Recent advances in the ruthenium-catalyzed hydroarylation of alkynes with aromatics: synthesis of trisubstituted alkenes

Abstract

The hydroarylation of alkynes with substituted aromatics in the presence of a metal catalyst via chelation-assisted C–H bond activation is a powerful method to synthesize trisubstituted alkenes. Chelation-assisted C–H bond activation can be done by two ways: (a) an oxidative addition pathway and (b) a deprotonation pathway. Generally, a mixture of cis and trans stereoisomeric as well as regioisomeric trisubstituted alkenes was observed in an oxidative addition pathway. In the deprotonation pathway, the hydroarylation reaction can be done in a highly regio- and stereoselective manner, and enables preparation of the expected trisubstituted alkenes in a highly selective manner. Generally, ruthenium, rhodium and cobalt complexes are used as catalysts in the reaction. In this review, a ruthenium-catalyzed hydroarylation of alkynes with substituted aromatics is covered completely. The hydroarylation reaction of alkynes with amide, azole, carbamate, phosphine oxide, amine, acetyl, sulfoxide and sulphur directed aromatics is discussed.

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Rajendran Manikandan

Rajendran Manikandan was born in Odaipatti, Tamilnadu, India, in 1986. He received his bachelor degree from Gandhigram Rural University in 2010. He received his master degree from Madurai Kamaraj University in 2012. He is currently pursuing his PhD under the guidance of Dr M. Jeganmohan at IISER Pune, India. His PhD research focuses on the C–H bond functionalization of organic molecules via metal-catalyzed C–H bond activation.

Masilamani Jeganmohan

Masilamani Jeganmohan was born in Vazhapattampalayam, Tamilnadu, India in 1978. He received his master degree in organic chemistry from University of Madras in 2001. He earned his Ph.D. from the National Tsing Hua University, Taiwan under the guidance of Prof. Chien-Hong Cheng in 2005 and pursued postdoctoral work in the same laboratory (2005–2009). Then, he moved to the Ludwig-Maximilians-Universität, Munich, Germany, for a postdoctoral study with Prof. Paul Knochel supported by Alexander von Humboldt foundation (2009 to 2010). At present, he is working as an assistant professor in Indian Institute of Science Education and Research, Pune (2010–till now). He was the recipient of the DAE Young Scientist Research Award (2011), the Science Academy Medal for a young associate, Indian Academy of Sciences (2012–2015), the Science Academy Medal for Young Scientists, Indian National Science Academy (2013), Alkyl Amines – the ICT Young Scientist Award by the Institute of Chemical Technology Mumbai (2013) and the ISCB Award of Appreciation for Chemical Science, CSIR-CDRI (2014), India. His research interest includes the development of new synthetic methods using metal complexes as catalysts, asymmetric synthesis and natural product synthesis.

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Introduction

The alkene subunits are present in various natural products, drug molecules and materials. In addition, alkenes are versatile synthetic intermediates which are widely used for various organic transformations.¹ The transition metal-catalyzed coupling of aromatic electrophiles or organometallic reagents with carbon–carbon π-components is a powerful route to synthesize alkene derivatives in a highly regio- and stereoselective manner.^2,3

Alkenes and alkynes are widely used as carbon–carbon π-components in the coupling reaction. Usually, alkenes reacted with aromatic electrophiles or organometallic reagents in the presence of a metal catalyst, providing disubstituted alkenes (Fig. 1)² and alkynes that reacted with aromatic electrophiles or organometallic reagents, affording trisubstituted alkenes (Fig. 1).³ Various metal complexes such as palladium, nickel, cobalt, rhodium, iron, etc. are widely used as catalysts in this type of alkenylation reaction. Aromatic iodides, aromatic bromides and aromatic triflates are frequently used as electrophiles in the reaction. Similarly, aromatic organometallic reagents such as borane, silane, stannane and magnesium are used as a transmetallating agent. Although this type of coupling reaction is very powerful to synthesize substituted alkenes, a preactivated coupling partner such as a C–X or C–Y is usually required on the aromatic moiety. A preactivated species such as X or Y is wasted at end of the reaction. If a similar type of reaction is carried out directly by the C–H bond of the aromatic moiety instead of a C–X or C–M, it would be more useful in organic synthesis. Because, this method would be highly atom- and step economical as well as an environmentally friendly process.

Fig. 1 Synthesis of alkenes by cross-coupling reaction.

Alternatively, alkene derivatives can also be prepared by a metal-catalyzed chelation-assisted alkenylation at the C–H bond of substituted aromatics with carbon–carbon π-components via C–H bond activation without having any preactivated species on the aromatic moiety (Fig. 2).⁴ There are several ways to activate the C–H bond of aromatics in the presence of metal catalysts.⁵ However, carrying out the C–H bond activation in a controlled and regioselective manner is a challenging task. This type of regioselective C–H bond activation can be done by a chelation-assisted metallation pathway (Fig. 3). Usually, a heteroatom such as a nitrogen or an oxygen containing directing group is needed on the aromatic moiety to activate the C–H bond in a highly regioselective manner. The heteroatom of the directing group coordinates with a metal centre via either σ or π bond and allows bringing the ortho C–H bond of aromatics in close proximity to the active metal centre. During this time, the C–H bond activation takes place very selectively at the ortho position providing a five membered metallacycle intermediate. There are two pathways, such as oxidative addition and deprotonation, possible to activate the C–H bond of an organic moiety (Fig. 3). In the oxidative addition pathway, a five membered hydrometallacycle intermediate I is formed and in the deprotonation pathway, a five membered metallacycle intermediate without having a hydride species II is formed. It is important to note that in the deprotonation pathway; usually a carbonate or acetate base is required to deprotonate the C–H bond of organic moiety. In the oxidative addition pathway, a metal species undergoes an oxidative addition with a C–H bond of aromatic moiety and providing a hydrometallacycle intermediate I. Generally, M(0) or M(I) active catalysts favour oxidative addition pathway and M(II)(OR)₂ or M(III)(OR)₂ catalysts favours deprotonation pathway. In this context, metal-catalyzed chelation-assisted ortho alkenylation of substituted aromatics with alkenes is well explored in the literature.⁴ An ortho alkenylation of substituted aromatics with alkynes has gained much attention quite recently.

Fig. 2 Synthesis of alkenes by C–H bond activation.

Fig. 3 Metal-catalyzed chelation-assisted C–H bond activation.

