An Intramolecular Wittig Approach toward Heteroarenes: Synthesis of Pyrazoles, Isoxazoles, and Chromenone-oximes

Abstract

α-Halohydrazones/ketoximes are transformed into trisubstituted pyrazoles/disubstituted isoxazoles by treatment with phosphine, acyl chloride, and a base. Mechanistic investigations revealed the in situ formation of azo/nitroso olefin intermediates which underwent a tandem phospha-Michael/N-or O-acylation/intramolecular Wittig reaction to afford the heteroarenes in moderate to good yields. Further, proper functionalization of α-haloketoximes and a change of conditions allowed the chemoselective synthesis of chromenone-oximes as well as rearranged isoxazoles, thereby realizing a diversity-oriented synthesis.

Update on the Synthesis of N‐Heterocycles via Cyclization of Hydrazones (2017–2021)

“…In 2019, Lin and co-workers achieved a metal-free strategy for the synthesis of pyrazoles/isooxazoles 404 in the presence of α-halohydrazones/ketoximes 403 with phosphine, acyl chlorides, and base (Scheme 62). [117] Notably, the catalytic system exhibits good tolerance to halogen, nitro, methyl, methoxyl, trifluoromethyl, and phenyl groups. Surprisingly, the less reactive hydrazone 404 c (R 1 = CH 3 ) is also suitable for this transformation and generates the desired product with a yield of 54%.…”

Six-membered ring systems: with O and/or S atoms

“…A chemoselective intramolecular Wittig approach is involved in the reaction of 2 0aroyloxy-a-chloroacetophenone oximes with acyl chlorides in the presence of Scheme 71 Scheme 72 7-methyl-1,5,7-triazabicyclo[4.4.0]dec-5-ene and are solvent dependent: in THF, isoxazoles are formed, while in dichloromethane, chromenone-oximes result (19OL4219). A wide range of 2-arylfurano[3,2-g]chroman-4-ones were synthesized in moderate to good yields through cycloisomerization reaction of 2 0 -hydroxyfuranochalcones mediated by sulfuric acid in refluxing ethanol (19S3431).…”

Molecular docking analysis of selected pyrimidine derivatives with human cyclin-dependent kinase 2

“…All the ligand molecules were allowed to be flexible and their torsional roots were detected and chosen. PDB files were further optimized and converted to pdbqt files for molecular docking by using AutoDock Tools 1.5.6 [ 24 ]. The X-ray structure of PDB id: 1HCK was accessible with the help of the protein data bank.…”