Ethyl γ‐Cyano‐α‐isocyanoalkanoates from α‐Metalated Ethyl Isocyano‐acetates or ‐propionates and Acrylonitriles

Isocyanoacetate Derivatives: Synthesis, Reactivity, and Application

“…Isocyanoacetates react with sulfenyl thiocyanates 459 to give R-addition products 468, which are supposed to be stable toward intermolecular cyclization but enter a series of transformations upon addition of triethylamine to yield 2-mercaptoimidazo [ Derivatives 484 can be converted to glutamic acid derivatives 485 by acid hydrolysis (Scheme 122). 248 Other activated olefins such as acrylonitriles 249 and R,βunsaturated ketones 250 Apparently, the more sterically hindered tert-butyl isocyanoacetate or the less acidic isocyanoacetamides could favor monoaddition, like monoalkylation of tert-butyl isocyanoacetate and isocyanoacetamides (section 3). For activated alkenes, with good leaving groups, such as nitroolefins, R,βunsaturated sulfones, and sulfides, the initially formed Michael adducts spontaneously cyclize to form pyrroles as the single product (see section 9.1).…”

“…R-Substituted isocyanoacetates, for example, 140, react with all types of activated alkenes to form monoadducts 491 in good yields (Scheme 124). 249 The combination of a Michael addition with a subsequent thermal cyclization via insertion of an isocyanide into the activated C-H bond leads to a variety of heterocyclic compounds. Thus, monoadducts of type 492, which can be generated in situ or obtained after isolation, can be cyclized to 1-and 2-pyrrolines 493 or 494 by heating with sodium ethoxide at 70-110 °C, thanks to the stabilization of the generated carbanion R to the electron-withdrawing X group.…”

“…Other activated olefins such as acrylonitriles and α,β-unsaturated ketones can be used as a Michael acceptors. Particularly reactive Michael components such as acrylonitrile, ethyl acrylate, and α,β-unsaturated carbonyls 487a gave mono- and bis-adducts in a ∼1:1 ratio.…”

“…For activated alkenes, with good leaving groups, such as nitroolefins, α,β-unsaturated sulfones, and sulfides, the initially formed Michael adducts spontaneously cyclize to form pyrroles as the single product (see section ). α-Substituted isocyanoacetates, for example, 140 , react with all types of activated alkenes to form monoadducts 491 in good yields (Scheme ) …”

“…The combination of a Michael addition with a subsequent thermal cyclization via insertion of an isocyanide into the activated C−H bond leads to a variety of heterocyclic compounds. Thus, monoadducts of type 492 , which can be generated in situ or obtained after isolation, can be cyclized to 1- and 2-pyrrolines 493 or 494 by heating with sodium ethoxide at 70−110 °C, thanks to the stabilization of the generated carbanion α to the electron-withdrawing X group. − The cyclization also takes place efficiently in the presence of catalytic amounts of Cu 2 O . The position of the double bond (formation of 1- or 2-pyrrolines) is determined by the structure of the starting adduct.…”