Addition of Aromatic C-H Bonds to Olefins

The RuH2(CO)(PPh3)3-catalyzed coupling of aromatic ketones with olefins is tolerant of several functional groups [4fj. In the reaction of m-substituted acetophenones, two different reaction sites are present. The C-C bond formation, generally. 

The use of a formyl group as a directing functionality is challenging because, in the case of the low-valent transition metal-catalyzed reaction of aldehydes with an olefin, aldehydes are prone to undergo decarbonylation or hydroacylation of the olefins. The following protocol to suppress the decarbonylation, one being steric and the other electronic in nature, can be used. In the case of the reaction of 1-methylin-dole-3-carboxaldehyde with ethylene, the ethylation product is also obtained in quantitative yield (Eq. 9.5) [13]. 

When the alkylation of 2-atylpyridines with olefins via a C-H bond cleavage was carried out with the aid of Ru(COD)(COT) (COD = 1,5-cydooctadiene COT = 1,3,5-cyclooctatriene) and the chiral phosphine (R),(S)-PPFOMe ((R),(S)-PPFOMe = (R)-T [(S)-2-(diphenylphosphino)ferrocenyl]ethyl methyl ether), the alkylation product 5 was obtained in 15% yield with 15% e.e. (Eq. 9.7) [22]. Although the chemical and optical yields are inadequate, this result suggests that the atropselective alkylation of a biaryl compound is possible by means of a chelation-assisted C-H/olefin coupling. 

Atyloxazolines (five-membered N,0-heterocycle) show reactivity for coupling reactions with olefins [23]. In the case of the reaction of atyloxazalines, the coupling reaction proceeded with unusual product selectivity. In this case, alkenylation products were obtained as the major isomer (Eq. 9.8), and two hydrogen atoms generated 

For the chelation-assisted catalytic reaction, Jt-electrons in a nitrile group are able to function as a directing group. The ruthenium-catalyzed alkylation of aromatic nitriles with triethoxyvinylsilane takes place predominantly at the ortho position (Eq. 9.10) [24]. This regioselectivity indicates the possibility of Jt-coordination of the CN group to the ruthenium in the catalytic cycle. 

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Ruthenium(ll)- and lridium(lll)-catalyzed Addition of Aromatic C-H Bonds to Olefins... 

Additions of aromatic C-H bond to olefins and acetylenes result in the formation of aryl-alkyl and aryl-alkenyl bonds. This type of addition reaction is not applicable to aryl-aryl bond formation. Catellani and Chiusoli [52] reported the first example of this type of arylation in 1985. To date, several arylation reactions of aromatic rings have been developed. In almost all cases, C-H bond cleavage proceeds through electrophilic substitution with transition-metal complexes [53]. 

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.). 

Progress on the addition of aromatic C-H bonds to olefins has been made by Periana with iridium catalysts - - and Gunnoe with ruthenium catalysts. - Both systems illustrate that the anti-Markovnikov addition products can be generated in larger quantities than the Markovnikov products, although mixtures of regioisomers are still observed. Intramolecular additions of the C-H bonds of electron-rich heterocycles to electron-deficient alkenes have also been reported (Equation 18.65). Most recently, Tilley has reported the addition of the C-H bond of methane across an olefin catalyzed by scandocene complexes. This reaction occurs, albeit slowly, with Markovnikov regiochemistry. 

Nitrogen atoms that are sp hybridized also function in the catalytic addition of aromatic C-H bonds to olefins. In contrast to the reactions in eqs 1 and 2, the Ru3(CO)i2-catalyzed reaction of W-methylaniline with styrene gives the branched product (eq 3). ... 

Hydroarylation of alkenes offers a more atom-economical process of catalytic C-H bond alkylation. It involves the transition-metal catalysed formal addition of the arene C-H bond onto C=C bonds. Especially T. B. Gtiimoe and his group have shown that ruthenium(II) catalysts favour the addition of aromatic C-H bonds to an olefin C=C bond. They have used ruthenium(II) catalysts of type TpRu-R(L) (NCMe) (Tp=hydrotris(pyrazolyl)borate) and demonstrated the efficiency of the formation of ethylbenzene via catalytic addition of benzene to ethylene [(Eq. 37)] [113-118]. Analogously the same type of catalyst TpRu-R(L)(NCMe) promotes the alkylation by ethylene at C2 position of furan and thiophene [119]. 

These catalytic reactions provide a unique pathway for addition of aromatic C-H bonds across C=C bonds. In contrast with Friedel-Crafts catalysts for olefin hydroarylation, the Ru-catalyzed hydrophenylation reactions of a-olefins selectively produce linear alkyl arenes rather than branched products. Although the selectivity is mild, the formation of anti-Markovnikov products is a unique feature of the Ru(II) and Ir(III) catalysts discussed herein. Typically, the preferred route for incorporation of long-chain linear alkyl groups into aromatic substrates is Friedel-Crafts acylation then Clemmensen reduction, and the catalysts described herein provide a more direct route to linear alkyl arenes. 

A variety of catalysts have been used for these hydroary lation reactions of the C-H bonds in aromatic ketones, imines, and 2-arylpyridines. The intermolecular additions of aromatic C-H bonds of aryl ketones to olefins reported by Murai were conducted with RuH fCO) (PPh3)3 as catalyst. [RuH2(H2)(PCy3)2] was shown subsequently to catalyze this process at room temperature and even the much different Rh(I) complex [Cp Rh(C,H3SiMe,),] catalyzes this reaction. Additions of the C-H bonds to N-Bu and N-Bn benzaldimines... 

