A fluorinated dendritic TsDPEN-Ru(II) catalyst for asymmetric transfer hydrogenation of prochiral ketones in aqueous mediaw

Asymmetric transfer hydrogenation (ATH) has been widely used as an efficient and practical method for preparation of optically pure secondary alcohols that are important key intermediates for the synthesis of a large number of pharmaceutical substances. One of the most attractive catalyst system is based on Ru-TsDPEN (TsDPEN= N-(p-tolylsulfonyl)-1,2diphenylethylenediamine) complexes, which was developed by Noyori in the 1990’s with HCO2H-NEt3 azeotropic mixture as hydrogen donor. In many cases, high activity and enantioselectivity can be achieved with this archetypal catalyst. A limitation of the methodology is that the Ru-TsDPEN catalyst cannot be easily separated from products and thus may erode the practical applicability. In order to recover and reuse the expensive and sometimes toxic catalysts, continuous efforts have been devoted to new catalyst systems for the ATH reactions. Among them, dendritic catalysts have received special attention since they have the potential to combine both the advantages of homogeneous and heterogeneous catalysts in just one system. However, in terms of catalyst activity and reusability, dendritic catalysts cannot outperform other types of immobilized catalysts, such as catalysts immobilized on silica or polymer. Herein we report a highly efficient fluorinated dendritic chiral mono-N-tosylated 1,2-diphenylethylenediamineruthenium complex, Ru-FTsDPEN, for the asymmetric transfer hydrogenation of prochiral ketones in aqueous medium. This new catalyst has exhibited unprecedented recycling ability up to twenty-six times. The required fluorinated dendrimer 1 was prepared by a six-step protocol starting from 3,5-dihydroxybenzoic acid and bromopentafluorobenzene (see ESI for details).w Condensation of 1 with the p-hydroxyphenylsulfonamido modified chiral ligand (S,S)-2 and consecutive deprotection of the Boc-group provided successively the fluorinated dendritic chiral ligand (S,S)-3, FTsDPEN, in 65% overall yield (Fig. 1). The pre-catalyst was generated by reaction of the ligand FTsDPEN 3 with [RuCl2(p-cymene)]2 in CH2Cl2 at 35 1C for 10 h with Et3N as a base. The transfer hydrogenation of acetophenone using Ru-(S,S)-3 as catalyst was employed as the model reaction. Three conditions, i.e. a 5 : 2 formic acid triethylamine azeotrope (mole ratio), HCOOH–NEt3 (1.2 : 1 initial mole ratio) in water and aqueous HCO2Na 2a were investigated. As shown in Table 1, faster rates were obtained in water with HCO2Na as reductant than with the other two conditions (Table 1, entries 3 vs. 1 and 2). The stereoselectivity can be further increased with addition of Fig. 1 Structures of compounds 1–3.