Tsuji-Trost reaction palladium-catalyzed reactions

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. 

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... 

The Tsuji-Trost Reaction (or Trost Allylation) is the palladium-catalyzed allylation of nucleophiles such as active methylenes, enolates, amines and phenols with allylic compounds such as allyl acetates and allyl bromides. 

Palladium(0)-catalyzed allylation of nucleophiles (the Tsuji-Trost reaction) is a versatile synthetic method that has gained immense popularity in recent years. Rarely applied to ambident nucleophilic aromatic heterocycles before 1991, the Tsuji-Trost reaction has been extensively used in the chemistry of these compounds since 1991. Two factors have played decisive roles in this increased interest in the Pd(0)-catalyzed allylation of such heterocyclic rings one is that, unlike other alkylation procedures, the Pd(0)-catalyzed allylation can sometimes give the product of thermodynamic control when applied to ambident nucleophiles and the second is that the Tsuji-Trost allylation has become one of the standard methods for synthesizing carbanucleosides, which are important antiviral compounds (93MI1, 93MI2). Of course, the double bond of an allylic system can be modified in different directions, thus adding versatility to the Tsuji-Trost reaction. 

Palladium(0)-catalyzed allylation of nucleophiles (Tsuji-Trost reaction) has become a powerful synthetic method owing to its versatility, broad... 

The Trost-Tsuji Reaction Palladium-Catalyzed Allylic Substitution ... 

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. 

Palladium(O)>catalyzed allylations of 4(5)-nitroimidazole, 2-methyl-4(5)-nitroimida-zole, 4(5)-bromoimidazole, and 4(5 )-melhoxyimidazole resulted in complicated mixtures, which did not necessarily reflect the tautomeric ratios of the starting material [7]. For example, poor regioselectivity for the products (123 and 124) 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 1-allylation products. In addition, removal of the V-imidazole allyl groups can be selectively effected under mild conditions by Pd-catalyzed K-allyl chemistry [81]. 

Leaving groups in the Tsuji-Trost reaction include acetates, halides, ethers, carbonates, sulfones, carbamates, epoxides, and phosphates. Reviews (a) Tsuji, J. In Handbook of Organopalladium Chemistry for Organic Synthesis, Negishi, E. deMeijere, A., Eds. Wiley-lnterscience New York, 2002 Vol II, Palladium-Catalyzed Nucleophile Substitution Involving Allyl Palladium, Propargyl-palladium and Related Derivatives, pp. 1669-1687. (b) Frost C. G. Howarth, J. Williams, J. M. J. Tetrahedron Asymmetry 1992, 3, 1089-1122. 

The allylation of active methylene compounds with allyl alcohols or their derivatives, called the Tsuji-Trost reaction, is a widely used process in academia as well as in industry. Ranu et al. have reported that the reaction of active methylene compounds with allyl acetate catalyzed by palladium(O) nanoparticles (Scheme 5.22) led to mono-allylation in water, whereas the reaction in THF provided the bis-allylated product. This is a remarkable example of controlling the direction of a reaction by water. 

Palladium-catalyzed reactions such as Suzuki, Heck, Trost-Tsuji and Stille have been modified in the presence of KF/A1203 without solvent under microwave irradiation conditions by Villemin et al. [10], These reactions rapidly afforded the product in moderate to excellent yields. For instance, a reaction of iodobenzene with arylboronic acids was completed in 2-15 min. Recently, improved methods under microwave irradiation have been reported [11-16] (Scheme 5.5). 

Palladium-catalyzed reactions have been widely investigated and have become an indispensable synthetic tool for constructing carbon-carbon and carbon-heteroatom bonds in organic synthesis. Especially, the Tsuji-Trost reaction and palladium(II)-catalyzed cyclization reaction are representative of palladium-catalyzed reactions. These reactions are based on the electrophilic nature of palladium intermediates, such as n-allylpalladium and (Ti-alkyne)palladium complexes. Recently, it has been revealed that certain palladium intermediates, such as bis-7i-allylpalladium, vinylpalladium, and arylpalladium, act as a nucleophile and react with electron-deficient carbon-heteroatom and carbon-carbon multiple bonds [1]. Palladium-catalyzed nucleophilic reactions are classified into three categories as shown in Scheme 1 (a) nucleophilic and amphiphilic reactions of bis-n-allylpalladium, (b) nucleophilic reactions of allylmetals, which are catalytically generated from n-allylpalladium, with carbon-heteroatom double bonds, and (c) nucleophilic reaction of vinyl- and arylpalladium with carbon-heteroatom multiple bonds. According to this classification, recent developments of palladium-catalyzed nucleophilic reactions are described in this chapter. 

The Tsuji-Trost reaction is the palladium-catalyzed substitution of allylic leaving groups by carbon nucleophiles. These reactions proceed via 7i-allylpalladium intermediates. 

Hallberg et al. have shown that microwaves accelerate palladium-catalyzed reactions (e.g. Suzuki, Heck, Tsuji-Trost, Stille) in solution or with supported polymers [127]. Most recently, Villemin and Caillot have reported that, in the Suzuki reaction, the use of a ligand-free palladium catalyst, palladium acetate, without the use of solvent under microwave irradiation produces good yields of biphenyl products, one of which is shown in Equation 89 [128]. 

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. ... 

In the twentieth century, palladium was the most important metal catalyst in transition metal-catalyzed organic transformations. First, many types of transformations can be catalyzed by a palladium catalyst, including the Heck reaction, the cross-coupling reaction, and the Tsuji-Trost reaction. Second, palladium is extraordinarily tolerant of nearly any type of organic functional group and its high chemoselectivity makes it feasible for use in functionalized or complex systems. Due to these characteristics, palladium is an ideal catalyst in cascade reactions and the total synthesis of natural products. 

