Alkynes electrophilic heteroatom cyclizations

Electrophilic heteroatom cyclizations of systems involving alkyne and allene ir-systems have attracted significant attention. A major difference from alkene cyclizations is that the electrophilic group in the initial product may be a vinyl substituent, and, in the case of metal electrophiles, possess different reactivity patterns than when attached to a saturated carbon. 

The electrophile-induced cyclization of heteroatom nucleophiles onto an adjacent alkene function is a common strategy in heterocycle synthesis (319,320) and has been extended to electrophile-assisted nitrone generation (Scheme 1.62). The formation of a cyclic cationic species 296 from the reaction of an electrophile (E ), such as a halogen, with an alkene is well known and can be used to N-alkylate an oxime and so generate a nitrone (297). Thus, electrophile-promoted oxime-alkene reactions can occur at room temperature rather than under thermolysis as is common with 1,3-APT reactions. The induction of the addition of oximes to alkenes has been performed in an intramolecular sense with A-bromosuccinimide (NBS) (321-323), A-iodosuccinimide (NIS) (321), h (321,322), and ICl (321) for subsequent cycloaddition reactions of the cyclic nitrones with alkenes and alkynes. 

Electrophile-mediated cyclization reactions of alkynes tethered to pendant heteroatom nucleophiles is an emerging strategy for the synthesis of heterocycles. This methodology has now been applied to the synthesis of pyrroles. The iodocyclization of 3-aminoalkynes 1 led to the formation of dihydropyrrole 2 <07TL7906>. Treatment of the latter with mesyl chloride in the presence of triethylamine then gave (i-iodopyrrolcs 3. 

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. 

Addition of heteroatoms across alkynes activated by NIS has also been described. Aryl ketones cyclize under mild conditions in a 5-endo-dig fashion to afford 3-iodofuran derivatives (eq 32). Normally, electrophiles such as I+ add to the 2- and 5-positions of a furan ring, rather than the 3- or 4-positions. 

---