A Rapid Entry to Diverse γ‐Ylidenetetronate Derivatives through Regioselective ­Bromination of Tetronic Acid Derived γ‐Lactones and Metal‐Catalyzed Postfunctionalization

Abstract

The synthesis of a series of diverse methyl and benzyl γ‐ylidenetetronate derivatives was accomplished through the condensation of methyl and benzyl tetronates with (hetero)aryl aldehydes in a new two‐ or three‐step aldolisation/dehydration sequence. The bromination of methyl and benzyl γ‐ylidenetetronates occurred under mild conditions to provide the corresponding C‐3‐brominated γ‐unsaturated lactones. Di‐ and tribrominated γ‐lactones were prepared under slightly different conditions. Some brominated materials were employed in representative Stille, Suzuki–Miyaura, and Sonogashira cross‐coupling reactions to yield functionalized methyl and benzyl γ‐ylidenetetronate derivatives. Compounds that resulted from the Sonogashira cross‐coupling reactions were desilylated and converted into 1,2,3‐triazole derivatives through a copper(I)‐catalyzed 1,3‐dipolar cycloaddition reaction with benzyl azide.

Collective synthesis of aspulvinone and its analogues by vinylogous aldol condensation of substituted tetronic acids with aldehydes

“…Firstly, a series of fully methylated products (12)(13)(14)(15)(16)(17)(18)(19) and partly ethylated ones (20-21) were synthesized using MeOH or EtOH as solvent. Then, some natural products protected by benzyl groups (22-30) were synthesized with similar conditions using MeCN as solvent.…”

“…In Chopin's work, they proposed a method for aldol condensation using 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) as the base in acetonitrile (MeCN) at 65 °C. 19 Initially, we used this method for aspulvinone's synthesis and successfully gained the desired product ( Table 1 , Entry 1). Then, the reactions were conducted at 65 °C employing DBU (2 eq.)…”

Evaluation of ferrocenyl-containing γ-hydroxy-γ-lactam-derived tetramates as potential antiplasmodials

“…-Ylidene-tetronates 12-19 were obtained through the condensation of methyl and benzyl tetronates 4a-b (methyl tetronate 4a being commercially available) with heteroaryl aldehydes 5-11, in a 2-steps aldolisation/dehydration sequence recently disclosed in our laboratory (Scheme 1) [12]. Scheme 1.…”

“…Scheme 1. General approach to prepare the -ylidene-tetronates 12-19 [12] Lactones 12-19 were engaged in a Ring Opening-Ring Closure (RORC) lactamization reaction with a series of ferrocenyl alkyl amines [Fc(CH2)nNH2; n = 1, 2, 3; Fc = Ferrocenyl] as well as with 4-trifluoromethylphenyl benzyl amine (for lactones 16 and 19) (Table 1, scheme 2). The transformation was conducted in anhydrous MeOH, in a sealed tube at 80°C, until complete consumption of the starting -lactone (overnight).…”

“…While synthetic antimalarials having a -lactam or pyrrolone skeleton have been scarcely explored [10], one can argue that molecules of general structure 1 are chloroquine-like structures and they may in part act through inhibition of hemozoin formation [11] as CQ. Since these tetramates are obtained easily through ring opening-ring closure (RORC) process of readily available -ylidene-tetronates [12] in the presence of amines [8], our next goal was to screen synthetic or commercially available amines in an effort to identify new potent tetramates not bearing a 4-aminoquinoline skeleton. From these screening experiments, ferrocenylcontaining -hydroxy--lactam tetramates were discovered as the most potent molecules.…”