Palladium-catalyzed C-H olefination is also a very useful protocol to synthesize oxygen-containing heterocycles, since it allows to functionalize the substrates with an unsaturated olefinic moiety which would constitute a Jt-conjugated structure or be elaborated further. Two pathways are often encountered in this approach (i) addition of the resulted arylpalladium complex to alkynes and subsequent protonation or transformation and (ii) addition of the arylpalladium complex to olefins and following palladium hydride elimination [7b, 20]. The current methods are mainly focused on the functionalization of aromatic C-H bonds to form benzo-oxacycles. 

Later, they also reported an intermolecular hydroacylations of 1,3-dienes with aromatic aldehydes yielding the corresponding j8,y-unsaturated ketones (Eq. 51) [79]. This reaction does not require a CO atmosphere. The addition of formyl C-H bond in formic acid esters and amides to olefins and conjugate... 

In 1989, Jordan reported Zr-catalyzed addition of the C-H bond in a-picoline to olefin [4]. Moore and coworkers found that Ru-catalyzed three component coupling of pyridine, carbon monoxide, and olefin took place, although the use of an excess amount of one component is required [5]. Subsequently, Murai and coworkers published highly efficient and selective functionalization of C-H bonds in aromatic ketones with olefins in the presence of a ruthenium catalyst [6],... 

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. 

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. ... 

In (C5Me5)Rh(C2H3SiMe3)2-catalyzed C-H/olefin coupling the effect of the coordination of the ketone carbonyl is different from that in the ruthenium-catalyzed reaction [10], In the rhodium-catalyzed reaction all C-H bonds on the aromatic ring are cleaved by the rhodium complex without coordination of the ketone carbonyl. Thus, C-H bond cleavage and addition of Rh-H to olefins proceed without coordination of the ketone carbonyl. After addition of the Rh-H species to the olefin, a coordinatively unsaturated Rh(aryl) (alkyl) species should be formed. Coordination of the ketone carbonyl group to the vacant site on the rhodium atom leads... 

Chatani and coworkers reported the effective carbonylation of the C-H bond in the aromatic ring via Ru3(CO)12-catalyzed reaction of olefins and CO with heteroaromatics (Eq. 101) [159] and substituted benzene (Eq. 102) [160]. For more examples of the acylation of five-membered heteroaromatic compound see Ref. [ 161 ]. The reaction is closely related to the process of the ortho alkylation of substituted aromatic compounds and involves an additional step of CO insertion. 

Watanabe reported that the addition of C-H bonds in aldehydes to olefins takes place efficiently ivith the aid of Ru3(CO)i2 under a CO atmosphere at 200 °C (Eq. 9.44) [62]. In the case of the reaction with 1-hexene, a mixture of linear and branched ketones was obtained in 35% and 12% yields, respectively. The use of a CO atmosphere is the key to accomplishing this reaction in a catalytic manner. These authors revealed the role of CO by means of isotope-labeling experiments using CO. The presence of CO is essential for suppressing the decarbonylation of aldehydes and for stabilizing the active catalyst species. Interestingly, the reaction using 1,3-dienes as an acceptor of the C-H bond proceeds in the absence of CO (Eq. 9.45) [63]. Aromatic and heteroaromatic aldehydes can also be used in this reaction. 

Immediate extensions of the Murai alkylation are already underway, e.g. catalytic addition of alkynes to aromatic C-H bonds, and alkylation of 2-phenylpyridines with olefins. ... 

It is therefore not surprising that the reactivities of arenes and alkanes in electrophilic substitution reactions are very different, with the former being much more active. At the same time, the mechanism of the interaction (oxidative addition) of both saturated and aromatic hydrocarbons with complexes of metals in a low oxidation state is in principle the same. The reactivities of arenes and alkanes in oxidative addition reactions with respect to low-valent metal complexes therefore usually differ insignificantly. Furthermore, a metal complex via the oxidative addition mechanism can easily cleave the C-H bond in olefin or acetylene. 

Aldehydes are stoichiometrically decarbonylated by reaction with (XL) under mild conditions (77, 98,110,113). Aromatic aldehydes yield aromatic hydrocarbons whereas aliphatic aldehydes form saturated hydrocarbons and olefins. The latter minor products can be considered to arise from a reverse hydroformylation reaction. The initial step of this reaction is probably the oxidative addition of an aldehyde C—H bond to the rhodium(I) complex. However, a stable adduct of this type has not yet been reported. The driving force in these reactions is derived from the stability of the carbonyl (LXIX). 

Other reactions of sulphonium ylides include o /9 -elimination,metal-mediated carbene-transfer to olefins, insertion into aromatic C—H bonds or other carbenoid-type processes, formation of Pd" complexes, addition to enones (forming cyclopropyl ketones or heterocycles ), reaction with isoquinoline 2-oxide, and [2,3]-sigmatropic rearrangements " [as in the case of (12) 1 or... 

In analogy to aromatic C-H bonds, alkenyl C-H bonds can also be activated by iron(III) salts in coupling reactions with magnesium or zinc organyls (Scheme 4-250). The reaction requires a pyridine or an imine moiety in proximity to the double bond that supports the C-H bond activation step by chelation of the intermediate iron complex. Tris(acetylacetonato)iron is employed in catalytic amounts and l-bromo-2-chIoroethane or l,2-dichloro-2-methylpropane functions as oxidant. In addition, in most cases a diamine base is added. The reaction results in the stereospecific substitution of the olefinic C-H bond syn to the coordinating group. ... 

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