In 1993, Murai's group reported a ruthenium-catalyzed chelation-assisted ortho alkylation of aromatic ketones with alkenes via C–H bond activation. In the reaction, aromatic ketones reacted with alkenes in the presence of RuH₂(CO)(PPh₃)₃, giving ortho alkylated aromatic ketones in a highly regioselective manner.^6a The C–H bond activation reaction proceeds via an oxidative addition pathway. Later, the same group demonstrated an ortho alkenylation of aromatic ketones with alkynes, leading to trisubstituted alkenes in the presence of a ruthenium catalyst (Fig. 4).^6b The hydroarylation reaction proceeds via a chelation-assisted oxidative addition of the ortho C–H bond of the aromatic ketone with a ruthenium catalyst providing a five-membered hydrometallacycle intermediate III. Later, an alkyne undergoes coordinative insertion into a metal–hydride bond of intermediate III followed by reductive elimination, providing a trisubstituted alkene derivative and regenerates an active Ru(0) catalyst for the next catalytic cycle. However, this type of hydroarylation reaction is not completely regio- and stereoselective. Mostly, a mixture of regio- and stereoisomeric trisubstituted alkenes was observed. For example, the aromatic ketone reacted with the symmetrical alkyne, diphenylacetylene, in the presence of a ruthenium catalyst, yielding a mixture of cis and trans stereoisomeric trisubstituted alkenes. Later, Murai's group has reported the hydroarylation of alkynes with various directing groups such as ester, nitrile and aldehyde substituted aromatics in the presence of a ruthenium catalyst.⁶ Later, a similar type of hydroarylation of alkynes with heteroatom substituted aromatics has been well explored by using various metal complexes such as rhodium, iridium, palladium, nickel, cobalt and manganese complexes as catalysts. Although it is one of the best methods to synthesize trisubstituted alkenes in one pot, the observation of a mixture of cis and trans stereoisomeric and regioisomeric products limits the synthetic application in organic synthesis.

Fig. 4 Metal-catalyzed chelation-assisted hydroarylation reaction.

The recent observation has clearly revealed that this type of regio- and stereoisomeric issues can be easily overcome by carrying out the hydroarylation reaction via a concerted deprotonation metallation pathway.⁷ In the reaction, substituted aromatics reacted with alkynes in the presence of a ruthenium catalyst, providing trisubstituted alkene derivatives in a highly regio- and stereoselective manner. Notably, the metal oxidant is not needed for the hydroarylation reaction unlike the ortho-alkenylation of aromatics with alkenes in the presence of metal catalysts. The catalytic reaction proceeds via a chelation-assisted acetate accelerated deprotonation at the ortho C–H bond of the hetero atom substituted aromatic with a metal complex (Rh or Ru), providing a metallacycle intermediate IV. Coordinative insertion of an alkyne into the metal–carbon bond of metallacycle followed by protonation in the presence of organic acid provides trisubstituted alkene derivative in a highly regio- and stereoselective manner (Fig. 4). The regiochemistry of the product of this reaction is completely reversed when compared with the regiochemistry of the product observed via an oxidative addition pathway. In the oxidative addition pathway, alkynes preferred to insert into a Ru–H bond of intermediate III compared with a Ru–C bond. In the deprotonation pathway, alkynes preferred to insert into a Ru–C bond of metallacycle intermediate IV.

Ruthenium, rhodium and cobalt complexes are widely used as a catalyst in the reaction. In 2010, Fagnou et al. reported a rhodium-catalyzed amide group assisted hydroarylation of alkynes with substituted indoles (Fig. 5).⁸ The hydroarylation reaction proceeds via a deprotonation metallation pathway. The reaction pathway was supported by a deuterium labelling experiment. In this review, we would like to focus on a ruthenium-catalyzed direct C–H bond hydroarylation of substituted aromatics with alkynes via a chelation-assisted deprotonation metallation pathway.

Fig. 5 Rhodium–catalyzed hydroarylation of alkynes with substituted indoles.

Ruthenium-catalyzed hydroarylation of alkynes with benzamides

In 2012, Miura's group reported a highly regio- and stereoselective hydroarylation of alkynes with substituted benzamides, providing trisubstituted alkenes in a highly regio- and stereoselective manner.^9a,b When N,N-dimethylbenzamide (1a) was treated with symmetrical diphenylacetylene (2a) in the presence of [{RuCl₂(p-cymene)}₂] (5.0 mol%), AgSbF₆ (20 mol%) and acetic acid (4.0 equiv.) in 1,4-dioxane at 100 °C for 5 h, a trisubstituted alkene 3a was observed in 82% yield (Scheme 1). It is important to note that the product 3a was obtained only in 43% yield without acetic acid under similar reaction conditions. In the meantime, no hydroarylation product 3a was observed in the presence of an acetate base, KOAc, instead of acetic acid. In the reaction, acetic acid acts as a proton donor as well as a base to activate the C–H bond of benzamide.

Scheme 1 Ruthenium-catalyzed hydroarylation of alkynes with N,N-dialkyl benzamides.

The hydroarylation reaction was compatible with various substituted alkynes. Particularly, unsymmetrical alkynes such as 1-phenyl-1-propyne (2b) and 1-phenyl-1-butyne (2c) regioselectively reacted with benzamide (1a), yielding trisubstituted alkenes 3b and 3c in 77% and 68% yields, respectively, in a highly regio- and stereoselective manner. In the reaction, alkyl groups such as Me and n-Bu substituted carbon of alkynes connected at the ortho carbon of 1a. Similarly, 1-phenyl-2-(trimethylsilyl)acetylene (2d) provided disubstituted alkene 3d in 63% yield along with trisubstituted alkene 3d′ in 17% yield, respectively. During the reaction, a silyl group was cleaved in product 3d. Apart from an internal alkyne, the reaction was also examined with a terminal alkyne, tris(isopropyl)-silylacetylene (2e). However, only 19% of disubstituted alkene 3e was observed. Under similar reaction conditions, substituted benzamides and cyclic benzamides also nicely participated in the reaction with diphenylacetylene (2a), yielding ortho alkenylated products 3f–h in good yields.

The alkenylation reaction was also compatible with substituted phenyl azoles (Scheme 2). Treatment of 1-phenylpyrazole (4a) with diphenylacetylene (2a) under similar reaction conditions gave bis alkenylated pyrazole derivative 5a in 85% yield. Similarly, substituted 1-phenylpyrazole 4 reacted with various symmetrical alkynes 2, providing the corresponding bis alkenylated pyrazole derivatives 5 in good yields. The alkenylation reaction was also examined with 2-phenylimidazoles. 2-Phenylimidazole (6a) underwent hydroarylation with 2a, yielding the corresponding mono alkenylated phenylimidazole derivative 7a in 79% yield. But, N-methyl-2-phenylimidazole (6b) provided mono alkenylated phenylimidazole 7b only in 65% yield. This is most likely due to the intramolecular steric hindrance of the N-Me group into an alkene moiety of compound 7b.

