Synthesis and resolution of diastereomers of (R,R)-1,2-cyclohexylenediamino-di-phenylmethylphosphonates Jarosław Lewkowski a,⇑ , Paweł Tokarz a , Tadeusz Lis b , Katarzyna S ´ lepokura b a Department of Organic Chemistry, Faculty of Chemistry, University of Lódz ´, Tamka 12, 91-403 Lódz ´, Poland b Faculty of Chemistry, University of Wrocław, F. Joliot-Curie 14, 50-383 Wrocław, Poland article info Article history: Received 27 February 2012 Accepted 5 April 2012 abstract Salen-like compounds, such as bis-aminophosphonic systems bearing a (R,R)-1,2-diamino-cyclohexyl (DACH) moiety, were synthesized by the addition of dialkyl phosphites to the azomethine bond of N,N 0 -dibenzylidene-1,2-diaminocyclohexane 2. Five bis-aminophosphonates, dimethyl, diethyl, diisopro- pyl, dibenzyl, and diallyl derivatives, were obtained in high diastereoselectivity. Three of these com- pounds, dimethyl 3a, diethyl 3b, and diisopropyl 3c derivatives, had the predominant diastereoisomers separated. A hypothetical explanation of the diastereoselectivity is also reported. Ó 2012 Elsevier Ltd. All rights reserved. 1. Introduction Salen-ligands 1 constitute a group of compounds with a broad range of applications. They have been used as catalysts in the ster- eoselective Strecker synthesis of amino acids, 1 and also in the asymmetric catalysis of modifications of the Mannich reaction such as the Kabatchnik-Fields reaction. 2–6 Recently, 7 the use of sat- urated derivatives of salen-ligands, such as DACH-based, N-tosylat- ed tetramines 1, was reported. They were applied to the asymmetric Henry reaction as Cu(I) complexes and turned out to be very much stereoselective. 1 HN NH Ph Ph NHTs TsHN It is well known that aminophosphonic derivatives bearing more than one amino- and more than one phosphonic moiety are as good ligands for coordinating metal ions. While the phos- phonic analogue of EDTA is the most well known, there are many other aminophosphonic chelating agents. As a result, a large number of salen applications involve amino- phosphonic acids because optically active aminophosphonic acids and their derivatives are biologically active compounds, which are widely used in pharmaceutical applications. 8,9 Therefore, much effort has been directed toward the development of the asymmet- ric hydrophosphonylation of carbonyl and imine compounds. All of these facts prompted us to perform a study on the catalytic properties of chiral salen-ligand derivatives bearing phos- phonic moieties that had saturated, sp 3 nitrogen atoms. Our aim was to construct a-aminophosphonates, whose structure would resemble salen-like ligand derivatives and would combine the chelating abilities of aminophosphonic groups with the strong ste- reodivergence action of salen compounds. Therefore, we performed the addition of phosphites to salen-like compounds in order to obtain aminophosphonic derivatives of salen-ligands, that is, bis-aminophosphonic systems bearing a (R,R)-1,2-diaminocyclohexyl (DACH) moiety. We expected that the presence of this optically active moiety would have a great influence on the stereoselectivity of the addition. These bis-amino- phosphonic systems bearing the (R,R)-DACH moiety have the po- tential to asymmetrically catalyze the Henry reaction and possibly also the Kabachnik–Fields reaction. 2. Results and discussion For the model compounds, we chose the benzaldehyde deriva- tives to prevent any of the substituents of the phenyl ring from having an additional influence on the stereochemistry. (R,R)-1,2- Diaminocyclohexane was isolated from a commercially available mixture of cis- and trans-isomers by crystallization of the (R,R)-iso- mer as its (+)-tartaric acid salt. Using the published procedure, 10 the condensation of (R,R)-cyclohexane-1,2-diammonium mono- (+)-tartrate with benzaldehyde was performed to give optically active N,N 0 -dibenzylidene-1,2-diaminocyclohexane 2, which was easily identified by comparison with the literature data. 10,11 0957-4166/$ - see front matter Ó 2012 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.tetasy.2012.04.007 ⇑ Corresponding author. E-mail address: jlewkow@uni.lodz.pl (J. Lewkowski). Tetrahedron: Asymmetry 23 (2012) 482–488 Contents lists available at SciVerse ScienceDirect Tetrahedron: Asymmetry journal homepage: www.elsevier.com/locate/tetasy