Diazo Strategy for the Synthesis of Pyridazines: Pivotal Impact of the Configuration of the Diazo Precursor on the Process

• Published in: Chemistry : a European journal Vol. 22; no. 1; pp. 174 - 184
• Main Authors: Nikolaev, Valerij A., Cantillo, David, Kappe, C. Oliver, Medvedev, Jury J., Prakash, G. K. Surya, Supurgibekov, Murat B.
• Format: Journal Article
• Language: English
• Published: Weinheim WILEY-VCH Verlag 04.01.2016; WILEY‐VCH Verlag; Wiley; Wiley Subscription Services, Inc
• Subjects: Bonding; Chemistry; Chemistry, Multidisciplinary; cyclization; Cycloaddition; Functional anatomy; Functional groups; Irradiation; Isomerization; Isomers; Mathematical analysis; phosphazenes; photochemistry; Physical Sciences; Precursors; Pyrazole; Pyrazoles; Pyridazines; Science & Technology; Stereochemistry; Strategy; Synthesis; Ultraviolet radiation; Wittig reactions; isomerization; REACTIVITY; DERIVATIVES SYNTHESIS; phosphazenes; CONVENIENT STRATEGY; cyclization; VINYLDIAZOCARBONYL COMPOUNDS; POTENT; Wittig reactions; photochemistry; WITTIG REACTION; BIOLOGICAL-ACTIVITY; CHEMISTRY; INHIBITORS; ANTIMICROBIAL ACTIVITY
• ISSN: 0947-6539; 1521-3765
• DOI: 10.1002/chem.201503448

Phosphazenes of vinyldiazocarbonyl compounds having cis stereochemistry of the functional groups on the vinyl bond readily produce pyridazines by a diaza‐Wittig process, whereas their counterparts with trans configuration remain intact under similar reaction conditions. Upon UV irradiation trans‐phosphazenes furnish pyridazines through a tandem trans‐to‐cis isomerization followed by intramolecular cyclization. At elevated temperatures trans‐(triphenyl)phosphazenes dissociate to give the initial vinyldiazo compounds, which produce pyrazoles in high yields. The first theoretical study on the mechanism of the diaza‐Wittig process by DFT calculations at the M06‐2X/6‐31G(d) level of theory suggest that for the cis‐phosphazenes a rapid tandem [2+2] cycloaddition/cycloelimination process with low energy barriers is preferred over trans isomers. Configuration is the key: The effect of the configuration of vinyldiazo compounds on the diaza‐Wittig cyclization to pyridazines was experimentally and theoretically demonstrated for the first time. Phosphazenes of vinyldiazocarbonyl compounds having cis stereochemistry at the vinyl bond readily produce pyridazines by a diaza‐Wittig process, whereas their trans counterparts remain intact under similar reaction conditions. Upon UV irradiation trans‐phosphazenes furnish pyridazines through a tandem trans‐to‐cis isomerization followed by intramolecular cyclization (see scheme).