Microwave‐Assisted Synthesis of Polysubstituted 4‐Quinolones from Deprotonated α‐Aminonitriles

Abstract

The α‐alkylation of deprotonated N‐aryl‐α‐aminonitriles with α‐bromoesters furnishes intermediates that can be cyclized to 4‐quinolones upon microwave irradiation. Alternatively, base‐induced dehydrocyanation of the alkylation products furnishes enaminoesters, which can, for example, be converted into quinoline‐3‐carboxylates.

Heterocycles from α‐Aminonitriles

“…[56] Couty and co-workers reported a related synthesis of the 2cyano azetidines 89 and 92 starting from b-amino alcohols 85 which were converted to the intermediate a-aminonitriles 88 and 91. [59] Compared to the classical Conrad-Limpach synthesis from b-ketoesters and anilines, [60] this method is of higher modularity but has limitations with respect to the steric bulk of the substitutent R 3 . Interestingly, in the case of phenylglycinol, the rearranged chloride is produced by formation of an intermediate aziridinium salt.…”

Microwaves in Heterocyclic Chemistry

“…(16.19)]. The products were easily purified by crystallization from EtOH (87-93%) [ The α-alkylation of deprotonated N-aryl-α-aminonitriles with α-bromo esters furnished intermediates that cyclized to 4-quinolines upon microwave irradiation at 250 • C [107]. Gorobets and co-workers quickly generated a library of 105 eight steps.…”

rac-4-{(E)-[1-Cyano-1-cyclohexyl-2-(1H-indol-3-yl)ethyl]iminomethyl}benzonitrile

“…For the synthesis, see: Somei et al (1980). For synthetic applications of deprotonated aminonitriles, see: Opatz (2009); Meyer et al (2005); in polysubstituted pyrroles, see: Bergner & Opatz (2007); in tetrahydroisoquinolines, see: Werner et al (2007); Ferenc & Opatz (2008); Romek & Opatz (2010).…”