Rapid and Stereocontrolled Synthesis of Racemic and Optically Pure Highly Functionalized Pyrrolizidine Systems via Rearrangement of 1,3-Dipolar Cycloadducts Derived from 2-Azetidinone-Tethered Azomethine Ylides

Abstract

This work describes a convenient procedure for the straightforward preparation of polyfunctionalized enantiopure pyrrolizidine systems. The methodology capitalizes on a HCl(g)-promoted reaction of the 1,3-dipolar cycloadducts derived from 2-azetidinone-tethered azomethine ylides, smoothly affording different types of highly functionalized bi- and tricyclic systems in racemic and optically pure forms. This process involves a selective bond cleavage of the four-membered ring, followed by a rearrangement under the reaction conditions. The synthetic route employed was shown to be compatible with a variety of 4-oxoazetidine-2-carbaldehydes, alpha-amino esters, or dipolarophiles, offering a versatile entry to pyrrolizidine systems.

Michael addition/pericyclization/rearrangement – a multicomponent strategy for the synthesis of substituted resorcinols

“…In our efforts to extend this chemistry with other Michael acceptors, N-phenylmaleimide (PMI) was employed in reactions with enedione-diazoacetate 3 based on its reactivity as an electrophile in conjugate addition reactions. 12,13 The intended reaction occurs but, unlike reactions with methyl vinyl ketone in which the Michael addition product (6) is stable under the reaction conditions, the Michael addition product is not observed and, instead, resorcinol 8 is directly produced under the reaction conditions. The major competing reaction is pericyclization/rearrangement of 3 that forms 5.…”

Synthesis, characterization and antibacterial activity of 1‐([6‐bromo‐2‐hydroxy‐naphthalen‐1‐yl]arylphenyl)methyl)‐3‐chloro‐4‐(arylphenyl)‐azetidin‐2‐one

“…Apart from their clinical use, these compounds have been used as synthons in the preparation of various heterocyclic compounds of biological significance. Besides, use of 2‐azetidinones as starting materials to prepare pyrrolizidines through 1,3‐dipolar cycloaddition reaction, 26 pyperidones via two‐carbon addition process, 27 indolizidines using aza Diels‐Alder cycloadducts with concomitant cyclization, 28 pyrroloxines using Diels‐Alder cyclo‐addition reaction, 29 γ‐lactams through N1‐C2 bond cleavage followed by hydrolysis reaction, 30 pyrroles, taxoids and macrolide natural products, 31 and many more derivatives of industrial importance due to their enhanced biological activities. Due to this, the investigation of chemistry and biology of these compounds continue to appeal the synthetic and medicinal organic chemists.…”

Four‐Component Regio‐ and Diastereoselective Synthesis of Pyrrolizidines Incorporating Spiro‐Oxindole/Indanedione via 1,3‐Dipolar Cycloaddition Reaction of Azomethine Ylides

“…Among various aza heterocycles, pyrrolizidine alkaloids are a class of heterocycles with significant biological activity . Approximately, 3% of the flowering plants and hundreds of vegetables contain pyrrolizidine alkaloids …”