Scheme 2 Ruthenium-catalyzed hydroarylation of alkynes with substituted 1-phenylpyrazoles or 2-phenylimidazoles.

A possible reaction mechanism was proposed to account for the hydroarylation of alkynes with benzamides (Scheme 3). ortho-Metallation of benzamide 1 with a ruthenium species provided a five-membered metallacycle intermediate 8 with a loss of H⁺ source. Coordinative insertion of an alkyne 2a into the Ru–C bond of intermediate 8 followed by protonation with AcOH provides trisubstituted alkene 3 and regenerates an active ruthenium catalyst for the next catalytic cycle.

Scheme 3 Proposed mechanism for the hydroarylation of alkynes with N,N-dialkyl benzamides.

It is believed that the C–H bond activation proceeds via a deprotonation metallation pathway (Scheme 4). To confirm the deprotonation pathway, deuterated benzamide 1a′ was taken and treated with alkyne 2a under similar reaction conditions. If the C–H bond activation proceeds via an oxidative addition pathway, ortho deuterium of benzamide 1a′ should be transferred into one of the alkene carbons of the expected product. Whereas, if the C–H bond activation reaction proceeds via a deprotonation pathway, deuterium incorporation should not take place and could afford AcOD as a side product. In the product, deuterium incorporation was not observed at the alkene carbon of product 3a′-d4. Thus, the C–H bond activation proceeds via a deprotonation metallation pathway. Later, an intermolecular competitive reaction of deuterated benzamide 1a′ with a simple benzamide 1a was conducted. A considerable primary isotope effect of 1 : 2 ratios of products 3a′-d4 and 3a was observed. This result suggested that the ortho C–H(D) bond cleavage is the rate-determining step as well as that the cleavage proceeds via a deprotonation metallation pathway.

Scheme 4 Competitive reaction of benzamide with deuterated benzamide.

In the same year, Li's group reported a ruthenium-catalyzed hydroarylation of alkynes with isoquinolone derivatives in the presence of acetic acid (Scheme 5).¹⁰ Treatment of N-methyl isoquinolone (10a) with diphenylacetylene (2a) in the presence of [{RuCl₂(p-cymene)}₂] (5 mol%), AgSbF₆ (20 mol%) and acetic acid (4.0 equiv.) in 1,4-dioxane at 100 °C for 18 h gave the expected alkenylated isoquinolone derivative 11a in 96% yield. The same reaction was also examined with other catalysts such as [RhCp*Cl₂]₂ and [IrCp*Cl₂]₂ under similar reaction conditions. In the iridium-catalyzed reaction, product 11a was observed in 86% yield and in the rhodium-catalyzed reaction, product 11a was observed only in 45% yield. This result clearly reveals that a ruthenium catalyst is suitable for the reaction. The hydroarylation reaction was also examined with N–H free isoquinolone (10b). However, in the reaction, the expected product 11b was observed only in 43% yield.

Scheme 5 The hydroarylation of alkynes with isoquinolone derivatives.

The hydroarylation reaction was examined with various symmetrical and unsymmetrical alkynes 2. In all cases, the hydroarylation reaction worked very well and gave the corresponding hydroarylation products in good yields. Particularly, 1-phenyl-1-propyne (2b) reacted with 10a providing the expected alkenylated product 11c in 83% yield in a highly regio- and stereoselective manner. In the reaction, an Me attached carbon of alkyne 2b connected at the C-8 position of isoquinolone derivative. Interestingly, in the reaction of 1-phenyl-1-silylacetylene with 10a, the expected hydroarylation product 11e was observed in 85% yield without silyl cleavage. However, in the previous Miura's reaction, the silyl group was cleaved (Scheme 1, product 3d).

In the reported hydroarylation of alkynes with benzamides, only N,N-disubstituted benzamides were examined. In 2011, Ackermann's group reported an oxidative cyclization of N-methyl benzamides with alkynes, providing substituted isoquinolone derivatives (Scheme 6).¹¹ In the reaction of N-methyl benzamide (12) with diphenylacetylene (2a), in the presence of a ruthenium catalyst and Cu(OAc)₂·H₂O in ether solvent, a minor amount of ortho alkenylated benzamide 13 was observed in 15% yield along with isoquinolone derivative 14 in 27% yield, respectively. This result clearly reveals that the N-methyl benzamides prefer cyclization reaction with alkynes rather than the hydroarylation reaction.

Scheme 6 The hydroarylation of diphenylacetylene with N-methyl benzamide.

Ruthenium-catalyzed hydroarylation of alkynes with aromatic carbamates

In 2012, we have reported a highly regio- and stereoselective weakly directing carbamate group assisted hydroarylation of alkynes with aryl carbamates in the presence of a ruthenium catalyst and pivalic acid.^12a When 4-methoxyphenyl diethylcarbamate (15a) was treated with ethyl but-2-ynoate (2e) in the presence of [{RuCl₂(p-cymene)}₂] (5.0 mol%), AgSbF₆ (20 mol%) and pivalic acid (5.0 equiv.) in 1,4-dioxane at 100 °C for 24 h, a trisubstituted alkene derivative 16a was observed in 77% yield (Scheme 7). The hydroarylation reaction was highly regio- and stereoselective; the ortho C–H bond of 15a was selectively inserted at the methyl group substituted carbon of alkyne 2e and only the E-stereoselective alkene derivative 16a was observed.

Scheme 7 The hydroarylation of alkynes with aromatic carbamates.

The scope of the hydroarylation reaction was examined with various sensitive functional groups such as I, Br, Cl, F and OMe substituted aromatic carbamates. In all reactions, the expected hydroarylation product was observed in good to moderate yields. The hydroarylation reaction was further examined with various unsymmetrical aromatic carbamates. For example, 3-methoxyphenyl diethylcarbamate (15b) reacted with ethyl but-2-ynoate (2e) at a less hindered C6–H under similar reaction conditions, yielding trisubstituted alkene derivative 16b in 79% yield. Sesamol carbamate 15c reacted with 2b at the sterically hindered C–H bond, providing 16c in 86% yield in a highly regioselective manner.

