TEMPO-Mediated Aza-Diels-Alder Reaction: Synthesis of Tetrahydropyridazines Using Ketohydrazones and Olefins.

A novel, facile, and efficient method for the synthesis of tetrahydropyridazines by a one-pot tandem reaction of easily accessible ketohydrazones and olefins in the presence of 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) has been successfully developed. The reaction involves the initial generation of azoalkenes from direct oxidative dehydrogenation of ketohydrazones using TEMPO as the commercially available oxidant, followed by a subsequent aza-Diels-Alder reaction with olefins.

Iminoxyl radical-promoted dichotomous cyclizations: efficient oxyoximation and aminooximation of alkenes.

A novel iminoxyl radical-involved metal-free approach to vicinal oxyoximation and aminooximation of unactivated alkenes is developed. This method utilizes the dichotomous reactivity of the iminoxyl radical to furnish a general difunctionalization on alkenes using simple tert-butyl nitrite (TBN) as the iminoxyl radical initiator as well the carbon radical trap. By using this protocol, oxime featured 4,5-dihydroisoxazoles and cyclic nitrones were facilely prepared from ß,γ- and γ,δ-unsaturated ketoximes, respectively.

Hydrazone radical promoted vicinal difunctionalization of alkenes and trifunctionalization of allyls: synthesis of pyrazolines and tetrahydropyridazines.

The intramolecular addition of hydrazone radicals to carbon-carbon double bonds was achieved by using TEMPO (2,2,6,6-tetramethyl-1-piperidinyloxy) or DIAD (diisopropyl azodicarboxylate) as the hydrazone radical initiator as well as the carbon radical scavenger. Consequently, alkenes were difunctionalized to afford pyrazolines and tetrahydropyridazines via C-N forming 5-exo-trig and 6-exo-trig cyclizations, respectively, and allyls were trifunctionalized to afford pyrazolines via C-N forming tandem 1,5-H-shift/5-exo-trig cyclizations under metal-free neutral conditions.