Geminal Repulsion Disrupts Diels-Alder Reactions of Geminally Substituted Cyclopentadienes and 4H-Pyrazoles

• Main Authors: Levandowski, Brian J (Author), Abularrage, Nile S (Author), Raines, Ronald T (Author)
• Format: Article
• Language: English
• Published: Elsevier BV, 2022-03-16T18:04:15Z.
• Subjects: Article
• Online Access: Get fulltext

 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-4H-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 gem-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 gem-dimethyl group in the transition state. The findings have implications for the use of cyclopentadienes in "click" chemistry.