The hydroarylation reaction was also examined with unsymmetrical alkynes such as hex-2-ynoate, methyl oct-2-ynoate, 1-phenyl-1-propyne, 1-phenyl-1-butyne and 1-phenyl-1-hexyne. In all reactions, the alkyl group substituted carbon of the alkyne connected at the ortho carbon of aromatic carbamates. But, methyl 3-phenylpropiolate (2f) reacted with 15c providing a mixture of regioisomeric products 16d and 16d′ in 89% combined yield in approximately a 1 : 1 ratio. Later, the ester group of trisubstituted alkene 16f was converted into the carboxylic acid derivative 17a in the presence of LiOH (2.0 equiv.) (Scheme 8). Whereas, 10.0 equiv. of LiOH cleaved both ester and carbamate moieties of compound 16g, giving phenol derivative 17b in 87% yield.

Scheme 8 Synthesis of phenol derivatives.

The hydroarylation reaction proceeds via a chelation-assisted deprotonation at the ortho C–H bond of aromatic carbamate with a ruthenium acetate species giving ruthenacycle intermediate 18 (Scheme 9). Coordinative insertion of an aromatic or ester group substituted alkyne into the metal–carbon bond of metallacycle 18 affords metallacycle intermediate 19 followed by protonation with RCOOH yielding an alkene derivative 16 in a highly regio- and stereoselective manner. The substituent on the alkyne moiety only decides the regiochemistry of the product. Coordinating groups such as Ph or ester group of alkynes 2 always prefer to stay near to the ruthenium metal in order to stabilize the ruthenacycle intermediate 19. In the alkyne, if two coordinating groups are there, both prefer to stay near to the ruthenium metal and thus a mixture of regioisomeric products was observed.

Scheme 9 Proposed reaction mechanism of aromatic carbamates with alkynes.

It is believed that the C–H bond activation proceeds via an acetate assisted deprotonation pathway instead of an oxidative addition pathway. The coupling reaction of sesamol carbamate 15c with ethyl but-2-ynoate (2e) in the presence of [{RuCl₂(p-cymene)}₂] (5 mol%), AgSbF₆ (20 mol%) and CD₃COOD (5.0 equiv.) in 1,4-dioxane at 100 °C for 16 h was examined (Scheme 9). In the reaction, instead of pivalic acid, CD₃COOD (5.0 equiv.) was used. In the coupling product 16h, 75% of deuterium incorporation was observed in an alkene C–H bond. This deuterium study clearly revealed that the present reaction proceeds via the deprotonation pathway.

In 2013, Wang's group reported ruthenium- and rhodium-catalyzed hydroarylation of alkynes with aromatic carbamates. In the reaction, 1-naphthyl carbamate (15d) reacted with diphenylacetylene (2a) in the presence of a ruthenium catalyst yielding the corresponding alkene derivative 16h in 50% yield (Scheme 10).^12b

Scheme 10 Ruthenium-catalyzed hydroarylation of alkynes with 1-naphthyl carbamate.

Ruthenium-catalyzed hydroarylation of alkynes with 2-aminobiphenyls and cumylamine

In 2013, Miura's group reported a ruthenium-catalyzed hydroarylation of alkynes with 2-aminobiphenyls or cumylamine.¹³ It is important to note that in the reaction a free NH₂ group acts as a directing group without any protection. Initially, the hydroarylation of diphenylacetylene (2a) with (1.0 equiv.) 2-aminobiphenyl (20a) (1.0 equiv.) in the presence of [{RuCl₂(p-cymene)}₂] (5 mol%), AgSbF₆ (20 mol%) and CH₃COOH (4.0 equiv.) in 1,4-dioxane at 100 °C for 3 h was tested (Scheme 11). However, in the reaction, hydroarylation product 21a was observed only in 52% GC yield. When the amount of diphenylacetylene (2a) was increased to 2.0 equiv., the expected hydroarylation product 21a was increased up to 70% GC yield. Further, the yield of hydroarylation product was increased up to 85% GC yield and 61% isolated yield at 80 °C in the presence of [{RuCl₂(benzene)}₂]. In the reaction, the [{RuCl₂(benzene)}₂] catalyst gave better yield compared with the [{RuCl₂(p-cymene)}₂] catalyst.

Scheme 11 The hydroarylation of alkynes with 2-aminobiphenyls and cumylamine.

Later, the hydroarylation reaction was further examined with Me, OMe, Cl and CF₃ substituted 2-aminobiphenyls 20b–e. In all these reactions, the expected hydroarylation products 21b–e were observed in 74–82% yields. Particularly, in the reaction of CF₃ substituted 2-aminobiphenyl 20e, alkenylation takes place at a less hindered C–H bond. Later, the reaction was examined with symmetrical and unsymmetrical alkynes. In the reaction of biphenyl aniline (20a) with 1-phenyl-1-propyne (2b), a mixture of stereoisomeric products 21e and 21e′ was observed in 51% combined yield in 61 : 39 ratios. The hydroarylation reaction also further examined with cumylamine (22). When cumylamine (22) was treated with diphenylacetylene (2a) under similar reaction conditions, the hydroarylation product 23a was observed in 67% yield.

To show that the C–H activation proceeds via a deprotonation metallation pathway and the corresponding metallation is a rate determining and reversible step, the reaction of deuterated 2-aminobiphenyl 20a-d₅ with 2a under similar reaction conditions for 30 min was carried out (Scheme 12). In the reaction, alkenylated product 21a-d_n was observed in 9% yield without any deuterium incorporation at the alkene C–H bond. This observation clearly indicates that the C–H bond activation proceeds via a deprotonation pathway.

Scheme 12 The hydroarylation of diphenylacetylene with deuterated 2-aminobiphenyl.

