Asymmetric nitroaldol reaction catalyzed by a chromium(III)–salen system Rafał Kowalczyk, Łukasz Sidorowicz and Jacek Skar _ zewski * Department of Organic Chemistry, Faculty of Chemistry, Wroclaw University of Technology, 50-370 Wroclaw, Poland Received 23 September 2007; accepted 17 October 2007 Available online 5 November 2007 Abstract—Chiral chromium(III)–salen-type complexes derived from 1,2-diaminocyclohexane and 1,2-diphenylethylenediamine were found to catalyze the enantioselective Henry reaction. Various arylaldehydes, trans-cinnamaldehyde, and cyclohexanecarbaldehyde reacted with nitromethane in the presence of (i-Pr) 2 NEt and salen–CrCl (2 mol %) to give the corresponding adducts in 40–76% ee and in moderate to good yields. Ó 2007 Elsevier Ltd. All rights reserved. 1. Introduction The asymmetric Henry (nitroaldol) reaction is a powerful synthetic tool for the formation of a new C–C bond and at least one stereogenic center. 1 Chiral nitroalcohols can be further transformed into synthetically useful derivatives such a carboxylic acids 2 and amino alcohols. 3 The nitro group is also a versatile source of other functionalities via displacement by the sulfur, azide as well as carbon nucleophiles. 4 Mechanistically, the nitroaldol reaction involves the addi- tion of a nitronate ion, which can be generated in situ by the deprotonation of nitroalkane with an external base. 5c The addition is facilitated either by a Lewis acid catalyst activating a carbonyl partner or by a suitable bifunctional catalyst that works as a Lewis acid–Brønsted base activat- ing and bringing both reactants together. 12 In recent years, effective catalysts have been developed, which provide some nitroalcohols with impressive stereo- selectivity. 5 Among them, those based on lanthanum(III), copper(II), cobalt(II), and zinc complexes were successfully employed. However, in many cases the relatively complex ligand structure and its substrate specificity limited broader applications in the direct nitroaldol reaction. Easy to obtain chiral salen-type ligands strongly coordinate many metals. 7 Although Schiff base metal complexes are very effective in many useful catalytic transformations 8 (privileged ligands), 6 only the cobalt(II)–salen complexes have been extensively tested in the nitroaldol reaction. 9,10 In spite of the catalyst effectiveness, the reaction required a long reaction time and suffered some problems in the purification of the product. All of these facts encouraged us to evaluate the other metal–salen systems in the Henry reaction. 2. Results and discussion The required chiral salen ligands 1 were prepared by the condensation of salicylic-type aldehydes with enantiomeri- cally pure diamines. 7,11 Their metal complexes were easily obtained from the ligands and commercially available AlMe 3 , Et 2 Zn, Ti(OPr-i) 4 , and the corresponding transi- tion metal salts (Scheme 1). Following the literature precedent, 9 we examined the reac- tion of nitromethane 3 with the aromatic aldehydes 2 in dichloromethane 13 in the presence of stoichiometric amounts of diisopropylethylamine (DIPEA) and 2 mol % of the respective metal–salen complex (Scheme 2). The results are summarized in Table 1. Thus, the reaction of 2-chlorobenzaldehyde with nitro- methane in the presence of DIPEA without a catalyst gave the racemic nitroalcohol in 81% yield (Table 1, entry 1). 0957-4166/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved. doi:10.1016/j.tetasy.2007.10.023 * Corresponding author. Tel.: +48 71 320 2464; fax: +48 71 328 4064; e-mail: jacek.skarzewski@pwr.wroc.pl Available online at www.sciencedirect.com Tetrahedron: Asymmetry 18 (2007) 2581–2586