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 Immobilized Gelatin–λ–Carrageenan on Magnetite Nanoparticles as an Efficient Organocatalyst for Enantioselective Biginelli Reaction Mohammad Taqi Jafari-Chermahini [b] and Hossein Tavakol* [a] A facile method for preparation of stabilized and functionalized nanoparticles (NPs) from magnetite by successive application of blended natural polymers (gelatin and λ–carrageenan) on Fe 3 O 4 core has been developed. Gelatin plays a privileged role in the catalytic active sites and it is responsible for the enantiomeric induction. λ–carrageenan endowed chemical stability for immobilization of gelatin on Fe 3 O 4 nanoparticles, thereby enhancing its stability and recoverability. The versatility of the modified NPs was proved by their excellent heteroge- neous catalytic activity in one–pot, three–component Biginelli cyclocondensation reaction involving an aromatic aldehyde, urea, and ethyl acetoacetate (or Dimedone) to afford optically active corresponding dihydropyrimidinones in acceptable yields. This novel and green protocol has several advantages such as high efficiency, reusability of the catalyst, using inexpensive and available compounds for the catalyst. Introduction Multicomponent reactions (MCRs) as powerful emerging synthetic protocols for generating molecular structure diversity have received increasing interests in organic and medicinal chemistry during the past few decades. [1] The Biginelli reaction, discovered by Italian chemist Pietro Biginelli in 1893, is an acid–catalyzed multicomponent acid–catalyzed cyclocondensa- tion reaction, allowing the synthesis of dihydropyrimidinones (DHPMs) using the reaction between urea, a dicarbonyl derivative and an aldehyde (or similar structure). [2] The interests on this reaction have increased since DHPMs and their derivatives were found to exhibit several useful applications such as antibacterial, antifungal, antiviral, anti–inflammatory, antioxidant and many other potent biological activities. [3] The heterocyclic Biginelli scaffold has also been obtained under various synthesis conditions such as water [4] or ionic liquids [5] as solvent. Alternatively, this reaction was conducted either under solvent–free conditions [6] or under microwave irradiation. [7] Among various activated catalysts, Baker’s yeast, [8] iodine, [9] Zeolite, [10] ion exchange resin, [11] ethyl polyphos- phate, [12] TMSCl, [13] TMSCl–NaI, [14] and FeCl 3 –Si(OEt)4 [15] have been used in this procedure. Dotsenko et al. published a review article showing the interest of the synthetic chemists to find better and more selective catalysts for the synthesis of DHPMs. [16] Regardless of all developed experiences toward better reaction conditions, many of these reported methods still has several drawbacks, including low product yields, long reaction times, high costs, non–sustainable catalysts and purification issues. [17] In addition to these limitations, asymmetric catalytic Biginelli reactions have been a long–standing challenge. [18] The first organocatalyst for highly enantioselective Biginelli reaction reported by Gong. [19] Thereafter, much effort has been devoted to present new and facile methodologies for the efficient synthesis of DHPMs. [20–23] However, only in recent years, some works on the asymmetric synthesis of Biginelli reaction has been accom- plished [24–27] and it is still desirable to develope novel strategies for this important transformation. In this line, the use of natural catalysts will be more acknowledged and we have decided to employ cheap and available natural polymers on the surface of the magnetite core and use this hybrid composite as catalyst. As our first choice, sulfated polysaccharides have been selected. Marine algae are the most abundant source of sulfated polysaccharides in the nature. [28] Carrageenans are natural linear sulfated anionic polysaccharides, extracted from the marine red algae and widely employed in food, pharma- ceutical and cosmetic industries. [29] Based on the content and the position of ester sulfate groups in the galactose repeating unit and their differences in solubility, they were classified as iota (ι), kappa (k), and lambda (λ) carrageenans. [30] λ–carra- geenan bears on the average 2.7 negative charges per repeating disaccharide unit [31] and its aqueous solutions are viscous, but do not make gel. [32] By several research groups including our group, it was successfully immobilized on the surface of inorganic materials and the produced composite was employed as catalyst. [33–34] Another natural polymer is gelatin, which is a denatured product of collagen as a super coiled right–handed triple helix. [35] Gelatin has zwitterion nature, at the above of its isoelectric point (IEP), it has a net positive charge and below [a] H. Tavakol Department of Chemistry, Isfahan University of Technology, Isfahan, Iran Tel: + 98-31-33913241 Fax: + 98-31-33913241 E-mail: h_tavakol@cc.iut.ac.ir [b] M. T. Jafari-Chermahini Department of Chemistry, Isfahan University of Technology, Isfahan, Iran Supporting information for this article is available on the WWW under https://doi.org/10.1002/slct.201803986 Full Papers DOI: 10.1002/slct.201803986 1895 ChemistrySelect 2019, 4, 1895 – 1902 © 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim