Arylation of 2-Furyl 4-Fluorophenyl Ketone: An Extension of Heck Chemistry towards Novel Integrase Inhibitors

Abstract

An optimized procedure for the direct and regioselective arylation of 2-acylfurans has been developed. The versatility of this protocol has been evaluated on a series of aryl and heteroaryl halides, thus obtaining a small collection of 2,5-disubstituted furans in moderate to good yields. Finally, the optimized protocol has been successfully applied to the synthesis of the HIV-1 integrase inhibitor 3 and could be further exploited for the generation of novel substituted furans as potential integrase inhibitors.

Methyl 2-hydroxy-4-iodobenzoate

“…It can also be found in various foods (Duthie & Wood, 2011). The title compound, 2-hydroxy-4-iodobenzoic acid methyl ester (methyl 4-iodosalicylate, C 8 H 7 IO 3 ) allows for an effective way of incorporating the said methyl salicylates within larger organic molecules, using such methodologies as McClure protocols (Franchi et al, 2010;McClure et al, 2001), Stille (Yoon et al, 2019;Stille, 1986) and Suzuki-Miyaura reactions (Fracaroli et al, 2014;Miyaura et al, 1979), which take advantage of the iodine atom at the 4-position of the aromatic ring for the formation of carbon-carbon bonds. The iodine atom is also capable of forming supramolecular synthons, which may be useful for crystal engineering (Desiraju, 1995;Cherukuvada et al, 2016;Mitchell et al, 2023).…”

Recent Advances in the Synthesis of 5-(Hetero)aryl Uracil Derivatives

“…Franchi, et al first reported a modified Heck reaction of 5-iodo-1,3-dimethyluracil (33) with reactive 4-fluorophenyl(2-furyl)methanone (34) to afford the 5-aryluracil 35 in a moderate yield (51%). 66 Later, Wnuk and colleagues found that the additive tetrabutylammonium fluoride (TBAF) effectively promoted the direct arylation of 5-halogenated nucleosides with less-reactive (hetero)aromatics, such as toluene (Scheme 13). 67 Wen et al used this method to synthesize 5-heteroaryluracil 37 in high yields, without the need for any ligands or the preparation of organometallic precursors or arylboronic acids, making the process suitable for the modification of nonactivated nucleosides.…”

Phosphine-free polystyrene-supported palladium(II) complex as an efficient catalyst for the Heck and Suzuki coupling reactions in water

“…In the past few years, the development of ligands has provided highly active homogeneous palladium catalysts for the Heck [41][42][43][44][45][46][47] and Suzuki [48][49][50][51] coupling reactions. However, homogeneous processes suffer from problems concerning separation of the expensive palladium catalysts from reaction mixture, and their reuse.…”