Hydroarylation of olefins

In 1993, Murai reported the reactions of aryl ketones witti ethylene and vinylsilanes to form the product from the addition of the C-H bond ortho to the carbonyl group to the olefin (Equation 18.49). This finding led to subsequent work on the addition of the C-H bonds of a variety of aromatic groups to a series of olefins. Catalysts that react under milder conditions than the original ones and extensions of the C-H activation to intramolecular cyclizations to form heterocyclic structures have made this reaction capable of being used in the synthesis of complex molecules. For example, alkylated diterpe-noids and (+)-lithospermic acid (Equations.18.50 and 18.51) have been synthesized using directed hydroarylation.  

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The hydroarylation of olefins is also achieved by using a ruthenium catalyst, TpRu(CO)(NCMe)(Ph) (Tp = hydridotris(pyrazolyl)borate) (Equation (34)).39 The reaction of benzene with ethene is catalyzed by the ruthenium complex to give ethylbenzene (TN = 51, TOF = 3.5 x 10 3mol 1 s-1 at 90 °G for 4h). The ruthenium-catalyzed reaction of benzene with propene gives the hydroarylation products with a 1.6 1.0 ratio of -propyl to isopropylbenzene, with 14 catalytic turnovers after 19 h. 

Ir(III) complexes can also be used to catalyze the hydroarylation of olefins [5, 6], The catalyst precursors (acac-0,0)2Ir(Ph)(L) (L= pyridine or H20) and [Ir(w-acac-0,0,C3)(acac-0,0)(acac-C3)]2 have been reported and are depicted in Scheme 3, with representative catalytic reactions. Among these catalyst precursors, (acac-0,0)2Ir(Ph)(H20) has been demonstrated to be the most active system [5], The lin-ear-to-branched ratios observed for Ir(III) catalyzed reactions of a-olefins are remarkably similar to those obtained using TpRu(CO)(NCMe)(Ph). For example, hydrophenylation of propene using 11 r (a-acac- O, O,C ) (acac-O, O) (acac-C3) ]2 as catalyst produces a 1.6 1 ratio of linear propylbenzene to cumene (identical to the ratio observed using the Ru(II) catalyst). Similar to the TpRu(CO)(NCMe)(R) catalysts, the regioselectivity of hydroarylation of ethylene that incorporates monoalkyl arenes produces meta- and para-disubstituted alkyl arenes in approximately 2 1 ratio without observation of ortho-disubstituted products. 

Scheme 4. Proposed mechanisms for catalytic hydroarylation of olefins (benzene and ethylene depicted as substrates note the catalyst precursors for Ir(lll) exhibit trans disposition of L and Ph).

The hydroarylation of olefins is relatively uncommon in photochemistry, despite a high interest in this process which allows the formation of an aryl-carbon bond via the direct activation of an aromatic, with no need for leaving groups in both components of the reaction. The process follows a photo-EOCAS (Electrophile-Olefin Combination Aromatic Substitution) mechanism [32], and is initiated by a PET reaction between an electron-rich aromatic and an electron-poor olefin, as illustrated in Scheme 3.14. 

Combined experimental and computational study of TpRu P(pyr)3 (NCMe)Me (pyr = N-pyrrolyl) Inter- and intramolecular activation of C-H bonds and the impact of sterics on catalytic hydroarylation of olefins... 

In parallel with the directed hydroarylation of olefins, a series of papers described the formation of ketones from heteroarenes, carbon monoxide, and an alkene. Moore first reported the reaction of CO and ethylene with pyridine at the position a to nitrogen to form a ketone (Equation 18.28). Related reactions at the less-hindered C-H bond in the 4-position of an A/-benzyl imidazole were also reported (Equation 18.29). - Reaction of CO and ethylene to form a ketone at the ortho C-H bond of a 2-arylpyridine or an N-Bu aromatic aldimine has also been reported (Equations 18.30 and 18.31). Reaction at an sp C-H bond of an N-2-pyridylpiperazine results in both alkylative carbonylation and dehydrogenation of the piperazine to form an a,p-unsaturated ketone (Equation 18.32). The proposed mechanism of the alkylative carbonylation reaction is shown in Scheme 18.6. This process is believed to occur by oxidative addition of the C-H bond, insertion of CO into the metal-heteroaryl linkage, insertion of olefin into the metal-acyl bond, and reductive elimination to form the new C-H bond in the product. 

