Ring-Chain Tautomerism in Organic Synthesis:  Synthesis of Heterocyclic Enamines from a Novel and Practical Formal Ring Transformation Reaction of Lactones

Abstract

A novel approach to heterocyclic enamines has been developed from the formal ring transformation reaction of lactones. The synthesis comprises consecutive Reformatsky reaction of lactones and mesylation of the resulting mixture of ring-chain tautomers in a one-pot reaction, followed by cyclocondensation reaction with primary amines. The synthetic application of this method was demonstrated by a straightforward preparation of indolizidine compounds via N-(3-bromopropyl)-substituted enamine intermediates. The use of cheap and readily available materials and reagents under very mild conditions renders this formal ring transformation method practical and applicable in the preparation of various heterocyclic enamines that are the precursors for (poly)hydroxylated alkaloid derivatives.

β-Enamino Esters in Heterocyclic Synthesis: Synthesis of Pyrazolone and Pyridinone Derivatives

“…β -Enamino esters are versatile intermediates for the synthesis of nitrogen containing compounds [ 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 ]. Also, they are important subunits present in some biologically important natural products as well as therapeutic agents [ 9 , 10 , 11 , 12 ].…”

Synthesis of 2-Alkylidenepyrrolidines and Pyrroles by Condensation of 1,3-Dicarbonyl Dianions with α-Azidoketones and Subsequent Intramolecular Staudinger−Aza-Wittig Reaction

“…For example, 2-alkylidenepyrrolidines have been prepared by the reaction of 1,3-dicarbonyl dianions with 1-bromo-2-chloroethane, nucleophilic replacement of the chloride by an azido group, and subsequent Staudinger−aza-Wittig reaction . In addition, 2-alkylidenepyrrolidines have been prepared by the reaction of 1,3-dicarbonyl dianions with aziridines 9 and by ring-transformation reactions of lactones …”

Synthesis of 2-Alkylidenepyrrolidines, Pyrroles, and Indoles by Condensation of Silyl Enol Ethers and 1,3-Bis-Silyl Enol Ethers with 1-Azido-2,2-dimethoxyethane and Subsequent Reductive Cyclization

“…For example, 2-alkylidenepyrrolidines have been prepared by reaction of 1,3-dicarbonyl dianions with 1-bromo-2-chloroethane, nucleophilic substitution of the chloride by sodium azide and subsequent aza-Wittig reaction of the ω-azido-β-ketoester thus formed . 2-Alkylidenepyrrolidines are available also by reaction of 1,3-dicarbonyl dianions with aziridines and by ring transformations of lactones …”