Palladium® complexes intermolecular reactions

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 2004, Molander et al. developed another type of chiral sulfur-containing ligands for the intermolecular Heck reaction. Thus, their corresponding novel cyclopropane-based phosphorus/sulfur palladium complexes proved to be active as catalysts for the reaction between phenyltriflate and dihydrofuran, providing at high temperature a mixture of the expected product and its iso-merised analogue (Scheme 7.7). The major isomer C was obtained with a maximum enantioseleetivity of 63% ee. 

The Heck reaction, a palladium-catalyzed vinylic substitution, is conducted with olefins and organohalides or pseudohalides are frequently used as reactants [15, 16], One of the strengths of the method is that it enables the direct monofunctionalization of a vinylic carbon, which is difficult to achieve by other means. Numerous elegant transformations based on Heck chemistry have been developed in natural and non-natural product synthesis. Intermolecular reactions with cyclic and acyclic al-kenes, and intramolecular cyclization procedures, have led to the assembly of a variety of complex and sterically congested molecules. 

The palladium-catalyzed arylation and alkenylation of olefins, which were first discovered in the 1970 s by Heck (7,2) and Mizoroki (3) and have been often called the "Heck reaction", are versatile synthetic means for making a carbon-carbon bond. These reactions have been extensively used for organic synthesis during the past two decades (4-7). However, no reports on the "asymmetric Heck reaction" have been appeared until very recently. Shibasaki reported an asymmetric intramolecular cyclization of alkenyl iodides to give c/j-decalin derivatives of 80-91% ee (8-10). Overman reported an intramolecular cyclization of alkenyl triflate, giving a chiral quaternary carbon center of 45% ee (77). We report herein the first example of intermolecular asymmetric Heck-type arylation of cyclic olefins catalyzed by (7 )-BINAP-coordinated palladium complexes (Scheme 1) (12,13). 

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]. 

In a similar manner, cyclopropane-containing benzvalene can be used as the alkene component in intermolecular Pauson-Khand reactions.Several examples of intermolecular Pauson-Khand cyclizations of methylenecyclopropanes and alkynes are reported to give bicyclic car-bocycles. Ethynylcyclopropyl-substituted chromium carbonyl complexes have also been used in palladium-catalyzed coupling reactions. 

The intermolecular asymmetric Heck reaction, a palladium-catalysed carbon-carbon bond forming process, is an efficient method for the preparation of optically active cyclic compounds.[1] Very recently, a new catalytic system has been developed based on palladium complexes having l-[4-(5)-tert-butyl-2-oxazolin-2-yl]-2-(5)-(diphenylphosphino)ferrocene (1) as the chiral ligand121 (Figure 5.2), which we have shown to be efficient catalysts for the enantioselective intermolecular Heck reaction of 2,3-dihydrofuran (2).[3] In contrast to complexes derived... 

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. 

An interesting generalization of the above reactions consists in the inclusion of an alkyne among the reagents. Since n-allyl palladium complexes have low reactivity as regards the intermolecular insertion of ordinary alkynes, this makes controlled benzyne-alkyne-alkene insertion possible (Scheme 41) [76]. 

The ophcally active Pd complex with a chiral allenyl ligand undergoes epimer-izahon in the presence of a catalytic amount of Pd(0) complex. This reaction does not involve the isomerization to the propargyl complex, but takes place via a dinuclear intermediate as depicted in Scheme 5.39. The -allenyl ligand in the dinuclear palladium intermediate may racemize via a vinyl-vinyidene intermediate. This type of reaction is prohahly involved in a kinetic resolution of racemic propargyl alcohols promoted hy chiral transihon metal complex [203]. The intermolecular allyl ligand transfer from Pd to Ee complexes occurs under... 

Guiry and coworkers [19] reported the preparation and testing of 2,2-dimethyl-2,3-dihydrofuran (22) as an interesting substrate for the intermolecular asymmehic Mizoroki-Heck reaction as this substrate only forms the one regioisomeric product 23. This allows for a true comparative test of a range of palladium complexes, and (7 )-BlNAP... 

To date, the large majority of asymmetric Mizoroki-Heck reactions reported have utilized palladium complexes of BINAP (5). However, since their first application to the asymmetric Mizoroki-Heck reaction, P,N ligands have proven successful and have thus received a greater amount of attention recently [30], The phosphinooxazoline PJSl ligands 41-45 developed independently by the groups of Pfaltz [31], Williams [32] and Hehnchen [33] have shown dramatic improvement in enantioselectivity in a number of asymmetric transformations, including the intermolecular asymmetric Mizoroki-Heck reaction [34]. 

The combination of palladium complex PdCl2(PPh3)2 with M0CI5, showed a high catalytic activity for the intermolecular reductive A -heterocyclization of 2-nitrobenzaldehyde or 2-nitrophenyl ketones with formamide. The corresponding quinazoline derivatives were produced in moderate yields (Table 9.2). For example, in the reaction of 2-nitrobenzaldehyde with formamide, quinazoline was obtained in a 46 % yield. The reaction goes through 2-nitrobenzaldiformamide as an intermediate. 

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. 

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. ... 

Intramolecular oxidative aminations of olefins have alsobeen studied, and many of these intramolecular processes were observed prior to the analogous intermolecular variants. The oxidative aminations of alkenes with arylamines and arylamine derivatives catalyzed by palladium complexes were shown by Hegedus to form indoles (Equation 16.120). These reactions were conducted with orf/io-allylaniline and ort/zo-allylaniline derivatives as substrate, Pd(NCMe)jCl2 as catalyst, and benzoquinone as oxidant. Intramolecular reactions of N-tosylated aliphatic amines were reported by Larock. ° For example, the tosylamide in Equation 16.121 imdergoes cyclization in high yield in the presence of dioxygen with Pd(OAc)j as catalyst in DMSO. A related reaction (Equation 16.122) was reported recently in toluene solvent with added pyridine. ... 

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 intennolecular acylpalladation corresponds to the addition of an acyl-palladium bond onto a rr-bond system of another molecule this elementary step can also be referred to as an insertion (Scheme I). This produces another organopalladium complex, which can in principle participate in subsequent propagation or termination reactions. This excludes processes that involve alkoxycarbonylation (R— = R O—) and hydrocarbonyla-tion (R— = H—). This section will focus on nonpolymeric intermolecular reactions of acylpalladium complexes with different 7r-bond systems (alkenes, imines, dienes, and alkynes). 

On the other hand, there are only a few reports of catalytic nonpolymeric reactions that involve the intermolecular reaction of an alkene with an acylpalladium complex. The first example was reported in 1968 while studying the decarbonylation of acyl chlorides in the presence of various palladium salts. For example, phenylpropionyl chloride gave styrene (53%) along with l,5-diphenyl-l-penten-3-one (10%) in the presence of catalytic amounts of PdCl2. The latter compound was probably formed via reaction of the acylpalladium complex, generated via oxidative addition in the acyl-chloride bond, with styrene itself formed via decarbonylation of the acylpalladium complex followed by /S-elimina-tion (Scheme 2). 

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