Reactions hydroarylation

COOEt COOEt Scheme 2.19 Products from the hydroarylation reactions of activated alkynes... 

Coumarins and quinolinones can be formed by hydroarylation reactions of alkynes (Equations (172)-(174)).7U42 142a... 

Product predictions for nucleophilic additions to C q, based on AMI calculations, show that among the many possible isomers a few are energetically favored [29]. Two areas within the molecule can be distinguished, which are the inert belt at the equator and the more reactive CgQ-like double bonds at the poles (Figure 3.4). Experimentally, hydroalkylation and hydroarylation reactions of C q under quantitative HPLC control yield predominantly one isomer of each C7oHR[4]. 

Intermolecular hydroamination or hydroarylation reactions of norbornene and cyclo-hexadiene carried out with catalytic amounts of Brpnsted or Lewis acid in ionic liquids have been found to provide higher selectivity and yields than those performed in classical organic solvents. This effect was attributed to the increases of the acidity of the medium and stabilization of ionic intermediates through the formation of supramolec-ular aggregates with the ionic liquid.38... 

Scheme 7. Scope ofthe hydroarylation reaction with aryl-substituted alkynes. Conditions ...

The Ru(II) catalysts currently used for olefin hydroarylation reactions are limited in terms of incorporation of substituents into the olefin substrate. For example, attempted hydrophenylation of isobutylene with TpRu(CO)(NCMe)(Ph) as catalyst does not yield new organic products. In addition, extension of catalysis to hetero-functionalized olefins using the TpRu(CO)(NCMe)(aryl) systems has not been successful. For electron-deficient olefins (e.g. styrene, methyl methacrylate, acrylonitrile) the TpRu(II) complexes initiate radical polymerization of the olefin in transformations that probably involve a Ru(III/II) redox change [4]. The... 

The reaction sequence in the vinylation of aromatic halides and vinyl halides, i.e. the Heck reaction, is oxidative addition of the alkyl halide to a zerovalent palladium complex, then insertion of an alkene and completed by /3-hydride elimination and HX elimination. Initially though, C-H activation of a C-H alkene bond had also been taken into consideration. Although the Heck reaction reduces the formation of salt by-products by half compared with cross-coupling reactions, salts are still formed in stoichiometric amounts. Further reduction of salt production by a proper choice of aryl precursors has been reported (Chapter III.2.1) [1]. In these examples aromatic carboxylic anhydrides were used instead of halides and the co-produced acid can be recycled and one molecule of carbon monoxide is sacrificed. Catalytic activation of aromatic C-H bonds and subsequent insertion of alkenes leads to new C-C bond formation without production of halide salt byproducts, as shown in Scheme 1. When the hydroarylation reaction is performed with alkynes one obtains arylalkenes, the products of the Heck reaction, which now are synthesized without the co-production of salts. No reoxidation of the metal is required, because palladium(II) is regenerated. 

Iodoarenes have also been used for the palladium catalyzed hydroarylation reactions of alkynes in ionic liquids.61 For instance, the reaction of 4-iodoanisole with diphenylacetylene and Et3N in [C4mim][BF4] at 80 °C afforded an 82% yield of 4-methoxylphenyl-l,2-diphenylethylene after 8 h using [Pd2(dba)3] (Scheme 11). However, repetitive catalytic runs resulted in a significant decrease in the yields. This could be prevented by using [(E,E,E)-1,6,11 -tris( -toluenesulfonyl)-l, 6,1 l-triazacyclopentadeca-3,8,13-triene]palladium(0) as the catalyst, which gave an 89% yield with only a slight loss of activity on recycle. 

Hydride terminated disilanes, 30-32 Hydroarylation reactions of alkynes, 273 Hydrogen atoms as ligands, 92-93 Hydrogenation reactions, 276-277 C-H bonds in, 276-277 Hydrosilanes dehydrocoupling of, 1-52 initiated by metals other than Group 4, 37 16... 

The catalytic functionalization of aromatic C-H bonds to form C-C bonds under mild conditions is an attractive economic objective. An efficient hydroarylation reaction between alkynes and alkenes to form C-C bonds has been described.43 The reactions are catalysed by Aum complexes under mild and even solvent-free conditions at ambient temperature. 

Trisubstituted furans were obtained by AuC13- or [(PPh3PAu)2Cl][BF4]-catalyzed hydroarylation reaction of Y-alkynylfurans in good yields, though the product with an exocyclic double bond is not stable <07T5879>. Similar cyclization reaction of furanyl... 

A new phosphine-functionalized N-heterocyclic carbene ligand as shown in Equation (171) for palladium-catalyzed hydroarylation reaction on 268 led to the formation of an aryl substituted compound 284 <2006SL1193>. 

