Palladium catalysts Tsuji allylation

While simple unactivated cyclopropanes have yet to be used for [3 + 2] cycloaddition, Tsuji and coworkers have developed a palladium-catalyzed cycloaddition reaction using electron-deficient vinylcy-clopropanes. Thus, vinylcyclopropane (43) undergoes smooth cyclization with methyl acrylate in the presence of a palladium catalyst to give vinylcyclopentane (44) as a mixture of diasteroisomers (equation 35). The cycloaddition probably proceeds through the zwitterionic ( ir-allyl)palladium intermediate (45) and its stepwise reaction with the acrylate (equation 36). Enones such as cyclopentenone and methyl vinyl ketone will also react. Reaction of the same vinylcyclopropane with phenyl isocyanate produces vi-nyllactam (46) (equation 37).Some cycloaddition reactions with (cyclopropyl)Fp complexes have also been reported. However, the substrates are limited to SO2 and TCNE and the yields have not been disclosed (equation 38). ... 

Enol carbonates react with alkylating agents in the presence of a palladium catalyst. The decarboxylative alkylation of allyl enol carbonates to the corresponding aUylcyclohexanone derivatives is known as the Tsuji alkylation. An asymmetric version of this reaction has been reported. The same reaction can be done using enolate anion and aUylic acetates with a palladium catalyst. ... 

Palladium Catalysts Palladium catalysts are effective and powerful for C—H bond functionalization. Carbene precursors and directing groups are commonly used strategies. Generally, sp3 C—H bond activation is more difficult than sp2 C—H bond activation due to instability of potential alkylpalladium intermediates. By choosing specific substrates, such as these with allylic C—H bonds, palladium catalytic systems have been successful. Both intramolecular and intermolecular allylic alkylation have been developed (Scheme 11.3) [18]. This methodology has presented another alternative way to achieve the traditional Tsuji-Trost reactions. 

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. 

In 1967 elimination of phenol from allyl phenyl ethers to form 1,3-diene in the presence of a palladium catalyst was reported briefly by Smutny. Later, Tsuji applied the Pd-catalyzed elimination reaction of terminal allylic compounds for the synthesis of terminal 1,3-dienes.Thus, elimination of acetic acid and phenol from allylic acetates and allyl phenyl ethers was carried out by refluxing the allylic compounds in dioxane or toluene in the presence of catalytic amounts of palladium acetate and PPha as a ligand for the palladium catalyst (Table 1). The allylic isomers were converted to the same products. No reaction takes place with allylic methyl ether, an allylic alcohol, or an allylic amine, which cannot easily form 7r-allylpalladium complexes by oxidative addition. 

Again we drew from the pioneering work of Prof. Tsuji, who demonstrated that allyl p-ketoesters, when treated with an achiral palladium catalyst and formic acid (presumably acting as both an acid and a reductant), produce a ketone product in excellent yield [28]. 

More recently, in 2003, Sorensen demonstrated an impressive, scalable synthesis of cytotoxic natural product (+)-FRl 82877 34, which employed an intramolecular Tsuji-Trost allylation reaction to prepare the 19-membered macrocycle 33. Exposure of allylic carbonate 32 to 10 mol% palladium catalyst under high dilution formed the key bond in good yield and complete diastereoselectivity. This key intermediate was subsequently converted to (+)-FRl 82877 34 via an intramolecular Diels-Alder reaction. 

The Tsuji-Trost reaction involves the coupling of allyl electrophiles with nucleophiles with a broad range of metal complexes, including those of nickel, palladium, platinum, rhodium, iron, ruthenium, etc (Scheme 13.37). " In a typical example, an allyl acetate or carbonate reacts with a palladium catalyst by displacement of the leaving group to give 7i-allyl palladium complexes that can undergo substitution by a nucleophile. 

The supported aqueous phase methodology was applied to the system Pd(OAc)2/5 TPPTS, a catalytic precursor for the Trost-Tsuji reaction. The characterization of the solid by 31P MAS NMR confirms the presence of Pd°(TPPTS)3 as the main surface species. The catalytic properties of the solid were tested for the allylic substitution of E-cinnamylethylcarbonate by different nucleophiles such as ethyl acetoacetate, dimethyl malonate, morpholine, phenol, and 2-mercapto-pyridine. The absence of palladium leaching was demonstrated, and having solved the problem of water leaching from the solid to the organic phase, the SAP-Pd catalyst was successfully recycled several times without loss in its activity. It was used in a continuous flow experiment which... 

For further details of this reaction, the reader is referred to Chapter 9. The catalytic allylation with nucleophiles via the formation of Ti-allyl metal intermediates has produced synthetically useful compounds, with the palladium-catalyzed reactions being known as Tsuji-Trost reactions [31]. The reactivity of Ti-allyl-iridium complexes has been widely studied [32] for example, in 1997, Takeuchi idenhfied a [lrCl(cod)]2 catalyst which, when combined with P(OPh)3, promoted the allylic alkylation of allylic esters 74 with sodium diethyl malonate 75 to give branched... 