Reductive elimination of ethane from five-coordinate Pt(IV) alkyl complexes has also led to the generation of three-coordinate complexes that have shown catalytic activity in the hydroarylation of olefins. In contrast to the f-Bu or Ph substituted pypyr ligands which underwent facile cyclometalation and trapping with ethylene (Scheme 7), when the Me-substituted ( pypyr)PtMe3 (4c) was heated in benzene solvent under a pressure of ethylene, ethyl benzene product was produced with a TON of 26 [94]. Other combinations of arenes and olefins were also observed to yield hydroarylation products when ( pypyr)PtMe3 complex 4c was used as a catalyst precursor. Presumably C-C reductive elimination of ethane is followed by C-H activation of the arene, reductive elimination of methane, and then... 

In a seminal paper, Matsumoto and coworkers reported an anti-Markovnikov hydroarylation of olefins catalyzed by a binuclear iridium(III) complex (Scheme 19.91) [133, 134], In contrast to conventional Friedel-Crafts alkylation of aromatic compounds with olefins, which follow Markovnikov s mle, mainly linear alkylbenzenes were obtained in this case, suggestive of a C-H activation mechanism. Although highly efHcient, the reaction led to regioisomeric mixtures. 

One remarkable reaction catalyzed by Rn complexes is the Murai conpling, in which alkyl arenes 44 are formed by hydroarylations of olefins. Interestingly, P-hydride elimination is not a problem in these reactions, as would be expected with other transition metal catalysts." " Murai-type protocols are especially nseful as they can employ electron-rich olefins, which are typically low-yielding snbstrates in Pd-catalyzed, oxidative Heck (Fujiwara-Moritani) reactions." " ... 

The use of nonactivated secondary alkyl halides as electrophiles in a copper-catalyzed direct alkylation of benzoxazoles has been described. Although methods exist for the direct alkylation of aromatic heterocycles, such as radical alkylations " and coupling of heterocycles with alkyl electrophiles, such methods are restricted to the incorporation of primary alkyl groups only. Secondary alkyl groups can be introduced by metal-catalyzed hydroarylation of olefins but in these cases examples are usually confined to activated alkyls such as benzyl or allyl. 

Periana and Goddard et al. also found that the iridium(III) vinyl bis-acetylace-tonate complex (Vinyl-Ir-Py, 26) catalyzes dimerization of olefins (e.g., 21) [106, 107]. Analogously to the hydroarylation of Scheme 8, the mechanism is proposed to... 

Ru(Tp)(Ph)(CO)(NCMe)] is able to catalyze the hydroarylation reactions of olefins. [Ru(Ph)(Tp)(CO)(T]2-olefin)] has been hypothesized as the species that precedes the insertion step, in which the presence of the strong jt-acid CO likely results in a preferred olefin orientation, the C=C bond being parallel to the Ru-phenyl bond.335... 

Oligomerizations, polymerizations and telomerizations are covered in other parts of this section, since C-C/C-C bond forming additions (dicarborations) are involved. Metal-mediated hydroalkylations of olefins with CH acidic compounds and hydroarylations with formal addition of aromatic C—H bonds to olefins are also known2, however, only a few examples of stereoselective applications have been reported (Section 1.5.8.2.6.). 

Palladium-catalysed hydroarylations and hydrovinylations of olefins and acetylenes have been reviewed. Vinyl iodide, for instance, reacts with internal acetylenes in the presence of (PPh3)2Pd(OAc)2, triethylamine and formic acid to yield the alkenes 204... 

Gold(lII) chloride and silver hexafluoroantimonate can also be used as catalyst for addition reactions of electron-rich arenes and heteroarenes to olefins. In a similar fashion, the intramolecular hydroarylation of aryl homoallyl ethers and related substrates takes place upon heating with AuCb and AgOTf in dichloroethane to 80 °C and affords dihydrobenzopyrans, tetrahydroquinolines, and tetralins with good yield (Scheme 4-18). ... 

