He Cyndi Qixin, Chen Tiffany Q, Patel Ashay, Karabiyikoglu Sedef, Merlic Craig A, Houk K N
Department of Chemistry and Biochemistry and ‡Department of Chemical and Biochemical Engineering, University of California , Los Angeles, California 90095, United States.
J Org Chem. 2015 Nov 6;80(21):11039-47. doi: 10.1021/acs.joc.5b02288. Epub 2015 Oct 28.
Density functional theory calculations were performed on a set of 13 transannular Diels-Alder (TADA) reactions with 10-18-membered rings. The results were compared with those for bimolecular and intramolecular Diels-Alder reactions in order to investigate the controlling factors of the high TADA reactivities. The effects of tether length, heteroatoms, and alkynyl dienophiles on reactivity were analyzed. We found a correlation between tether length and reactivity, specifically with 12-membered macrocycles undergoing cycloaddition most readily. Furthermore, modifying 12-membered macrocycles by heteroatom substitution and utilizing alkynyl dienophiles enhances the reaction rates up to 10(5)-fold.
对一组具有10至18元环的13个跨环狄尔斯-阿尔德（TADA）反应进行了密度泛函理论计算。将结果与双分子和分子内狄尔斯-阿尔德反应的结果进行比较，以研究高TADA反应活性的控制因素。分析了连接链长度、杂原子和炔基亲双烯体对反应活性的影响。我们发现连接链长度与反应活性之间存在相关性，特别是12元大环最容易发生环加成反应。此外，通过杂原子取代修饰12元大环并使用炔基亲双烯体可使反应速率提高高达10^5倍。