Ruthenium-catalyzed hydroarylation of alkynes with phenylphosphine oxides

In the same year, Miura's group demonstrated the hydroarylation of alkynes with phenylphosphine oxides in the presence of a ruthenium catalyst.¹⁴ Treatment of triphenylphosphine oxide (25a) (2.0 equiv.) with diphenylacetylene (2a) (1.0 equiv.) in the presence of [{RuCl₂(p-cymene)}₂] (5 mol%), AgSbF₆ (20 mol%) and 1-Ad-COOH (1.0 equiv.) in 1,4-dioxane at 100 °C for 5 h gave ortho alkenylated triphenylphosphine oxide 26a in 74% yield (Scheme 13). It is important to note that the phosphine oxide was surrounded by three phenyl groups and several reactive sites are around. Thus, apart from 26a, other ortho alkenylated products were also observed. Interestingly, the expected product 26a in 82% yield was observed exclusively without any other ortho alkenylated products in the presence of an excess amount of triphenylphosphine oxide (5.0 equiv.). Pivalic acid, 2,6-dimethylbenzoic acid and AcOH were also equally effective for the reaction. Further, the hydroarylation reaction was examined with Me, OMe, F, Cl and CF₃ substituted triphenyl phosphine oxides 25. In these substrates, the expected hydroarylation products were observed in good yields 26. Particularly, meta methyl substituted triphenyl phosphine oxide 25c, the C–H bond activation takes place at the less hindered side (product 26c). The hydroarylation reaction was also compatible with alkyl(diphenyl) and dialkyl(phenyl)phosphine oxides 25d–e (see, products 26d–e). The hydroarylation reaction also worked very well with various symmetrical alkynes 2. Unsymmetrical alkyne 2h reacted efficiently with 25a under similar reaction conditions providing the expected hydroarylation product 26f in 58% yield in a highly regio- and stereoselective manner. Later, ortho alkenylated triphenylphosphine oxide 26g was converted into ortho alkenylated triphenylphosphine 27a in 66% yield in the presence of (4-NO₂C₆H₄O)₂P(O)OH and (EtO)₂MeSiH.

Scheme 13 The hydroarylation of alkynes with phenylphosphine oxides.

Ruthenium-catalyzed hydroarylation of alkynes with anilides

In 2014, we have reported a ruthenium-catalyzed hydroarylation of alkynes with acetanilides.¹⁵ The catalytic reaction provides ortho-alkenylated anilides in good to excellent yields in a highly regio- and stereoselective manner. The reaction of 4-hydroxy anilide (28a) with 1-phenyl-1-propyne (2b) in the presence of [{RuCl₂(p-cymene)}₂] (5.0 mol%), AgSbF₆ (20 mol%) and pivalic acid (5.0 equiv.) in iso-PrOH at 100 °C for 12 h gave ortho alkenylated anilide (29a) in 78% yield (Scheme 14). The hydroarylation reaction is highly stereoselective, the ortho C–H bond of 28a coupled with the methyl substituted carbon of alkyne 2b. It was observed that the acetanilides underwent oxidative cyclization with alkynes in the presence of rhodium or ruthenium catalysts and acetate base providing indole derivatives (Fig. 6). But, in the presence of an organic acid, RCOOH, source instead of a base, ortho-alkenylated anilides were observed. It is noteworthy that the organic acid favours hydroarylation reaction and base favours oxidative cyclization reaction.

Scheme 14 The hydroarylation of 1-phenyl-1-propyne with anilides.

Fig. 6 Oxidative cyclization of anilides with alkynes.

The hydroarylation reaction was compatible with various functional groups such as OH, OMe, F, Cl, Br, I, CN and ester substituted anilides (Scheme 14). Treatment of ester substituted anilide 28f with 2b gave trisubstituted alkene 29f in 71% yield. In the substrate 28f, directing groups such as NHCOMe and ester were present. However, alkenylation takes place chemoselectively at the ortho carbon to NHCOMe of 28f. The hydroarylation reaction was also examined with unsymmetrical acetanilides 28g–h. 2-Naphthyl acetamide 28g reacted with 2a, providing trisubstituted alkene derivative 29g in excellent 82% yield, in which C–H bond activation takes place at the C3–H of 28g. In contrast, 3,4-(methylenedioxy)anilide (28h) reacted with 2a, yielding product 29h in 81% yield in which hydroarylation takes place at a sterically hindered C–H bond of 28h.

The scope of the hydroarylation reaction was further examined with various unsymmetrical alkynes such as 1-phenyl-1-butyne, 1-phenyl-1-hexyne, 1-phenyl-2-(trimethylsilyl) acetylene, ethyl 2-butynoate, methyl hex-2-ynoate and methyl oct-2-ynoate (Scheme 15). In these reactions, the expected hydroarylation product was observed in good to excellent yields. In all these alkynes, alkyl substituted carbon of alkynes was regioselectively connected at the ortho carbon of acetanilide. Methyl phenyl propiolate (2g) having two coordinating groups such as Ph and ester on the alkyne provided a mixture of hydroarylation products 29l and 29l′ in 81% combined yields in a 60 : 40 ratio. Interestingly, 2-thienyl substituted alkyne 2h provided hydroarylation products 29m and 29m′ in 75% combined yields in a 3 : 1 ratio. Surprisingly, alkyne 2i having Ph and CH₂Ph provided a single coupling product 29n in 62% yield. To know the coordinating ability of Ph and ester groups, anilide 28i was treated with 2b (1.0 equiv.) and 2f (1.0 equiv.) under similar reaction conditions. In the reaction, alkyne 2b coupling product 29a was observed in a major 59% yield and alkyne 2f coupling product 29i in a lesser 32% yield, respectively. This result clearly reveals that the Ph coordinates with a Ru metal is better than ester coordinates.

Scheme 15 The hydroarylation of unsymmetrical alkynes with anilides.

Later, ortho-alkenylated acetanilides 29a and 29d were efficiently converted into ortho-alkenylated anilines 30a and 30b in 93% and 91% yields, respectively, in the presence of a 1 : 1 mixture of 17% HCl and THF at 100 °C for 17 h (Scheme 16).

Scheme 16 Synthesis of ortho alkenylated aniline derivatives.

Further, the hydroarylation reaction was tested with a weak ester directing group substituted aromatic moiety. Treatment of methyl piperonate (31) with diphenylacetylene (2a) under similar reaction conditions provided the hydroarylation product 32 in 71% yield in a highly regioselective manner (Scheme 17).

Scheme 17 The hydroarylation of diphenylacetylene with methyl piperonate.

A possible reaction mechanism was proposed to account for the hydroarylation of alkynes with anilides (Scheme 18). AgSbF₆ likely removes the Cl⁻ ligand from the [{RuCl₂(p-cymene)}₂] complex, providing ruthenium species 33. Coordination of the carbonyl group of anilide 31 to a ruthenium species 33 followed by ortho-metallation provides a six-membered ruthenacycle intermediate 34. Coordinative regioselective insertion of alkyne 2 into the Ru–carbon bond of intermediate 34 provides intermediate 35. Protonation at the Ru–C bond of intermediate 35 in the presence of RCOOH affords the hydroarylation product 29 and regenerates the active ruthenium species 33 for the next catalytic cycle. To support the role of organic acid, 28i was treated with 2b in the presence of CD₃COOD instead of pivalic acid under similar reaction conditions. In the reaction, product d-29i was observed in 40% yield with 76% of deuterium incorporation at the alkene carbon. Meanwhile, 67% deuterium incorporation was observed at the ortho carbon of anilide in product d-29i. This result clearly shows that the ortho C–H bond cleavage of anilide 28 and intermediate 34 formation is a reversible process.

