Beijing National Laboratory for Molecular Sciences (BNLMS), Key Laboratory of Bioorganic Chemistry and Molecular Engineering of the Ministry of Education, College of Chemistry, Peking University, Beijing 100871, P. R. China.
Department of Chemistry and Biochemistry, New Mexico State University, MSC 3C, Las Cruces, New Mexico 88003, United States.
J Org Chem. 2021 Jan 15;86(2):1419-1429. doi: 10.1021/acs.joc.0c01960. Epub 2021 Jan 5.
The mechanisms of [8 + 2] cycloaddition reactions between dienylfurans/dienylisobenzofurans and the activated alkyne, DMAD (dimethyl acetylenedicarboxylate), have been investigated by DFT calculations. The former [8 + 2] reaction is stepwise, starting from attack of the diene substituent on furan, not the furyl moiety in dienylfurans, to DMAD to give a diradical intermediate, which then undergoes ring closure to form the second bond between DMAD and the furan moiety, generating the final [8 + 2] cycloadducts. In contrast, the latter [8 + 2] reaction starts from [4 + 2] cycloaddition of the diene in the furan ring of dienylisobenzofurans toward DMAD, followed by the rate-determining stepwise [1,5]-vinyl shift, forming the [8 + 2] products. The different mechanisms of [8 + 2] reactions are attributed to the facts that for dienylfurans, the reactive diene part is the diene substituent on furan, but in the case of dienylisobenzofurans, it is the diene in the furan ring (its reaction with DMAD to generate an aromatic benzene ring is the driving force for this regiochemistry). Consequently, the [8 + 2] reactions begin with the reaction of the most reactive part of tetraene (either the diene substituent on furan for dienylfurans or the diene in the furan ring for dienylisobenzofurans) with DMAD. FMO analysis and kinetic study have been carried out to gain more information of the reaction mechanisms. Two [8 + 2] reactions of dienylisobenzofurans with different substituents toward DMAD have also been further analyzed by DFT calculations in this paper.
通过 DFT 计算研究了二烯基呋喃/二烯基异苯并呋喃与活化炔烃 DMAD（二甲乙酰基丁二炔）之间的[8+2]环加成反应的机理。前者[8+2]反应是分步进行的，从二烯取代基攻击呋喃开始，而不是从二烯基呋喃中的呋喃部分开始，与 DMAD 反应生成双自由基中间体，然后进行环化反应，在 DMAD 和呋喃部分之间形成第二个键，生成最终的[8+2]环加成产物。相比之下，后者[8+2]反应从二烯基异苯并呋喃中呋喃环上的二烯与 DMAD 的[4+2]环加成开始，然后是速率决定的分步[1,5]-乙烯基迁移，形成[8+2]产物。[8+2]反应的不同机理归因于以下事实：对于二烯基呋喃，反应性二烯部分是呋喃上的二烯取代基，但在二烯基异苯并呋喃的情况下，它是呋喃环中的二烯（它与 DMAD 反应生成芳香苯环是这种区域化学的驱动力）。因此，[8+2]反应从四烯（对于二烯基呋喃，是呋喃上的二烯取代基；对于二烯基异苯并呋喃，是呋喃环中的二烯）最具反应性的部分与 DMAD 的反应开始。进行了 FMO 分析和动力学研究，以获得更多关于反应机理的信息。本文还通过 DFT 计算进一步分析了两种具有不同取代基的二烯基异苯并呋喃与 DMAD 的[8+2]反应。
