Tsuji-Trost reaction, palladium chemistry

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. 

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). 

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. 

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. 

The field of palladium catalysis is also progressing rapidly. The Tsuji-Trost and Mizoroki-Heck reactions have been mentioned earher, however other C-C coupling reactions (Miyaura-Suzuki, Sonogashira and Stille) are now extensively used in organic chemistry, and the search for non-polluting Sonogashira and Miyaura-Suzuki reactions is being actively pursued. 

The use of palladium(II) 7i-allyl complexes in organic chemistry has a rich history. These complexes were the first examples of a C-M bond to be used as an electrophile [1-3]. At the dawn of the era of asymmetric catalysis, the use of chiral phosphines in palladium-catalyzed allylic alkylation reactions provided key early successes in asymmetric C-C bond formation that were an important validation of the usefulness of the field [4]. No researchers were more important to these innovations than Prof. B.M. Trost and Prof. J. Tsuji [5-10]. While most of the early discoveries in this field provided access to tertiary (3°) stereocenters formed on a prochiral electrophile [Eq. (1)] (Scheme 1), our interest focused on making quaternary (4°) stereocenters on prochiral enolates [Eq. (2)]. Recently, we have described decarboxylative asymmetric allylic alkylation reactions involving prochiral enolates that provide access to enantioenriched ot-quatemary carbonyl compounds [11-13]. We found that a range of substrates (e.g., allyl enol carbonates,... 

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