Amberlyst A21 Catalyzed Chromatography-Free Method for Multicomponent Synthesis of Dihydropyrano[2,3‑<i>c</i>]pyrazoles in Ethanol

Amberlyst A21 was found to be an extremely efficient catalyst for synthesis of a series of 6-amino-4-alkyl/aryl-3-methyl-2,4-dihydropyrano­[2,3-<i>c</i>]­pyrazole-carbonitriles by a four-component reaction of a mixture of ethyl acetoacetate, hydrazine hydrate, aldehyde, and malononitrile in ethanol at room temperature. The catalytic efficiency of Amberlyst A21 was compared with some other resin-bound free and anionic bases in order to ascertain the best catalyst for the said conversion. The catalyst was found to work extremely well also for acyclic/cyclic ketones to give corresponding dihydropyrano­[2,3-<i>c</i>]­pyrazoles or their spirocyclic variants. Easy recovery of the catalyst and its reusability, room temperature reaction conditions, short reaction time, excellent yields, no chromatographic purification, and evasion of environmentally hazardous solvents in the entire reaction process may make this protocol very useful for academia and industry

Organocatalyzed Enantioselective Direct Mannich Reaction of α‑Styrylacetates

An organocatalyzed direct Mannich reaction of unactivated α-styrylacetates was realized for the first time. By using a quinidine-derived C6′-urea catalyst, the direct Mannich reaction of α-styrylacetates and <i>N</i>-tosylimines gave the desired β-amino esters in high yields, diastereoselectivities, and ee values. The reaction provides a highly stereoselective (up to 96:4 dr and 97% ee) and the most straightforward synthesis of functionalized <i>N</i>-tosylated β-amino esters. The products can be used as precursors for the highly selective synthesis of tetrahydrofuran derivatives