Galkin Konstantin I, Zakharova Daria V, Aysin Rinat R, Danshina Anastasia A, Pak Alexandra M, Sandulenko Irina V, Novikov Roman A, Egorova Ksenia S
N.D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Leninsky Prospekt, 47, 119991 Moscow, Russia.
Center for Project Activities, Moscow Polytechnic University (Moscow Polytech), Bolshaya Semyonovskaya Str., 38, 107023 Moscow, Russia.
Int J Mol Sci. 2025 Jul 8;26(14):6550. doi: 10.3390/ijms26146550.
In the chemistry of bio-based furans, the Diels-Alder reaction plays an important role as a renewable route for the synthesis of fuels, fine chemicals, and monomers. Nonetheless, the unfavorable kinetic and thermodynamic parameters inherent to the Diels-Alder reaction involving furans as dienes often lead to the reversibility of cycloaddition, resulting in decreased equilibrium conversion and diastereoselectivity. In this study, we present a new strategy for overcoming the problem of reversibility in chemical reactions. We demonstrate that conducting the reaction under solvent-free conditions can facilitate the transition from a molten state formed by the initial reactants to a solid phase containing the reaction product along with an excess of the initial substrate. According to our results, such a liquid-to-solid transition of the reaction mixture can lead to exceptionally high conversion and diastereoselectivity in the furan-maleimide Diels-Alder reaction, particularly for challenging electron-poor furanic substrates. Our approach enables the reversible furan-maleimide Diels-Alder reaction to be performed in a cleaner and more environmentally friendly manner, free from the complexities associated with the use of solvents and the need for purification from side products.
在生物基呋喃化学中，狄尔斯-阿尔德反应作为合成燃料、精细化学品和单体的可再生途径发挥着重要作用。然而，涉及呋喃作为双烯体的狄尔斯-阿尔德反应固有的不利动力学和热力学参数常常导致环加成反应的可逆性，从而降低平衡转化率和非对映选择性。在本研究中，我们提出了一种克服化学反应可逆性问题的新策略。我们证明，在无溶剂条件下进行反应能够促进从初始反应物形成的熔融态向包含反应产物以及过量初始底物的固相转变。根据我们的结果，反应混合物的这种液-固转变能够在呋喃-马来酰亚胺狄尔斯-阿尔德反应中带来极高的转化率和非对映选择性，尤其是对于具有挑战性的贫电子呋喃底物。我们的方法使可逆的呋喃-马来酰亚胺狄尔斯-阿尔德反应能够以更清洁、更环保的方式进行，避免了与使用溶剂相关的复杂性以及从副产物中进行纯化的需求。
