−1574

ACS Omega

Article

Scheme 1. Comparison of Different Reaction Protocols for the Synthesis of Biaryl Ketones (a) and Ynones (b)

Figure 2. High catalytic turnover palladacyclic (I), (II) and pincer complex (III), (IV).

turnover catalyst for the CSM cross-coupling of aryl iodides.72 Notably, the reaction could be carried out using 10−6 mol % of palladium and catalytic turnovers of the order of 107 were observed. Recently, we have also documented oxime palladacycle (Figure 2, II) as a robust and high-turnover catalyst for the CS cross-coupling of aryl iodides.73 The reaction could be driven using a palladium loading of 10−3 mol %, resulting in catalytic turnovers of the order of 104. Palladacycles are cyclic palladium complexes incorporating at least a single carbon−palladium bond. Pincers belong to the family of palladacycles and incorporate two fused palladacycles. In the 1970s, Shaw,74 Noltes,75 and van Koten75 first reported the synthesis of pincer complexes. Over the years, many pincer complexes have been synthesized and their multifaceted catalytic applications systematically documented.76−84 However, the NCN, PCP, and SCS pincer complexes are the most common as they can be easily synthesized from palladium sources, which are commonly used. In 2000, Bedford and coworkers reported the first bis(phosphinite)-based PCP palladium pincer complex as a high-turnover catalyst for the Suzuki− Miyaura cross-coupling of aryl bromides and chlorides.85 A maximum TON of 190 000 could be achieved in the case of aryl bromides. In 2007 and 2010, Frech and co-workers reported the aminophosphine palladium pincer complexes (Figure 2, III and IV) for the Suzuki−Miyaura cross-coupling of aryl bromides and chlorides.86,87 Advantageously, while using complex III, the aryl bromides could be coupled between 5 and 30 min at a catalyst loading of 10−3 mol %, thus resulting in maximum catalytic turnovers of 105 and activated aryl chlorides could be coupled within 180 min at a catalyst loading of 0.1 mol %, resulting in maximum turnovers of 103. The same group reported the palladium pincer-catalyzed Sonogashira cross-coupling under additive- and amine-free conditions.88 A range of electronically deactivated, sterically hindered, and functionalized aryl iodides and aryl bromides were coupled with several alkynes at low

carbonylative cross-coupling, typically higher palladium loadings are necessary. Noncarbonylative cross-coupling reactions, on the other hand, can be driven more efficiently and smoothly at lower palladium loadings. In fact, even a 50 ppb palladium contamination in commercially available sodium carbonate catalyzes the Suzuki−Miyaura cross-coupling of aryl bromides.50 Thus, higher catalytic turnover numbers (TONs) and turnover frequencies (TOFs) are generally observed in the case of noncarbonylative cross-coupling reactions compared to carbonylative cross-coupling reactions. This is due to the fact that, in carbonylative cross-coupling reactions, excess of π-acidic CO is present compared to palladium. The reactivity of palladium toward oxidative addition of the aryl halide is greatly reduced due to binding of CO with palladium. Moreover, facile aggregation of palladium atoms in the presence of CO leads to the formation of nonactive palladium species, thereby reducing the catalytic activity. Thus, achieving high catalytic TONs and TOFs through low palladium loadings in carbonylative crosscoupling reactions is challenging. It is however essential to use palladium in minimum quantities given its high cost and to reduce the existing metal contamination in the environment. Additionally, since biaryl ketone and ynone synthesis forms part of the pharmaceutical and fine chemical industry, it is essential to reduce the contamination of palladium in the end product down to the ppm level. Palladacyclic complexes have been exhaustively reported as high-turnover catalysts for noncarbonylative cross-coupling reactions.51−65 They are known to catalyze reactions at extremely low palladium loadings, thus resulting in high catalytic turnovers and, in some cases, enzymatic turnovers.66 However, they have been seldom reported as high-turnover palladium precursors for carbonylative cross-coupling reactions.67−71 In 2015, we reported Bedford’s mixed tricyclohexylphosphine− triarylphosphite palladacyclic complex (Figure 2, I) as a high1561


ACS Omega

Article

of no concern, when benchmarked across various parameters, by the GlaxoSmithKline solvent selection guide.100 Moreover, ethylene and propylene carbonate have higher boiling points compared to amide (N,N-DMF and DMA), ethereal (dioxane, MTBE, and THF), and hydrocarbon (anisole and toluene) solvents. This not only results in lower atmospheric emissions, but also makes them safe to handle and store. Further, since organic cyclic carbonates are made up of only carbon, hydrogen, and oxygen, oxides of nitrogen and sulfur are not produced and emitted on their combustion or incineration. Carbonylation reactions are known to proceed efficiently in cyclic carbonates. This is mainly attributed to the high solubility of CO in cyclic carbonates. Okamoto’s group has done extensive research on the application of propylene carbonate as an advantageous solvent for the synthesis of polycarbonates by oxidative carbonylation of bisphenol A.101−103 Propylene carbonate is also known to stabilize palladium clusters/colloidal palladium accessible from bulk palladium104 and has been applied for Sonogashira cross-coupling of aryl chlorides105 and cyclocarbonylation reactions.106 Recently, we have reported the Pd/C-catalyzed phenoxycarbonylation of aryl iodides under CO surrogacy in propylene carbonate as a sustainable solvent.107 Taking into consideration our continued interest in developing high-turnover catalysts and identifying environmentally benign and sustainable solvents for carbonylation reactions, we herein report the first aminophosphine pincer complex-catalyzed carbonylative Suzuki−Miyaura and carbonylative Sonogashira cross-coupling in propylene carbonate (Scheme 2).

catalyst loadings and short reaction times, wherein maximum catalytic turnovers of 106 were observed, while using complex III. Both the complexes can be readily synthesized from dichloro(bis(1,1′,1″-(phosphinetriyl)tripiperidine))palladium as a template and 1,3-diaminobenzene or resorcinol to generate the aromatic pincer core at the palladium center. The protocol does not require the need for synthesis and purification of airand moisture-sensitive ligand systems and hence represents a facile, short, and high-yielding methodology for the synthesis of the pincer complex from inexpensive starting materials. Both the complexes are thermally stable up to 150 °C and do not undergo any decomposition in an oxygen atmosphere for more than a week. After a comprehensive literature survey, we found that, to the best of our knowledge, palladium-based pincer complexes have not been reported as precatalysts for the CSM and CS crosscoupling. We also found that both the aforementioned reactions have been typically carried out in hydrocarbon solvents (anisole or toluene), dioxane, dimethylacetamide (DMA), methyl tertbutyl ether (MTBE), N,N-dimethylformamide (N,N-DMF), and tetrahydrofuran (THF). Although the reactions proceed efficiently in these solvents, amide, ethereal, and hydrocarbon solvents are hazardous, toxic, and unsustainable. In present-day chemistry, the effect of reaction solvents on health, safety, and environment needs a meticulous examination. In the course of time, there will be constraint and restriction on production of solvents and their usage under Registration, Evaluation, Authorisation and restriction of CHemicals (REACH89)a regulation passed by the European Union. Hence, we envisaged in identifying an alternate sustainable solvent for both the reactions. Organic cyclic carbonates are environmentally friendly solvents in synthetic chemistry as they are nontoxic, biodegradable, odorless, and possess low vapor pressure.90−96 Inexpensive, industrial-scale, and sustainable methodologies for their synthesis from renewable feedstocks have been established.97−99 Ethylene carbonate and propylene carbonate (Figure 3) have been rated good to excellent, showing points

■

RESULTS AND DISCUSSION Carbonylative Sonogashira Cross-Coupling. We initiated the reaction optimization by monitoring the carbonylative cross-coupling between iodobenzene 1a and phenylacetylene 2a, resulting in the synthesis of 1,3-diphenylprop-2-yn-1-one 3a in toluene using 0.1 mol % pincer complex III (Table 1). The effect of CO pressure and base revealed that the reaction proceeded with 99% conversion and 96% selectivity when a CO pressure of 2 bar was applied and K2CO3 was taken as the base. Other inorganic (Na2CO3 and K3PO4) and organic bases (Et3N, TMEDA) gave inferior results (Table 1, entries 1−3 and 4−8). The solvent study showed that the reaction proceeded well in toluene, with slightly decreased selectivity observed in the case of N,N-DMF and dioxane (Table 1, entries 9−11). Delightfully, the former hazardous solvents could be avoided, as the reaction proceeded well in ethylene and propylene carbonate (Table 1, entries 12 and 13). Propylene carbonate being a liquid at room temperature was chosen as the solvent of choice. The time and temperature study showed that a reaction time of 5 h and a

Figure 3. Structures of ethylene carbonate (A) and propylene carbonate (B).

Scheme 2. Comparison of Previous Reaction Protocols with the Current Protocol

1562


ACS Omega

Article

Table 1. Optimization of Reaction Parameters for Carbonylative Sonogashira Cross-Couplinga

entry

CO pressure (bar)

1 2 3

1 2 4

4 5 6 7 8

base

time (h)

temperature (°C)

K2CO3 K2CO3 K2CO3

5 5 5

100 100 100

2 2 2 2 2

K2CO3 Na2CO3 K3PO4 Et3N TMEDAb

5 5 5 5 5

100 100 100 100 100

9 10 11 12 13

2 2 2 2 2

K2CO3 K2CO3 K2CO3 K2CO3 K2CO3

5 5 5 5 5

100 100 100 100 100

14 15 16 17

2 2 2 2

K2CO3 K2CO3 K2CO3 K2CO3

2 4 5 6

100 100 100 100

18 19 20

2 2 2

K2CO3 K2CO3 K2CO3

5 5 5

80 100 110

solvent

conversionc (%)

selectivityc (%)

TONd

TOF (h−1)

99 99 98

89 96 95

881 940 931

176 188 186

99 83 85 69 70

96 94 89 78 84

950 780 756 538 588

190 156 151 107 117

99 98 92 88 97

96 91 90 92 96

950 891 828 809 931

190 178 165 161 186

63 90 96 97

95 96 97 96

598 864 931 931

299 216 186 155

79 97 98

95 96 95

750 931 931

150 186 186

Effect of CO Pressure toluene toluene toluene Effect of Base toluene toluene toluene toluene toluene Effect of Solvent toluene N,N-DMF dioxane ethylene carbonate propylene carbonate Effect of Time propylene carbonate propylene carbonate propylene carbonate propylene carbonate Effect of Temperature propylene carbonate propylene carbonate propylene carbonate

a

Reaction conditions: 1a (0.5 mmol), 2a (0.6 mmol), [Pd, III] (0.1 mol %), base (1.0 mmol), solvent (10 mL). bTMEDA = N,N,N′,N′tetramethylethylenediamine. cConversion and selectivity were based on iodobenzene and determined by gas chromatography−mass spectrometry (GC−MS). dTON = mol product per mol Pd.

