Practical synthesis and mechanistic study of polysubstituted tetrahydropyrimidines with use of domino multicomponent reactions
2009; Elsevier BV; Volume: 65; Issue: 23 Linguagem: Inglês
10.1016/j.tet.2009.03.071
ISSN1464-5416
AutoresQiuhua Zhu, Huanfeng Jiang, Jinghao Li, Min Zhang, Xiujun Wang, Chaorong Qi,
Tópico(s)Synthesis and biological activity
ResumoThe practical synthesis of polysubstituted tetrahydropyrimidines 4 from but-2-ynedioates 1, amines 2, and formaldehyde 3 through a domino process of one-pot multicomponent reactions (MCRs) and the detailed mechanistic studies are described. The MCRs were performed under extremely mild reaction conditions and offered the desired products in excellent yields. The detailed studies on the mechanism of the MCRs proved that: (1) the proton-promoted domino sequence is composed of hydroamination, aza–ene-type reaction, nucleophilic addition, and dehydration–cyclization; (2) solvents could control the hydroamination stereoselectivity of 1 and 2: Z-isomers in proton solvents with Z/E up to 95:5 and E-isomers in non-proton solvents with E/Z up to 98:2, and Z-isomers are more stable than E-isomers; (3) Z- and E-enamine intermediates led to the same desired products via aza–ene-type reaction model. Calculations verified the aza–ene-type process in the MCRs.
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