Elsevier

Tetrahedron

Volume 68, Issue 26, 1 July 2012, Pages 5248-5257
Tetrahedron

Asymmetric hydrogenation of N-alkyl and N-aryl ketimines using chiral cationic Ru(diamine) complexes as catalysts: the counteranion and solvent effects, and substrate scope

https://doi.org/10.1016/j.tet.2012.03.019Get rights and content

Abstract

Asymmetric hydrogenation of N-alkyl and N-aryl ketimines catalyzed by chiral cationic η6-arene-(N-monosulfonylated diamine) Ru(II) complexes has been investigated. Strong counteranion and solvent effects on the enantioselectivity were observed. The ruthenium catalyst bearing non-coordinating BArF anion was found to be particularly effective for the hydrogenation of acyclic and exocyclic N-alkyl ketimines in the presence of (Boc)2O in dichloromethane or even under solvent-free conditions, providing chiral amines with up to >99% ee and full conversions. Alternatively, the ruthenium catalyst bearing achiral phosphate anion together with corresponding phosphoric acid as the additive was also efficient for the hydrogenation of N-alkyl ketimines in the absence of (Boc)2O with excellent enantioselectivities and full conversions. For N-aryl ketimines lower enantiomeric excesses were observed by using the ruthenium catalyst bearing BArF anion. This catalytic protocol thus provides a facile and practical access to optically active amines and has been successfully employed in the gram-scale synthesis of enantiomerically pure (+)-sertraline.

Introduction

Chiral amines are one type of the most important building blocks because of their wide applications in the pharmaceutical, agrochemical, and fine chemical industries, and considerable research efforts have been put into the development of efficient methods for their synthesis.1 Among the reported approaches, the asymmetric hydrogenation of imines, which are readily prepared from the corresponding amine derivatives and carbonyl compounds, catalyzed by chiral transition metal complexes is one of the most useful methods for preparing optically active amines.2 In contrast to the great success achieved in the asymmetric hydrogenation of olefins or ketones,3 however, limited success has been achieved in the asymmetric hydrogenation of imines, particularly acyclic imines. This is because imines have some chemical peculiarities that make their stereoselective reduction more complex than that of ketones or olefins. First, imine compounds are often sensitive to hydrolysis. Second, the presence of E and Z isomers as well as enamine can be a problem for selective hydrogenation. Third, the imine and the amine product as well as the by-product due to hydrolysis can be catalyst poisons. Therefore, it is highly desirable to develop more efficient, stable, and practical catalyst systems for the asymmetric hydrogenation of imines, particularly acyclic imines.

In the past decade, a variety of chiral metal catalysts, including Ti, Zr, Rh, Ru, Ir, and Pd complexes, have been successfully employed to the asymmetric hydrogenation of imines.4, 5, 6, 7, 8, 9 Among them, homogenous Ir complexes with chiral P,P- or P,N-ligands have attracted particular attention.7, 8 For example, in 2001, Zhang and co-workers reported asymmetric hydrogenations of N-aryl imines with excellent enantioselectivity catalyzed by an iridium complex bearing a chiral 1,1′-bisphosphanylferrocene (f-binaphane).7d In 1997, Pfaltz and co-workers first developed chiral phosphanyloxazoline Ir complexes with non-coordinating anions for the asymmetric hydrogenation of imines to afford products with up to 89% ee.8a Most recently, an iridium complex bearing a new chiral phosphine-oxazoline ligand (SIPHOX) with a rigid and bulky spirobiindane scaffold developed by Zhou could catalyze the hydrogenation of acyclic N-aryl ketimines under ambient pressure with excellent enantioselectivities and full conversions.8i In addition, a significant industrial process that used the Ir-catalyzed asymmetric hydrogenation of an N-arylimine (106 turnovers and 80% ee) has also been developed.7c Despite these impressive advances, however, most of those catalysts are usually effective for N-aryl ketimines. Successful examples in the hydrogenation of N-alkyl ketimines, particularly with Ru-catalysts are rare.6 Most recently, some iridium complexes were found to be effective catalysts in the hydrogenation of N-alkyl ketimines.7(j), 7(k), 8(e), 8(j) One of the most notable examples was reported by Ding and co-workers in the hydrogenation of a variety of acyclic N-alkyl ketimines with >90% ee by using P,N-ligand-modified Ir complex.8j

