title: Reaction of Aldehydes/Ketones with Electron-Deficient 1,3,5-Triazines Leading to Functionalized Pyrimidines as Diels-Alder/Retro-Diels-Alder Reaction Products: Reaction Development and Mechanistic Studies.
abstract: Catalytic inverse electron demand Diels-Alder (IEDDA) reactions of heterocyclic aza-dienes are rarely reported since highly reactive and electron-rich dienophiles are often found not compatible with strong acids such as Lewis acids. Herein, we disclose that TFA-catalyzed reactions of electron-deficient 1,3,5-triazines and electron-deficient aldehydes/ketones can take place. These reactions led to highly functionalized pyrimidines as products in fair to good yields. The reaction mechanism was carefully studied by the combination of experimental and computational studies. The reactions involve a cascade of stepwise inverse electron demand hetero-Diels-Alder (ihDA) reactions, followed by retro-Diels-Alder (rDA) reactions and elimination of water. An acid was required for both ihDA and rDA reactions. This mechanism was further verified by comparing the relative reactivity of aldehydes/ketones and their corresponding vinyl ethers in the current reaction system.
authors.affiliation: The Center for Combinatorial Chemistry and Drug Discovery of Jilin University, The College of Chemistry and The School of Pharmaceutical Sciences, Jilin University , 1266 Fujin Rd., Changchun, Jilin 130021, P. R. China.
authors.forename: Kai
authors.initials: K
authors.lastname: Yang
authors.affiliation: The Center for Combinatorial Chemistry and Drug Discovery of Jilin University, The College of Chemistry and The School of Pharmaceutical Sciences, Jilin University , 1266 Fujin Rd., Changchun, Jilin 130021, P. R. China.
authors.forename: Qun
authors.initials: Q
authors.lastname: Dang
authors.affiliation: Beijing National Laboratory for Molecular Sciences (BNLMS), Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education, College of Chemistry, Peking University , Beijing 100871, China.
authors.forename: Pei-Jun
authors.initials: PJ
authors.lastname: Cai
authors.affiliation: Beijing National Laboratory for Molecular Sciences (BNLMS), Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education, College of Chemistry, Peking University , Beijing 100871, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Gao
authors.affiliation: Beijing National Laboratory for Molecular Sciences (BNLMS), Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education, College of Chemistry, Peking University , Beijing 100871, China.
authors.forename: Zhi-Xiang
authors.initials: ZX
authors.lastname: Yu
authors.affiliation: The Center for Combinatorial Chemistry and Drug Discovery of Jilin University, The College of Chemistry and The School of Pharmaceutical Sciences, Jilin University , 1266 Fujin Rd., Changchun, Jilin 130021, P. R. China.
authors.forename: Xu
authors.identifier: 0000-0003-4877-8383
authors.initials: X
authors.lastname: Bai