Huang Wei, Wen Kangqiao, Laughlin Scott T, Escorihuela Jorge
Department of Chemistry, Stony Brook University, 100 Nicolls Road, Stony Brook, NY 11790, USA.
Departamento de Química Orgánica, Universitat de València, Avda. Vicente Andrés Estellés s/n, Burjassot, 46100 Valencia, Spain.
Org Biomol Chem. 2024 Oct 23;22(41):8285-8292. doi: 10.1039/d4ob01263a.
Over the past two decades, click chemistry transformations have revolutionized chemical and biological sciences. Among the different strain-promoted cycloadditions, the inverse electron demand Diels-Alder reaction (IEDDA) has been established as a benchmark reaction. We have theoretically investigated the IEDDA reaction of -bicyclo[6.1.0]nonyne (-BCN) with 2-pyran-2-one, 2-thiopyran-2-one, 2-pyran-2-thione and 2-thiopyran-2-thione. These 2-(thio)pyran-2-(thi)ones have displayed different reactivity towards -BCN. Density functional theory (DFT) calculations show, in agreement with experiments, that -BCN reacts significantly faster with 2-thiopyran-2-one compared to other 2-(thio)pyran-2-(thi)one derivatives because of the lower distortion energy. Experimentally determined second-order rate constants for the reaction of a 2-pyran-2-thione with different strained derivatives, including a 1-methylcyclopropene derivative and several cycloalkynes (-BCN, (1,8)-bicyclo[6.1.0]non-4-yne-9,9-diyl)dimethanol, dibenzocycylooctyne and a light activatable silacycloheptyne, were used to validate the computational investigations and shed light on this reaction.
在过去的二十年里，点击化学转化彻底改变了化学和生物科学。在不同的应变促进环加成反应中，逆电子需求狄尔斯-阿尔德反应（IEDDA）已成为一个基准反应。我们从理论上研究了 -双环[6.1.0]壬炔（-BCN）与2-吡喃-2-酮、2-硫代吡喃-2-酮、2-吡喃-2-硫酮和2-硫代吡喃-2-硫酮的IEDDA反应。这些2-（硫代）吡喃-2-（硫代）酮对 -BCN表现出不同的反应活性。密度泛函理论（DFT）计算表明，与实验结果一致，由于较低的扭曲能，-BCN与2-硫代吡喃-2-酮的反应速度明显快于其他2-（硫代）吡喃-2-（硫代）酮衍生物。实验测定了2-吡喃-2-硫酮与不同应变衍生物（包括1-甲基环丙烯衍生物和几种环炔烃（-BCN、(1,8)-双环[6.1.0]壬-4-炔-9,9-二基）二甲醇、二苯并环辛炔和一种光可激活硅环庚炔）反应的二级速率常数，以验证计算研究并阐明该反应。
