Alkenylation aromatic ketone

Similarly, ketimines (benzylimines of aromatic ketones) undergo the rhodium-catalyzed ortho-alkenylation with alkynes to give or/ o-alkenylated aromatic ketones after hydrolysis.61 This method is applied to an efficient one-pot synthesis of isoquinoline derivatives by using aromatic ketones, benzylamine, and alkynes under Rh catalysis (Equation (55)). 

Nitrogen functionality also assists the alkylation of ortho-Cr-H bonds of aromatics, as shown in Equations (10)—(12). In the case of aromatic imines, Ru3(GO)i2 exhibits a high catalytic activity.8-10 This reaction gives the alkylation product together with the alkenylation product in the reaction with triethoxyvinylsilane. Rhodium catalysts show the same activity to give the alkylation product.11,12,12a For example, the Rh(i)-catalyzed reaction of the imine of aromatic ketones with methyl acrylate... 

This C-H/olefin coupling can be extended to coupling with acetylenes [6], The reaction of aromatic ketones with internal acetylenes gives the ortho alkenylated product in high yield (Scheme 2), but reaction with terminal acetylenes does not afford the coupling product. With terminal acetylenes, dimerization of acetylenes occurs as a predominant reaction. 

Woodgate et al. [51] applied the C-H/acetylene coupling to the ortho-selective alkenylation of terpene derivatives (Eq. 27). The basic feature of this reaction is the same as the alkenylation reaction of Murai et al. The combination of acetophenone and diynes provides a new entry for the copolymerization of aromatic ketones with acetylenes. Weber et al. [50] studied extensive reactions of ruthenium-catalyzed C-H/acetylene coupling with respect to the step-growth copolymerization of aromatic ketones and acetylenes (Eq. 28). These coupling reactions provide a new route to the preparation of trisubstituted styrene derivatives. 

The Murai reaction (Scheme 4), the replacement of an ortho-CH on an aromatic ketone by an alkyl group derived from a substrate olefin, is catalyzed by a variety of Ru complexes. This C bond formation occurs via chelate directed C-H bond activation (cyclometalation) in the first step, followed by alkene insertion into RuH and reductive elimination of the alkylated ketone. In a recent example of the use of a related cyclometalation in complex organic synthesis, Samos reports catalytic arylation (Suzuki reaction) and alkenylation (Heck reaction) of alkyl segments of a synthetic intermediate mediated by Pd(II). 

Various vinylsilanes, olefins or acetylenes insert into the ortho C-H bond of aromatic ketones in the presence of catalytic amount of ruthenium complexes in high yields [21,22], The C-H bond cleavage reaction of aromatic ketones also involves orthometallation which is promoted by prerequisite coordination of the carbonyl group to ruthenium (Scheme 14.9) [21], This type of reaction has a wide generality for aromatic and alkenyl ketones with a variety of alkenes. 

THE RuH2(CO) (PPh3)3- CATALYSED ALKYLATION, ALKENYLATION, AND ARYLATION OF AROMATIC KETONES VIA CARBON-HYDROGEN BOND CLEAVAGE... 

Described in this section is a convenient synthetic procedure for preparation of RuH2(CO)(PPh3)3,[3 61 which is a highly effective catalyst for the conversion of carbon-hydrogen bonds to carbon-carbon bonds, and typical procedures for RuH2-(CO)(PPh3)3-catalysed reactions of aromatic ketones with olefins/2 3 71 acetylenes/41 and arylboronates/51 giving ortho alkylation, alkenylation, and arylation products, respectively. 

Besides halides, alkenyl boronates and alkenyl acetates can be employed for C-H bond alkenylation under Ru catalysis. Kakiuchi and coworkers demonstrated that aromatic ketones and 2-phenylpyridines undergo regioselective alkenylation effectively on treatment with alkenyl boronates [72] and alkenyl acetates [73], respectively (Scheme 18.72 and Scheme 18.73). 

