美国加州大学洛杉矶分校K. N. Houk研究团队揭示了环己二烯胺[8+2]与[4+2]环加成反应的机理和选择性。相关研究成果于2021年1月8日发表国际知名学术期刊《美国化学会志》。

研究人员表示，取决于七氟乙烯上存在的取代基金鸡纳生物碱催化的2-环己烯酮与肌醇酮和各种七氟乙烯的环加成反应生成[8+2]或[4+2]环加合物。

研究人员报道了含有二酯和巴比妥酸取代基的七氟乙烯的新实验结果，结合计算研究阐明了控制[8+2]和[4+2]环加成途径的因素，包括这些高阶环加成的化学选择性、区域选择性和立体选择性。质子化金鸡纳生物碱伯胺催化剂与2-环己烯酮反应形成线性二胺中间体，随后进行逐步的[8+2]或[4+2]环加成。对流层酮和不同的七氟乙烯最初均形成[8+2]环加合物。

最终产物是由[8+2]环加成反应的可逆性和[4+2]产物的相对热稳定性决定的。其中质子化的催化剂和环庚三烯酮/庚富烯之间的立体相互作用区别，导致过渡态表现出立体异构体的结构区别。巴比妥酸七氟乙烯的[8+2]环加成得到的产物具有前所未有的五元环和六元环的反式融合，而从氰基七氟乙烯酯和二酯七氟乙烯中得到的[8+2]环加合物具有顺式关系。利用ωB97X-D密度泛函的DFT计算解释了立体选择性的机理、热力学和起源。

附：英文原文

Title: [8+2] vs [4+2] Cycloadditions of Cyclohexadienamines to Tropone and Heptafulvenes—Mechanisms and Selectivities

Author: Xiangyang Chen, Mathias Kirk Thgersen, Limin Yang, Rune F. Lauridsen, Xiao-Song Xue, Karl Anker Jrgensen, K. N. Houk

Issue&Volume: January 8, 2021

Abstract: The cinchona-alkaloid-catalyzed cycloaddition reactions of 2-cyclohexenone with tropone and various heptafulvenes give [8+2] or [4+2] cycloadducts, depending on the substituents present on the heptafulvene. We report the results of new experiments with heptafulvenes, containing diester and barbiturate substituents, which in combination with computational studies were performed to elucidate the factors controlling [8+2] vs [4+2] cycloaddition pathways, including chemo-, regio-, and stereoselectivities of these higher-order cycloadditions. The protonated cinchona alkaloid primary amine catalyst reacts with 2-cyclohexenone to form a linear dienamine intermediate that subsequently undergoes a stepwise [8+2] or [4+2] cycloaddition. Both tropone and the different heptafulvenes initially form [8+2] cycloadducts. The final product is ultimately decided by the reversibility of the [8+2] cycloaddition and the relative thermal stability of the [4+2] products. The stereoisomeric transition states are distinguished by the steric interactions between the protonated catalyst and tropone/heptafulvenes. The [8+2] cycloaddition of barbiturate-heptafulvene afforded products with an unprecedented trans-fusion of the five- and six-membered rings, while the [8+2] cycloadducts obtained from cyanoester-heptafulvene and diester-heptafulvene were formed with a cis-relationship. The mechanism, thermodynamics, and origins of stereoselectivity were explained through DFT calculations using the ωB97X-D density functional.

DOI: 10.1021/jacs.0c10966

Source: https://pubs.acs.org/doi/10.1021/jacs.0c10966