Short Communication 1,4-Michael additions of cyclic-β-ketoesters catalyzed by DNA in aqueous media Cristina Izquierdo, Javier Luis-Barrera, Alberto Fraile ⁎, José Alemán ⁎⁎ Departamento de Química Orgánica (Módulo 1), Universidad Autónoma de Madrid, 28049 Madrid, España abstract article info Article history: Received 13 May 2013 Received in revised form 18 July 2013 Accepted 13 August 2013 Available online 28 August 2013 Keywords: Catalysis DNA 1,4-Michael-addition Aqueous medium In this work, we describe the 1,4-Michael addition of the 1,3-dicarbonyl compounds to activated ethylenes under st-DNA catalysis in water. The reaction of the β-ketoester 4 with nitroolefins and conjugated carbonyls proceeds quite well, whereas other less activated ethylenes exhibit low or null reactivity. The catalyst can be recovered and reused for several catalytic cycles without significantly diminishing its efficiency. These reactions are similarly catalyzed by GMP, methyl-adenine and ethyl guanine, which suggests that the catalytic activity of st-DNA could be associated to the basic nature of their nucleotides' integrants. © 2013 Elsevier B.V. All rights reserved. 1. Introduction The development of sustainable chemical processes is one of the most important features in modern chemistry. It has become a world- wide key research area to provide solutions to important societal de- mands by optimizing the use of natural resources and minimizing waste and environmental impact. Thus, European society has recently realized the importance of implementing sustainable chemistry in our industry by creating the European Technology Platform (ETP) for Sustainable Chemistry (http://www.suschem.org/). Among the rele- vant methods toward achieving this goal, catalysis represents a key and central approach. Both Organocatalysis [1] and Metal Catalysis [2] have emerged as solutions for the problems originated in this context. Despite the enormous advances made toward both types of catalysis, there is still a search for more efficient and general catalysts or methods, and challenges remain from economic and ecological points of view. The use of new ligands in metal-catalysis and also new organocatalysts requires the design and synthesis of complicated structures with a large sequence of steps, especially for carrying out the asymmetric version of the chosen reaction [3]. Nature, our bioinspiration, controls chemical reactivity with differ- ent approaches, mainly by the use of enzymes which are able to select between hundreds of reactants in solution at very low concentrations. Biopolymers such as DNA are potentially interesting as catalysts as far as it could ideally coordinate two reagents (A and B) through different non-covalent interactions producing their approach and making easier their reaction. The resulting product would be released from the DNA, which could be incorporated again into the catalytic cycle (Fig. 1). The low price of DNA (compared with that of the most widely used ligands for metal catalysis or organocatalysts), its multiple binding sites (allowing the reaction to proceed with low catalyst loadings), and its compatibility with the use of inexpensive “green” solvents such as water [4] (which in its turn allows reusing it after recovering them from the aqueous solution) are three features conferring it an ad- ditional interest in catalysis. Despite this potential interest, only two papers [5,6] have been re- ported that concern the use of the DNA as the only catalyst. Both of them describe 1,2-additions to carbonyl groups and evolve with scarce stereochemical control [7]. Thus, it would be highly desirable to explore the DNA catalytic ability in other reactions. In this sense, we fixed our at- tention in the behavior of double bonds bearing EWG and in this paper we describe the 1,4-addition of β-ketoesters to different Michael accep- tors catalyzed by st-DNA [8]. 2. Experimental 2.1. Material and methods All reagents and chemicals were purchased from commercial sources (Sigma-Aldrich, U.S.A.) and used without further purifications. Solvents were purified by standard procedures [9]. NMR spectra were acquired on a Bruker 300 spectrometer, running at 300, and 75 MHz for 1 H and 13 C, respectively. Chemical shifts (δ) are reported in ppm relative to residual solvent signals (CDCl 3 , 7.26 ppm for 1 H NMR, CDCl 3 , 77.0 ppm for 13 C NMR). 13 C NMR spectra were acquired on a broad band decoupled mode. Catalysis Communications 44 (2014) 10–14 ⁎ Corresponding author. ⁎⁎ Corresponding author. Tel./fax: +34 914973875. E-mail addresses: alberto.fraile@uam.es (A. Fraile), jose.aleman@uam.es (J. Alemán). 1566-7367/$ – see front matter © 2013 Elsevier B.V. All rights reserved. http://dx.doi.org/10.1016/j.catcom.2013.08.015 Contents lists available at ScienceDirect Catalysis Communications journal homepage: www.elsevier.com/locate/catcom