Palladium(0)-Catalyzed Allylation of Ambident Nucleophilic Aromatic Heterocycles

Publisher Summary 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: (1) unlike other alkylation procedures, the Pd(0)-catalyzed allylation can sometimes give the product of thermodynamic control when applied to ambident nucleophiles and (2) the Tsuji–Trost allylation has become one of the standard methods for synthesizing carbanucleosides that are important antiviral compounds. The chapter presents the Pd(0)-catalyzed allylations of aromatic ambident heterocyclic compounds, including all rings for which an aromatic tautomeric or resonance form can be written. Cases of carbon (C) vs. oxygen (O), C vs. nitrogen (N), N vs. oxygen (O), and sulfur (S) vs. N allylation are discussed from all available viewpoints: regioselectivity, kinetic vs. thermodynamic control, mechanism, stereochemistry, and targeted molecules. In other cases, the N vs. N allylations are reported, including a discussion of the effects of the substituents on the regioselectivity. The chapter is organized by size of the ring and, within the size, by the nature and number of the heteroatom(s) contained in the ring. Recently, Pd(0)-catalyzed allylation of purine bases and structurally related heterocycles has become one of the standard methods for preparing carbanucleosides having, in many cases, real antiviral activity.