Table 2. Effect of Catalyst Loading for Carbonylative Sonogashira Cross-Couplinga entry 1 2 3 4 5b 6b 7

III (Pd mol %) −1

10 10−2 10−3 10−4 10−4 10−5 blank

conversionc (%) 99 96 79 52 86 34 00

TOF (h−1)

selectivityc (%)

TONd

96 95 93 94 94 74 00

9.5 × 10 9.1 × 103 7.3 × 104 4.8 × 105 8.0 × 105 2. 5 × 106 2

1.9 × 102 1. 8 × 103 1. 4 × 104 9.7 × 104 1. 0 × 105 3. 1 × 105

Reaction conditions: 1a (0.5 mmol), 2a (0.6 mmol), CO (2 bar), K2CO3 (1.0 mmol), propylene carbonate (10 mL) at 100 °C for 5 h. b120 °C for 8 h. cBased on iodobenzene, determined by GC−MS, and calculated as an average of triplicate measurements. dmol product per mol Pd.

a

temperature of 100 °C are required for achieving maximum conversion and selectivity (Table 1, entries 14−20). Having optimized the reaction conditions, we focussed our attention on the effect of catalyst loading (Table 2). The catalyst loading study showed that, as the palladium loading is decreased from 10−1 to 10−4 mol %, the conversion of 1a drastically drops from 99 to 52%. This resulted in catalytic TONs and TOFs of 105 and 104, respectively (Table 2, entries 1−4). The conversion and selectivity toward 3a at palladium loading of 10−4 mol % could be increased by carrying out the reaction at 120 °C for 8 h (Table 2, entry 5). Further decrease in palladium loading drastically brings down the conversion and selectivity, although a catalytic TON of 106 could be observed (Table 2, entry 6). Subsequently, we studied the scope of

substrates that could be synthesized at low palladium loadings under the optimized conditions (Table 3). Aromatic ring with electron-releasing substitutent (ortho- and para-OCH3) could be smoothly coupled with phenylacetylene and N,N-dimethyl-substituted phenylacetylene to furnish the products 3b and 3c in 76 and 84% yields, respectively (Table 3, entries 1 and 2). Polyaromatic naphthyl ynones 3d−f could be synthesized in 81, 85, and 79%, yields respectively (Table 3, entries 3−5). Incidentally, aliphatic cyclic alkyne-cyclopropylacetylene could also be coupled with 1-iodonaphthalene to afford the ynone 3g in 74% yield (Table 3, entry 6). Aromatic ring with electron-withdrawing substituents (para-Cl and ortho-Cl) could be coupled resulting in ynones 3h and 3i in 82 and 78% yields, respectively. Ynone 3j could be synthesized in 75% yield by 1563


ACS Omega

Article

Table 3. Scope of Pincer Complex-Catalyzed Carbonylative Sonogashira Cross-Couplinga

a Reaction conditions: 1 (0.5 mmol), 2 (0.6 mmol), [Pd, III] (10−4 mol %), CO (2 bar), K2CO3 (1.0 mmol), propylene carbonate (10 mL) at 120 °C for 8 h. bIsolated yields. cTON = mol product per mol Pd. dTOF in h−1. e[Pd, III] (10−1 mol %), GC−MS yield.

1−7). It is well a well-known fact that the carbonylative Suzuki− Miyaura cross-coupling proceeds well in nonpolar solvents. In polar aprotic solvents like N,N-DMF, formation of the corresponding carboxylic acid is observed.13 The solvent screening showed that the reaction proceeds well in anisole and dioxane with lower values of selectivity observed in N,NDMF (Table 4, entries 8−10). However, to our delight, the reaction proceeded efficiently in ethylene and propylene carbonate as alternate polar aprotic solvents (Table 4, entries 11 and 12). The time and temperature screening revealed that the reaction could be carried out at 100 °C in 3 h with a 95% conversion and 94% selectivity (Table 4, entries 13−19). We subsequently proceeded to study the effect of catalyst loading (Table 5). The palladium loading could be decreased up to 10−5 mol %, resulting in a conversion and selectivity of 81 and 89%, respectively, and catalytic turnovers of the order of 106 at 100 °C for 3 h (Table 5, entries 1−5). Bringing down the palladium loading from 10−5 to 10−6 mol % results in a drastic decrease in conversion (Table 5, entry 6). However, increasing the reaction temperature and time to 120 °C and 5 h, respectively, resulted in a conversion of 85%. To our delight, a catalytic turnover of 107 was observed (Table 5, entry 7). Decreasing the palladium loading further leads to a decrease in conversion, although resulting in a catalytic TON of 108 (Table 5, entry 8). Next, we screened the scope of substrates that could be synthesized through the CSM cross-coupling catalyzed by the pincer complex (Table 6).

coupling 1-bromo-4-iodobenzene and 4-fluorophenylacetylene (Table 3, entry 9). However, aromatic ring bearing strong electron-withdrawing substituents (para-nitro and cyano) could not be carbonylatively coupled to afford the corresponding ynones and only the corresponding noncarbonylative crosscoupling products were obtained. Increasing the palladium loading to 10−1 mol % and CO pressure to 8 bar did not result in the synthesis of the ynone. However, delightfully, on applying low palladium loading and under a CO pressure of 2 bar, heteroaromatic thiophene-containing ynones 3k−n could be synthesized in 68−86% yields (Table 3, entries 10−13). Attempts to carbonylatively couple the challenging orthodisubstituted aryl iodide failed under the optimized condition. However, increasing the palladium loading to 10−1 mol % resulted in a 19% yield of the ynone 3o (Table 3, entry 14). The tetramethoxy ynone 3p could be synthesized in 87% yield from 5-iodo-1,2,3-trimethoxybenzene and 4-methoxyphenylacetylene (Table 3, entry 15). Carbonylative Suzuki−Miyaura Cross-Coupling. Next, we turned our attention to optimize the reaction conditions for the carbonylative cross-coupling between iodobenzene 1a and phenylboronic acid 4a, leading to the synthesis of benzophenone 5a in anisole using 0.1 mol % of pincer complex III (Table 4). The CO pressure and base screening showed that the reaction could be advantageously carried out at atmospheric pressure of CO and that K2CO3 gives superior conversion and selectivity compared to other inorganic and organic bases (Table 4, entries 1564


ACS Omega

Article

Table 4. Optimization of Reaction Parameters for Carbonylative Suzuki Cross-Couplinga

entry

CO pressure (bar)

base

time (h)

temperature (°C)

1 2

1 2

K2CO3 K2CO3

3 3

100 100

3 4 5 6 7

1 1 1 1 1

K2CO3 Na2CO3 K3PO4 Et3N TMEDAb

3 3 3 3 3

100 100 100 100 100

8 9 10 11 12

1 1 1 1 1

K2CO3 K2CO3 K2CO3 K2CO3 K2CO3

3 3 3 3 3

100 100 100 100 100

13 14 15 16

1 1 1 1

K2CO3 K2CO3 K2CO3 K2CO3

0.5 1 2 3

100 100 100 100

17 18 19

1 1 1

K2CO3 K2CO3 K2CO3

3 3 3

80 100 110

solvent

Effect of CO Pressure anisole anisole Effect of Base anisole anisole anisole anisole anisole Effect of Solvent anisole N,N-DMF dioxane ethylene carbonate propylene carbonate Effect of Time propylene carbonate propylene carbonate propylene carbonate propylene carbonate Effect of Temperature propylene carbonate propylene carbonate propylene carbonate

conversionc (%)

selectivityc (%)

TONd

TOF (h−1)

94 92

93 95

874 874

291 291

94 88 73 37 41

93 85 89 49 39

874 748 649 181 159

291 249 216 60 53

94 98 89 91 95

93 19 86 79 94

874 186 765 718 893

291 62 255 239 297

6 60 89 95

80 89 90 94

48 534 801 893

96 534 400 297

81 95 95

91 94 96

737 893 912

245 297 304

a

Reaction conditions: 1a (0.5 mmol), 4a (0.75 mmol), [Pd, III] (0.1 mol %), base (1.5 mmol), solvent (10 mL). bTMEDA = N,N,N′,N′tetramethylethylenediamine. cConversion and selectivity were based on iodobenzene and determined by GC−MS. dTON = mol product per mol Pd.

trile could be coupled with 4-fluorophenylboronic acid to afford ketones 5d and 5e in 77 and 79% yields, respectively (Table 6, entries 3 and 4). Ketone 5f, bearing a meta-fluoro and paracyano substituent, 5g, bearing a meta-fluoro and methylenedioxy unit, and 5h, bearing difluoro and biphenyl functionality could be synthesized in 73, 84, and 80% yields, respectively (Table 6, entries 5−7). Polyaromatic, naphthyl biaryl ketones 5i and 5j could be synthesized from 1-iodonaphthalene in 83 and 78% yields, respectively (Table 6, entries 8 and 9). Polyhalogenated ketones 5k and 5l could be synthesized in 75 and 76% yields, respectively (Table 6, entries 10 and 11). The more challenging ortho-disubstituted ketone 5m could be synthesized from 2iodo-meta-xylene in 68% yield, incorporating a palladium loading of 10−2 mol % (Table 6, entry 12). Notably, under a CO pressure of 1 bar and palladium loading of 10−6 mol %, heteroaromatic thiophene-containing ketones 5n and 5o could be synthesized in 82 and 81%, yields (Table 6, entries 13 and 14). To demonstrate the practical applicability of the developed protocol, (4-methoxyphenyl)(3,4,5-trimethoxyphenyl)methanone (5p)an antineoplastic, and benzophenone-3 (oxybenzone) (5q)a sunscreen agent, were synthesized. (4Methoxyphenyl)(3,4,5-trimethoxyphenyl)methanone is a cytotoxic compound belonging to the phenstatin family, which causes cell apoptosis by inhibiting tubulin polymerization.109−113 Oxybenzone is a photostabilizer and photoprotective agent capable of absorbing UVB and short-wave UVA rays, thus providing a broad-spectrum protection against

Table 5. Effect of Catalyst Loading for Carbonylative Suzuki−Miyaura Cross-Couplinga entry 1 2 3 4 5 6 7b 8b 9

III (Pd mol %) −1

10 10−2 10−3 10−4 10−5 10−6 10−6 10−7 blank

conversionc (%) 99 97 95 91 81 51 85 44 00

selectivityc (%) 96 95 94 95 89 74 89 46 00

TOF (h−1)

TONd 9.5 × 10 9.2 × 103 8.9 × 104 8.6 × 105 7.2 × 106 3.7 × 107 7.5 × 107 2.0 × 108 2

3.1 × 102 3.0 × 103 2.9 × 104 2.8 × 105 2.4 × 106 1.2 × 107 1.5 × 107 4.0 × 107

a

Reaction conditions: 1a (0.5 mmol), 4a (0.75 mmol), CO (1 bar), K2CO3 (1.5 mmol), propylene carbonate (10 mL) at 100 °C for 3 h. b 120 °C for 5 h. cBased on iodobenzene, determined by GC−MS and calculated as an average of triplicate measurements. dmol product per mol Pd.

The CSM cross-coupling of aryl iodides bearing electronwithdrawing substituents is known to undergo biaryl formation without the insertion of CO.108 However, we observed that aryl iodide bearing a para- and meta-nitro substituent could be smoothly coupled with 4-cyanophenylboronic acid and 4flurophenylboronic acid leading to the synthesis of biaryl ketones 5b and 5c in 81 and 82% yields, respectively (Table 6, entries 1 and 2). 1-Bromo-4-iodobenzene and 4-iodobenzoni1565


ACS Omega

Article

Table 6. Scope of Pincer Complex-Catalyzed Carbonylative Suzuki−Miyaura Cross-Couplinga

a Reaction conditions: 1 (0.5 mmol), 4 (0.75 mmol), [Pd, III] (10−6 mol %), CO (1 bar), K2CO3 (1.5 mmol), propylene carbonate (10 mL) at 120 °C for 5 h. bIsolated yields. cTON = mol product per mol Pd. dTOF in h−1. e[Pd, III] (10−2 mol %).