The Ir-catalyzed version via path A was disclosed by the authors group. In the reaction of 1-naphthols, an [IrCl(cod)]2/PtBu3 catalyst system is effective for the C-H bond alkenylation at the peri position (Scheme 18.86) [85]. Recently, Shibata and coworkers [86] reported that aromatic ketones undergo ortho alkenylation in the presence of a cationic Ir catalyst. 

The cross-coupling reactions of organoboronic acids and carbon monoxide with hyper-valent iodonium salts affords unsymmetrical ketones (Scheme 30). The reaction proceeds smoothly at room temperature and in most cases completes within 0.5 h. Aryl-, alkenyl-, and alkynyliodonium salts react with arylboronic adds in the presence of 0.5% of Pd(PPh3)4 and 1.2 equiv of K2CO3 in DME to provide unsymmetrical aromatic ketones in high yields (Scheme 30). Phenylboronic acid dimethyl ester can be utilized as efficiently as phenylboronic acid. In most cases, a small amount of the direct crosscoupling product (R—Ph, less than 7-8%) is produced. 

Figure 4.35 A cross-section of results for the Ru-catalyzed orfho-alkenylation of aromatic ketones as described by Padala and Jeganmohan [69].

The same research group also investigated the hydroarylation of the vinyl side chain of poly(vinylmethylsiloxane) via ruthenium-catalyzed alkenylation of the ortho C—H bonds of aromatic ketones with vinylsilanes (Fig. 18B), a reaction originally developed by Murai. The functionalization reaction was regioselective, giving anti-Markovnikov addition of the 10-position C—H bond of 9-acetylphenanthrene across the pendant... 

Nickel-bpy and nickel-pyridine catalytic systems have been applied to numerous electroreductive reactions,202 such as synthesis of ketones by heterocoupling of acyl and benzyl halides,210,213 addition of aryl bromides to activated alkenes,212,214 synthesis of conjugated dienes, unsaturated esters, ketones, and nitriles by homo- and cross-coupling involving alkenyl halides,215 reductive polymerization of aromatic and heteroaromatic dibromides,216-221 or cleavage of the C-0 bond in allyl ethers.222... 

When methylene bisphosphonate (169) is reacted in a Horner reaction with an aromatic aldehyde, the alkenyl phosphonate 170 is produced (Scheme 5.25). By metalation with LDA in THF, this is converted to the vinyllithium intermediate 171 that, with the ketone 172, affords a Baylis-Hillman reaction-type product, 173 on base treatment, this is converted to the arylallene 174 [67]. 

This chemistry was extended to a catalytic enantioselective alkenylation and phenylation of aldehydes and a-ketoesters. Using CuF-DTBM-SEGPHOS complex, products were obtained with excellent enantioselectivity from a wide range of aldehydes including aromatic and aliphatic aldehdyes, [Eq. (13.26)]. Previously catalytic enantioselective vinylation and phenylation are restricted using the corresponding zinc reagents. The active nucleophile is proposed to be an alkenyl or phenyl copper, based on NMR studies. The chiral CuF catalyst can also be applied to a catalytic enantioselective aldol reaction to ketones... 

Aromatic carboxylic acids, a,/f-unsaturated carboxylic acids, their esters, amides, aldehydes and ketones, are prepared by the carbonylation of aryl halides and alkenyl halides. Pd, Rh, Fe, Ni and Co catalysts are used under different conditions. Among them, the Pd-catalysed carbonylations proceed conveniently under mild conditions in the presence of bases such as K2CO3 and Et3N. The extremely high toxicity of Ni(CO)4 almost prohibits the use of Ni catalysts in laboratories. The Pd-catalysed carbonylations are summarized in Scheme 3.9 [215], The reaction is explained by the oxidative addition of halides, and insertion of CO to form acylpalladium halides 440. Acids, esters, and amides are formed by the nucleophilic attack of water, alcohols and amines to 440. Transmetallation with hydrides and reductive elimination afford aldehydes 441. Ketones 442 are produced by transmetallation with alkylmetal reagents and reductive elimination. 

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