Department of Chemistry, Indian Institute of Engineering Science and Technology, Shibpur, Botanic Garden, Howrah 711103, India.
J Org Chem. 2023 Mar 17;88(6):3650-3665. doi: 10.1021/acs.joc.2c02867. Epub 2023 Feb 28.
Herein, we report a Zn(II)-catalyzed solvent-free sustainable synthesis of tri- and tetra-substituted pyridines using alcohols as the primary feedstock and NHOAc as the nitrogen source. Using a well-defined air-stable Zn(II)-catalyst, , featuring a redox-active tridentate azo-aromatic pincer, 2-((4-chlorophenyl)diazenyl)-1,10-phenanthroline (), a wide variety of unsymmetrical 2,4,6-substituted pyridines were prepared by three-component coupling of primary and secondary alcohols with NHOAc. Catalyst is equally compatible with the four-component coupling. Unsymmetrical 2,4,6-substituted pyridines were also prepared via a four-component coupling of a primary alcohol with two different secondary alcohols and NHOAc. A series of tetra-substituted pyridines were prepared up to 67% yield by coupling primary and secondary alcohols with 1-phenylpropan-1-one or 1,2-diphenylethan-1-one and NHOAc. The -catalyzed reactions also proceeded efficiently upon replacing the secondary alcohols with the corresponding ketones, producing the desired tri- and tetra-substituted pyridines in higher yields in a shorter reaction time. A few control experiments were performed to unveil the mechanistic aspects, which indicates that the active participation of the aryl-azo ligand during catalysis enables the Zn(II)-complex to act as an efficient catalyst for the present multicomponent reactions. Aerial oxygen acts as an oxidant during the Zn(II)-catalyzed dehydrogenation of alcohols, producing HO and HO as byproducts.
在此，我们报告了一种使用醇作为主要原料和 NHOAc 作为氮源，通过 Zn(II)催化无溶剂可持续合成三取代和四取代吡啶的方法。使用一种定义明确的空气稳定的 Zn(II)催化剂 ，其特征是具有氧化还原活性的三齿偶氮芳基夹持配体 2-((4-氯苯基)重氮基)-1,10-菲咯啉（），通过醇与 NHOAc 的三组分偶联，制备了多种不对称的 2,4,6-取代吡啶。催化剂 同样与四组分偶联兼容。通过醇与两种不同的仲醇与 NHOAc 的四组分偶联，也制备了不对称的 2,4,6-取代吡啶。通过醇与 NHOAc 与 1-苯基丙烷-1-酮或 1,2-二苯乙酮的偶联，制备了一系列四取代吡啶，产率高达 67%。用相应的酮取代仲醇，-催化的反应也能有效地进行，在更短的反应时间内以更高的产率得到所需的三取代和四取代吡啶。进行了一些控制实验以揭示其机理方面，结果表明，芳基偶氮配体在催化过程中的积极参与使 Zn(II)配合物能够作为本多组分反应的有效催化剂。空气中的氧气在 Zn(II)催化醇脱氢过程中充当氧化剂，产生 HO 和 HO 作为副产物。
