在水相中甲酸与与三乙胺对亚胺的不对称氢化

CH2Cl2 and H2O as solvents (Table 1). The precatalyst was generated by treating (1S,2S)-Ts-DPEN (0.0075 mmol) with [RhCl2(Cp*)2] (0.0025 mmol) in water (1 mL) at 40 °C for 1 h,11 and the reduction was started by introducing the HCOOH−NEt3 (F/T) azeotrope (1.0 mL ; molar ratio F/T = 2.5/1) and 1a with a substrate/catalyst (S/C) ratio of 100:1. Table 1. Comparison of ATH of 1a with 2.5/1 F/T in CH2Cl2 and in H2Oa
entry 1 2 3 4 5
a
catalyst Rh-TsDPEN Rh-TsDPEN Rh-TsDPEN Rh-TsDPEN Rh-TsDPEN
f/t ratio 2.5/1 2.5/1 2.5/1 5.0/1 5.0/1
solvent CH2Cl2 H2O H2O H2O H2O
time (min) 10 60 1440 180 300
conv (%)b 99 9 99 0 2
ee (%)c 89 ndd 2 ndd ndd
Reaction conditions: 1a, 0.5 mmol; [RhCp*Cl2]2, 0.0025 mmol; (1S,2S)-TsDPEN, 0.0075 mmol; F/T, 1 mL; H2O, 1 mL; temp, 40 °C. b Determined by GC equipped with HP-1 column. cDetermined by HPLC equipped with chiral column. dNot determined. Received: March 26, 2015 Published: May 29, 2015
Letter pubs.acs.org/OrgLett
Asymmetric Transfer Hydrogenation of Imines in Water by Varying the Ratio of Formic Acid to Triethylamine
Vaishali S. Shende, Sudhindra H. Deshpande, Savita K. Shingote, Anu Joseph, and Ashutosh A. Kelkar*
2878
DOI: 10.1021/acs.orglett.5b00889 Org. Lett. 2015, 17, 2878−2881
© 2015 American Chemical Society
Organic Letters As reported in the literature,2a the reaction proceeded smoothly with CH2Cl2 as solvent with F/T (2.5/1) as the H donor and 99% of imine 1a was converted into (R)-2a in 10 min with 89% ee (Table 1, entry 1). To our surprise, with H2O as solvent, a much slower reaction rate was observed (Table 1, entry 2). Thus, only 9% conversion was observed for the reduction of 1a at 40 °C in 1 h; the conversion rose to 99% after a prolonged time of 1440 min with a decrease in ee to 2% (Table 1, entry 2). The major difference was that the pH value of the azeotrope−water system was 3 at the beginning of the reaction, while that of the F/T azeotrope (2.5/1)−CH2Cl2 (organic solvent) was 5. We have investigated the effect of the initial pH of F/T by systematically varying the molar ratio of F/T in water, and the results are presented below. The ATH of imine 1a (0.5 mmol) was performed in water (1 mL) at various initial solution pH values by adjusting the F/T molar ratios in a 0.5 to 5.0 range; the total solution volume was kept constant at 2.0 mL. Figure 1a shows the graph of turnover
E
was found that ATH of imine is pH dependent. Significant improvement in imine conversion with excellent enantioselectivity was observed for a wide range of imine derivatives with Rh-(1S,2S)-TsDPEN catalyst under an optimum F/T ratio in water with a short reaction time. To initiate this study, we examined the ATH of imine 1a as a model substrate to amine 2a as the product (Scheme 1) using Scheme 1. ATH of Imine 1a by Varying FA−TEA Ratio
Chemical Engineering and Process Development Division, CSIR-National Chemical Laboratory, Pune, India
S Swk.baidu.compporting Information *
ABSTRACT: Asymmetric transfer hydrogenation (ATH) of imines has been performed with variation in formic acid (F) and triethylamine (T) molar ratios in water. The F/T ratio is shown to affect both the reduction rate and enantioselectivity, with the optimum ratio being 1.1 in the ATH of imines with the Rh-(1S,2S)-TsDPEN catalyst. Use of methanol as a cosolvent enhanced reduction activity. A variety of imine substrates have been reduced, affording high yields (94−98%) and good to excellent enantioselectivities (89−98%). In comparison with the common azeotropic F−T system, the reduction with 1.1/1 F/T is faster. nantiomerically enriched active amines are significant synthetic precursors for biologically active molecules in medical, pharmaceutical, agricultural sciences, flavor, and fragrance industries.1 Different methods have been utilized for the synthesis of enantiomerically pure amines in the past few years.2 Asymmetric transfer hydrogenation (ATH) of imines is one of the most popular methods due to its operational simplicity and avoidance of the use of hazardous hydrogen gas and pressure vessels.3 Various chiral catalysts have been investigated for ATH of imines, but the most outstanding to date are the Ru and Rh complexes with the optically active Ntoluenesulfonyl-1,2-diphenylethylenediamine (TsDPEN) ligand4 in organic solvents with a formic acid−triethylamine azeotrope as a H donor.2−4 The choice of reaction medium and H donor is important in achieving an ATH reaction with high efficiency. The metal catalyzed ATH of imines is mostly performed in an azeotropic mixture of formic acid (HCOOH) and triethylamine (NEt3) (F−T), with the F/T molar ratio being 5:2 or with HCOONa as the hydrogen source and water as the solvent.3−5 Recently we have reported a significant enhancement in ATH of imines in water with the use of methanol as a cosolvent.6 The activity as well as enantioselectivity is very good with an azeotropic F/T and Rh or Ru complex/TsDPEN catalyst system.2−6 However, it is observed in the literature that the main drawback of ATH in an azeotropic F/T is that some catalytic complexes exhibit sluggish activity and require a longer induction period under acidic conditions.7 ATH of ketones has been investigated in water using F/T as the hydrogen donor, and the activity as well as enantioselectivity was found to be dependent on the F/T ratio (initial pH of the reaction mixture).7b,8 To the best of our knowledge there are no reports on the effect of the F/T ratio (initial pH of the reaction mixture) on the activity and enantioselectivity of ATH of imines with water as solvent, and there are very few reports on pH dependent ATH of imines.10 Herein we wish to report our results on the ATH of imines in water with F/T as the H donor. Variation of the F/T ratio in ATH of imines with water as a solvent was investigated, and it