Aiylation catalyzed

In the last years several publications appeared describing palladium-catalyzed a-arylations of ketone enolates for the synthesis of a-aryl ketones, involving ketone eno-lates, silyl enol ethers and intramolecular a-aiylation of ketone enolates . In this process, an enolate is generated from a ketone in the presence of an aryl halide, and a palladium catalyst couples this enolate with the aryl halide. Iwama and Rawal proposed... 

Until recently, a-substitution of carbonyl compounds was largely restricted to those cases where alkyl groups, such as Me, allyl, and benzyl, were introduced via classical enolate alkylation. a-Aiylation of ketones with aryl halides can be effected using K in NH3 [120-123]. However, this reaction does not appear to be satisfactory for selective -alkenylation and a-alkynylation. -Arylation of ketones has also been catalyzed by Ni [124] and Pd [125,126]. The Pd-catalyzed version employed enolstannanes. This reaction has also been applied to a-alkenylation [127]. However, these reactions appear to be of very limited scope. Thus, the Pd-catalyzed procedures appear to be satisfactory mainly for a-substitution of methyl ketones. Furthermore, none of them addresses the critical question of how to control the regiochemistry of c-substitution, i.e., a vs. a. Critically needed from the viewpoint of selective synthesis were... 

Table 10. Aiylated and vinylated propionates by palladium-catalyzed reaction of zinc homoenolate (Ref. [29,40])...

Both Buchwald and Hartwig have explored the use of palladium-catalyzed amination for the synthesis of dendrimers and polyanilines. Dendrimers, such as 48, can be easily assembled through sequential aiylation of aminoanilines.89 These dendrimers are useful in creating metal-organic frameworks and often can exhibit interesting electronic effects, such as diradicals, and as optical materials. Polymeric anilines 49 are of intense interest due to their unique electrical conducting properties. Using the... 

FUJIWARA Arytalion,Carboxylation A mid Pd catalyzed aiylation or caiboxylation of a Pd activated double bond. 

Palladium-CatalYzed Aiylations of Amines and a-C—H Acidic Compounds... 

I 4 Copper-Catalyzed Arylations of Amines and Alcohols with Boron-Based Aiylating Reagents... 

I 5 Metal-Catalyzed Aiylations of Nonactivated Alkyl (Pseudo) Halides via Cross-Coupling Reactions Table 5.4 Copper-catalyzed cross-coupling reactions between unactivated alkyl halides and aryl metal reagents. copper catalyst... 

Intermolecular Metal-Catalyzed Direct Aiylation of Arenes I 373... 

I 77 Biaryl Synthesis through Metal-Catalyzed C-H Aiylation Itami [32] Kempe[33]... 

Biary Synthesis through Metal-Catalyzed C-H Aiylation... 

A palladium-catalyzed intramolecular cyclization of enolate O-aiylation and thio-enolate S-arylation was reported by Willis and co-workers in 2006. A catalyst generated from Pd2(dba)3 and the ligand DPEphos effects the key bond formation to deliver a variety of substituted products from both cyclic and acyclic precursors. The analogous thio-ketones undergo C-S bond formation using identical reaction conditions and were converted to ben-zothiophene products. A cascade sequence that produces the required a-atyl ketones in situ has also been developed (Scheme 2.6). 

More recently, a palladium-catalyzed intramolecular C-H arylation with mesylated compounds was reported by Kalyani and co-workers. A sequential mesylation-arylation protocol using phenols as substrates vras described as well. This method allows for the synthesis of diverse heterocyclic motifs, including dibenzofurans, carbazoles, and indoles, in good yields (Scheme 2.30). The intermolecular aiylations were efficient for the coupling of azoles with electronically diverse mesylates. 

Scheme 2.36 Pd-catalyzed intramolecular Heck cyclization and aiylation.

