Palladium® complexes intermolecular additions

Metal complexes of heterocyclic compounds display reactivities changed greatly from those of the uncomplexed parent systems. All of the -electron system(s) of the parent heterocycle can be tied up in the complex formation, or part can be left to take part in alkenic reactions. The system may be greatly stabilized in the complex, so that reactions, on a heteroatom, for example, can be performed which the parent compound itself would not survive. Orbital energy levels may be split and symmetries changed, allowing hitherto forbidden reactions to occur. In short, a multitude of new reaction modes can be made possible by using complexes dimerization of azirines with a palladium catalyst serves as a typical example (Scheme 81). A variety of other insertion reactions, dimerizations, intramolecular cyclizations, and intermolecular addition reactions of azirines are promoted by transition metals. 

Some other intermolecular C-H activations involving the NHC ligand have been observed during the synthesis of particular NHC-containing pincer -type complexes also called CCC-NHC complexes. In addition to zirconium- and rhodium-based complexes (210) and (211)/ several examples involving palladium of general structure (271) have been synthesized. Whereas Faller... 

The product of the palladation reaction exists as an active intermediate and cannot be isolated in general. However, the product of palladation was isolated as a stable compound in the reaction of cyclooctadiene palladium complex with carbanions such as malonate or alcoholate. Further reaction of the complex with base to give bicyclo (6,1,0) nonene and bicyclo (3,3,0) octane systems was reported by Takahashi and Tsuji 108>. The reactions are understood as intra-and intermolecular nucleophilic addition reactions. 

The oxidative addition of disilanes occurs to palladium complexes of isonitrile ligands and platinum complexes of trialkylphosphine ligands as part of tiie catalytic silylation of alkynes and aryl halides. The addition of stannylboranes to Pd(0) complexes has also been reported,and the addition of diboron compounds to many metal systems, such as Pt(0) complexes (Equation 6.67), is now common. These reactions all occur with metal complexes that do not undergo intermolecular reactions with alkane C-H bonds, let alone C-C bonds. Thus, the Lewis acidic character of these reagents must accelerate the coordination of substrate and cleavage of the E-E bonds. 

Examples of palladium- and rhodium-catalyzed hydroaminations of alkynes are shown in Equations 16.90-16.92 and Table 16.9. The reaction in Equation 16.90 is one of many examples of intramolecular hydroaminations to form indoles that are catalyzed by palladium complexes. The reaction in Equation 16.91 shows earlier versions of this transformation to form pyrroles by the intramolecular hydroamination of amino-substituted propargyl alcohols. More recently, intramolecular hydroaminations of alkynes catalyzed by complexes of rhodium and iridium containing nitrogen donor ligands have been reported, and intermolecular hydroaminations of terminal alkynes at room temperature catalyzed by the combination of a cationic rhodium precursor and tricyclohexylphosphine are known. The latter reaction forms the Markovnikov addition product, as shown in Equation 16.92 and Table 16.9. These reactions catalyzed by rhodium and iridium complexes are presumed to occur by nucleophilic attack on a coordinated alkyne. 

In contrast with the initial report employing boronic esters that follow a Pd(II)/ (0) pathway [52], the current methodology is proposed to occur via a Pd(II)/ (IV) mechanism. No reaction was observed in the presence of a Pd(0) source or in the absence of the silver salt. A plausible catalytic cycle involves an initial C-H activation step of palladium complex A to provide palladacycle B, followed by oxidative addition of the aryl iodide to give a highly reactive Pd(IV) complex C, which undergoes rapid reductive elimination to provide the desired product and a Pd(II) complex D (Scheme 30). The last step is loss of iodide, mediated by the silver salt. The use of the weakly coordinating -NHTf group by the Yu lab has allowed for the development of the first intermolecular and enantioselective C(sp )-H activation via a Pd(n)/(IV) catalytic cycle. 

The whole transformation is an oxidative intramolecular 1,4-addition. Stereochemistry of the 1,4-addition is explained by an intramolecular anti attack of the allylsilane moiety to a Pd(II)-coordinated diene functionality in 26 to generate (jt-allyl)palladium complex 27 followed by an intermolecular anti attack of a chloride ion. The substrate allylsilane is easily prepared by the reaction of the corresponding allylic acetate with PhMCjSiLi. 

