Carbon nucleophiles soft nucleophile coupling

Arylation or alkenylation of soft carbon nucleophiles such as malonate is carried out by using a copper catalyst, but it is not a smooth reaction. The reaction of malononitrile, cyanoacetate, and phenylsulfonylacetonitrile with aryl iodide is possible by using a Pd catalyst to give the coupling products. 

Dienes and allylarcncs can be prepared by the Pd-catalyzcd coupling of allylic compounds with hard carbon nucleophiles derived from alkenyl and aryl compounds of main group metals. Allylic compounds with various leaving groups can be used. Some of them are unreactive with soft nucleophiles, but... 

For Pd-catalyzed cross-coupling reactions the organopalladium complex is generated from an organic electrophile RX and a Pd(0) complex in the presence of a carbon nucleophile. Not only organic halides but also sulfonium salts [38], iodonium salts [39], diazonium salts [40], or thiol esters (to yield acylpalladium complexes) [41] can be used as electrophiles. With allylic electrophiles (allyl halides, esters, or carbonates, or strained allylic ethers and related compounds) Pd-i73-jt-allyl complexes are formed these react as soft, electrophilic allylating reagents. 

Similarly palladium-catalyzed nucleophilic allylic coupling of 1-vinylcyclopropan-l-ol and its derivatives with stabilized (soft) and nonstabilized (hard) carbon nucleophiles occurred regioselectively without ring opening of the three-membered ring to give, for example, 9. ... 

In a series of outstanding papers, Pinhey et al have shown that aryllead tricarboxylates react with soft nucleophiles to afford C-arylation products. These aryllead derivatives behave as aryl cation equivalents in reactions which involve a ligand coupling mechanism (see section 7.5).9 2 ju most cases, the reactions proceed in chloroform at 40-60 C in the presence of pyridine as a base with a ratio of substrate to organolead derivative to pyridine of 1 1 3. The substrates which easily undergo C-arylation include phenols, p-dicarbonyl compounds and their vinylogues, a-cyanoesters, a-hetero-substituted ketones, enamines and nitroalkanes. A very limited number of non-carbon nucleophiles has also been reported to react. 

The [i-aUyl complexes can react with several types of nucleophiles, giving rise to the corresponding substitution products. O- and N-nucleophiles as well as soft carbon nucleophiles attack the t-allyl complex directly at the aUylic position, while hard C-nucleophiles react via transmetaUations [2c, 3]. If the nucleophihc attack occurs under an atmosphere of CO, insertion of CO can occur, yielding carbonyl compounds [4]. Alkenes and aUcynes can also insert into allyhnetal bonds, a protocol that is used preferentially for cycUzations [5]. Cyclizations can also occur, if the 7t-allylmetal complex contains an internal nucleophilic center. If the metalallyl complex acts as a nucleophile, direct coupling with aryl halides [6] or additions to electrophiles such as aldehydes, ketones, or imines are possible [7]. This review focuses on C-C coupling reactions via these tt-allyhnetal (or in some cases, a-allyhnetal) intermediates. 

In addition to allylation of soft carbon nucleophiles, aoss-coupling of rr-allylpalla-dium intermediates with hard carbon nucleophiles of organometaUic compounds of main group metals is possible. Cross-couphng of allyhc compounds occurs by transmetallation between 7r-allylpalladium intermediates and organometaUic compounds of Mg, Zn, B, Al, Si, Sn, and Hg, and subsequent reductive elimination. These carbon-carbon bondforming reactions are discussed in Sect JIL2. 

Diazo ketones also possess an electrophilic diazo group, and hence are susceptible to diazo-coupling reactions with suitable soft nucleophiles. Examples are given in equations (11) and (12). Phospha-zines such as (19) are useful synthetic intermediates in their own right. The carbon terminus of the 1,3-dipole possesses nucleophilic properties and can participate in aldol-type reactions with the particularly electrophilic carbonyl groups in 1,2-di- and 1,2,3-tri-carbonyl compounds. Intramolecular condensations occur with greater ease (equation 13). Reaction of diazo ketones of the type summarized in equations (9)-(12) have been thoroughly reviewed. ... 

TT-Allyl palladium species normally only couple with soft nucleophiles (e.g. malonate enolates) it is thus of interest to note that, in the presence of EtaN-HMPA, the relatively hard enolate of methyl cyclohexanecarboxylate reacts with a rr-allyl palladium complex derived from allyl chloride to give the a-cyclopropyl ester (128) in 70% yield. Initial attack by the enolate appears to occur at the central carbon of the complex. The reaction may prove to be limited to enolates of esters with a-branching. The application of high pressures... 

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