In 2013, a palladium-catalyzed double M-aiylation of l,2-diamino(hetero)-arenes with l,2-dihalo(hetero)arenes for the synthesis of phenazines and pyridoquinoxalines was developed by Laha and co-workers. A variety of functional groups, which included base-sensitive groups, were tolerated under the optimized conditions to afford phenazines or p3aidoquinoxalines in good to excellent yields (Scheme 3.4). 

An efficient synthetic approach to obtain new quinoxalinones and oxazi-nones based on Cu-catalyzed Ullmann-lype reaetions was developed in 2011." % intramolecular N-aiylation of pyrrole and indole carboxamides... 

Oxcarbazepine (Trileptal) has become the most widely prescribed drug for the treatment of epilepsy, both in adults and children. Additionally, oxcarbazepine is also effective in the treatment of mood disorders and mania. In 2005, a five-step procedure was developed for its synthesis. 2 -Aminoacetophenone and 1,2-dibromobenzene were used as starting materials. The key steps accomplished sequentially are palladium-catalyzed intermolecular a-arylation of ketone enolates and intramolecular N-aiylation reactions (Scheme 4.1). 

Gevorgyan and co-workers reported a mild, practical, and efficient method for the synthesis of symmetrical and unsymmetrical o-biphenols, o-phenol-naphthols, and o-binaphthols. The method involves a Pd-catalyzed intramolecular C-H aiylation of unsymmetrical bis-aiylo)q silanes to give the seven-membered oxasilacycles, which, via a consecutive routine TBAF deprotection, furnish valuable unsymmetrical o-biphenols and o-binaphthols. In 2013, the intramolecular cyclization of di-ortAo-bromoaiylo q acetal and o/tfto-bromoaiylo y acetal to the corresponding dibenzo[l,3]dioxepines was developed. ... 

Recently, a copper-catalyzed process for the construction of pyrrolobenzoxazepinones from 2-(2-iodopheno3gr)-l-(l//-pyrrol-2-yl)ethanones was described. A variety of pyrrolobenzoxazepinone derivatives were synthesized from the corresponding substrates by intramolecular Cu-catalyzed Ullmann N-aiylations in good to excellent yields (Scheme 4.8). 

In 2008, Fujii, Ohno and their co-workers developed an interesting method for the preparation of indole-fused 1,4-diazepines by eopper-catalyzed domino three-component coupling-indole formation-lV-aiylation. ... 

Mechanisms of Direct Arylations A plausible mechanism for Pd -catalyzed intermo-lecular direct arylations with ArX (X=C1, Br, I) involves (i) oxidative addition of a Pd catalyst into an aryl halide, (ii) intermolecular C—H activation, and (iii) reductive elimination to release the aiylated prodnct and regenerate the catalyst (Scheme 24.2a) [1,5, 6,8]. 

The copper-catalyzed cascade annulation of nitriles, diaryliodonium salts, and alkynes was recently described by Chen and coworkers. N-Arylation of the nitrile resulted in an V-arylnitrilium intermediate, which was trapped by the aUcyne and subsequently underwent electrophilic annulation to yield substituted quinolines (Scheme 6d) [107]. The concept was later varied to reach polycyclic quinolines, quinazolines, quinazolinimine, and acridine scaffolds [108—110], A similar cascade reaction delivered iminobenzoxazines by N-aiylation of ort/io-cyanoanilides followed by C-O cyclization [111], and the reactimi of nitriles with [1,1-biphenyl]-derived iodonium salts resulted in phenanthiidines [112]. The corresponding C-arylation cascade reactions are discussed in Sect. 4.3. 

Inter-Intra Tandem Processes Involving Pd-Catalyzed a-Arylation of Carbonyl Compounds with 1,2-Dibromoarenes. 1,2-Dibromoarenes have been shown to undergo Pd-catalyzed inter-intra tandem processes leading to the formation of cyclic compounds, as summarized in Scheme 28. In some examples, however, the cyclization process itself does not actually involve Pd-catalyzed a-aiylation. It instead involves either an interesting diaryl ether formation (Sect, in.3.3) or intramolecular Heck reaction (Sect IV.2.2). 

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