Co(ii) mediated cascade cyclization of unactivated olefins to afford N-alkylacetamided tetrahydropyridazines and dihydropyrazoles

Abstract

We demonstrate an efficient and simple protocol to obtain structurally varied tetrahydropyridazine and dihydropyrazole scaffolds, via Co(OAc)₂·4H₂O salt catalysed cascade cyclization of unactivated alkenes without external coupling partners under nitrogen-free conditions. In this strategy, an N-alkylacetamide group is effortlessly attached to the tetrahydopyridazine skeleton by reacting N-homoallylacetohydrazides and N-allylacetohydrazides with different N-alkylformamides as a solvent cum radical source through intramolecular 6-endo-trig and 5-endo-trig cyclization, respectively. The salient features of this protocol include the use of easily available and inexpensive cobalt salt as a catalyst, one-pot conversion, and good functional group tolerance even in heteroatomic systems, affording in total 31 new compounds in good yields. Numerous control experiments including radical trapping experiments along with Hammett analysis were performed to elucidate the mechanistic details of this cascade cyclization reaction.