Other pathways are available for hydroarylation of heterocycles. A mechanistic study by Bergman and Elhnan was conducted on intramolecular reactions of imidazole-type heterocycles. These mechanistic studies have shown that the C-H activation of the imidazole is followed by isomerization to generate an N-heterocyclic carbene ligand (Equation 18.60). Following this isomerization, the olefin appears to couple with the carbene by a [2+2] process to generate the carbon-carbon bond, followed by proton transfer to generate a rhodium hydride and reductive elimination to form the C-H bond. 

A series of arylations of olefins by C-H bond cleavage without direction by an ortho functional group has also been reported, and these reactions can be divided into two sets. In one case, the C-H bond of an arene adds across an olefin to form an alkylarene product. This reaction has been called hydroarylation. In a second case, oxidative coupling of an arene with an olefin has been reported. This reaction forms an aryl-substituted olefin as product, and has been called an oxidative arylation of olefins. The first reaction forms the same t)q)es of products that are formed from Friedel-Crafts reactions, but with selectivity controlled by the irietal catalyst. For example, the metal-catalyzed process can form products enriched in the isomer resulting from anti-Markovnikov addition, or it could form the products from Markovnikov addition with control of absolute stereochemistry. Examples of hydroarylation and oxidative arylation of olefins are shown in Equations 18.63 - and 18.64. ... 

The mechanism of olefin hydroarylation has been studied by both experimental and theoretical methods. These results are summarized in Scheme 18.12 for the ruthenium system, but similar results have been obtained on the iridium system. Experimental studies have shown that a metal-aryl complex reacts with the olefin to gener--ate a p-arylalkyl intermediate. Computational studies by the two groups have suggested that this alkyl intermediate reacts with arenes by a pathway that lies in between the... 

Finally, the hydroarylation of electron-deficient olefins with polyfluoroarenes was described by Zhao et al. [132] (Scheme 19.90). In addition to acrylates, acrylamides and vinyUcetones were successful couphng partners. 

Phosphine oxide directing groups enable both redox-neutral and oxidative C-H olefinations (Scheme 23.17) [76, 77], In combination with [Ru(p-cymene)Clj]j, cw-selective hydroarylations of alkynes can be achieved. Furthermore, in the presence of [Cp RhCy/AgSbF, Cu(OAc)j, and AgjCOj, oxidative C-H olefinations are possible with electron-poor olefins as coupling partners. The latter reactions proceed with complete selectivity for the fran -product. 

In contrast to C-H arylations and olefinations, C-H alkylations are a rather recent development. Interestingly, these reactions can proceed under oxidative or redox-neutral conditions and use different alkyl precursors [78-80]. One of the earliest examples for this reaction was published by Murai and coworkers, using olefins as reactants [81]. The overall hydroarylation of the olefin with a Ru catalyst leads to ort/ro-alkyl-substituted aryl ketones, which are difficult to synthesize selectively with classical methods (Scheme 23.18). 

Up to now, it is doubtful whether the manufacture of such profens via an AHF step can really compete with industrially well-established methods [20], especially when extremely high enantiomeric excess values are targeted. A first problem prior to the hydroformylation is faced by the high production costs of the required olefinic substrates. The common pathway via the aryl-X coupling reaction may be useful only in laboratory scale or for the synthesis of more sophisticated vinyl aromates (Scheme 4.60) [21]. Also, the current level of hydroarylation of alkynes, such as acetylene, is far from apphcation [22]. 

In both Chapters 1 to 3, we saw a wide range of synthetic targets that can be assessed by catalytic coupling reactions, most of which can also be accessed by C-H activation chemistry. We will also consider hydroarylation reactions of olefins in this chapter, as it is basically an arylation of masked alkyl groups. 

Cobalt-catalyzed C—H functionalization reactions are currently classified into two main categories based on their hypothetical catalytic cycles (i) hydroarylation of alkynes and olefins and (ii) C—H/electrophile coupling. A separate category involving arylzincation of alkynes has also been proposed. This chapter explores cobalt-catalyzed hydroarylation and C—H electrophile coupling since 2007. 

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