Scheme 18 Proposed reaction mechanism of anilides with unsymmetrical alkynes.

In the hydroarylation of substituted propiolates with anilides, ortho alkenylated anilides 29 was observed in good to excellent yields. This hydroarylation reaction was carried out at 100 °C. If the same hydroarylation reaction was carried out at 130 °C, 2-quinolinone derivative 36 was observed along with the hydroarylation product 29. In the reaction, only 5.0 equiv. of pivalic acid was used. Interestingly, only 2-quinolinone derivatives were observed in the presence of 10.0 equiv. of pivalic acid. The cyclization of 3,4-dimethoxy acetanilide (28i) with ethyl-2-butynoate (2e) in the presence of [{RuCl₂(p-cymene)}₂] (5.0 mol%), AgSbF₆ (20 mol%) and pivalic acid (10.0 equiv.) in iso-PrOH at 130 °C for 24 h provided 4-methyl substituted-2-quinolinone 36 in 86% isolated yield (Scheme 19).¹⁶

Scheme 19 Cyclization of substituted anilides with propiolates.

In the reaction, initially ortho alkenylated anilide 29 was formed as described in the mechanism in Scheme 18. Under the reaction conditions, ortho alkenylated anilide 29 was converted into 2-quinolinone derivative 36. To confirm that the ortho alkenylated anilide is a key intermediate, product 29i was prepared separately and treated with pivalic acid in iso-PrOH solvent at 130 °C for 24 h without a ruthenium catalyst (Scheme 19). As expected, 2-quinolinone derivative 36 was observed in 75% yield. This result clearly reveals that the carboxylic acid or solvent iso-PrOH accelerates trans–cis isomerization of the double bond of compound 28ivia Michael addition. Intramolecular nucleophilic addition of NHCOMe to the ester moiety followed by a loss of the acetyl group leads to 2-quinolinone 36. In the reaction, organic acid plays multiple roles such as acting as a proton source, the corresponding acetate anion deprotonates the C–H bond, accelerating cis–trans isomerization and deacylation of anilide to aniline.

Ruthenium-catalyzed hydroarylation of alkynes with aromatic sulfoxides

Recently, we have reported a regio- and stereoselective hydroarylation of alkynes with aromatic sulfoxides in the presence of a less expensive ruthenium catalyst.¹⁷ In the reaction, terminal metal oxidant was not used and only Ru(II) species was involved in the complete catalytic cycle without changing the metal oxidation state. It is important to note that, Miura's group reported the hydroarylation of alkynes with aromatic sulfoxides in the presence of a highly expensive rhodium complex (Scheme 20). However, Cu(OAc)₂ was used as a terminal metal oxidant to regenerate the active rhodium catalyst. Treatment of methyl phenyl sulfoxide (37a) with 1-phenyl-1-propyne (2b) in the presence of [{RuCl₂(p-cymene)}₂] (5 mol%), AgSbF₆ (20 mol%) and pivalic acid (5.0 equiv.) in 1,4-dioxane at 100 °C for 24 h gave the expected hydroarylation product 38a in 75% yield. The hydroarylation reaction was highly regioselective and the methyl group substituted carbon of alkyne 2b was connected at the ortho C–H bond of 37a. The hydroarylation reaction was also highly stereoselective giving only E-stereoisomeric trisubstituted alkene derivative 38a. The hydroarylation reaction was compatible with various functional groups such as Br, Cl and CHO substituted aromatic sulfoxides. Particularly, electron-deficient CHO substituted aromatic sulfoxide 37d reacted with 2b providing the corresponding hydroarylation product 38d in 51% yield. Unsymmetrical meta methoxy phenyl sulfoxide 37e reacted regioselectively with alkyne 2b, yielding product 38e in 57% yield in which the ortho C–H bond activation takes place at a less hindered C–H bond of 37e.

Scheme 20 The hydroarylation of alkynes with aromatic sulfoxides.

The scope of hydroarylation reaction was further examined with various unsymmetrical and symmetrical alkynes. In all reactions, the expected hydroarylation product was observed in good to moderate yields in a highly regio- and stereoselective manner. Particularly, bromo substituted alkyne 2i reacted regioselectively with 37a, affording the corresponding alkene derivative 38f in 63% yield (Scheme 20). In the reaction, n-butyl substituted alkyne carbon connected at the ortho C–H bond of 37a.

When compound 38g was treated with acetic anhydride (10.0 equiv.) at 140 °C for 1 h, α-acyloxy-thioether 39 was observed in 87% yield (Scheme 21). Subsequently, ortho alkenylated phenyl sulfoxide 38h was treated with CF₃SO₃H at room temperature for 24 h followed by an addition of a 9 : 1 ratio of water/pyridine, affording 2,3-disubstituted benzothiophene derivative 40 in 67% yield.

Scheme 21 Transformation of ortho alkenylated aromatic sulfoxides.

To show the role of organic acid in the hydroarylation reaction, the reaction of 37g with 2b in the presence of CD₃COOD instead of pivalic acid was tested under similar reaction conditions (Scheme 22). In the reaction, deuterium incorporation was observed at the alkene carbon of hydroarylation product d-38g. This result clearly reveals that the AcOH acts as a proton donor in the reaction.

Scheme 22 The hydroarylation of alkyne with phenyl sulfoxide in CD₃COOD.

AgSbF₆ controlled E to Z stereoselective transformation of trisubstituted alkenes

Very recently, Hong's group reported a ruthenium-catalyzed Z stereoselective hydroarylation of alkynes with substituted aromatics.¹⁸ Generally, E stereoselective alkene derivatives can be prepared efficiently in the hydroarylation proceeds via a deprotonation pathway. In the oxidative addition pathway, a stereoisomeric mixture of E and Z alkene derivatives was prepared. In the Hong's method, Z stereoselective alkene derivatives were prepared efficiently in the presence of an excess amount of AgSbF₆. This hydroarylation reaction also proceeds via a deprotonation pathway. Initially, in the reaction, E stereoselective alkene derivatives were observed. But, in the presence of an excess AgSbF₆ catalyst, E stereoselective alkene derivatives were converted into Z stereoselective alkene derivatives.