Carbon-carbon cross-conphng reactions are among the most useful and most widely stndied synthetic transformations [23]. Palladium-catalyzed reactions for carbon-carbon bond formation, inclnding the Suzuki, Heck, Sonogashira, Tsuji-Trost, and... 

Thus, [HRh(C0)(TPPTS)3]/H20/silica (TPPTS = sodium salt of tri(m-sulfophenyl)phopshine) catalyzes the hydroformylation of heavy and functionalized olefins,118-122 the selective hydrogenation of a,/3-unsaturated aldehydes,84 and the asymmetric hydrogenation of 2-(6 -methoxy-2 -naphthyl)acrylic add (a precursor of naproxen).123,124 More recently, this methodology was tested for the palladium-catalyzed Trost Tsuji (allylic substitution) and Heck (olefin arylation) reactions.125-127... 

The formation of chromane derivatives has also been realised in the palladium catalyzed intramolecular nucleophilic substitution of allyl carbonates (Tsuji-Trost reaction). In most cases the reaction is accompanied by the formation of a new centre of chirality. Using Trost s chiral ligand the ring closure was carried out in an enantioselective manner. The asymmetric allylation of the phenol derivative shown in 4.20. was achieved both in good yield and with excellent selectivity.23... 

The palladium catalyzed intramolecular nucleophilic substitution of allyl alcohol derivatives (Tsuji-Trost reaction) has successfully been extended to the closure of a seven membered ring. The coupling of the allyl alcohol unit and the enamide was the key step in the preparation of the natural product claviciptic acid (5.14.),14... 

It is very well known that jr-allyl palladium complex 1, which is a key intermediate for the Tsuji-Trost type allylation, has an electrophilic character and reacts with nucleophiles to afford the corresponding allylation products. We discovered that bis 7r-allyl palladium complex 2 is nucleophilic and reacts with electophiles such as aldehydes [27] and imines [28-32] (Scheme 2, Structure 2). We have also shown that bis 7r-allyl palladium complex 2 can act as an amphiphilic catalytic allylating agent it reacts with both nucleophilic and electrophilic carbons at once to produce double allylation products [33]. These complexes incorporate two allyl moieties that can bind with different hapticity to palladium (Scheme 3). The different complexes may interconvert by ligand coordination. The complexes 2a, 2b and 2c are called as r]3,r]3-bisallypalladium complex (also called bis-jr-allylpalladium complex), r)l,r)3-bis(allyl)palladium complex, -bis(allyl)palladium complex, respectively. Bis zr-allyl palladium complex 2 can easily be generated by reaction of mono-allylpalladium complex 1 and allylmetal species 3 (Scheme 4) [33-36]. Because of the unique catalytic activities of the bis zr-allyl palladium complex 2, a number of interesting cascade reactions appeared in the literature. The subject of the present chapter is to review some recent synthetic and mechanistic aspects of the interesting palladium catalyzed cascade reactions which in-... 

Tsuji-Trost allylation reactions offer multiple pathways to tetrahydrofuran synthesis including C-C bond-formation steps. A palladium-catalyzed sequence of allylic alkylation and Hiyama cross-coupling provides a convenient synthesis of 4-(styryl)-lactones (Scheme 67) <2006SL2231>. 

Tsuji, J. Palladium-catalyzed nucleophilic substitution involving allylpalladium, propargylpalladium, and related derivatives the Tsuji-Trost reaction and related carbon-carbon bond formation reactions overview of the palladium-catalyzed carbon-carbon bond formation viart-allylpalladium and propargylpalladium intermediates, in Handbook of Organopalladium Chemistry for Organic Synthesis (ed. Negishi, E.-L), 2, 1669-1687 (John Wiley Sons, New York, 2002). 

Negishi, E.-i. Palladium-catalyzed cross-coupling involving 3-hetero-substituted compounds. Palladium-catalyzed a-substitution reactions of enolates and related derivatives other than the Tsuji-Trost allylation reaction. Handbook of Organopalladium Chemistry for Organic Synthesis 2002, 1, 693-719. 

Palladium-catalyzed nucleophilic substitution of allylic substrates (Tsuji-Trost coupling) is a most important methodology in organic synthesis and therefore it is no wonder that such reactions have been developed also in aqueous systems. Carbo- and heteronucleophiles have been found to react with allylic acetates or carbonates in aqueous acetonitrile or DMSO, in water or in biphasic mixtures of the latter with butyronitrile or benzonitrile, affording the products of substitution in excellent yields (Scheme 6.19) [7-11,14,45,46], Generally, K2C03 or amines are used as additives, however in some cases the hindered strong base diazabicycloundecene (DBU) proved superior to other bases. 

The comparison of intramolecular carbopalladation reactions of allenes and alkenes outlined in Schemes 9-5 and 9-6 illustrates that not every transition metal catalyzed ring closure necessarily involves a template effect. Others, however, clearly benefit from it. A prototype example is the palladium catalyzed cycloisomerization of alkenyl epoxides carrying distal pre-nucleophiles [38, 39], representing one variant of the famous Tsuji-Trost allylation [40]. 

Randomly hydroxylated and methylated CD (RM-yS-CD) with different cavity sizes have been used as biphasic aqueous catalysts in a palladium catalyzed Tsuji-Trost reaction with water-insoluble alkylallylcarbonates and alkylallylurethanes as substrates (Figure 4.6c). The reaction rate and substrate selectivity strongly depended on the cavity size of the CD. The cavity size is a crucial factor in controlling the substrate selectivity. Moreover, phosphanes that did not interact with the methylated CD were the most... 

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