Pd-Catalyzed Ring Restructuring of Oxazolidines with Alkenes Leading to Fused Polycyclic Indolizines

Abstract

A palladium-catalyzed reaction of N-propargyl oxazolidines with alkenes for the synthesis of indolizidines has been developed. Through a sequential 6-exo-dig cyclization/proton transfer/[3+2] cycloaddition/cycloreversion/aromatization process, a series of fused polycyclic indolizines are obtained in moderate to good yields with high functional group tolerance. Experimental and theoretical studies suggest that the [3+2] cycloaddition/cycloreversion of the oxazolidine ring probably involves C–C and C–O bond cleavage, providing a new ring restructuring approach for the synthesis of heterocycles.

Recent Advances in the Synthesis of Five‐membered Nitrogen Heterocycles Induced by Palladium Ions and Complexes

“…Van der Eycken et al have applied N-propargyloxazolidines 45 and alkenes, mainly acrylic ester derivatives, with Pd(PPh 3 ) 4 in a two-step synthesis of a variety of fused tricyclic indolizines (Scheme 133). [157] The role of DDQ (2,3-dichloro-5,6-dicyano-1,4benzoquinone) in this ring restructuring process was to induce the aromatization of 1-pyrroline intermediates (Scheme 134). In The last example is about the synthesis of pyrido[1,2a]benzimidazoles 46 by the Lei group executing electrooxidative intramolecular CÀ H/NÀ H coupling reactions of substituted N-(para-tolyl)pyridin-2-amines through cycloamination and concomitant hydrogen evolution.…”

“…have applied N ‐propargyloxazolidines 45 and alkenes, mainly acrylic ester derivatives, with Pd(PPh 3 ) 4 in a two‐step synthesis of a variety of fused tricyclic indolizines (Scheme 133). [157] The role of DDQ (2,3‐dichloro‐5,6‐dicyano‐1,4‐benzoquinone) in this ring restructuring process was to induce the aromatization of 1‐pyrroline intermediates (Scheme 134). In a mechanistic interpretation including DFT calculations, intermediate A , generated in oxidative addition and intramolecular alkyne insertion, reacted with the ester leading to intermediate B .…”

CuS Morphology Control for Enhanced Catalytic Performance in A3 Coupling Reaction

“…[4] This kind of compound can further react with alkenes for the synthesis of an important pharmacophore-indolizidines. [5] In this kind of the A 3 coupling catalyzing reaction, efficient activation of the reactant alkyne terminated hydrogen is the crucial part, and therefore the construction of catalysts to promote the cleavage of CÀ H bond has become popular research direction of many scholars. [6] Transition element like copper, zinc, silver have proved catalytic performance for the synthesis of propargylamine.…”