UV ray damage.1 The CSM cross-coupling of 5-iodo-1,2,3trimethoxybenzene with 4-methoxyphenylboronic acid resulted in the synthesis of 5p in 78% yield. On the other hand, oxybenzone could be synthesized in 65% yield by carbonylatively cross-coupling 2-iodo-5-methoxyphenol with phenylboronic acid (Scheme 3). Synthesis of 5p and 5q could be carried out resulting in catalytic turnovers of 105 and 104, respectively. Comparison of Catalytic Activity. Next, we carried out a comparative study of the palladium pincer complex (III) with conventional palladium sources Pd(OAc)2 and PdCl2(PPh3)2 as well as with oxime palladacycle (II) for CS cross-coupling and with Bedford’s palladacycle (I) for the CSM cross-coupling (Table 7). In the case of CS cross-coupling, at 10−4 mol %

Table 7. Comparison of Palladacyclic Complexes with Conventional Palladium Precursors entry

catalyst

conv.i (%)

select.i (%)

TONj

TOF (h−1)

a

1 2 3b 4c 5 6d 7 8 9f 10g 11 12h

Scheme 3. Carbonylative Synthesis of (4Methoxyphenyl)(3,4,5-trimethoxyphenyl)methanone (5p) and Oxybenzone (5q)

Carbonylative Sonogashira III 85 95 8.0 × 105 Pd(OAc)2 05 32 1.6 × 104 Pd(OAc)2 19 40 7.6 × 104 Pd(OAc)2 26 44 1.1 × 105 PdCl2(PPh3)2 11 41 4.5 × 104 III 82 91 7.4 × 105 Carbonylative Suzuki−Miyaurae III 84 91 7.6 × 107 Pd(OAc)2 06 21 1.2 × 106 Pd(OAc)2 22 36 7.9 × 106 Pd(OAc)2 30 39 1.1 × 107 PdCl2(PPh3)2 18 32 5.7 × 106 III 83 92 7.6 × 107

1.0 × 105 2.0 × 103 9.5 × 103 1.0 × 104 5.6 × 103 9.3 × 104 1.5 × 107 2.5 × 105 1.5 × 106 2.3 × 106 1.1 × 106 1.5 × 107

a Reaction conditions: 1a (0.5 mmol), 2a (0.6 mmol), [Pd] (10−4 mol %), CO (2 bar), K2CO3 (1.0 mmol), propylene carbonate (10 mL) at 120 °C for 8 h. b10−3 mol % DMAP. c10−3 mol % ethylenediamine. d Scale up: 1a (5 mmol), 2a (6 mmol), [Pd] (10−4 mol %), CO (2 bar), K2CO3 (10 mmol), propylene carbonate (20 mL) at 120 °C for 8 h. eReaction conditions: 1a (0.5 mmol), 4a (0.75 mmol), [Pd] (10−6 mol %), CO (1 bar), K2CO3 (1.5 mmol), propylene carbonate (10 mL) at 120 °C for 5 h. f10−5 mol % DMAP. g10−5 mol % ethylenediamine. hScale up: 1a (5 mmol), 4a (7.5 mmol), [Pd] (10−6 mol %), CO (1 bar), K2CO3 (15 mmol), propylene carbonate (20 mL) at 120 °C for 5 h. iBased on iodobenzene, determined by GC− MS and calculated as an average of triplicate measurements. jmol product per mol Pd.

1566


ACS Omega

Article

Figure 4. Plot of conversion vs time. (a) Carbonylative Sonogashira cross-coupling: 1a (0.5 mmol), 2a (0.6 mmol), [Pd, III] (10−1 mol %), CO (2 bar), K2CO3 (1.0 mmol), propylene carbonate (10 mL) at 100 °C. (b) Carbonylative Suzuki−Miyaura cross-coupling: 1a (0.5 mmol), 4a (0.75 mmol), [Pd, III] (10−1 mol %), CO (1 bar), K2CO3 (1.5 mmol), propylene carbonate (10 mL) at 100 °C.

Figure 5. HR-TEM images (a−c) and particle size distribution (d) of the in situ synthesized palladium nanoparticles.

Figure 6. (a) XPS survey scan of in situ synthesized palladium nanoparticles and (b) XPS image showing Pd 3d5/2 and 3d3/2 binding energy.

what the pincer complex achieves (Table 7, entries 3, 4, 9, and 10). Notably, both the cross-coupling reactions could be carried out in gram scale (5 mmol) without any change in catalytic activity (Table 7, entries 6 and 12). Mechanistic Insight. To gain insight into the reaction mechanism, a time-dependent conversion study was carried out for both the cross-coupling reactions using 0.1 mol % III at 100 °C. When conversion was plotted as a function of time, we observed sigmoidal-shaped curves114 and a 60 min induction period in the case of CS cross-coupling and a 30 min induction period in the case of CSM cross-coupling (Figure 4). Moreover, the addition of 15 mol % tetra-n-butylammonium bromide, a salt which stabilizes palladium nanoparticles in catalytic reactions,114 leads to a drastic drop in conversion and catalytic activity. These results strongly point to the formation of heterogeneous palladium species (palladium nanoparticles/ nanoclusters or colloidal palladium), resulting from the

palladium loading, the pincer exhibits a conversion and selectivity of 85 and 95%, respectively, compared to Pd(OAc)2 (5 and 32%) and PdCl2(PPh3)2 (11 and 41%) (Table 7, entries 1, 2, and 5). In the case of CSM cross-coupling, at 10−6 mol % palladium loading, the pincer effects a conversion and selectivity of 84 and 91%, respectively, compared to Pd(OAc)2 (6 and 21%) and PdCl2(PPh3)2 (18 and 32%) (Table 7, entries 7, 8, and 11). The catalytic TONs thus observed in the case of pincer catalysis in CS cross-coupling are 50 and 17 times greater than those observed in the case of Pd(OAc)2 and PdCl2(PPh3)2, respectively. In the case of CSM cross-coupling, they are 63 and 13 times greater than those observed for Pd(OAc)2 and PdCl2(PPh3)2, respectively. The combination of Pd(OAc)2 with amine ligands 4-dimethylaminopyridine (DMAP) and ethylenediamine for the CS and CSM cross-coupling results in better values of conversion and selectivity compared to only using Pd(OAc)2. However, the catalytic activity still falls short of 1567


ACS Omega

Article

Figure 7. Proposed mechanism for the palladium pincer-catalyzed carbonylative Sonogashira and carbonylative Suzuki-−Miyaura cross-coupling.

and robustness of the pincer complex in effecting higher catalytic activity at lower palladium loadings. The plot of the time-dependent conversion study showed a brief induction period with a sigmoidal-shaped curve. Addition of tetra-n-butylammonium bromide resulted in a decrease in the catalytic activity, thus indicating the formation of heterogeneous palladium species from the pincer architecture. The isolation and characterization of the in situ formed heterogeneous palladium species revealed the formation of Pd(0) nanoparticles with narrow particle size distribution and an average particle size of 6.5 nm. Hence, both the carbonylative cross-coupling reactions proceed through the classical Pd(0)/Pd(II) pathway. Thus, the combination of low palladium loadings and high catalytic turnovers through the application of the palladium pincer complex as a precatalyst in propylene carbonate represents a sustainable process for the synthesis of biaryl ketones and ynones.

decomposition of the pincer architecture due to the reducing nature of gaseous CO.115 To isolate and characterize the heterogeneous palladium species formed in situ, the CSM cross-coupling reaction of 1a and 4a was carried out using 4.6 mol % (∼15 mg) of III for 5 h. The reaction mixture was then centrifuged at 10 000 rpm for 30 min. The supernatant propylene carbonate was decanted carefully and the black residue was washed with water and ethanol and characterized by field-emission gun (FEG)scanning electron microscopy (SEM) (Figure 1, Supporting Information), energy-dispersive spectrometry (Figure 2, Supporting Information), high-resolution transmission electron microscopy (HR-TEM), and X-ray photoelectron spectroscopy (XPS). HR-TEM analysis (Figure 5) reveals narrow particle size distribution with no appreciable agglomeration. Formation of palladium nanoparticles with an average particle size of about 6.5 nm was observed. The XPS study (Figure 6) reveals binding energies of 336.3 and 341.4 eV corresponding to the Pd(0) 3d5/2 and 3d3/2 energy levels. The pincer thus acts as a reservoir and dispenses highly energetic palladium nanoparticles under the reaction conditions. Hence, the reaction mechanism proceeds through the classical Pd(0)/Pd(II) redox pathway (Figure 7).

■

EXPERIMENTAL SECTION General. The aminophosphine palladium pincer complex (III) was sourced from Sigma-Aldrich and was used as received. All chemicals and solvents were sourced from different commercial vendors and used as received without any additional purification. Catalyst stock solutions dissolved in propylene carbonate of varying concentrations (10−1−10−10 mol %) were made by taking known catalyst concentration (1 mol %), which was followed by successive dilutions of the initial catalyst solution. Special precautions for the preparation of the catalyst stock solutions were not taken, and the catalysts were handled in air. The progress of the reaction was monitored by GC−MS and thin-layer chromatography using Merck silica gel 60 F254 plates. The reaction products were visualized with a 254 nm UV lamp. The GC−MS-QP 2010 instrument (Rtx-17, 30 m × 25 mm ID, film thickness (df) = 0.25 μm) (column flow, 2 mL min−1; 100− 240 °C at 10 °C min−1 rise) was used for the mass analysis of the products. Purification of the products was carried out by column chromatography on 100−200 mesh silica gel. The 1H NMR spectra were recorded on 500 MHz spectrometers in CDCl3 using tetramethylsilane (TMS) as an internal standard. The 13C NMR spectra were recorded on 125 MHz spectrometers in

■

CONCLUSIONS In conclusion, through this work, we have established the first pincer complex-catalyzed carbonylative Sonogashira (CS) and carbonylative Suzuki−Miyaura (CSM) cross-coupling in propylene carbonate as an eco-friendly aprotic solvent. Advantageously, applying the aminophosphine palladium pincer complex (III) as the precatalyst allowed the CS cross-coupling to be carried out at a palladium loading of 10−4 mol % and the CSM cross-coupling to be carried out at 10−6 mol %, thus resulting in catalytic turnovers of the order of 105 and 107, respectively. A range of biaryl ketones and ynones could be synthesized, including the synthesis of an antineoplastic and a photostabilizer cum photoprotective agent. The comparison of the palladium pincer complex (III) with conventional palladium precursors Pd(OAc)2 and PdCl2(PPh3)2 shows the superiority 1568


ACS Omega

Article

petroleum ether−ethyl acetate as the eluent, to yield 5p and 5q as the pure products. Scale-Up Study. Carbonylative Sonogashira CrossCoupling. Iodobenzene (5 mmol, 1.020 g), phenylacetylene (6.0 mmol, 0.612 g), [Pd, III] (10−4 mol %), and K2CO3 (10 mmol, 1.382 g) in 20 mL of propylene carbonate were added to a 100 mL stainless steel autoclave. The autoclave was closed and flushed three times with CO. It was then pressurized with CO to 2 bar (∼30 psi) at ambient temperature. The reaction mixture was stirred with a mechanical stirrer (450 rpm) at 120 °C for 8 h. The pressure was carefully released after cooling to room temperature. To remove traces of product, the reactor vessel was washed with ethyl acetate (4 × 5 mL). The layer of ethyl acetate was washed with water (3 × 5 mL), dried over Na2SO4, and evaporated by rotary evaporation to obtain the crude product. The crude product was subjected to GC−MS analysis. Carbonylative Suzuki−Miyaura Cross-Coupling. Iodobenzene (5 mmol, 1.020 g), phenylboronic acid (7.5 mmol, 0.910 g) [Pd, III] (10−6 mol %), and K2CO3 (15 mmol, 2.070 g) in 20 mL of propylene carbonate were added to a 100 mL stainless steel autoclave. The autoclave was closed and flushed three times with CO. It was then pressurized with CO to 1 bar (∼15 psi) at ambient temperature. The reaction mixture was stirred with a mechanical stirrer (450 rpm) at 120 °C for 5 h. The pressure was carefully released after cooling to room temperature. To remove traces of product, the reactor vessel was washed with ethyl acetate (4 × 5 mL). The layer of ethyl acetate was washed with water (3 × 5 mL), dried over Na2SO4, and evaporated by rotary evaporation to obtain the crude product. The crude product was subjected to GC−MS analysis. 1-(2-Methoxyphenyl)-3-phenylprop-2-yn-1-one (3b). 89.7 mg, yield 76%. 1 H NMR (400 MHz, CDCl3): δ 8.08 (d, J = 6.3 Hz, 1H), 7.62 (d, J = 8.0 Hz, 2H), 7.54 (d, J = 8.2 Hz, 1H), 7.41 (dt, J = 14.0, 6.6 Hz, 3H), 7.09−6.98 (m, 2H), 3.96 (s, 3H). 13C{1H} NMR (100 MHz, CDCl3): δ 176.7, 159.8, 135.0, 132.9, 132.6, 130.4, 128.5, 126.7, 120.6, 120.2, 112.1, 91.6, 89.1, 55.9. GC−MS (electron ionization (EI), 70 eV): m/z (%): 236 (40), 235 (100), 207 (46), 178 (20), 129 (76). 3-(4-(Dimethylamino)phenyl)-1-(4-methoxyphenyl)prop2-yn-1-one (3c). 117.3 mg, yield 84%. 1 H NMR (400 MHz, CDCl3): δ 8.18 (d, J = 7.8 Hz, 2H), 7.55 (d, J = 8.8 Hz, 2H), 6.96 (d, J = 8.7 Hz, 2H), 6.65 (d, J = 8.8 Hz, 2H), 3.88 (s, 3H), 3.03 (s, 6H). 13C{1H} NMR (100 MHz, CDCl3): δ 176.7, 163.9, 151.6, 134.9, 131.6, 130.7, 113.6, 111.5, 105.8, 96.5, 87.5, 55.5, 40.0. GC−MS (EI, 70 eV): m/z (%): 279 (100), 251 (19), 236 (45), 172 (22), 144 (18). 1-(Naphthalen-1-yl)-3-phenylprop-2-yn-1-one (3d). 103.8 mg, yield 81%. 1 H NMR (400 MHz, CDCl3): δ 9.25 (d, J = 8.7 Hz, 1H), 8.65 (d, J = 7.3 Hz, 1H), 8.08 (d, J = 8.1 Hz, 1H), 7.90 (d, J = 8.1 Hz, 1H), 7.68 (t, J = 7.9 Hz, 3H), 7.58 (q, J = 8.0, 7.2 Hz, 2H), 7.44 (dd, J = 16.8, 6.6 Hz, 3H). 13C{1H} NMR (100 MHz, CDCl3): 13 C NMR (101 MHz, chloroform-d) δ 179.7, 135.1, 134.5, 133.8, 132.9, 132.9, 130.7, 130.6, 128.9, 128.6, 128.6, 126.7, 125.9, 124.4, 120.3, 91.7, 88.5. GC−MS (EI, 70 eV): m/z (%): 256 (72), 255 (100), 202 (11), 129 (38). 3-(4-Methoxyphenyl)-1-(naphthalen-1-yl)prop-2-yn-1one (3e). 121.6 mg, yield 85%. 1 H NMR (400 MHz, CDCl3): δ 9.21 (d, J = 8.7 Hz, 1H), 8.61 (d, J = 7.3 Hz, 1H), 8.08 (d, J = 8.1 Hz, 1H), 7.90 (d, J = 8.2 Hz, 1H), 7.70−7.53 (m, 5H), 6.93 (d, J = 7.8 Hz, 2H), 3.85 (s, 3H). 13 C{1H} NMR (100 MHz, CDCl3): δ 179.8, 161.5, 135.0, 134.7,

