Dunscomb Rachel J, Frye Connor W, Murray Xavier, Tonks Ian A
Department of Chemistry, University of Minnesota-Twin Cities, 207 Pleasant Street SE, Minneapolis, Minnesota 55455, USA.
Chem Commun (Camb). 2025 Jun 10;61(48):8695-8698. doi: 10.1039/d5cc01979f.
While dihydropyrimidine cores are found in a number of bioactive molecules, 1,2-dihydropyrimidine regioisomers remain relatively underexplored due to a scarcity of simple synthetic routes to access them. Here, a modular, multicomponent synthesis to 1,2-dihydropyrimidines from alkynes, nitriles, aldehydes, and Ti imido complexes is reported, proceeding through a key diazatitanacycle intermediate that was previously exploited for pyrazole and α-diimine synthesis. The 1,2-dihydropyrimidines are formed through [2+2]-cycloaddition of an aldehyde with the diazatitanacycle synthetic intermediate, followed by cycloreversion to a 1,5-diazatriene that undergoes facile electrocyclization to the 1,2-dihydropyrimidine.
虽然二氢嘧啶核心存在于许多生物活性分子中，但由于缺乏简单的合成路线来获取1,2 - 二氢嘧啶区域异构体，它们仍相对未被充分研究。在此，报道了一种从炔烃、腈、醛和钛亚胺配合物模块化多组分合成1,2 - 二氢嘧啶的方法，该方法通过一个关键的二氮杂钛环中间体进行，该中间体以前曾用于吡唑和α - 二亚胺的合成。1,2 - 二氢嘧啶是通过醛与二氮杂钛环合成中间体的[2 + 2]环加成反应形成的，随后环化转化为1,5 - 二氮三烯，该三烯易于电环化生成1,2 - 二氢嘧啶。
