Tsuji-Trost reaction addition reactions

The catalytic version of allylation of nucleophiles via 7r-allylpaUadium intermediates was discovered in 1970 using allylic esters and aUyl phenyl ethers as substrates (Scheme Formation of 7r-allylpaUadium complexes by oxidative addition of various allylic compounds to Pd(0) and subsequent reaction of electrophilic rr-allylpalladium complexes with soft carbon nucleophiles are the basis of the catalytic allylation. After the reaction, Pd(0) is regenerated, which undergoes oxidative addition to the allylic compounds again, making the whole reaction catalytic. The efficient catalytic cycle is ascribed to the characteristic feature that Pd(0) is more stable than Pd(II). Allylation of carbon nucleophiles with allyhc compounds via TT-allylpalladium complexes is called the Tsuji-Trost reaction. The reaction has wide synthetic applications, particularly for cyclization. " ... 

The Tsuji-Trost reaction is the palladium-catalyzed allylation of nucleophiles [110-113]. In an application to the formation of an A-glycosidic bond, the reaction of 2,3-unsaturated hexopyranoside 97 and imidazole afforded A-glycopyranoside 99 regiospecifically at the anomeric center with retention of configuration [114], Therefore, the oxidative addition of allylic substrate 97 to Pd(0) forms the rc-allyl complex 98 with inversion of configuration, then nucleophilic attack by imidazole proceeds with a second inversion of configuration to give 99. 

Pd(0)-catalyzed allylations of 4(5)-nitroimidazole, 2-methyl-4(5)-nitroimidazole, 4(5)-bromoimidazole and 4(5)-methoxyimidazole resulted in complicated mixtures, which did not necessarily reflect the tautomeric ratios of the starting material [7], For example, poor regioselectivity for the products (70 and 71) was observed in the Tsuji-Trost reaction of 4(5)-bromoimidazole with cinnamyl carbonate. However, the same reaction with 4(5)-nitroimidazole and 2-methyl-4(5)-nitroimidazole led predominantly to the l-allylation products. In addition, removal of the 77-imidazole allyl groups can be selectively effected under mild conditions by Pd-catalyzed ic-allyl chemistry [55],... 

The efficient catalytic cycle is ascribed to the characteristic feature that Pd(0) is more stable than Pd(II). Reactions of 7t-allylpalladium complexes with carbon nucleophiles are called Tsuji Trost reactions. In addition to Pd, other transition metal complexes, such as those of Mo [26], Rh [27] and other metals, are used for catalytic allylation. 

Flahaut et al. investigated the potential of chiral amino functionalised carbene ligands in the Tsuji-Trost reaction [252], In the absence of phosphane, the system (see Figure 3.85) generated the product in 33% yield after 2 days. The addition of 7 mol% (2.3 equiv.) PPh resulted in complete conversion after just 1 h. The assumption is that the phosphane replaces the hanilabile amino sidearm carrying the chiral information. This is confirmed by a rapid drop in ee (76% down to 10%). 

A wide variety of nucleophiles add to an -rf-allyl ligand. Desirable nucleophiles typically include stabilized carbanions such as CH(COOR)2 or 1° and II0 amines. Unstabilized nucleophiles such as MeMgBr or MeLi often attack the metal first and then combine with the n-allyl by reductive elimination. The Tsuji-Trost reaction, which is typified by the addition of stabilized carbanions to T 3—allyl ligands complexed to palladium followed by loss of the resulting substituted alk-ene, comprises an extremely useful method of constructing new C-C bonds, and many applications of this reaction have appeared in the literature.61 Equation 8.43 illustrates an example of a Pd-catalyzed addition of a stabilized enolate to an allyl acetate.62 The initial step in the catalytic cycle is oxidative addition of the allyl acetate to the Pd(0) complex, followed by nq1 to nq3—allyl isomerization, and then attack by the nucleophile to a terminal position of the T 3—allyl ligand. We will discuss the Tsuji-Trost reaction, especially in regard to its utility in chiral synthesis,63 more extensively in Chapter 12. 

The Tsuji-Trost reaction is the Pd-catalyzed allylation of nucleophiles [105] with allylic halides, acetates, carbonates, etc. This transformation proceeds via intermediate allylpalladium complexes (e.g. 110), and typically proceeds with overall retention of stereochemistry. In addition, the trapping of the intermediate allylpalladium complex usually occurs at the least hindered carbon. A representative example of this transformation is shown below in an application to the formation of an 7V-glycosidic bond. Treatment of 2,3-unsaturated hexopyranoside 109 with imidazole in the presence of a Pd(0) catalyst... 

Palladium-catalyzed allylic substitution reactions, known as Tsuji-Trost reactions, are a well-established method for carbon-carbon bond forming processes [48]. The generally accepted mechanism for this reaction involves the oxidative addition of the allylic substrate to Pd(0) to provide a Jt-allylpalladium complex. The subsequent reaction of the electrophilic 7t-allylpalladium complex with the nucleophile affords the substituted product and Pd(0), which is regenerated to start the catalytic cycle (Scheme 7.26). 

Domino Nucleophilic Addition-Tsuji-Trost Reaction 301... 

A complementary functional cyclopropane assembly relies on the utilization of the Tsuji-Trost reaction [101], A highly enantio and diastereoselective cou-pling/cyclopropanation sequence of acyclic amides 85 with allyl carbonates 86 is illustrated in Scheme 5.30 [102], In this reaction, a scarcely described addition of the nucleophilic enolate intermediate onto the central carbon of the i-allyl palladium is involved, which affords the corresponding cyclopropane. 

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