Levandowski Brian J, Abularrage Nile S, Raines Ronald T
Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States.
Tetrahedron. 2021 Jul 2;91. doi: 10.1016/j.tet.2021.132160. Epub 2021 Apr 24.
We have experimentally and computationally explored the sluggish Diels-Alder reactivities of the geminally substituted 5,5-dimethylcyclopentadiene and 5,5-dimethyl-2,3-diazacyclopentadiene (4,4-dimethyl-4-pyrazole) scaffolds. We found that geminal dimethylation of 1,2,3,4-tetramethylcyclopentadiene to 1,2,3,4,5,5-hexamethylcyclopentadiene decreases the Diels-Alder reactivity towards maleimide by 954-fold. Quantum mechanical calculations revealed that the decreased Diels-Alder reactivities of -dimethyl substituted cyclopentadienes and 2,3-diazacyclopentadienes are not a consequence of unfavorable steric interactions between the diene and dienophile as reported previously, but a consequence of the increased repulsion within the -dimethyl group in the transition state. The findings have implications for the use of cyclopentadienes in "click" chemistry.
我们通过实验和计算研究了偕二取代的5,5-二甲基环戊二烯和5,5-二甲基-2,3-二氮杂环戊二烯（4,4-二甲基-4-吡唑）骨架的狄尔斯-阿尔德反应活性较低的情况。我们发现，1,2,3,4-四甲基环戊二烯偕二甲基化生成1,2,3,4,5,5-六甲基环戊二烯后，其与马来酰亚胺的狄尔斯-阿尔德反应活性降低了954倍。量子力学计算表明，偕二甲基取代的环戊二烯和2,3-二氮杂环戊二烯的狄尔斯-阿尔德反应活性降低并非如先前报道的那样是由于二烯和亲双烯体之间不利的空间相互作用，而是过渡态中偕二甲基基团内排斥作用增加的结果。这些发现对环戊二烯在“点击”化学中的应用具有启示意义。
