Catalyst‐Free One‐Pot Regioselective Synthesis of Spiropyrrolizines Using 1,3‐Dipolar Cycloaddition Reaction

Abstract

Synthesis of functionalized spiro[acenaphthylene‐1,3′‐pyrrolizin]‐2‐ones and spiroindeno[1,2‐b]quinoxaline‐11,3′‐pyrrolizines has been reported by one‐pot condensation of active carbonyl compounds, L‐proline/L‐thioproline and 3‐methyl‐4‐nitro‐5‐styrylisoxazoles in MeOH under reflux. This multicomponent strategy afforded corresponding spiro products in 94–98% yield with high diastereo‐ and regioselectivity. The structure has been further confirmed by X‐ray analysis of single crystal of one of the compounds. The striking feature of this work is avoidance of usage of toxic catalysts for this one‐pot synthesis.

Recent advancement in the synthesis of diverse spiro-indeno[1,2-b]quinoxalines: a review

“…Recently, Khurana et al 65 extended this reaction and synthesized spiroindeno[1,2-b]quinoxaline-11,3 0 -pyrrolizines 56/thia-pyrrolizines 57 via the four-component domino reaction of reactants 1, 2, dipolarophile 54 and L-proline 16d/L-thioproline 16e with regio-and diastereoselectively (Scheme 37).…”

Recent applications of ninhydrin in multicomponent reactions

“…As a part of their synthetic plan, Khurana and Gupta developed a convenient four-component approach to access isoxazole-linked spiro-indenoquinoxaline pyrrolizines 101 involving ninhydrin 1, substituted PDA 77, L-proline/thioproline 24 and 3-methyl-4-nitro-5-styrylisoxazoles 100 in MeOH (Scheme 31). 113 The catalyst-free simple protocol provides high regioselectivity in a short time frame. Chowhan and co-workers accomplished a similar type of isoxazole pendant compound 102 through a four-component reaction with high regio-and diastereoselectivity.…”

Graphene Oxide Catalyzed Synthesis of Fused Chromeno Spiro Pyrrolidine Oxindoles via Tandem Decarboxylation and 1,3-Dipolar Cycloaddition

“…The conformational constraints and juxtaposition of reactants frequently lead to readily cycloaddition with complete or very high selectivity. For the reasons mentioned above, 1,3-DCR has been described as "the single most important method for the construction of heterocyclic five-membered rings" (Jørgensen, 2002;Gupta and Khurana., 2019;Thadem et al, 2021). Major hurdles that regularly occur in organic synthesis are atom economy and novel and efficient reactions, which can answer both the ecological aspect and target-oriented synthesis (de Graaff et al, 2012;Lledó et al, 2019).…”

“…The conformational constraints and juxtaposition of reactants frequently lead to readily cycloaddition with complete or very high selectivity. For the reasons mentioned above, 1,3-DCR has been described as “the single most important method for the construction of heterocyclic five-membered rings” ( Jørgensen, 2002 ; Gupta and Khurana., 2019 ; Thadem et al, 2021 ).…”