Chemoenzymatic preparation of optically active anthracene derivatives F. Javier Quijada a , Javier González-Sabín b , Francisca Rebolledo a, * , Vicente Gotor a, * a Departamento de Química Orgánica e Inorgánica, Universidad de Oviedo, 33071 Oviedo, Spain b Entrechem, SL, Edificio Científico-Tecnológico, Campus de El Cristo, 33006 Oviedo, Spain article info Article history: Received 13 October 2008 Accepted 31 October 2008 Available online 29 November 2008 abstract Syntheses and lipase-catalyzed resolutions of a trans-2-aminocyclopentanol rac-2 and trans-cyclopen- tane-1,2-diamine rac-3, bearers of an anthracene unit, have been effectively carried out. Burkholderia cepacia lipase catalyzed the transesterification of the b-amino alcohol with very high enantioselectivity (E > 200). Lipase B from Candida antarctica showed moderate enantioselectivity in the acetylation of the diamine when 1-phenylethyl acetate was used as an acyl donor. In addition, the treatment of the opti- cally active diamine (1S,2S)-3 (ee = 95%) with pyridine-2,6-dicarbonyl dichloride yielded the bis(aminoa- mide) 6, which was tested as a chiral solvating agent (CSA) of carboxylic acids. Ó 2008 Elsevier Ltd. All rights reserved. 1. Introduction Optically active b-amino alcohols and vicinal diamines are interesting compounds that have been shown to be effective in the treatment of a wide variety of human disorders. 1 Moreover, they have been widely used as chiral resolving agents and ligands in asymmetric synthesis. 2,3 Amongst the diamines, the commer- cially available enantiopure trans-cyclohexane-1,2-diamine has perhaps been the most used, 4 which is in contrast with the scarcity of applications of its homologous trans-cyclopentane-1,2-dia- mine. 5 Recently, we described a very useful procedure to obtain a variety of optically active trans-cyclopentane-1,2-diamine deriv- atives, 6 such as the bis(aminoamide) 1 (Fig. 1) which is used as chi- ral solvating agent (CSA) of carboxylic acids. 7 It is worthy to note that apart from chromatographic and capillary electrophoretic methods, NMR spectroscopy using CSAs is a fast and accurate methodology for the determination of the enantiomeric composi- tion of a chiral carboxylic acid. 8 In this sense, we have demon- strated that the presence of the pyridine-2,6-dicarboxamide fragment is a key structural feature for the discriminating ability of the CSA. 9 This fragment ensures a pincer-like conformation for the bis(aminoamide), which is stabilized by two intramolecular H-bonds formed between the NH groups and the pyridine nitrogen. In connection with this work and with the idea of testing the importance of the aromatic moiety over the tertiary amine of the bis(aminoamide), we herein planned the synthesis of a pyridine- 2,6-dicarboxamide derived from the optically active diamine (1S,2S)-3 (Fig. 2) bearing an anthracene unit. The presence of this group could increase the efficacy of the resulting bis(aminoamide) as a CSA due to the higher diamagnetic anisotropy of the anthryl ring 10 with respect to the phenyl group of 1. In addition, due to the interest in non-racemic anthracene derivatives in cycloaddition reactions, 11 and as templates for asymmetric Diels–Alder/retro Diels–Alder strategies, 12 we also carried out the resolution of the b-amino alcohol (±)-2, which is a precursor in the synthesis of (±)-3 (Scheme 1). 2. Results and discussion The synthesis of (±)-trans-3 was carried out following the meth- odology that we recently developed for the preparation of different 0957-4166/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved. doi:10.1016/j.tetasy.2008.10.029 * Corresponding authors. Tel./fax: +34 985103448 (V.G.). E-mail addresses: frv@uniovi.es (F. Rebolledo), vgs@fq.uniovi.es (V. Gotor). N O N O N N N 1 H H Figure 1. Optically active bis(aminoamide) as a CSA. NH 2 N OH N (±)-3 (±)-2 Figure 2. b-Amino alcohol and 1,2-diamine bearer of an anthracene unit. Tetrahedron: Asymmetry 19 (2008) 2589–2593 Contents lists available at ScienceDirect Tetrahedron: Asymmetry journal homepage: www.elsevier.com/locate/tetasy