Chemo‐ and Diastereoselective Synthesis of Pyrazolo‐tetrahydropyridines via Multicomponent Sequential Aza‐Diels‐Alder Reactions in Water

Abstract

In this study, we report a novel and an efficient strategy for the synthesis of chemo‐ and diastereoselective synthesis of pyrazolo‐tetrahydropyridines via a one‐pot multi‐component intramolecular Aza‐Diels–Alder reactions (ADARs) from benzoylacetonitrile derivatives, phenylhydrazine, salicylaldehyde derivatives, and styrenesulfonyl or cinnamoyl chloride in H2O as a green solvent. This synthesis procedure was also designed to follow the group‐assisted purification (GAP) chemistry, which can avoid traditional purification such as recrystallization and chromatography methods.

Diels–Alder Cycloaddition Reactions in Sustainable Media

“…A chemo-and diastereoselective synthetic multicomponent route to pyrazolotetrahydropyridines involving an intramolecular aza-Diels-Alder reaction was disclosed by Shaabani and coworkers (Scheme 34) [109]. A plethora of pyrazolo-tetrahydropyridines 151 was efficiently prepared from benzoylacetonitrile derivatives 146, hydrazines 147, aromatic aldehydes 150 and styrenesulfonyl or cinnamoyl chloride in water in the presence of base, using the group-assisted purification (GAP) chemistry strategy.…”

Highly Efficient Chemoselective Synthesis of Pyrrolo[2,3-c]pyrazole Bearing Oxindole via Sequential Condensation–Michael Addition–Intramolecular Cyclization Reactions

“…The second step is the reaction of 3-phenacylideneoxindole (4a) with 5-aminopyrazole (3a), which is formed in the first step. According to our previous report, 11 the optimized conditions for the synthesis of 5-aminopyrazole (3a) was used. In a pilot experiment, phenylhydrazine (2a) is reacted with benzoylacetonitrile (1a) to produce 5-aminopyrazole (3a) under neat conditions at 120 °C.…”