Syntheses of Tetrahydropyridazine and Tetrahydro-1,2-diazepine Scaffolds through Cycloaddition Reactions of Azoalkenes with Enol Diazoacetates

Abstract

Catalyst-dependent [4 + 2]-cycloaddition reactions of azoalkenes from α-halohydrazones with enol diazoacetates have been developed. A [4 + 2]-cycloaddition of enol diazoacetates with in situ formed azoalkenes produces tetrahydropyridazinyl-substituted diazoacetates promoted by only CsCO. In contrast, donor-acceptor cyclopropenes, which are formed in situ from enol diazoacetates by Rh(OAc)-catalyzed dinitrogen extrusion, undergo [4 + 2]-cycloaddition with azoalkenes to yield bicyclo[4.1.0]tetrahydropyridazines. These stable cycloaddition products undergo subsequent one-step transformations to form 6-alkylidenetetrahydropyridazines and 4,5,6,7-tetrahydro-1,2-diazepine derivatives in good yields.

Cycloaddition reactions of enoldiazo compounds

“…81 As depicted in Scheme 5, the reactive azoalkenes were readily accessed by treating α-halohydrazones 13 with stoichiometric amounts of inorganic base (Cs 2 CO 3 ), which subsequently reacted with a wide range of enoldiazoacetates 1 to afford tetrahydropyridazinyl-substituted diazoacetates 14 in moderate to good yields. It is noteworthy that an unexpected tetrahydropyridazine derivative was obtained when cycloadduct 14 was treated with copper(I) catalysts, which was due to acetyl migration from nitrogen, and the formation of an intermediate oxazolium salt accounted for the acetyl migration outcome.…”

“…It is noteworthy that an unexpected tetrahydropyridazine derivative was obtained when cycloadduct 14 was treated with copper(I) catalysts, which was due to acetyl migration from nitrogen, and the formation of an intermediate oxazolium salt accounted for the acetyl migration outcome. 81 …”

“…As part of their continuous efforts to explore the synthetic potential of enoldiazo compounds, Doyle, Xu, and co-workers 81 recently developed dirhodium(II)-catalyzed/base-promoted [2+4]-cycloaddition reactions of enoldiazoacetates 1 with α-halohydrazones 13 (Scheme 31). This transformation occurred through [2+4]-cycloaddition between donor–acceptor cyclopropenes 60 and azoalkenes, which were generated in situ from 1 and 13 in the presence of rhodium(II) acetate and caesium carbonate, respectively.…”

“…Moreover, the resulting cyclopropane-fused tetrahydropyridazine scaffolds 69 were readily transformed into tetrahydrodiazepine derivatives 70 upon deprotection. 81 …”

“…81 In the absence of transition metal catalysts, tetrahydropyridazinyl-substituted diazoacetates 14 are obtained under basic conditions; whereas cyclopropane-fused tetrahydropyridazines 69 are produced with catalysis of rhodium(II) acetate under otherwise identical conditions.…”