When chromone (41a) was treated with diphenylacetylene (2a) in the presence of [{RuCl₂(p-cymene)}₂] (5 mol%), AgSbF₆ (16 mol%), Cu(OAc)₂ (10 mol%) and acetic acid (2.0 equiv.) in 1,2-dichloroethane at 100 °C for 6 h, a stereoisomeric mixture of alkenylated product 42a was observed in 94% yield in a 91 : 9 E/Z ratio (Scheme 23). If the same reaction was done in the presence of an excess amount of AgSbF₆ (20 mol%) under the same reaction conditions, the stereoisomer of alkene derivative was reversed and producing product 43a in 87% yield in an 8 : 92 E/Z ratio. AgSbF₆ plays an important role for the stereoselective isomerization of an alkene derivative. In the reaction, alkenylation takes place at the C-5 position of chromone (41a). The alkenylation reaction was examined with various substituted chromone derivatives and alkynes. In all these reactions, the expected trisubstituted alkene derivatives were observed in good to excellent yields. To prove the role of AgSbF₆, E-stereoisomeric alkene derivative 42d was prepared separately and treated with AgSbF₆ in acetic acid at 100 °C for 2 h. In the reaction, the reversed stereoisomeric chromone derivative 43d was observed in 87% yield in a 9 : 91 E : Z ratio. In was proposed that the isomerization process takes place through the formation of the alkyl cation 44 followed by the bond rotation to drive the transformation of E-alkenyl into the thermodynamically more stable Z-isomer in the presence of AgSbF₆ catalyst.

Scheme 23 The hydroarylation of alkyne with chromones.

The alkene isomerization reaction was further examined with ortho alkenylated anilides, aromatic carbamates, esters, sulfoxides and phosphonates in the presence of AgSbF₆ and acetic acid (Scheme 24). In all these reactions, a mixture of stereoselective alkene derivatives 46 was observed in a major amount of >92% of Z stereoisomer. The representative examples of these reactions were shown in Scheme 24.

Scheme 24 Silver-catalyzed stereoisomerization of trisubstituted alkenes.

Ruthenium-catalyzed 1,2,3-triazole directed hydroarylation of alkynes with aromatics

Recently, Liu's group reported a ruthenium-catalyzed 1,2,3-triazole directed hydroarylation of alkynes with aromatics.¹⁹ In the reaction, bis alkenylated aromatics were observed and the alkenylation takes place at the both ortho C–H bonds of the phenyl group. Treatment of 1-benzyl-4-phenyl-1H-1,2,3-triazole (47a) with diphenylacetylene (2a) in the presence of [{RuCl₂(p-cymene)}₂] (5 mol%), AgSbF₆ (20 mol%) and Cu(OAc)₂·H₂O (20 mol%) in toluene at 100 °C for 2.5 h gave bis alkenylated aromatic 48a in 90% yield (Scheme 25). In the reaction, the active cationic ruthenium acetate species was generated by the reaction of [{RuCl₂(p-cymene)}₂], AgSbF₆ (20 mol%) and Cu(OAc)₂. Later, the ortho C–H bond of the phenyl group was deprotonated by an acetate species of an active ruthenium catalyst providing a metallacycle intermediate and AcOH. The corresponding AcOH acts as a proton source and protonates at one of the alkene C–H bonds affording an alkene derivative and regenerates the active catalyst for the next catalytic cycle. Apart from Cu(OAc)₂, NaOAc can also be used as acetate source to activate the C–H bond for the reaction. Next, the hydroarylation reaction was examined with various substituted 1,2,3-triazole substituted aromatics. The reaction worked very well in all cases and the expected bis alkenylated aromatics were observed in good to excellent yields 48b–f. The reaction was compatible with F, Cl, CF₃, NO₂ and OMe substituents on the aromatic ring of substituted 1,2,3-triazole derivatives. The hydroarylation reaction was also examined with various symmetrical alkynes. In all cases, the expected bis alkenylated products were observed in good yields. Unsymmetrical alkynes such as 1-phenyl-1-propyne and 1-phenyl-1-hexyne reacted efficiently with 47a, yielding the expected bis alkenylated aromatics 48g and 48h in a highly regio- and stereoselective manner. Methyl as well as hexyl substituted carbon of alkynes were connected at the ortho C–H bond of the phenyl group.

Scheme 25 The hydroarylation of alkynes with 1,2,3-triazole substituted aromatics.

Ruthenium-catalyzed 2-pyridyl or carbamide directed alkenylation at the C2-position of indole derivatives with alkynes

In 2014, Zeng's group reported a ruthenium-catalyzed 2-pyridyl directed hydroarylation of alkynes with indoles.^20a The reaction of N-(2-pyridyl)indole (49a) with diphenylacetylene (2a) in the presence of [{RuCl₂(p-cymene)}₂] (7 mol%), AgSbF₆ (20 mol%) and pivalic acid (1.0 equiv.) in 1,4-dioxane solvent at 110 °C for 24 h gave C2-alkenylated N-(2-pyridyl)indole (50a) in 54% yield (Scheme 26). Later, the yield of the reaction was increased up to 98% by changing the solvent 1,4-dioxane into dimethylformamide. In the reaction, 2-pyridyl acts as a directing group to activate the C2–H of indole. As 2-pyridyl is a strong chelating group, the catalytic reaction can proceed efficiently with a neutral ruthenium species and the cationic ruthenium species was not needed.

Scheme 26 E-Stereoselective C–2 alkenylation of indoles with alkynes.

The hydroarylation reaction was examined with various sensitive functional groups such as OMe, F, Cl, Br, NO₂, CN and CO₂Me substituent on the aromatic ring of indole derivatives. In all these substrates, the hydroarylation reaction worked very nicely yielding the expected alkene derivatives in good to excellent yields 50b–f. Next, the hydroarylation reaction was examined with various unsymmetrical alkynes. Particularly, 3-phenylprop-2-yn-1-ol reacted nicely with 49a giving the corresponding alkene derivative 50g in 89% yield, in which, the CH₂OH group substituted carbon of alkyne was connected at the C2-position of indole. Meanwhile, the hydroarylation reaction was examined with diyne and enyne (products 50j and 50k). Interestingly, the hydroarylation reaction was compatible with terminal alkynes. However, in the reaction, a mixture of 1,1-disubstituted alkene and 1,2-disubstituted alkene derivatives was observed. The hydroarylation reaction also worked nicely with N-(2-pyridyl)pyrrole (49m). However, in the reaction, a mixture of diene derivatives 50m and 50m′ was observed. Later, the 2-pyridyl group of alkene derivative 50a was cleaved in the presence of MeOTf and a free N–H indole derivative 51a was observed in 90% yield (Scheme 27).

