Lewis Acid Catalyzed Annulation of Cyclopropane Carbaldehydes and Aryl Hydrazines: Construction of Tetrahydropyridazines and Application Toward a One-Pot Synthesis of Hexahydropyrrolo[1,2-b]pyridazines

Abstract

In this report, a facile synthesis of tetrahydropyridazines via a Lewis acid catalyzed annulation reaction of cyclopropane carbaldehydes and aryl hydrazines has been demonstrated. Moreover, the generated tetrahydropyridazine further participated in a cycloaddition reaction with donor-acceptor cyclopropanes to furnish hexahydropyrrolo[1,2- b]pyridazines. We also performed these two steps in one pot in a consecutive manner. In addition, a monodecarboxylation reaction of hexahydropyrrolo[1,2- b]pyridazine was achieved with a good yield.

Regioselective Brønsted Acid-Catalyzed Annulation of Cyclopropane Aldehydes with N′-Aryl Anthranil Hydrazides: Domino Construction of Tetrahydropyrrolo[1,2-a]quinazolin-5(1H)ones

“…To evaluate our hypothesis, we started the investigation with cyclopropane aldehyde 1a and anthranil hydrazide 2a as model substrate, and the results are summarized in Table . The knowledge gained from the success of our recent studies on the reactivity of CAs with N -benzyl amines and aryl hydrazine derivatives , drove us to start this optimization with different Brønsted acids at room temperature. First, we started with the reaction of 1a and 2a in the presence of 30 mol % acetic acid in ethanol; the desired cycloadduct 3aa was obtained in 10% yield (Table , entry 1).…”

“…trans-2-Phenylcyclopropane-1-carbaldehyde (1b). 12 Benzaldehyde (1.0 g, 9.43 mmol), 1b (0.69 g, 4.72 mmol), 50% overall yield, white solid. 1 trans-2-(p-Tolyl)cyclopropane-1-carbaldehyde (1c).…”

“…Later, in 2015, Schneider et al introduced the one-pot [3+2] cycloheteroannulation of bis-silyl dienediolate with 2-aminobenzamide-derived imines to furnish highly substituted pyrrolo­[1,2- a ]­quinazolinones in good yields (Scheme A) . Recently, our group has reported the annulation of cyclopropane aldehydes (CAs) with various aryl hydrazines toward the formation of tetrahydropyridazine derivatives under Lewis acid catalysis (Scheme B) . Envisioned by our previous work on cyclopropanes and synthetic utility of donor–acceptor cyclopropanes (DACs) and hydrazides, we thought to utilize cyclopropane aldehydes and N ′-aryl benzohydrazides as the building block for the synthesis of pyrroloquinazoline derivatives using facile reaction conditions (Scheme C).…”

Donor–Acceptor Cyclopropanes as an Expedient Building Block Towards the Construction of Nitrogen‐Containing Molecules: An Update

“…Very recently, our group presented a facile access to tetrahydropyridazines 110 via Lewis acid‐catalyzed annulation of cyclopropane‐carbaldehydes 108 and arylhydrazines 109 (Scheme a) . The product tetrahydropyridazine 110 was also subjected to a [3+2] cycloaddition reaction with 2‐arylcyclopropane 1,1‐dicarboxylate 3 to render hexahydropyrrolo[1,2‐ b ]pyridazine derivatives 111a and 111b (Scheme b).…”

β-Nitroacrylates: New Key Precursors of Indole-2-Carboxylates via Fischer Indole Synthesis

“…β-Nitroacrylates 1 were synthesized by the Henry reaction-elimination process, starting from nitroalkanes and alkyl glyoxalates [23,24]. Arylhydrazines were purchased from Sigma-Aldrich as hydrochloride salts and were converted into the free bases by treatment with potassium carbonate in water [25].…”