CDCl3. Chemical shifts were reported in parts per million (δ) relative to tetramethylsilane as an internal standard, and J (coupling constant) values were reported in hertz. The splitting patterns of protons are described as s (singlet), d (doublet), dd (doublet of doublets), t (triplet), and m (multiplet). Field emission gun high-resolution transmission electron microscopy (300 kV) was carried out on Tecnai (FEI) G2, F30 instrument. X-ray photoelectron spectroscopy was carried out on AXIS Supra (Kratos Analytical, U.K.). Typical Procedure for Carbonylative Sonogashira Cross-Coupling. Aryl iodide (0.5 mmol), phenylacetylene (0.6 mmol), [Pd, III] (10−4 mol %), and K2CO3 (1.0 mmol) in 10 mL of propylene carbonate were added to a 100 mL stainless steel autoclave. Subsequently, the autoclave was closed and flushed three times with CO. The autoclave was then pressurized with CO to 2 bar (∼30 psi) at ambient temperature. The reaction mixture was stirred with a mechanical stirrer (450 rpm) at 120 °C for 8 h. The pressure was carefully released after cooling to room temperature. To remove traces of product, the reactor vessel was washed with ethyl acetate (3 × 5 mL). The ethyl acetate layer was washed with water (2 × 5 mL), dried over Na2SO4, and evaporated by rotary evaporation to obtain the crude product. The crude product was subjected to purification by column chromatography (silica gel, 100−200 mesh size), with petroleum ether−ethyl acetate as the eluent, to yield the pure product. Typical Procedure for Carbonylative Suzuki−Miyaura Cross-Coupling. Aryl iodide (0.5 mmol), aryl boronic acid (0.75 mmol), [Pd, III] (10−6 mol %), and K2CO3 (1.5 mmol) in 10 mL of propylene carbonate were added to a 100 mL stainless steel autoclave. Subsequently, the autoclave was closed and flushed three times with CO. The autoclave was then pressurized with CO to 1 bar (∼15 psi) at ambient temperature. The reaction mixture was stirred with a mechanical stirrer (450 rpm) at 120 °C for 5 h. The pressure was carefully released after cooling to room temperature. To remove traces of product, the reactor vessel was washed with ethyl acetate (3 × 5 mL). The ethyl acetate layer was washed with water (2 × 5 mL), dried over Na2SO4, and evaporated by rotary evaporation to obtain the crude product. The crude product was subjected to purification by column chromatography (silica gel, 100−200 mesh size), with petroleum ether−ethyl acetate as the eluent, to yield the pure product. Typical Procedure for Synthesis of 5p and 5q. In the case of 5p, 5-iodo-1,2,3-trimethoxybenzene (0.5 mmol), 4methoxyphenylboronic acid (0.75 mmol), [Pd, III] (10−4 mol %), and K2CO3 (1.5 mmol) in 10 mL of propylene carbonate were added to a 100 mL stainless steel autoclave. In the case of 5q, 2-iodo-5-methoxyphenol (0.5 mmol), phenylboronic acid (0.75 mmol), [Pd, III] (10−3 mol %), and K2CO3 (1.5 mmol) in 10 mL of propylene carbonate were added to a 100 mL stainless steel autoclave. In both the cases, the autoclave was closed and flushed with CO three times. The autoclave was then pressurized with CO to 1 bar (∼15 psi) at ambient temperature. The reaction mixture was stirred with a mechanical stirrer (450 rpm) at 120 °C for 5 h. The pressure was carefully released after cooling to room temperature. To remove traces of product, the reactor vessel was washed with ethyl acetate (3 × 5 mL). The ethyl acetate layer was washed with water (2 × 5 mL), dried over Na2SO4, and evaporated by rotary evaporation to obtain the crude product. The crude product was subjected to purification by column chromatography (silica gel, 100−200 mesh size), with 1569


ACS Omega

Article

1-(Thiophen-2-yl)-3-(p-tolyl)prop-2-yn-1-one (3m). 90.5 mg, yield 80%. 1 H NMR (400 MHz, CDCl3): δ 7.98 (d, J = 3.0 Hz, 1H), 7.70 (d, J = 4.8 Hz, 1H), 7.54 (d, J = 7.8 Hz, 2H), 7.18 (dd, J = 12.5, 5.8 Hz, 3H), 2.38 (s, 3H). 13C{1H} NMR (100 MHz, CDCl3): δ 169.8, 145.0, 141.6, 135.0, 134.9, 133.0, 129.4, 128.3, 116.7, 92.4, 86.3, 21.7. GC−MS (EI, 70 eV): m/z (%): 226 (100), 198 (85), 197 (49), 143 (59). 3-(4-Fluorophenyl)-1-(thiophen-2-yl)prop-2-yn-1-one (3n). 78.3 mg yield 68%. 1 H NMR (400 MHz, CDCl3): δ 7.99 (d, J = 2.8 Hz, 1H), 7.73 (d, J = 3.5 Hz, 1H), 7.69−7.63 (m, 2H), 7.18 (t, J = 3.5 Hz, 1H), 6.95 (t, J = 8.3 Hz, 2H). 13C{1H} NMR (100 MHz, CDCl3): δ 169.6, 164.0 (d, J = 254.0 Hz), 144.8, 135.3 (d, J = 4.6 Hz), 135.2, 135.0, 128.3, 116.2 (d, J = 22.3 Hz), 115.2 (d, J = 21.5 Hz), 90.6, 86.3. GC−MS (EI, 70 eV): m/z (%): 230 (93), 202 (100), 170 (15), 147 (54), 119 (16). 1-(2,6-Dimethylphenyl)-3-phenylprop-2-yn-1-one (3o). GC−MS yield: 19%. GC−MS (EI, 70 eV): m/z (%): 233(100), 202 (16), 191 (36), 132 (20), 104 (10). 3-(4-Methoxyphenyl)-1-(3,4,5-trimethoxyphenyl)prop-2yn-1-one (3p). 141.9 mg, yield 87%. 1 H NMR (400 MHz, CDCl3): δ 7.60 (d, J = 7.1 Hz, 2H), 7.49 (d, J = 1.6 Hz, 2H), 6.96−6.90 (m, 2H), 3.95 (d, J = 1.6 Hz, 6H), 3.94 (d, J = 1.6 Hz, 3H), 3.85 (d, J = 1.6 Hz, 3H). 13C{1H} NMR (100 MHz, CDCl3): δ 176.8, 161.7, 153.0, 143.3, 135.0, 132.3, 129.1, 114.4, 106.7, 94.1, 86.7, 61.0, 56.2, 55.4. GC−MS (EI, 70 eV): m/z (%): 326 (100), 283 (50), 255 (10), 159 (30). 4-(4-Nitrobenzoyl)benzonitrile (5b). 102.1 mg, yield 81%. 1 H NMR (400 MHz, CDCl3): δ 8.35 (t, J = 10.5 Hz, 2H), 7.91 (dd, J = 18.6, 8.1 Hz, 2H), 7.85−7.77 (m, 2H), 7.73 (t, J = 8.4 Hz, 2H). 13C{1H} NMR (100 MHz, CDCl3): δ 193.2, 150.2, 141.3, 139.6, 132.5, 130.7, 130.2, 123.8, 117.6, 116.6. GC−MS (EI, 70 eV): m/z (%): 252 (57), 151 (10), 150 (67), 130 (100), 102 (41). (4-Fluorophenyl)(3-nitrophenyl)methanone (5c). 100.5 mg, yield 82%. 1 H NMR (400 MHz, CDCl3): δ 8.55 (s, 1H), 8.41 (d, J = 9.4 Hz, 1H), 8.07 (d, J = 7.7 Hz, 1H), 7.82 (dd, J = 8.8, 5.4 Hz, 2H), 7.69 (t, J = 7.9 Hz, 1H), 7.18 (t, J = 8.6 Hz, 2H). 13C{1H} NMR (100 MHz, CDCl3): δ 192.6, 165.8 (d, J = 256.1 Hz), 148.0, 138.8, 135.2, 132.6 (d, J = 9.4 Hz), 132.4 (d, J = 3.0 Hz), 129.7, 126.7, 124.4, 115.9 (d, J = 22.1 Hz). GC−MS (EI, 70 eV): m/z (%): 245 (25), 123 (100), 95 (40), 75 (13). (4-Bromophenyl)(4-fluorophenyl)methanone (5d). 107.4 mg, yield 77%. 1 H NMR (400 MHz, CDCl3): δ 7.84−7.77 (m, 2H), 7.65− 7.60 (m, 4H), 7.16 (t, J = 7.9 Hz, 2H). 13C{1H} NMR (100 MHz, CDCl3): δ 194.1, 165.4 (d, J = 254.8 Hz), 136.1, 133.3 (d, J = 3.1 Hz), 132.5 (d, J = 9.2 Hz), 131.6, 131.3, 127.5, 115.6 (d, J = 21.9 Hz). GC−MS (EI, 70 eV): m/z (%): 280 (28), 278 (31), 199 (18), 183 (28), 123 (100). 4-(4-Fluorobenzoyl)benzonitrile (5e). 88.9 mg, yield 79%. 1 H NMR (400 MHz, CDCl3): δ 7.84 (d, 2H), 7.82 (d, 2H), 7.78 (d, J = 8.4 Hz, 2H), 7.17 (d, J = 8.4 Hz, 2H). 13C{1H} NMR (100 MHz, CDCl3): δ 193.5, 165.8 (d, J = 256.1 Hz), 141.0, 132.7 (d, J = 9.4 Hz), 132.5 (d, J = 3.0 Hz), 132.2, 130.0, 117.9, 116.0, 115.7. GC−MS (EI, 70 eV): m/z (%): 225 (46), 130 (22), 123 (100), 102 (20), 95 (33). 4-(3-Fluorobenzoyl)benzonitrile (5f). 82.2 mg, yield 73%. 1 H NMR (400 MHz, CDCl3): δ 7.86 (d, J = 7.6 Hz, 2H), 7.79 (d, J = 7.6 Hz, 2H), 7.53 (d, J = 7.4 Hz, 1H), 7.48 (d, J = 7.6 Hz,

