Advancements in Inverse-Electron-Demand Diels–Alder Cycloaddition of 2-Pyrones: Mechanisms, Methodologies
Nasser Thallaj

Prof. Dr. Nasser Thallaj, Pharmaceutical Chemistry and Drug Quality Control Department, Faculty of Pharmacy, Al-Rachid Privet University, Damascus (Syria), West Asia. 

Manuscript received on 13 September 2024 | Revised Manuscript received on 27 September 2024 | Manuscript Accepted on 15 October 2024 | Manuscript published on 30 October 2024 | PP: 33-48 | Volume-4 Issue-6, October 2024 | Retrieval Number: 100.1/ijapsr.F405504061024 | DOI: 10.54105/ijapsr.F4055.04061024

Open Access | Editorial and Publishing Policies | Cite | Zenodo | OJS | Indexing and Abstracting
© The Authors. Published by Lattice Science Publication (LSP). This is an open-access article under the CC-BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)

Abstract: The Diels-Alder (DA) cycloaddition is well-known for its effectiveness in synthesizing natural products and multifunctional materials. This article specifically explores the inverse-electron-demand Diels-Alder (IEDDA) cycloaddition involving 2-pyrones, which display ambiphilic properties due to their unique electronic characteristics. We investigate the mechanisms underlying IEDDA, with a focus on how electron-donating and electron-withdrawing substituents influence reactivity and product selectivity. Various methodologies are reviewed, encompassing non-catalytic and catalytic approaches. Special attention is given to advancements in microwave-assisted techniques and high-pressure conditions, which enhance both reaction efficiency and selectivity. Additionally, the synthesis of chiral bridged bicyclic lactones from substituted 2-pyrones is examined, illustrating their versatility in organic synthesis. This review underscores the significance of IEDDA cycloaddition in pioneering new synthetic routes for building complex molecular structures.

Keywords: Diels–Alder Cycloaddition; Inverse-Electron-Demand; 2-Pyrones; Electrophilic Dienes; Microwave-Assisted Synthesis; Chiral Bicyclic Lactones; Reaction Mechanisms.
Scope of the Article: Pharmaceutical Chemistry