Substrate‐Controlled [5+1] Annulation of 5‐Amino‐1H‐phenylpyrazoles with Alkenes: Divergent Synthesis of Multisubstituted 4,5‐Dihydropyrazolo[1,5‐a]quinazolines

Abstract

A new and efficient [5+1] annulation reaction for the first synthesis of 5,5‐disubstituted 4,5‐dihydropyrazolo[1,5‐a]quinazolines is described. This transition‐metal‐free tandem cyclization was performed with 5‐amino‐1H‐phenylpyrazole and readily available electron‐deficient olefinic ester. The reaction proceeds via an aza‐Michael addition/Truce‐Smiles rearrangement/SNAr cyclization pathway, which was verified by DFT calculations. The participation of Truce‐Smiles rearrangement is substrate dependent and could prompt the process of cascade reactions. It is also the first report of alkenes acting as one‐carbon synthons for [5+1] hetero‐annulations.

Design, synthesis, and insecticidal activities of novel 5‐substituted 4,5‐dihydropyrazolo[1,5‐a]quinazoline derivatives

“…Applying a similar [5 + 1] hetero‐annulation strategy as previously reported, 20 5,5‐disubstituted 4,5‐dihydropyrazolo[1,5‐ a ]quinazoline derivative 4a was obtained in good yield by reacting fipronil with diethyl bromomalonate. Compared to the previous reaction, dialkyl bromomalonates was used instead of electron‐deficient alkenes to act as the one‐carbon synthon during the annulation process, and a non‐chiral quaternary carbon center was constructed.…”

“…Starting from different substituted anilines and 2,3‐dicyanopropionate ethyl ester, phenylpyrazoles 2a – 2l were first prepared and then functionalized with trifluoromethyl sulfonyl moiety to obtain intermediates 3a – 3l 36 . The 4,5‐dihydropyrazolo[1,5‐ a ]quinazoline scaffolds were then constructed through the [5 + 1] annulation of compounds 3 with dialkyl bromomalonates under basic conditions, 20 leading to compounds 4a – 4m in moderate yields (35–68%). Mechanism of the key annulation reaction is shown in Fig.…”

“…A high‐efficient [5 + 1] hetero‐annulation was developed during the optimization of reaction conditions to obtain compound A 20 . Compared to previous strategies to obtain 4,5‐dihydropyrazolo[1,5‐ a ]quinazolines, 21–24 this new method features better operability and milder reaction conditions.…”

“… 18 Recently in our group, a 4,5‐dihydropyrazolo[1,5‐ a ]quinazoline derivative (compound A , Fig. 1) was developed by forming an additional heterocycle ring on fipronil, 19,20 and was found to exhibit promising insecticidal activity against P. xylostella .…”

Design, synthesis and insecticidal‐activity evaluation of N‐pyridylpyrazolo‐5‐methyl amines and its derivatives

“…[22][23][24] As shown in Scheme 2, the target compounds 8a and 8b were obtained with intermediate 7, different olefins, and potassium carbonate with yield of 93% to 95%. [25] The target compound 9a was synthesized by reacting intermediate 7 with acetyl chloride with yield of 91%. Compound 7 was reacted with the corresponding carboxylic acid to obtain the target compounds 9b-9t with yield of 70% to 95%.…”