A few additional Pd-catalyzed schemes have been employed for Ilac type cyclization chemistry. Palladium-phenanthroline complexes were used by the Ragaini group to prepare indoles via the intermolecular cyclization of nitroarenes and alkynes in the presence of carbon monoxide <06JOC3748>. Jia and Zhu employed Pd-catalysis for the annulation of o-haloanilines with aldehydes <06JOC7826>. A one-pot Ugi/Heck reaction was employed in the preparation of polysubstituted indoles from a four-component reaction system of acrylic aldehydes, bromoanilines, acids, and isocyanides <06TL4683>. 

Attempts to employ allenes in palladium-catalyzed oxidations have so far given dimeric products via jr al lyI complexes of type 7i62.63. The fact that only very little 1,2-addition product is formed via nucleophilic attack on jral ly I complex 69 indicates that the kinetic chloropalladation intermediate is 70. Although formation of 70 is reversible, it is trapped by the excess of allene present in the catalytic reaction to give dimeric products. The only reported example of a selective intermolecular 1,2-addition to allenes is the carbonylation given in equation 31, which is a stoichiometric oxidation64. 

Palladium(II) salts, in the form of organic solvent soluble complexes such as PdCl2(RCN)2, Pd(OAc>2 or Li2PdCU, are by far the most extensively utilized transition metal complexes to activate simple (unactivated) alkenes towards nucleophilic attack (Scheme 1). Alkenes rapidly and reversibly complex to pal-ladium(II) species in solution, readily generating alkenepalladium(II) species (1) in situ. Terminal monoalkenes are most strongly complexed, followed by internal cis and trans (respectively) alkenes. Geminally disubstituted, trisubstituted and tetrasubstituted alkenes are only weakly bound, if at all, and intermolecular nucleophilic additions to these alkenes are rare. 

The palladium-catalyzed [3 + 2] cycloaddition of vinylic oxirane 20a [42] and aziridine 20b [39] with the activated olefin 4a for the formation of five membered cyclic ether 21a and pyrrolidine derivative 21b has also been reported in our laboratories. The mechanistic issue is very much similar to that discussed in Scheme 9. Pd(0) catalyst added oxidatively to 20 to produce the 7r-allylpalladium complex 22. The Michael addition of a hetero nucleophile in 22 to the activated olefin 4a gives 23 which undergoes intramolecular nucleophilic attack on the inner 7r-allylic carbon atom to give the cy-clized products 21 and Pd(0) species is generated (Scheme 10). Similarly, the palladium-catalyzed [3 + 2] cycloaddition of vinylic oxirane 20a with the N-losylimincs 24 is also known (Scheme 11) [43]. Intermolecular cycloaddition of vinyl epoxides and aziridines with the heterocumulenes such as isocyanates, carbodiimides and isothiocyanates is also known [44,45]. Alper et al. reported the regio- and enatioselective formation of the thiaolidine, oxathiolane, and dithiolane derivatives by the palladium-catalyzed cyclization reaction of 2-vinylthiirane with heterocumulenes [46]. 

The catalytic cycle in Scheme 21 is adapted from that proposed by Jolly et al. " for the dimerization of 1,3-butadiene with intermolecular trapping as discussed above. In the model the bisdiene coordinates around a reduced palladium center (e.g., 66) and undergoes oxidative addition with cyclization (oxidative coupling) via the yyn-addition of carbon and palladium across the diene to afford the intermediate palladacycle 68. Protonation of the Tj -allyl in an Se2 fashion leads to the aUcene complex 69, and stereospecific anfi-addition... 

Nucleophilic attack of stabilized carbon nucleophiles on coordinated olefins is also known. Hegedus developed the alkylation of olefins shown in Equation 11.31. The (olefin)palladium(II) chloride complexes did not react with malonate nucleophiles, but the triethylamine adduct does react with this carbon nucleophile to provide the alkylation product. This reaction has recently been incorporated into a catalytic alkylation of olefins by Widenhoefer. - Intramolecular reaction of the 1,3-dicarbonyl compounds with pendant olefins in the presence of (GHjCNl PdCl occurs to generate cyclic products containing a new C-C bond (Equation 11.32). Some intermolecular reactions with ethylene and propylene have also been developed by this group. Deuterium labeling studies (Equation 11.32) have shown that the addition occurs by external attack on the coordinated olefin. ... 

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