Synthesis of (2,2,2-trifluoroethyl) substituted pyridazin-3(2H)-ones and 1,5-dihydropyrrol-2-ones from α,β-unsaturated γ-lactones and hydrazines

Incorporation of a 3-(2,2,2-Trifluoroethyl)-γ-hydroxy-γ-lactam Motif in the Side Chain of 4-Aminoquinolines. Syntheses and Antimalarial Activities

“…They are prepared in 7–8 steps from commercially available perfluoroalkyl esters 1 – 3 . The first key perfluoroketene dithioacetal building blocks 4 – 10 ,,,, ( 6 and 8 are new compounds) were obtained in three steps (Scheme ) using our published procedures from the reduction of the esters 1 – 3 using lithium aluminum hydride in diethyl ether at 0 °C followed by aqueous acid hydrolysis to give the corresponding aldehyde hydrates, which are directly treated with appropriate thiols in the presence of TiCl 4 in dichloromethane to provide the corresponding dithioacetals. HF elimination of the latter in the presence of potassium hydroxide under phase transfer catalysis yielded the compounds 4 – 10 .…”

“…For some years we have been developing methodologies to generate fluoroalkylated heterocycles using perfluoroketene dithioacetals as versatile building blocks. − Among the different heterocyclic structures that have been disclosed, γ-lactams bearing a trifluoroethyl moiety were readily obtained from the reaction of primary amines and several α,β-unsaturated γ-lactones, as well as from the treatment of fluoroalkylated γ-ketothioesters with diisopropylamine followed by addition of various primary amines (Figure ) …”

Preparation of 3,5-diarylsubstituted 5-hydroxy-1,5-dihydro-2H-pyrrol-2-ones via base-assisted cyclization of 3-cyanoketones

“…1). 13 A typical synthetic approach to these nitrogen-based heterocycles involves the reaction of ve-membered lactone precursors with ammonia [14][15][16][17] or amines, 18,19 reductive cyclization of nitroolens with 1,3-diketones, 20 or various aldol-type cyclocondensations. [21][22][23][24] In application to the synthesis of 3,5-diarylsubstituted 5-hydroxy-1,5-dihydro-2H-pyrrol-2-one, just a handful of synthetic approaches provided decent results, 23,25 while most of the described protocols rely on the utilization of precursors that are quite exotic.…”