In comparison with chiral phosphorus ligands, chiral diamine ligands are more readily available, easily tunable, and air-stable.10 Their metallic complexes, such as Ru(II)-complex of chiral N-monosulfonylated 1,2-diphenylethylene-diamine (DPEN), have proven to be powerful catalysts for asymmetric transfer hydrogenation of ketones and imines,11 although they were long neglected in the hydrogenation of unsaturated compounds.12, 13, 14 Most recently, chiral cationic metallic complexes of N-monosulfonylated diamine were successfully employed in the asymmetric hydrogenation of heteroaromatic compounds and imines.13, 14 Recently, we reported that the cationic ruthenium complexes of chiral monotosylated diamines were very efficient catalysts for the asymmetric hydrogenation of a broad range of quinoline derivatives in methanol,13a ionic liquid13b or even under solvent-free conditions,13d providing chiral 1,2,3,4-tetrahydroquinolines with up to >99% ee. Later, this catalytic system has proven to be highly enantioselective for the asymmetric hydrogenation of quinoxalines13f and N-alkyl imines.13(g), 13(h) It was noted that the achiral counteranions influenced the enantioselectivity significantly. At the same time, Xiao and co-workers demonstrated that a rhodium complex bearing chiral N-monosulfonylated DPEN was an efficient catalyst for the asymmetric hydrogenation of cyclic imines in the presence of AgSbF6.14a They further found that a combination of the Ir complex together with a chiral bulky phosphate anion could efficiently hydrogenate a variety of acyclic N-aryl imines with excellent enantioselectivities.14(b), 14(c) In 2009, Ikariya and co-workers used chiral iridium complex of N-monosulfonylated 1,2-cyclohexanediamime (CYDN) for the asymmetric hydrogenation of acyclic N-alkyl ketimines in the presence of silver salts with moderate enantioselectivity.14e Despite these impressive achievements, acyclic imines remain very challenging substrates in terms of both enantioselectivity and substrate scope. On the basis of our preliminary results,13g herein, we reported our detailed study on the asymmetric hydrogenation of N-alkyl and N-aryl ketimines catalyzed by chiral cationic Ru(diamine) complexes. It was found that a wide range of imines including acyclic N-alkyl ketimines, exocyclic N-alkyl ketimines, and acyclic N-aryl ketimines were successfully hydrogenated with good to excellent enantioselectivities (up to >99% ee) and reactivities (ton up to 2000). To the best of our knowledge, in the cases of acyclic N-alkyl ketimines, the levels of enantioselectivity and substrate generality are the highest among all known catalytic systems. In addition, this catalytic protocol was successfully employed in the gram-scale synthesis of enantiomerically pure (+)-sertraline at highly concentrated conditions.

Section snippets

Synthesis of monosulfonylated diamine-containing ruthenium catalysts

Since the pioneering work reported by Noyori and co-workers, a number of Ru-, Rh-, and Ir-complexes of monosulfonylated diamines have been synthesized and proven to be powerful catalysts for asymmetric transfer hydrogenation of ketones.11 For our study, chiral diamines DPEN and CYDN were chosen as the ligands. Ten Ru, Rh, and Ir complexes bearing chloride as anion were prepared according to the well-established method. The anion Cl was then exchanged to the weakly coordinating counteranions,

Conclusions

In summary, we have demonstrated that chiral cationic η6-arene-(N-monosulfonylated diamine) Ru(II) complexes are very effective catalysts for the asymmetric hydrogenation of N-alkyl and N-aryl ketimines. A wide range of N-alkyl ketimines, including acyclic and exocyclic N-alkyl ketimines, were efficiently hydrogenated with chiral cationic Ru(diamine) catalyst bearing non-coordinating BArF anion in the presence of (Boc)2O in 1,2-dichloroethane or even under solvent-free conditions with up to

General

Unless otherwise noted, all experiments were carried out under an atmosphere of nitrogen using standard Schlenk techniques or in a nitrogen-filled glove box. HPLC analyses were performed on a VARIAN PROSTAR 210 liquid chromatograph. All organic solvents were dried using standard, published methods and were distilled before use. Commercially available reagents were used throughout without further purification other than those detailed below. All catalysts were prepared according to the published

Acknowledgements

Financial supports from the National Natural Science Foundation of China (Grant No. 20973178), the National Basic Research Program of China (973 Program, Nos. 2010CB833300 and 2011CB808600), and the Chinese Academy of Sciences are greatly acknowledged.

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