134.1, 133.8, 133.2, 130.7, 128.7, 128.5, 126.6, 126.0, 124.4, 114.3, 112.1, 92.8, 88.4, 55.4. GC−MS (EI, 70 eV): m/z (%): 286 (76), 285 (100), 258 (28), 243 (60), 215 (53), 159 (41), 129 (28). 3-(4-Fluorophenyl)-1-(naphthalen-1-yl)prop-2-yn-1-one (3f). 108.3 mg, yield 79%. 1 H NMR (400 MHz, CDCl3): δ 9.22 (d, J = 8.7 Hz, 1H), 8.61 (d, J = 7.2 Hz, 1H), 8.09 (d, J = 8.1 Hz, 1H), 7.91 (d, J = 8.1 Hz, 1H), 7.68 (t, J = 6.0 Hz, 2H), 7.58 (q, J = 8.0, 7.4 Hz, 2H), 7.12 (t, J = 8.0 Hz, 2H). 13C{1H} NMR (100 MHz, CDCl3): δ 179.5, 163.9 (d, J = 253.6 Hz), 135.2, 135.1, 134.4, 133.8, 132.8, 130.7, 128.9, 128.5, 126.7, 125.9, 124.4, 116.4 (d, J = 3.3 Hz), 116.1 (d, J = 22.3 Hz), 90.6, 88.3. 3-Cyclopropyl-1-(naphthalen-1-yl)prop-2-yn-1-one (3g). 81.5 mg, yield 74%. 1 H NMR (400 MHz, CDCl3): δ 9.14 (d, J = 8.7 Hz, 1H), 8.45 (d, J = 7.3 Hz, 1H), 8.02 (d, J = 8.2 Hz, 1H), 7.86 (d, J = 8.1 Hz, 1H), 7.67−7.59 (m, 1H), 7.53 (t, J = 7.6 Hz, 2H), 1.53 (p, J = 6.6 Hz, 1H), 1.06−0.99 (m, 4H). 13C{1H} NMR (100 MHz, CDCl3): δ 179.7, 134.6, 134.1, 133.7, 133.1, 130.6, 128.6, 128.4, 126.5, 125.9, 124.3, 99.5, 77.1, 9.7, 0.0. GC−MS (EI, 70 eV): m/ z (%): 220 (50), 219 (100), 205 (24), 164 (64), 127 (33). 1-(4-Chlorophenyl)-3-phenylprop-2-yn-1-one (3h). 98.7 mg, yield 82%. 1 H NMR (400 MHz, CDCl3): δ 8.14 (d, J = 8.4 Hz, 2H), 7.67 (d, J = 8.1 Hz, 2H), 7.48 (d, J = 7.1 Hz, 3H), 7.42 (t, J = 6.8 Hz, 2H). 13C{1H} NMR (100 MHz, CDCl3): δ 176.6, 140.7, 135.2, 133.0, 130.9, 130.8, 128.9, 128.7, 119.8, 93.6, 86.5. GC−MS (EI, 70 eV): m/z (%): 240 (86), 212 (98), 201 (30), 176 (28), 139 (100). 1-(2-Chlorophenyl)-3-phenylprop-2-yn-1-one (3i). 93.9 mg, yield 78%. 1 H NMR (400 MHz, CDCl3): δ 8.08 (d, J = 8.3 Hz, 1H), 7.64 (d, J = 7.5 Hz, 2H), 7.50−7.44 (m, 3H), 7.40 (t, J = 7.3 Hz, 3H). 13 C{1H} NMR (100 MHz, CDCl3): δ 176.7, 135.8, 133.5, 133.3, 133.0, 132.5, 131.5, 130.9, 128.6, 126.8, 119.9, 93.9, 88.2. GC− MS (EI, 70 eV): m/z (%): 240 (45), 212 (80), 176 (23), 139 (100). 1-(4-Bromophenyl)-3-(4-fluorophenyl)prop-2-yn-1-one (3j). 113.7 mg, yield 75%. 1 H NMR (400 MHz, CDCl3): δ 8.09−8.01 (m, 2H), 7.71− 7.61 (m, 4H), 7.12 (t, J = 7.8 Hz, 2H). 13C{1H} NMR (100 MHz, CDCl3): δ 176.7, 164.1 (d, J = 254.4 Hz), 135.5, 135.4 (d, J = 8.9 Hz), 132.0, 130.8, 129.6, 116.3 (d, J = 22.4 Hz), 115.9 (d, J = 3.4 Hz), 92.5, 86.4. GC−MS (EI, 70 eV): m/z (%): 302 (43), 276 (54), 274 (61), 194 (22), 147 (100). 3-Phenyl-1-(thiophen-2-yl)prop-2-yn-1-one (3k). 88.1 mg, yield 83%. 1 H NMR (400 MHz, CDCl3): δ 8.03−7.95 (m, 1H), 7.71 (d, J = 4.8 Hz, 1H), 7.64 (d, J = 8.0 Hz, 2H), 7.46 (d, J = 7.1 Hz, 1H), 7.40 (t, J = 7.3 Hz, 2H), 7.20−7.15 (m, 1H). 13C{1H} NMR (100 MHz, CDCl3): 13C NMR (101 MHz, chloroform-d) δ 169.7, 144.8, 135.2, 135.1, 133.0, 130.8, 128.6, 128.3, 119.8, 91.7, 86.4. GC−MS (EI, 70 eV): m/z (%): 212 (90), 183 (100), 152 (20), 129 (65). 3-(4-Methoxyphenyl)-1-(thiophen-2-yl)prop-2-yn-1-one (3l). 104.2 mg, yield 86%. 1 H NMR (400 MHz, CDCl3): δ 7.98 (d, J = 2.7 Hz, 1H), 7.70 (d, J = 4.9 Hz, 1H), 7.61 (d, J = 8.9 Hz, 2H), 7.17 (t, J = 4.3 Hz, 1H), 6.92 (d, J = 8.8 Hz, 2H), 3.85 (s, 3H). 13C{1H} NMR (100 MHz, CDCl3): δ 169.8, 161.7, 145.0, 135.0, 134.8, 134.7, 128.2, 114.4, 111.6, 92.9, 86.3, 55.4. GC−MS (EI, 70 eV): m/z (%): 242 (100), 214 (39), 199 (60), 159 (38). 1570


ACS Omega

Article

2H), 7.33 (t, J = 7.6 Hz, 1H). 13C{1H} NMR (100 MHz, CDCl3): 13C NMR (101 MHz, chloroform-d) δ 193.6, 162.5 (d, J = 249.1 Hz), 140.5, 138.2 (d, J = 6.4 Hz), 132.3, 130.3 (d, J = 7.7 Hz), 130.1, 125.8 (d, J = 3.1 Hz), 120.3 (d, J = 21.4 Hz), 117.8, 116.7 (d, J = 22.6 Hz), 115.9. GC−MS (EI, 70 eV): m/z (%): 225 (69), 130 (69), 123 (100), 102 (39), 95 (40). Benzo[d][1,3]dioxol-5-yl(3-fluorophenyl)methanone (5g). 102.6 mg, yield 84%. 1 H NMR (400 MHz, CDCl3): δ 7.49 (d, J = 7.7 Hz, 1H), 7.46−7.40 (m, 2H), 7.34 (d, J = 9.1 Hz, 2H), 7.25 (t, J = 8.2 Hz, 1H), 6.85 (d, J = 8.4 Hz, 1H), 6.06 (s, 2H). 13C{1H} NMR (100 MHz, CDCl3): δ 193.5, 162.3 (d, J = 248.0 Hz), 151.8, 148.0, 140.1 (d, J = 6.4 Hz), 131.2, 129.8 (d, J = 7.8 Hz), 126.9, 125.3 (d, J = 3.1 Hz), 118.9 (d, J = 21.3 Hz), 116.4 (d, J = 22.5 Hz), 109.7, 107.7, 101.9. GC−MS (EI, 70 eV): m/z (%): 244 (59), 149 (100), 123 (15), 121 (24), 95 (26). (2-Fluoro-[1,1′-biphenyl]-4-yl)(3-fluorophenyl)methanone (5h). 117.7 mg, yield 80%. 1 H NMR (400 MHz, CDCl3): δ 7.65 (d, J = 1.4 Hz, 1H), 7.64−7.60 (m, 1H), 7.60−7.56 (m, 3H), 7.56−7.50 (m, 2H), 7.50−7.38 (m, 4H), 7.34−7.26 (m, 1H). 13C{1H} NMR (100 MHz, CDCl3): δ 193.4, 163.7, 160.9 (d, J = 65.4 Hz), 158.1, 139.1 (d, J = 6.3 Hz), 137.5 (d, J = 6.7 Hz), 134.5, 133.5 (d, J = 13.7 Hz), 130.7 (d, J = 3.5 Hz), 130.1 (d, J = 7.7 Hz), 129.0 (d, J = 3.1 Hz), 128.6, 128.5, 125.8 (d, J = 40.4 Hz), 119.6 (d, J = 21.4 Hz), 117.6 (d, J = 24.5 Hz), 116.6 (d, J = 22.5 Hz). GC−MS (EI, 70 eV): m/z (%): 294 (73), 199 (100), 170 (30), 123 (40), 95 (28). (4-Fluorophenyl)(naphthalen-1-yl)methanone (5i). 103.9 mg, yield 83%. 1 H NMR (400 MHz, CDCl3): δ 8.04 (d, J = 7.8 Hz, 1H), 7.98 (d, J = 8.0 Hz, 1H), 7.88 (ddd, J = 12.3, 6.1, 1.6 Hz, 3H), 7.57− 7.45 (m, 4H), 7.10 (t, J = 8.6 Hz, 2H). 13C{1H} NMR (100 MHz, CDCl3): δ 196.3, 165.8 (d, J = 255.4 Hz), 136.0, 134.6 (d, J = 2.9 Hz), 133.6, 133.0 (d, J = 9.4 Hz), 131.3, 130.8, 128.4, 127.4, 127.2, 126.5, 125.5, 124.3, 115.6 (d, J = 21.9 Hz). GC− MS (EI, 70 eV): m/z (%): 250 (85), 155 (78), 127 (100), 95 (60), 75 (24). 4-(1-Naphthoyl)benzonitrile (5j). 100.3 mg, yield 78%. 1 H NMR (400 MHz, CDCl3): δ 8.12 (d, J = 7.8 Hz, 1H), 8.05 (d, J = 7.7 Hz, 1H), 7.93 (d, J = 6.8 Hz, 3H), 7.75 (d, J = 7.3 Hz, 2H), 7.61−7.46 (m, 4H). 13C{1H} NMR (100 MHz, CDCl3): δ 196.2, 141.7, 134.7, 133.7, 132.4, 132.2, 130.7, 130.5, 128.7, 128.5, 127.7, 126.7, 125.3, 124.2, 117.9, 116.2. GC−MS (EI, 70 eV): m/z (%): 257 (100), 256 (50), 155 (99), 127 (70), 102 (22). (4-Chloro-2-fluorophenyl)(4-fluorophenyl)methanone (5k). 94.7 mg, yield 75%. 1 H NMR (400 MHz, CDCl3): 7.89−7.77 (m, 2H), 7.50 (t, J = 7.2 Hz, 1H), 7.30−7.24 (m, 1H), 7.20 (d, J = 9.5 Hz, 1H), 7.17− 7.11 (m, 2H). 13C{1H} NMR (100 MHz, CDCl3): δ 190.71, 166.04 (d, J = 256.0 Hz), 159.85 (d, J = 256.2 Hz), 138.61 (d, J = 10.1 Hz), 133.50, 132.37 (d, J = 10.5 Hz), 131.62 (d, J = 3.8 Hz), 125.21 (d, J = 14.7 Hz), 125.03 (d, J = 3.6 Hz), 117.11 (d, J = 25.3 Hz), 115.78 (d, J = 22.1 Hz). GC−MS (EI, 70 eV): m/z (%): 252 (46), 157 (38), 123 (100). (4-Bromo-2-fluorophenyl)(4-chlorophenyl)methanone (5l). 119.1 mg, yield 76%. 1 H NMR (400 MHz, CDCl3): δ 7.74 (d, J = 8.5 Hz, 2H), 7.45 (d, J = 7.6 Hz, 4H), 7.36 (d, J = 9.4 Hz, 1H). 13C{1H} NMR (100 MHz, CDCl3): δ 191.1, 158.4, 141.0, 140.1, 135.4, 131.8 (d, J = 3.3 Hz), 131.0, 128.9, 128.0 (d, J = 3.6 Hz), 120.1, 119.9.

GC−MS (EI, 70 eV): m/z (%): 314 (35), 312 (28), 203 (32), 201 (35), 139 (100). (2,6-Dimethylphenyl)(phenyl)methanone (5m). 71.5 mg, yield 68%. 1 H NMR (400 MHz, CDCl3): δ 7.80 (d, J = 7.9 Hz, 2H), 7.58 (t, J = 7.4 Hz, 1H), 7.44 (t, J = 7.4 Hz, 2H), 7.24 (d, J = 7.0 Hz, 1H), 7.07 (d, J = 7.6 Hz, 2H), 2.11 (s, 6H). 13C{1H} NMR (100 MHz, CDCl3): δ 200.4, 139.6, 136.9, 134.1, 133.6, 129.3, 128.8, 128.7, 127.5, 19.3. GC−MS (EI, 70 eV): m/z (%): 210 (86), 209 (100), 195 (35), 194 (28), 133 (56), 105 (72), 77 (63). Thiophen-2-yl(thiophen-3-yl)methanone (5n). 79.7 mg, yield 82%. 1 H NMR (400 MHz, CDCl3): δ 8.05 (dd, J = 2.7, 1.0 Hz, 1H), 7.76 (dd, J = 3.8, 1.1 Hz, 1H), 7.71−7.63 (m, 1H), 7.61−7.56 (m, 1H), 7.36 (dd, J = 5.0, 2.9 Hz, 1H), 7.18−7.08 (m, 1H). 13 C{1H} NMR (100 MHz, CDCl3): δ 181.1, 143.9, 141.0, 133.6, 133.5, 132.1, 128.1, 127.9, 126.3. GC−MS (EI, 70 eV): m/z (%): 194 (48), 166 (8), 111 (100), 83 (25), 45 (4). (4-Chlorophenyl)(thiophen-2-yl)methanone (5o). 90.2 mg, yield 81%. 1 H NMR (400 MHz, CDCl3): δ 7.79 (d, J = 8.6 Hz, 2H), 7.73−7.69 (m, 1H), 7.60 (dd, J = 3.7, 1.0 Hz, 1H), 7.45 (d, J = 8.6 Hz, 2H), 7.17−7.12 (m, 1H). 13C{1H} NMR (100 MHz, CDCl3): δ 186.8, 143.1, 138.6, 136.3, 134.7, 134.4, 130.5, 128.7, 128.0. GC−MS (EI, 70 eV): m/z (%): 222 (35), 187 (15), 139 (23), 111 (100), 75 (15). (4-Methoxyphenyl)(3,4,5-trimethoxyphenyl)methanone (5p). 117.9 mg, yield 78%. 1 H NMR (400 MHz, CDCl3): δ 7.80 (d, J = 8.9 Hz, 2H), 7.00 (d, J = 1.4 Hz, 2H), 6.95 (d, J = 8.4 Hz, 2H), 3.90 (d, J = 1.6 Hz, 3H), 3.87 (d, J = 1.6 Hz, 3H), 3.85 (d, J = 1.4 Hz, 6H). 13C{1H} NMR (100 MHz, CDCl3): δ 194.6, 163.0, 152.7, 141.4, 133.3, 132.3, 130.2, 113.5, 107.3, 60.9, 56.2, 55.4. (2-Hydroxy-4-methoxyphenyl)(phenyl)methanone (5q). 77.6 mg, yield 68%. 1 H NMR (400 MHz, CDCl3): δ 12.67 (s, 1H), 7.65−7.59 (m, 2H), 7.58−7.43 (m, 4H), 6.51 (d, J = 2.4 Hz, 1H), 6.39 (dd, J = 9.0, 2.5 Hz, 1H), 3.85 (s, 3H). 13C{1H} NMR (100 MHz, CDCl3): 13C NMR (101 MHz, chloroform-d) δ 200.0, 166.3, 166.1, 138.2, 135.2, 131.4, 128.8, 128.2, 113.1, 107.3, 101.0, 55.6. GC−MS (EI, 70 eV): m/z (%): 228 (64), 227 (100), 151 (68), 77 (16).

■

ASSOCIATED CONTENT

* Supporting Information S

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acsomega.8b02886. Copies of 1H, 13C NMR, and SEM spectra of the products (PDF)

■

AUTHOR INFORMATION

Corresponding Author

*E-mail: [email protected], bm.bhanage@gmail. com. ORCID

Bhalchandra M. Bhanage: 0000-0001-9538-3339 Notes

The authors declare no competing financial interest. 1571


ACS Omega

■

Article

(19) Zheng, G.; Wang, P.; Cai, M. A New Route to Biaryl Ketones via Carbonylative Suzuki Coupling Catalyzed by MCM-41-supported Bidentate Phosphine Palladium(0) Complex. Chin. J. Chem. 2009, 27, 1420−1426. (20) Tambade, P. J.; Patil, Y. P.; Panda, A. G.; Bhanage, B. M. Phosphane-Free Palladium Catalyzed Carbonylative Suzuki Coupling Reaction of Aryl and Heteroaryl Iodides. Eur. J. Org. Chem. 2009, 3022−3025. (21) Cai, M.; Zheng, G.; Zha, L.; Peng, J. Carbonylative Suzuki− Miyaura Coupling of Arylboronic Acids with Aryl Iodides Catalyzed by the MCM-41-Supported Bidentate Phosphane Palladium(II) Complex. Eur. J. Org. Chem. 2009, 1585−1591. (22) Khedkar, M. V.; Tambade, P. J.; Qureshi, Z. S.; Bhanage, B. M. Pd/C: An Efficient, Heterogeneous and Reusable Catalyst for Phosphane-Free Carbonylative Suzuki Coupling Reactions of Aryl and Heteroaryl Iodides. Eur. J. Org. Chem. 2010, 6981−6986. (23) Cai, M.; Peng, J.; Hao, W.; Ding, G. A phosphine-free carbonylative cross-coupling reaction of aryl iodides with arylboronic acids catalyzed by immobilization of palladium in MCM-41. Green Chem. 2011, 13, 190−196. (24) Li, H.; Yang, M.; Qi, Y.; Xue, J. Ligand-Free Pd-Catalyzed Carbonylative Cross-Coupling Reactions under Atmospheric Pressure of Carbon Monoxide: Synthesis of Aryl Ketones and Heteroaromatic Ketones. Eur. J. Org. Chem. 2011, 2662−2667. (25) Qureshi, Z. S.; Deshmukh, K. M.; Tambade, P. J.; Bhanage, B. M. A Simple, Efficient, and Recyclable Phosphine-Free Catalytic System for Carbonylative Suzuki Coupling Reaction of Aryl and Heteroaryl Iodides. Synthesis 2011, 2, 243−250. (26) Niu, J.-R.; Huo, X.; Zhang, F.-W.; Wang, H.-B.; Zhao, P.; Hu, W.Q.; et al. Preparation of Recoverable Pd Catalysts for Carbonylative Cross-Coupling and Hydrogenation Reactions. ChemCatChem 2013, 5, 349−354. (27) Khedkar, M. V.; Sasaki, T.; Bhanage, B. M. Efficient, recyclable and phosphine-free carbonylative Suzuki coupling reaction using immobilized palladium ion-containing ionic liquid: synthesis of aryl ketones and heteroaryl ketones. RSC Adv. 2013, 3, 7791−7797. (28) Zhou, Q.; Wie, S.; Han, W. J. In Situ Generation of Palladium Nanoparticles: Ligand-Free Palladium Catalyzed Pivalic Acid Assisted Carbonylative Suzuki Reactions at Ambient Conditions. J. Org. Chem. 2014, 79, 1454−1460. (29) Niu, J.; Liu, M.; Wang, P.; Long, Y.; Xie, M.; Li, R.; Ma, J. Stabilizing PdII on hollow magnetic mesoporous spheres: a highly active and recyclable catalyst for carbonylative cross-coupling and Suzuki coupling reactions. New J. Chem. 2014, 38, 1471−1476. (30) Jiao, N.; Li, Z.; Wang, Y.; Liu, J.; Xia, C. Palladium nanoparticles immobilized onto supported ionic liquid-like phases (SILLPs) for the carbonylative Suzuki coupling reaction. RSC Adv. 2015, 5, 26913− 26922. (31) Zawartka, W.; Pośpiech, P.; Cypryk, M.; Trzeciak, A. M. Carbonylative Suzuki−Miyaura coupling catalyzed by palladium supported on aminopropyl polymethylsiloxane microspheres under atmospheric pressure of CO. J. Mol. Catal. A: Chem. 2016, 417, 76−80. (32) Sun, X.; Zheng, Y.; Sun, L.; Lin, Q.; Su, H.; Qi, C. Immobilization of palladium (II) complexes on ethylenediamine functionalized core− shell magnetic nanoparticles: An efficient and recyclable catalyst for aerobic oxidation of alcohols and carbonylative Suzuki coupling reaction. Nano-Struct. Nano-Objects 2016, 5, 7−14. (33) Hao, C. Y.; Wang, D.; Li, Y. W.; Dong, L. L.; Jin, Y.; Zhang, X. R.; Zhu, H. Y.; Chang, S. Carbonylative coupling of aryl tosylates/triflates with arylboronic acids under CO atmosphere. RSC Adv. 2016, 6, 86502−86509. (34) Ahmed, M. S. M.; Mori, A. Carbonylative Sonogashira Coupling of Terminal Alkynes with Aqueous Ammonia. Org. Lett. 2003, 5, 3057− 3060. (35) Liang, B.; Huang, M.; You, Z.; Xiong, Z.; Lu, K.; Fathi, R.; Chen, J.; Yang, Z. Pd-Catalyzed Copper-Free Carbonylative Sonogashira Reaction of Aryl Iodides with Alkynes for the Synthesis of Alkynyl Ketones and Flavones by Using Water as a Solvent. J. Org. Chem. 2005, 70, 6097−6100.

ACKNOWLEDGMENTS P.G. acknowledges the Council of Scientific and Industrial Research (CSIR), New Delhi, Government of India, for providing a Senior Research Fellowship (SRF). The authors acknowledge the Sophisticated Analytical Instrumentation Facility (SAIF), Indian Institute of Technology (IIT) Bombay, for carrying out FEG-HR-TEM (300 kV) analysis. The authors also acknowledge the Central Surface Analytical Facility, Indian Institute of Technology (IIT) Bombay, for carrying out XPS analysis.

■

REFERENCES

(1) Budavari, S. The Merck Index, 11th ed.; Merck & Co., Inc.: New Jersey, 1989. (2) Gore, P. H. The Friedel-Crafts Acylation Reaction and its Application to Polycyclic Aromatic Hydrocarbons. Chem. Rev. 1955, 55, 229−281. (3) Davis, R. B.; Scheiber, D. H. The Preparation of Acetylenic Ketones Using Soluble Silver Acetylides. J. Am. Chem. Soc. 1956, 78, 1675−1678. (4) Logue, M. W.; Moore, G. L. Cuprous trimethylsilylacetylide. Preparation and reaction with acid chlorides. J. Org. Chem. 1975, 40, 131−132. (5) Corriu, R. J. P.; Huynh, V.; Moreau, J. J. E. Uses of Si-N bonds in organic synthesis. A direct synthesis of functional protected propargylic primary amines. Tetrahedron Lett. 1984, 25, 1887−1890. (6) Walton, D. R. M.; Waugh, F. Friedel-crafts reactions of bis(trimethylsilyl)polyynes with acyl chlorides; a useful route to terminal-alkynyl ketones. J. Organomet. Chem. 1972, 37, 45−56. (7) Logue, M. W.; Teng, K. Palladium-catalyzed reactions of acyl chlorides with (1-alkynyl)tributylstannanes. A convenient synthesis for 1-alkynyl ketones. J. Org. Chem. 1982, 47, 2549−2553. (8) Chen, L.; Li, C.-J. A Remarkably Efficient Coupling of Acid Chlorides with Alkynes in Water. Org. Lett. 2004, 6, 3151−3153. (9) Cox, R. J.; Ritson, D. J.; Dane, T. A.; Berge, J.; Charmant, J. P. H.; Kantacha, A. Room temperature palladium catalysed coupling of acyl chlorides with terminal alkynes. Chem. Commun. 2005, 1037−1039. (10) Palimkar, S. S.; Lahoti, R. J.; Srinivasan, K. V. A novel one-pot three-component synthesis of 2,4-disubstituted-3H-benzo[b][1,4]diazepines in water. Green Chem. 2007, 9, 146−152. (11) Nishihara, Y.; Inoue, E.; Okada, Y.; Takagi, K. Sila-Sonogashira Cross-Coupling Reactions of Activated Aryl Chlorides with Alkynylsilanes. Synlett 2008, 3041−3045. (12) Brunet, J.-J.; Chauvin, R. Synthesis of diarylketones through carbonylative coupling. Chem. Soc. Rev. 1995, 24, 89−95. (13) Ishiyama, T.; Kizaki, H.; Miyaura, N.; Suzuki, A. Synthesis of Unsymmetrical Biaryl Ketones via Palladium-Catalyzed Carbonylative Cross-Coupling Reaction of Arylboronic Acids with Iodoarenes. Tetrahedron Lett. 1993, 34, 7595−7598. (14) Quintero-Duque, S.; Dyballa, K. M.; Fleischer, I. Metal-catalyzed carbonylation of alkynes: key aspects and recent development. Tetrahedron Lett. 2015, 56, 2634−2650. (15) Kobayashi, T.; Tanaka, M. Carbonylation of Organic Halides in the Presence of Terminal Acetylenes; Novel Acetylenic Ketone Synthesis. J. Chem. Soc., Chem. Commun. 1981, 333−334. (16) Ishiyama, T.; Kizaki, H.; Hayashi, T.; Suzuki, A.; Miyaura, N. Synthesis of Unsymmetrical Biaryl Ketones via Palladium-Catalyzed Carbonylative Cross-Coupling Reaction of Arylboronic Acids with Iodoarenes. J. Org. Chem. 1998, 63, 4726−4731. (17) Mingji, D.; Liang, B.; Wang, C.; You, Z.; Xiang, J.; Dong, G.; Chen, J.; Yang, Z. A Novel Thiourea Ligand Applied in the PdCatalyzed Heck, Suzuki and Suzuki Carbonylative Reactions. Adv. Synth. Catal. 2004, 346, 1669−1673. (18) Zheng, S.; Xu, L.; Xia, C. Highly efficient N-Heterocyclic carbene−palladium complex-catalyzed multicomponent carbonylative Suzuki reaction: novel practical synthesis of unsymmetric aryl ketones. Appl. Organomet. Chem. 2007, 21, 772−776. 1572


ACS Omega

Article

(36) Rahman, M. T.; Fukuyama, T.; Kamata, N.; Sato, M.; Ryu, I. Low pressure Pd-catalyzed carbonylation in an ionic liquid using a multiphase microflow system. Chem. Commun. 2006, 2236−2238. (37) Liu, J.; Chen, J.; Xia, C. A simple and efficient recyclable phosphine-free catalytic system for alkoxycarbonylation and carbonylative Sonogashira coupling reactions of aryl iodides. J. Catal. 2008, 253, 50−56. (38) Liu, J.; Peng, X.; Sun, W.; Zhao, Y.; Xia, C. Magnetically Separable Pd Catalyst for Carbonylative Sonogashira Coupling Reactions for the Synthesis of α,β-Alkynyl Ketones. Org. Lett. 2008, 10, 3933−3936. (39) Awuah, E.; Capretta, A. Access to Flavones via a MicrowaveAssisted, One-Pot Sonogashira−Carbonylation−Annulation Reaction. Org. Lett. 2009, 11, 3210−3213. (40) Hao, W.; Sha, J.; Sheng, S.; Cai, M. The first heterogeneous carbonylative Sonogashira coupling reaction catalyzed by MCM-41supported bidentate phosphine palladium(0) complex. J. Mol. Catal. A: Chem. 2009, 298, 94−98. (41) Wu, X.-F.; Neumann, H.; Beller, M. A General and Convenient Palladium-Catalyzed Carbonylative Sonogashira Coupling of Aryl Bromides. Chem. − Eur. J. 2010, 16, 12104−12107. (42) Wu, X.-F.; Sundararaju, B.; Neumann, H.; Dixneuf, P. H.; Beller, M. A General Palladium-Catalyzed Carbonylative Sonogashira Coupling of Aryl Triflates. Chem. − Eur. J. 2011, 17, 106−110. (43) Wu, X.-F.; Neumann, H.; Beller, M. Convenient and General Palladium-Catalyzed Carbonylative Sonogashira Coupling of Aryl Amines. Angew. Chem., Int. Ed. 2011, 50, 11142−11146. (44) Wu, X.-F.; Neumann, H.; Beller, M. Palladium-catalyzed carbonylative coupling of benzyl chlorides with terminal alkynes to give 1,4-diaryl-3-butyn-2-ones and related furanones. Org. Biomol. Chem. 2011, 9, 8003−8005. (45) Wang, Y.; Liu, J.; Xia, C. Cross-linked polymer supported palladium catalyzed carbonylative Sonogashira coupling reaction in water. Tetrahedron Lett. 2011, 52, 1587−1591. (46) Bai, C.; Jian, S.; Yao, X.; Li, Y. Carbonylative Sonogashira coupling of terminal alkynes with aryl iodides under atmospheric pressure of CO using Pd(II)@MOF as the catalyst. Catal. Sci. Technol. 2014, 4, 3261−3267. (47) Zhao, H.; Cheng, M.; Zhang, J.; Cai, M. Recyclable and reusable PdCl2(PPh3)2/PEG-2000/H2O system for the carbonylative Sonogashira coupling reaction of aryl iodides with alkynes. Green Chem. 2014, 16, 2515−2522. (48) Hao, Y.; Jiang, J.; Wang, Y.; Jin, Z. The thermoregulated ligand− palladium catalyzed carbonylative Sonogashira coupling of aryl iodides with terminal alkynes in water. Appl. Organomet. Chem. 2015, 29, 608− 611. (49) Tan, C.; Wang, P.; Liu, H.; Zhao, X. L.; Lu, Y.; Liu, Y. Bifunctional ligands in combination with phosphines and Lewis acidic phospheniums for the carbonylative Sonogashira reaction. Chem. Commun. 2015, 51, 10871−10874. (50) Arvela, R. K.; Leadbeater, N. E.; Sangi, M. S.; Williams, V. A.; Granados, P.; Singer, R. D. A Reassessment of the Transition-Metal Free Suzuki-Type Coupling Methodology. J. Org. Chem. 2005, 70, 161−168. (51) Herrmann, W. A.; Bohm, V. P. W.; Reisinger, C.-P Application of palladacycles in Heck type reactions. J. Organomet. Chem. 1999, 576, 23−41. (52) Dupont, J.; Pfeffer, M.; Spencer, J. PalladacyclesAn Old Organometallic Family Revisited: New, Simple, and Efficient Catalyst Precursors for Homogeneous Catalysis. Eur. J. Inorg. Chem. 2001, 1917−1927. (53) Catellani, M. Catalytic Multistep Reactions via Palladacycles. Synlett 2003, 3, 0298−0313. (54) Bedford, R. B. Palladacyclic catalysts in C−C and C−heteroatom bond-forming reactions. Chem. Commun. 2003, 1787−1796. (55) Bedford, R. B.; Cazin, C. S. J.; Holder, D. The development of palladium catalysts for C-C and C-heteroatom bond forming reactions of aryl chloride substrates. Coord. Chem. Rev. 2004, 248, 2283−2321.

(56) Farina, V. High-Turnover Palladium Catalysts in Cross-Coupling and Heck Chemistry: A Critical Overview. Adv. Synth. Catal. 2004, 346, 1553−1582. (57) Beletskaya, I. P.; Cheprakov, A. V. Palladacycles in catalysis−a critical survey. J. Organomet. Chem. 2004, 689, 4055−4082. (58) Dupont, J.; Consorti, C. S.; Spencer, J. The Potential of Palladacycles: More Than Just Precatalysts. Chem. Rev. 2005, 105, 2527−2571. (59) Alacid, E.; Alonso, D. A.; Botella, L.; Nájera, C.; Pacheco, M. C. Oxime palladacycles revisited: stone-stable complexes nonetheless very active catalysts. Chem. Rec. 2006, 6, 117−132. (60) Dupont, J., Pfeffer, M., Eds.; Palladacycles: Synthesis, Characterization and Applications, 1st ed.; Wiley-VCH Verlag GmbH & Co. KGaA, 2008. (61) Dupont, J.; Flores, F. R. Palladacycles in Catalysis. In Handbook of Green Chemistry, Green Catalysis: Homogeneous Catalysis; Anastas, P. T., Crabtree, R. H., Eds.; Wiley-VCH: Weinheim, Germany, 2009; Vol. 1, pp 319−342. (62) Alonso, D. A.; Nájera, C. Oxime-derived palladacycles as source of palladium nanoparticles. Chem. Soc. Rev. 2010, 39, 2891−2902. (63) Mo, D.-L.; Zhang, T.-K.; Ge, G.-C.; Huang, X.-J.; Ding, C.-H.; Dai, L.-X.; Hou, X.-L. The Applications of Palladacycles as TransitionMetal Catalysts in Organic Synthesis. Synlett 2014, 25, 2686−2702. (64) Bruneau, A.; Roche, M.; Alami, M.; Messaoudi, S. 2Aminobiphenyl Palladacycles: The “Most Powerful” Precatalysts in C−C and C−Heteroatom Cross-Couplings. ACS Catal. 2015, 5, 1386−1396. (65) Nájera, C. Oxime-Derived Palladacycles: Applications in Catalysis. ChemCatChem 2016, 8, 1865−1881. (66) Alonso, D. A.; Nájera, C.; Pacheco, C. Oxime-Derived Palladium Complexes as Very Efficient Catalysts for the Heck−Mizoroki Reaction. Adv. Synth. Catal. 2002, 344, 172−183. (67) Grigg, R.; Zhang, L.; Collar, S.; Keep, A. Isoindolinones via a room temperature palladium nanoparticle-catalysed 3-component cyclative carbonylation−amination cascade. Tetrahedron Lett. 2003, 44, 6979−6982. (68) Fairlamb, I. J. S.; Grant, S.; McCormack, P.; Whittall, J. Alkoxyand amidocarbonylation of functionalised aryl and heteroaryl halides catalysed by a Bedford palladacycle and dppf: a comparison with the primary Pd(II) precursors (PhCN)2PdCl2 and Pd(OAc)2. Dalton Trans. 2007, 859−865. (69) Begouin, A.; Queiroz, M.-J. R. P. Palladium-Catalysed Multicomponent Aminocarbonylation of Aryl or Heteroaryl Halides with [Mo(CO)6] and Aryl- or -Heteroarylamines Using Conventional Heating. Eur. J. Org. Chem. 2009, 2820−2827. (70) Chen, G.; Leng, Y.; Yang, F.; Wang, S.; Wu, Y. PalladacycleCatalyzed Carbonylation of Aryl Iodides or Bromides with Aryl Formates. Chin. J. Chem. 2013, 31, 1488−1494. (71) Friis, S. D.; Skrydstrup, T.; Buchwald, S. L. Mild Pd-Catalyzed Aminocarbonylation of (Hetero)Aryl Bromides with a Palladacycle Precatalyst. Org. Lett. 2014, 16, 4296−4299. (72) Gautam, P.; Bhanage, B. M. Palladacycle-Catalyzed Carbonylative Suzuki−Miyaura Coupling with High Turnover Number and Turnover Frequency. J. Org. Chem. 2015, 80, 7810−7815. (73) Gautam, P.; Bhanage, B. M. Oxime Palladacycle Catalyzed Carbonylative Sonogashira Cross-Coupling with High Turnovers in PEG as a Benign and Recyclable Solvent System. ChemistrySelect 2016, 1, 5463−5470. (74) Moulton, C. J.; Shaw, B. L. Transition metal−carbon bonds. Part XLII. Complexes of nickel, palladium, platinum, rhodium and iridium with the tridentate ligand 2,6-bis[(di-t-butylphosphino)methyl]phenyl. J. Chem. Soc., Dalton Trans. 1976, 1020−1024. (75) van Koten, G.; Timmer, K.; Noltes, J. G.; Spek, A. L. A novel type of Pt−C interaction and a model for the final stage in reductive elimination processes involving C−C coupling at Pt; synthesis and molecular geometry of [1,N,N′-η-2,6-bis{(dimethylamino)methyl}toluene]iodoplatinum(II) tetrafluoroborate. J. Chem. Soc., Chem. Commun. 1978, 250−252. 1573


ACS Omega

Article

(99) Shaikh, A. G.; Sivaram, S. Organic Carbonates. Chem. Rev. 1996, 96, 951−976. (100) Alder, C. M.; Hayler, J. D.; Henderson, R. K.; Redman, A. M.; Shukla, L.; Shuster, L. E.; Sneddon, H. F. Updating and further expanding GSK’s solvent sustainability guide. Green Chem. 2016, 18, 3879−3890. (101) Okamoto, M.; Sugiyama, J.-I.; Takeuchi, K. Halogen-Free Solvent for Oxidative Carbonylation of Bisphenol A to Polycarbonate. J. Appl. Polym. Sci. 2007, 106, 2840−2842. (102) Okamoto, M.; Ishii, H.; Sugiyama, J.-I. Homogeneous Palladium Catalyst for the Oxidative Carbonylation of Bisphenol A to Polycarbonate in Propylene Carbonate. J. Appl. Polym. Sci. 2008, 109, 758−762. (103) Okamoto, M.; Sugiyama, J.-I.; Yamamoto, T. Heterogeneous Pd Catalyst for Oxidative Carbonylation of Bisphenol A to Polycarbonate. J. Appl. Polym. Sci. 2008, 110, 3902−3907. (104) Reetz, M. T.; Lohmer, G. Propylene carbonate stabilized nanostructured palladium clusters as catalysts in Heck reactions. Chem. Commun. 1996, 1921−1922. (105) Torborg, C.; Huang, J.; Schulz, T.; Schäffner, B.; Zapf, A.; Spannenberg, A.; Börner, A.; Beller, M. Improved Palladium-Catalyzed Sonogashira Coupling Reactions of Aryl Chlorides. Chem. − Eur. J. 2009, 15, 1329−1336. (106) Vasapollo, G.; Mele, G.; Maffei, A.; Sole, R. D. Palladiumcatalysed cyclocarbonylation reactions in dimethyl carbonate, an ecofriendly solvent and ring-opening reagent. Appl. Organomet. Chem. 2003, 17, 835−839. (107) Gautam, P.; Kathe, P.; Bhanage, B. M. Pd/C catalyzed phenoxycarbonylation using N-formylsaccharin as a CO surrogate in propylene carbonate, a sustainable solvent. Green Chem. 2017, 823− 830. (108) Bumagin, N. A.; Ponomaryov, A. B.; Beletskaya, I. P. Ketone synthesis via palladium-catalyzed carbonylation of organoaluminium compounds. Tetrahedron Lett. 1985, 26, 4819−4822. (109) Cushman, M.; Nagarathnam, D.; Gopal, D.; He, H.-M.; Lin, C. M.; Hamel, E. Synthesis and evaluation of analogs of (Z)-1-(4methoxyphenyl)-2-(3,4,5-trimethoxyphenyl)ethene as potential cytotoxic and antimitotic agents. J. Med. Chem. 1992, 35, 2293−2306. (110) Liou, J.-P.; Chang, C.-W.; Song, J.-S.; Yang, Y.-N.; Yeh, C.-F.; Tseng, H.-Y.; Lo, Y.-K.; Chang, Y.-L.; Chang, C.-M.; Hsieh, H.-P. Synthesis and Structure−Activity Relationship of 2-Aminobenzophenone Derivatives as Antimitotic Agents. J. Med. Chem. 2002, 45, 2556− 2562. (111) Magalhães, H. I. F.; Bezerra, D. P.; Cavalcanti, B. C.; Wilke, D. V.; Rotta, R.; de Lima, D. P.; Beatriz, A.; Alves, A. P. N. N.; Bitencourt, F. d. S.; de Figueiredo, I. S. T.; Alencar, N. M. N.; Costa-Lotufo, L. V.; Moraes, M. O.; Pessoa, C. In vitro and in vivo antitumor effects of (4methoxyphenyl)(3,4,5-trimethoxyphenyl)methanone. Cancer Chemother. Pharmacol. 2011, 68, 45−52. (112) Magalhães, H. I. F.; Cavalcanti, B. C.; Bezerra, D. P.; Wilke, D. V.; Paiva, J. C. G.; Rotta, R.; de Lima, D. P.; Beatriz, A.; Burbano, R. R.; Costa-Lotufo, L. V.; Moraes, M. O.; Pessoa, C. Assessment of genotoxic effects of (4-methoxyphenyl)(3,4,5-trimethoxyphenyl)-methanone in human lymphocytes. Toxicol. In Vitro 2011, 25, 2048−2053. (113) Magalhães, H. I. F.; Wilke, D. V.; Bezerra, D. P.; Cavalcanti, B. C.; Rotta, R.; de Lima, D. P.; Beatriz, A.; Moraes, M. O.; Diniz-Filho, J.; Pessoa, C. (4-Methoxyphenyl)(3,4,5-trimethoxyphenyl)methanone inhibits tubulin polymerization, induces G2/M arrest, and triggers apoptosis in human leukemia HL-60 cells. Toxicol. Appl. Pharmacol. 2013, 272, 117−126. (114) Widegren, J. A.; Finke, R. G. A review of the problem of distinguishing true homogeneous catalysis from soluble or other metalparticle heterogeneous catalysis under reducing conditions. J. Mol. Catal. A: Chem. 2003, 198, 317−341. (115) Stromnova, T. A.; Moiseev, I. I. Palladium(I) carbonyl complexes. Russ. J. Coord. Chem. 1998, 24, 227−241.

(76) Albrecht, M.; van Koten, G. Platinum Group Organometallics Based on “Pincer” Complexes: Sensors, Switches, and Catalysts. Angew. Chem., Int. Ed. 2001, 40, 3750−3781. (77) van der Boom, M. E.; Milstein, D. Cyclometalated PhosphineBased Pincer Complexes: Mechanistic Insight in Catalysis, Coordination, and Bond Activation. Chem. Rev. 2003, 103, 1759−1792. (78) Singleton, J. T. The uses of pincer complexes in organic synthesis. Tetrahedron 2003, 59, 1837−1857. (79) Szabó, K. J. Palladium-Pincer-Complex-Catalyzed Transformations Involving Organometallic Species. Synlett 2006, 2006, 811−824. (80) Benito-Garagorri, D.; Kirchner, K. Modularly Designed Transition Metal PNP and PCP Pincer Complexes based on Aminophosphines: Synthesis and Catalytic Applications. Acc. Chem. Res. 2008, 41, 201−213. (81) Bedford, R. B. Palladacyclic catalysts in C−C and C−heteroatom bond-forming reactions. Chem. Commun. 2003, 1787−1796. (82) Selander, N.; Szabó, K. J. Synthesis and transformation of organoboronates and stannanes by pincer-complex catalysts. Dalton Trans. 2009, 6267−6279. (83) Selander, N.; Szabó, K. J. Catalysis by Palladium Pincer Complexes. Chem. Rev. 2011, 111, 2048−2076. (84) Szabó, K. J., Wendt, O. F., Eds.; Pincer and Pincer-Type Complexes: Applications in Organic Synthesis and Catalysis; Wiley-VCH Verlag GmbH & Co. KGaA, 2014. (85) Bedford, R. B.; Draper, S. M.; Scully, P. N.; Welch, S. L. Palladium bis(phosphinite) ‘PCP’-pincer complexes and their application as catalysts in the Suzuki reaction. New J. Chem. 2000, 24, 745−747. (86) Bolliger, J. L.; Blacque, O.; Frech, C. M. Short, Facile, and HighYielding Synthesis of Extremely Efficient Pincer-Type Suzuki Catalysts Bearing Aminophosphine Substituents. Angew. Chem., Int. Ed. 2007, 46, 6514−6517. (87) Bolliger, J. L.; Frech, C. M. The 1,3-Diaminobenzene-Derived Aminophosphine Palladium Pincer Complex {C 6 H 3 [NHP(piperidinyl)2]2Pd(Cl)}−A Highly Active Suzuki−Miyaura Catalyst with Excellent Functional Group Tolerance. Adv. Synth. Catal. 2010, 352, 1075−1080. (88) Bolliger, J. L.; Frech, C. M. Highly Convenient, Clean, Fast, and Reliable Sonogashira Coupling Reactions Promoted by Aminophosphine-Based Pincer Complexes of Palladium Performed under Additive and Amine-Free Reaction Conditions. Adv. Synth. Catal. 2009, 351, 891−902. (89) Registration, Evaluation, Authorisation and restriction of CHemicals (REACH). http://www.hse.gov.uk/reach/. (90) Parker, H. L.; Sherwood, J.; Hunt, A. J.; Clark, J. H. Cyclic Carbonates as Green Alternative Solvents for the Heck Reaction. ACS Sustainable Chem. Eng. 2014, 2, 1739−1742. (91) Kerton, F. M., Marriott, R., Eds.; Alternative Solvents for Green Chemistry; Royal Society of Chemistry: London, 2013. (92) Fischmeister, C.; Doucet, H. Greener solvents for ruthenium and palladium-catalysed aromatic C−H bond functionalization. Green Chem. 2011, 13, 741−753. (93) Schäffner, B.; Schäffner, F.; Verevkin, S. P.; Börner, A. Organic Carbonates as Solvents in Synthesis and Catalysis. Chem. Rev. 2010, 110, 4554−4581. (94) Wang, J.-L.; He, L.-N.; Miao, C.-X.; Li, Y.-N. Ethylene carbonate as a unique solvent for palladium-catalyzed Wacker oxidation using oxygen as the sole oxidant. Green Chem. 2009, 11, 1317−1320. (95) Bayardon, J.; Holz, J.; Schäffner, B.; Andrushko, V.; Verevkin, S.; Preetz, A.; Börner, A. Propylene Carbonate as a Solvent for Asymmetric Hydrogenations. Angew. Chem., Int. Ed. 2007, 46, 5971−5974. (96) Reetz, M. T.; Lohmer, G. Propylene carbonate stabilized nanostructured palladium clusters as catalysts in Heck reactions. Chem. Commun. 1996, 1921−1922. (97) Sakakura, T.; Kohno, K. The synthesis of organic carbonates from carbon dioxide. Chem. Commun. 2009, 1312−1330. (98) Eghbali, N.; Li, C.-J. Conversion of carbon dioxide and olefins into cyclic carbonates in water. Green Chem. 2007, 9, 213−215. 1574


Aminophosphine Palladium Pincer-Catalyzed Carbonylative

Recommend Documents