While this protocol relied on the in situ generation of the relevant phosphite for catalytic hydroarylation reactions, Murai and coworkers developed effective methodologies for the direct use of Lewis-basic substrates, such as acetophenone 20 (Scheme 9) [18, 59], Thereby, regioselective ruthenium-catalyzed anti-Markovnivkov alkylations and alkenylations were accomplished using alkenes or alkynes [60] as substrates, respectively. Recently, an extension of this protocol to terminal alkynes was reported, which involved a phosphine ligand-free catalytic system (see below), along with stoichiometric amounts of a peroxide [61]. 

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... 

Another interesting hydroarylation reaction of alkynes with arenes using a dinuclear palladium complex as catalyst has been reported (Eq. 71) [161], although the precise mechanism is unclear. Trialkylboranes act as effective promoters for this reaction. 

C-bound or 0-bound vinylpalladium (40 or 41) is formed by the exchange reaction of 39 with phenol. Finally reductive elimination yields the hydroarylation product 42 and then coumarin 43 [12], The hydroarylation reaction has been carried out with phenolic substrates, and it is interesting to know whether the Pd(0)-catalyzed reaction can be applied to non-phenolic substrates such as mesitylene or not, but so far no example has been given. On the other hand, Pd(II)-catalyzed hydroarylation with mesitylene proceeds smoothly. 

Cp ligand, showed the best catalytic activity in terms of yield and enantiose-lectivity in the target asymmetric hydroarylation reaction. However, no reaction occurred under similar reaction conditions with the analogous yttrium (L45C-Y) and gadolinium (L45c-Gd) complexes. 

Ruthenium has a rich chemistry of hydroarylation reactions [22], but it has also been used successfully by Milstein and coworkers [23] as a catalyst for oxidative couplings of the Fujiwara-Moritani type (Figure 4.12). Under an atmosphere of carbon monoxide (6 bar), various ruthenium precursors effectively promoted the reaction of acrylates (e.g., 4g) with benzene (2a) to give a 1 1 ratio of the (E)-cinnamate 5i and methyl propionate 12, rather than the expected hydroarylation product methyl 3-phenylpropionate. Added oxygen (2 bar) could partly take over the role of the reoxidant from the alkene, resulting in an increase in the incorporahon of the alkene into the cinnamate product, giving a ratio of up to 3 1 of the arylated to the reduced acrylate. 

For recent reviews on catalytic hydroarylation reactions, see (a) Bandini,... 

The present section summarizes reductive Mizoroki-Heck-type arylations-that is, palladium-catalyzed hydroarylation reactions of alkenes-which are essentially limited to (hetero-)norbomenes (Section 7.3.2). It should be noted however, that only a handful of remarkable examples are known that are not based on the bicyclo[2.2.1]heptane framework (see Section 7.3.3). 

In this chapter, the intermolecular multicomponent aromatic ring construction reactions and intramolecular single-component aromatic ring construction reactions are described. Among them, the [2+2+2] cycloaddition and intramolecular hydroarylation reactions are the most widely employed and reliable method. Various polycyclic and sterically hindered aromatic compounds have been synthesized by this method. In the past 10 years, the asymmetric [2+2+2] cycloaddition and intramolecular hydroarylation reactions have been developed, which enabled the enantioselec-tive synthesis of sterically hindered chiral aromatic compounds, such as axially chiral biaryls, planar chiral cyclophanes, and helically chiral heUcenes. Details of the transition metal-mediated aromatic ring construction reactions are comprehensively covered in the recently published book... 

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. 

Acetylenes and acrylates show analogous Re-catalyzed hydroarylation reactions, but in lower yields. Overall, this method provides a transition metal-directed C-H-functionaUzation of thiophene aldehydes. 

The title compound is proposed to react with FeCls to form a highly reactive cationic Fe(OTf)3 complex. Interactions between the propynoic substrate and Fe(OTf)3 generate a highly electrophilic complex, which readily undergoes electrophilic aromatic substitution, followed by protonation. The electron-rich nature of the thusly-fonned indolyl acrylate encourages an additional hydroarylation reaction to generate the bis(indol-3-yl) products. 

T. Kitamura, Transition-metal-catalyzed hydroarylation reactions of alkynes through direct functionaUzalion of C-H bonds a convenient tool for organic synthesis, Eur. J. Org. Chem. (2009) 1111-1125. 

P. de Mendoza, A.M. Echavarren, Synthesis of arenes and heteroarenes by hydroarylation reactions catalyzed by electrophilic metal complexes, Pure Appl. Chem. 82 (2010) 801-820. 

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