Soft carbon nucleophiles allylic derivatives

The nature of the ligands on the palladium in ir-allyl complexes can influence the regioselectivity exhibited by soft carbon nucleophiles. ir-Allylpalladium complexes generated from methylenecycloalkanes provide an example of the effect of ligands on regiochemistry. The complexes derived from methylene-cyclopentane and methylenecycloheptane both exhibit exclusive exocyclic addition by the anion of methyl(methylsulfonyl) acetate with triphenylphosphine ligands on the Pd (equation 223). In contrast, the complex derived from methylenecyclohexane yields a 62 38 ratio of exocyclic endocyclic addition (equation 226). 

Addition of MeMgl158 or PhLi160 to ir-allylpalladium complexes derived from methylenenoibomane exhibits selective C—C bond formation at die more hindered allyl terminus. Soft carbon nucleophiles with the same allyl species show the opposite regioselectivity (equation 252).158,160... 

Reactions of soft carbon nucleophiles derived from active methylene compounds such as /3-keto esters or malonates proceed by attack of the nucleophiles at the central sp carbon of the allenyl complexes. The attack of the nucleophiles generates cr-allyl anion intermediates, which are regarded as palladium-carbene complexes. These intermediates pick up a proton from the active methylene compound to form 7r-allylpalladium complexes, which undergo further reaction with the nucleophile as expected, and hence the alkenes are formed by introduction of two molecules of the carbon nucleophiles (Scheme 21). 

Pd-catalyzed reactions of allylic esters such as aUyl acetates, carbonates, and phosphates with soft carbon nucleophiles such as malonate esters are useful for carbon-carbon bond formation (Sects. V.2.1.1-V.2.1.5). hi this section, Pd-catalyzed substitution reactions of nitrogen-containing allylic derivatives such as allylic amines, ammonium salts, tosylim-ides, and nitro compounds are described (Scheme 1). The allylic derivatives of other group 15 atoms have never been used as allyl unit source in Pd-catalyzed alkylation reactions so far. 

In general, Pd-catalyzed reaction of propargyl compounds provides synthetically valuable allenyl compounds through addition, transmetallation, or oxypalladation of allenylpalla-dium intermediates. Exceptionally, soft carbon nucleophiles such as malonate and methyl acetoacetate attack the sp carbon of allenylpalladium intermediates to afford allylic compounds and furan derivatives. 

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... 

Transition metal-catalyzed allylic alkylation is generally considered to involve mechanistically four fundamental steps as shown in Scheme 1 coordination, oxidative addition, ligand exchange, and reductive elimination. A key step of the catalytic cycle is an initial formation of a (7r-allyl)metal complex and its reactivity. The soft carbon-centered nucleophiles, defined as those derived from conjugate acids whose pAj, < 25, usually attack the allyl ligand from the opposite side... 

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. ... 

Catalytic reactions of allylic electrophiles with carbon or heteroatom nucleophiles to form the products of formal S 2 or S 2 substitutions (Equation 20.1) are called "catalytic allylic substitution reactions." Tliese reactions have become classic processes catalyzed by transition metal complexes and are often conducted in an asymmetric fashion. The aUylic electrophile is typically an allylic chloride, acetate, carbonate, or other t)q e of ester derived from an allylic alcohol. The nucleophile is most commonly a so-called soft nucleophile, such as the anion of a p-dicarbonyl compound, or it is a heteroatom nucleophile, such as an amine or the anion of an imide. The reactions with carbon nucleophiles are often called allylic alkylations. 

Although transition metal-catalyzed allylic alkylation has become one of the most powerful methods in chemical synthesis, the formation of ether bonds using this process has been slow to evolve.119-121 The main reasons for this disparity are the lower nucleophilicity and higher basicity of oxygen nucleophiles, particularly those derived from aliphatic alcohols, compared to their carbon or nitrogen analogs. However, this notion has rapidly been revised, as recent advances in the O-allylation area have largely addressed the issue of the reactivity mismatch between the hard alkoxide and the soft 7r-allylmetal species to provide a considerable body of literature. 

After these initial results by Tsuji, this elementary step was incorporated into a catalytic process by Hata and co-workers at Toray Industries and by Atkins and co-workers at Union Carbide. These groups reported reactions of allylic phenyl ethers, allylic alcohols, and allylic acetates with carboxylates, alcohols, primary and secondary amines, and methyl acetoacetate catalyzed by Pd(0) complexes and precursors to Pd(0) complexes (Equation 20.3). - After these initial reports, early developments focused on reactions of "soft" carbanions derived from 3-dicarbonyl compounds, cyanoesters, and related compounds containing two electron-withdrawing groups attached to the nucleophilic carbon. Although these reactions occur with allylic halides in the absence of a catalyst, these reactions are greatly accelerated by palladium catalysts. Thus, the palladium catalyst allows these reactions to occur under mild conditions with allylic acfetates, which are more accessible than allylic halides, and with selectivities that are altered by the metal catalyst. 

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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