Carbon-heteroatom double bonds cyclizations

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. 

Five-membered carbo- or heterocycles can be prepared with the aid of heteroatom-substituted carbene complexes in several different ways. In the following sections the focus will be on cyclization reactions in which the carbon-metal double bond plays a decisive role. 

The converse situation in which ring closure is initiated by the attack of a carbon-based radical on the heteroatom has been employed only infrequently (Scheme 18c) (66JA4096). The example in Scheme 18d begins with an intramolecular carbene attack on sulfur followed by rearrangement (75BCJ1490). The formation of pyrrolidines by intramolecular attack of an amino radical on a carbon-carbon double bond is exemplified in Scheme 19. In the third example, where cyclization is catalyzed by a metal ion (Ti, Cu, Fe, Co " ), the stereospecificity of the reaction depends upon the choice of metal ion. 

A typical radical cyclization involves the attack of a radical center on an sp carbon of a double bond (or other unsaturated group) in the chain. If the chain includes one or more heteroatoms, then a heterocycle will be formed. In Scheme 4.44, we examine the cyclization of a radical to form a 5-membered ring (a pyrrolidine) by this process. Note the practice of showing single-electron processes with single-barbed arrows ( fish hooks ). 

The influence of substituents on the double bond, on the aliphatic chain, and on the carbon radical has been extensively studied in the case of irreversible cyclization processes. In this section, the results obtained by Walling, Beckwith, Julia, and their coworkers using alkyl-substituted 5-hexenyl radicals are described. The influence of heteroatoms and of stabilizing groups is discussed in another section. 

Intramolecular addition of heteroatomic radicals to a double bond is, in most of the cases studied, a more general and more efficient process than intramolecular addition of carbon radicals. It is thus possible to propose new methods for the preparation of heterocyclic compounds and to consider that these processes are involved in important biogenetic schemes such as penicillin or prostaglandin biosynthesis. It is not always easy to conclude that a free radical process is involved because of the possibility of competitive ionic cyclizations. 

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