Synthesis of C-substituted triazoles, isoxazoles, and pyrazoles by 1,3-dipolar cycloaddition to acetylenic sugars

Abstract

Addition of phenyl azide to 3,5-di- O-acetyl-6,7-dideoxy-1,2- O-isopropylidene-β- l- idio-hept-6-ynofuranose ( 1) and subsequent saponification gave a 4-substituted 1-phenyl-1,2,3-triazole derivative ( 3) whose optical rotatory dispersion (o.r.d.) curve was positive. The α- d- gluco analog ( 5) of 1 similarly gave the 5-epimer ( 7) of 3; its o.r.d. curve was negative. Both 3 and 7 were degraded to the known 1-phenyl-1,2,3-triazole-4-carboxaldehyde. Similarly, addition of 2,4,6-trimethylbenzonitrile N-oxide to 1 or 5 gave the corresponding, crystalline 3-mesitylisoxazoles as single products; 13C-n.m.r. spectroscopy was used to establish the orientation of addition. Related 3-mesitylisoxazoles ( 11 and 13) were obtained from 1,2:3,4-di- O-isopropylidene- d- glycero-α- d-galacto -oct-7-ynopyranose ( 10) and its l- glycero 6-epimer ( 12), respectively; 11 showed the expected, large levorotation, and the 6-epimer 13 was also levorotatory. Benzonitrile ( N-phenyl)imine, prepared in situ from 1-(α-chlorobenzylidene)-2-phenylhydrazine and base, did not react with 10 (or its 6-epimer 12), but did react with the 6-keto analog to give a 5-substituted 1,3-diphenyl-1,2-diazole.