Domingo Luis R, Picher M Teresa, Sáez José A
Departamento de Química Orgánica, Universidad de Valencia, Dr. Moliner 50, 46100 Burjassot, Valencia, Spain.
J Org Chem. 2009 Apr 3;74(7):2726-35. doi: 10.1021/jo802822u.
The regioselective hetero-Diels-Alder (HDA) reaction of asymmetric tetrazines (TTZs) with electron-rich (ER) ethylenes has been studied with use of DFT methods at the B3LYP/6-31G* level of theory. The reaction is a domino process that comprises three consecutive reactions: (i) a HDA reaction between the TTZ and the ER ethylene; (ii) a retro-Diels-Alder reaction with loss of nitrogen; and (iii) a beta-hydrogen elimination with formation of the final pyridazines. The first polar HDA reaction, which is associated to the nucleophilic attack of the ER ethylene to the electrophilically activated TTZ, is the rate and regioselectivity determining step of the domino process. The unexpected regioselectivity of these HDA reactions is explained within the polar cycloaddition model by using the conceptual DFT. Although the nucleophilic attack of the ER ethylene over the para position relative to the methylsulfinyl substituent could favor the charge transfer, it is energetically more unfavorable because it diminishes the electron density at the electronegative TTZ core.
利用密度泛函理论（DFT）方法，在B3LYP/6 - 31G*理论水平下研究了不对称四嗪（TTZs）与富电子（ER）乙烯的区域选择性杂环狄尔斯-阿尔德（HDA）反应。该反应是一个多米诺过程，包括三个连续反应：（i）TTZ与ER乙烯之间的HDA反应；（ii）伴随氮损失的逆狄尔斯-阿尔德反应；（iii）形成最终哒嗪的β-氢消除反应。第一个极性HDA反应与ER乙烯对亲电活化的TTZ的亲核进攻有关，是多米诺过程的速率和区域选择性决定步骤。通过使用概念性DFT，在极性环加成模型中解释了这些HDA反应出乎意料的区域选择性。尽管ER乙烯相对于甲亚砜取代基在对位的亲核进攻有利于电荷转移，但在能量上更不利，因为它降低了亲电TTZ核心处的电子密度。