Scheme 27 Synthesis of E-stereoselective C2-alkenylated indole derivative.

Very recently, the same group reported a ruthenium-catalyzed carbamide directed Z-stereoselective hydroarylation of alkynes with indole derivatives.^20b In the previous report, by employing the 2-pyridyl group, alkenylation was done at the C2-position of indole in a highly E-stereoselective manner. In the present work, by employing the carbamide group, alkenylation was done at the C2-position of indole in a highly Z-stereoselective manner. It is important to note that during the reaction, the carbamide group was cleaved and only provided Z-stereoselective alkene derivatives. When N-benzyl-1H-indole-1-carboxamide (52a) was treated with diphenylacetylene (2a) in the presence of [{RuCl₂(p-cymene)}₂] (10 mol%), Cu(OAc)₂ (0.5 equiv.) and acetic acid (1.0 equiv.) in 1,2-dichloroethane at 100 °C for 24 h, a Z-stereoselective C2-alkenylated indole derivative 53a was observed in 80% yield (Scheme 28). The optimization studies clearly revealed that the AcOH is crucial to increase the yield of the product 53a.

Scheme 28 Z-Stereoselective C–2 alkenylation of indoles with alkynes.

The scope of hydroarylation reaction was examined with OMe, F, Br, Cl and CO₂Me substituted indole derivatives and N-carbamide substituted pyrrole. In all these reactions, Z-stereoselective alkene derivatives were observed in good to excellent yields 53b–g. The hydroarylation reaction was also examined with various unsymmetrical alkynes. Interestingly, 1-phenyl-1-propyne, 1-phenyl-1-butyne and 4-methoxyphenyl phenyl alkynes reacted regioselectively with 52a providing C2-alkenylated indole derivatives 53h–k in good yields in a highly Z-regioselective manner.

A possible reaction mechanism was proposed to account for the present Z-stereoselective alkenylation reaction (Scheme 29). The ortho C–H bond of the indole group was deprotonated by an acetate species of the ruthenium catalyst providing a metallacycle intermediate 54. Later, the nucleophilic attack of amide nitrogen 54 into an alkyne 2 with the assistance of Cu(OAc)₂ forms an alkenylated intermediate 55 and isocyanate 56 as a byproduct. Then, the acetate anion undergoes nucleophilic attack with isocyanate 56 forming amide 57 with the release of CO₂. At the same time, an alkenylated metal intermediate 55 could be further isomerized followed by protonation, producing the final free (N–H) (Z)-alkenyl indoles 53 and regenerating the active catalyst (Scheme 29).

Scheme 29 Proposed mechanism for the hydroarylation of alkynes with indoles.

Ruthenium-catalyzed sulfur assisted hydroarylation of alkynes with benzylthioethers

Very recently, Villuendas and Urriolabeitia reported a ruthenium-catalyzed hydroarylation of alkynes with benzylthioethers leading to ortho alkenylated benzylthioethers in good to moderate yields (Scheme 30).²¹ Treatment of thioether 58a with hex-3-yne (2a) in the presence of [{RuCl₂(p-cymene)}₂] (10 mol%), KPF₆ (10 mol%) and Cu(OAc)₂·H₂O (1.0 equiv.) in an electron deficient HFIP solvent at 100 °C for 0.5 h under microwave irradiation (150 W) gave a mixture of mono as well as bis alkenylated benzylthioether 59a in 78% yield. To avoid the bis alkenylation, one of the ortho carbons of benzylthioether was blocked by Me, CF₃, Cl and NO₂ groups and treated with 2a under similar reaction conditions. In the reaction, only mono alkenylated benzylthioethers 59b–e were observed in good to moderate yield. The hydroarylation reaction was examined with various S substituted benzylthioethers. In these reactions also, the expected alkenylated product was observed in good yields 59f–h. Later, the hydroarylation reaction was examined with unsymmetrical alkynes. However, in the reaction, a mixture of regio- as well as stereoisomeric products was observed 59i–k.

Scheme 30 The hydroarylation of alkyne with benzylthioethers.

Conclusions

In the present review, a ruthenium-catalyzed hydroarylation of alkynes with substituted aromatics providing trisubstituted alkene derivatives in a highly regio- and stereoselective manner was discussed elaborately. The hydroarylation reaction was explored with amide, azole, carbamate, phosphine oxide, amine, acetyl and sulfoxide directed aromatics with alkynes. The hydroarylation reaction was examined with various symmetrical and unsymmetrical alkynes. In all these reactions, the expected alkene derivatives were observed in a highly regio- and stereoselective manner. In the alkyne, if a coordinating group such as an aryl or an ester is present in one of the carbons and a non-coordinating alkyl group in the another carbon, the C–H bond of the aromatic moiety prefers to connect at the alkyl substituted carbon of the alkyne and the coordinating group of the alkyne and the aromatic moiety are trans to each other. In the unsymmetrical alkyne, if both carbons have coordinating groups such as Ph and ester, a mixture of regioisomeric products was observed. A possible reaction mechanism of these reactions was proposed and the proposed mechanism was strongly supported by experimental evidence. Particularly, deuterium labelling and kinetic studies clearly revealed that the C–H bond activation step is a rate determining step and the C–H bond activation proceeds via a deprotonation pathway.

There are still several challenges in a ruthenium-catalyzed hydroarylation reaction. Mostly, a higher reaction temperature is needed for the C–H bond functionalization. We believe that it can be done at room temperature by designing new ruthenium catalysts or to find out the suitable reaction conditions with the existing catalysts. The hydroarylation reaction can be explored with a weak chelating group substituted aromatics. Apart from sp² C–H bond functionalization, sp³ C–H bond functionalization should also be explored. In addition, in the hydroarylation reaction, only the alkyne carbon–carbon π-component is used. It can also be extended with other carbon–carbon π-components such as alkenes and allenes. We believe that these issues could be easily overcome in the future investigations.

Acknowledgements

We thank the CSIR (02(0179)/14/EMR-II), DST (SR/S1/OC-26/2011) and INSA (SP/YSP/99/2014), India for supporting this research. R. M. thanks the CSIR for a fellowship.

Notes and references

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