Lu Hao, Li Xinyu, Wang Zhiqing, Du Peng, Yin Shuang-Feng, Kambe Nobuaki, Qiu Renhua
State Key Laboratory of Chemo/Biosensing and Chemometrics, Advanced Catalytic Engineering Research Center of the Ministry of Education, College of Chemistry and Chemical Engineering, Hunan University, Changsha 410082, P. R. China.
The Institute of Scientific and Industrial Research, Osaka University, 8-1Mihogaoka, Ibaraki, Osaka 567-0047, Japan.
J Org Chem. 2024 Nov 1;89(21):15574-15582. doi: 10.1021/acs.joc.4c01636. Epub 2024 Oct 17.
The synthesis of multifunctionalized dihydropyridinones from aldehydes and ketones involves at least a three-step process, making route shortening a challenging task, especially in achieving a one-pot four-component synthesis via aldehydes and ketones precondensation. Herein, we discovered a [1 + 2 + 1 + 2] four-component domino cyclization reaction, a novel concept in 4CRs with commercially available ketones and aldehydes, which by initially combining aldehydes and ketones with Meldrum's acid and ammonium acetate (NHOAc), respectively, they give dihydropyridones (>110 examples). This transformation features inexpensive additives and readily available starting materials, making it appropriate for rapid access to relevant pharmaceutical molecules containing dihydropyridinone-derived heterocycles. Also these compounds can be conveniently converted into trisubstituted and tetrasubstituted pyridines.
由醛和酮合成多功能二氢吡啶酮至少涉及三步过程，这使得缩短路线成为一项具有挑战性的任务，特别是在通过醛和酮预缩合实现一锅四组分合成方面。在此，我们发现了一种[1 + 2 + 1 + 2]四组分多米诺环化反应，这是4CRs中一个新的概念，使用市售的酮和醛，通过首先分别将醛和酮与丙二酸亚异丙酯和醋酸铵（NHOAc）结合，得到二氢吡啶酮（>110个实例）。这种转化具有廉价的添加剂和容易获得的起始原料，适合快速获得含有二氢吡啶酮衍生杂环的相关药物分子。而且这些化合物可以方便地转化为三取代和四取代吡啶。