By 1984, the palladium-catalyzed aUyhc alkylation reaction had been extensively studied as a method for carbon-carbon bond formation, whereas the synthetic utility of other metal catalysts was largely unexplored [1, 2]. Hence, prior to this period rhodium s abihty to catalyze this transformation was cited in only a single reference, which described it as being poor by comparison with the analogous palladium-catalyzed version [6]. Nonetheless, Yamamoto and Tsuji independently described the first rhodium-catalyzed decarboxylation of allylic phenyl carbonates and the intramolecular decarboxylative aUylation of aUyl y9-keto carboxylates respectively [7, 8]. These findings undoubtedly laid the groundwork for Tsuji s seminal work on the regiospecific rho-... 

Since its discovery by Tsuji [15,16] and catalytic expansion by Hata [17] and Atkins [18], allylic substitution has become the most popular palladium-catalyzed method for carbon-carbon bond formation along with crosscoupling reactions. However, the first report using NHC in this transformation only appeared recently [19]. An imidazolium salt with a bulky substituent on the nitrogen atoms, IPr HC1, was found to be a suitable ligand for allylic substitution with soft nucleophiles (Scheme 2). Pd2(dba)3 as palladium source and Cs2C03 as base completed the catalyst system. 

In their enantioselective total synthesis of the alkaloid cephalotaxine (246), Tietze and Schirok [127] used a combination of a Tsuji-Trost and a Mizoroki-Heck reaction (Scheme 8.62). It was necessary to adjust the reactivity of the two palladium-catalysed transformations to allow a controlled process. Reaction of 243a using Pd(PPh3)4 as catalyst led to 244, which furnished 245 in a second palladium-catalysed reaction. In this process, the nucleophilic substitution of the allylic acetate is faster than the oxidative addition of the arylbromide moiety in 243a however, if one uses the iodide 243b, then the yield drops dramatically due to an increased rate of the oxidative addition. 

Ally lie substitution (the Tsuji-Trost reaction) is among the most synthetically useful processes in palladium catalysis. As the catalytic efficiency of allylic substitution is often moderate (5-10 mol % of Pd catalyst are usually used), and phosphine-free systems are generally inefficient, the recycling of catalyst is the only feasible way to make the process more economical. Various phase-separation techniques have been tried for this reaction. In what concerns the rate of reaction and catalytic efficiency, such ligands as TPPTS are likely to be less effective compared to PhsP.f Thus, the main reason for the use of hydrophilic ligands in allylic substitution is the design of recyclable systems. 

Thanks to the fundamental studies of Tsuji, Trost, and others, palladium-catalyzed allylic substitution has become a versatile, widely used process in organic synthesis [40]. The search for efficient enantioselective catalysts for this class of reactions is an important goal of current research in this field [41]. It has been shown that chiral phosphine ligands can induce substantial enantiomeric excesses in Pd-catalyzed reactions of racemic or achiral allylic substrates with nucleophiles [42]. Recently, promising results have also been obtained with chiral bidentate nitrogen ligands [43]. We have found that palladium complexes of neutral aza-semicorrin or methylene-bis(oxazoline) ligands are effective catalysts for the enantioselective allylic alkylation of l,3-diphenyl-2-propenyl acetate or related substrates with dimethyl malonate (Schemes 18 [25,30] and 19 [44]). 

The research groups of Trost and Tsuji have shown that in the presence of a palladium(O) catalyst vinyl epoxides can be regio- and stereo-selectively alkylated with various carbon acids under neutral conditions the main products are E-allylic alcohols resulting from 1,4-addition, e.g. (107) - (108). The reaction tolerates ester and ether groups. In the presence of a base, alkyl-lithiums... 

The basic mechanism of the Tsuji-Trost reaction is as follows All palladium precatalysts are converted to the active palladium(0) catalyst 11 in situ, most commonly by phosphine in phosphine assisted catalytic cycles. Following coordination of the allylic reagent 1 to the palladium(0) catalyst 11, oxidative addition occurs to give Jt-allylpalladium(II) complexes 13/14 (this step is also known as ionization). Complexes 13/14 can interconvert via ligand exchange... 

Several other metal catalysts have been shown to mediate the Tsuji-Trost reaction, with molybdenum being the most developed. Trost first reported the use of molybdenum for allylic alkylation in 1982. The most important aspect of the use of this metal is its regiocomplimentary with the palladium-catalyzed process. While palladium preferentially gives linear adducts (in the absence of electronic bias), molybdenum gives preferentially branched adducts. ... 

The Overman esterification is a palladium-catalyzed formation of enantioenriched allyl esters from carboxylic esters with primary allyl imidates. From a mechanistic point of view, it is related to the Tsuji-Trost reaction. It proceeds under quite mild conditions with high enantiomerically access if the COP ([Ti -(5)-2-(4-methylethyl)-oxazolinylcyclo-pentadienyl]-(T] -tetraphenylcyclobutadiene)cobalt) complex is used. For example, Kirsch and co-workers used the Pd-catalyzed Overman esterification " in their approach to 1,3-polyols starting from (Z)-allylic trichloroacetimidates to build up the stereogenic centers. By choice of the required enantiomer of COP-OAc catalyst, every possible diastereoisomer is accessible in high stereoselectivity (Experimental Procedure below). 

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