1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 z Organic & Supramolecular Chemistry Nitroalkane-Mediated Multicomponent Synthesis of β-Enaminones Kiran B. Manjappa, [a] Ya-An Yang, [a] Santosh S. Mysore, [b] and Ding-Yah Yang* [a] A multicomponent synthesis of β-enaminones is explored using nitroalkane as a reagent and a solvent. The one-pot reaction of 1,3-diketone, aldehyde, and amine using nitromethane as the solvent resulted β-enaminones exclusively. When the same reaction was performed in nitroethane, however, lactone ring- opening of coumarin moiety was observed, leading to the formation of hydroxy-β-enaminones. The possible mechanisms for these reactions are deduced and the substrate scope of the reaction is investigated. Introduction Enaminone moiety has been found in the molecular skeleton of various natural products [1] and pharmacophores. [2] They not only can serve as building blocks in the preparation of various bio-active amino acids, [3] peptides, [4] and alkaloids [5] but also possess a wide range of biological activities. For instance, it is well-documented that enaminones are associated with phar- macological activities such as antimicrobial, antibacterial, anti- inflammatory, and antileukemia properties. [6] Besides, some β- enaminones were also found to be potent herbicides. [7] When chelated with metals such as Pd or Ni, the resulting complexes usually exhibit antitumor activities, [8] as outlined in Figure 1. Owing to their diverse biological activities, many method- ologies for the synthesis of β-enaminones have been reported in the literature. [9] In spite of numerous methods being available, a simple and efficient procedure for the preparation of β-enaminones remains desired. Since past decades, the multicomponent reactions (MCRs) [10] have been proven to be a useful synthetic strategy for the preparation of pharmaceuti- cally active molecules [11] as well as functional materials. [12] Among various reported MCRs, the one-pot coupling of 1,3- diketone, aldehyde, and amine in different solvents that gives a pseudo four component product (Scheme 1) has been consid- ered to be one of the most frequently employed MCRs. [13] Nevertheless, when aldehyde is replaced by the corresponding nitrostyrene, the major product for this MCR was found to be the β-enaminones. [9b,c] To the best of our knowledge, no effort has been made to synthesize β-enaminones from commercially available 1,3-diketone, aldehyde, and amine. Herein, we report an easy and rapid one-pot preparation of β-enaminones via nitroalkane-mediated coupling of 4-hydroxycoumarin, alde- hyde, and amine. Scheme 1 shows the previous reports of MCRs of 1,3- diketone, aldehyde/nitrostyrene, and amine under various conditions. The traditional approach for the synthesis of β- [a] Dr. K. B. Manjappa, Y.-A. Yang, Prof. D.-Y. Yang Department of Chemistry, Tunghai University, No. 1727, Sec. 4, Taiwan Boulevard, Xitun District, Taichung 40704, Taiwan E-mail: yang@thu.edu.tw [b] Dr. S. S. Mysore Center for Incubation, Innovation, Research and Consultancy(CIIRC), Jyo- thy Institute of Technology, Thataguni, Off Kanakapura Road, Bangalore - 560082, Karnataka, India Supporting information for this article is available on the WWW under https://doi.org/10.1002/slct.201802742 Figure 1. Some biologically potent β-enaminones. Scheme 1. Previous synthesis of β-enaminones. Full Papers DOI: 10.1002/slct.201802742 10701 ChemistrySelect 2018, 3, 10701–10705 © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim