Theoretical and Computational Chemistry Laboratory, Department of Chemistry, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana.
J Mol Graph Model. 2021 Dec;109:108033. doi: 10.1016/j.jmgm.2021.108033. Epub 2021 Sep 12.
The molecular mechanism of the double (3 + 2) cycloaddition (32CA) reaction between nitrile oxides and allenoates has been studied using density functional theory at the M06-2X/6-311G (d,p) level of theory. In the first 32CA, the nitrile oxide adds chemo- and regio-selectively to the C-C double bond of the allenoate closest to the carboxylate group followed by a subsequent regioselective addition to the olefinic bond of the isoxazoline intermediate. The rate constant for the preferred pathway (formation of 4-methylene-2-isoxazoline intermediate) in the reaction of ethyl substituted allenoate and mesitonitrile oxide is 5.3 × 10 s in THF which is about 13 times faster than the closest competing step (formation of its regioisomer 5-methylene-2-isoxazoline intermediate) which has a rate constant of 4.4 × 10 s. Strong electron-donating groups (EDGs) and electron-withdrawing groups (EWGs) decrease activation barriers and hence increase the reaction rate. Also, the dimerization of nitrile oxide to form furaxon is found to be kinetically unfavored.
通过在 M06-2X/6-311G(d,p)理论水平上的密度泛函理论，研究了腈氧化物和烯丙酸盐之间的双（3+2）环加成（32CA）反应的分子机制。在第一个 32CA 中，腈氧化物化学选择性和区域选择性地添加到最靠近羧酸盐基团的烯丙酸盐的 C-C 双键上，随后对异噁唑啉中间体的烯烃键进行进一步的区域选择性添加。在乙基取代的烯丙酸盐和甲亚硝胺氧化物的反应中，首选途径（形成 4-亚甲基-2-异噁唑啉中间体）的速率常数在 THF 中为 5.3×10 s，比最接近的竞争步骤（形成其区域异构体 5-亚甲基-2-异噁唑啉中间体）快约 13 倍，其速率常数为 4.4×10 s。强供电子基团（EDG）和吸电子基团（EWG）降低了活化能垒，从而提高了反应速率。此外，还发现腈氧化物二聚形成呋咱是动力学上不利的。
