Elsevier

Catalysis Communications

Volume 146, November 2020, 106128
Catalysis Communications

Short communication
Chelate ring size effects of Ir(P,N,N) complexes: Chemoselectivity switch in the asymmetric hydrogenation of α,β-unsaturated ketones

https://doi.org/10.1016/j.catcom.2020.106128Get rights and content

Highlights

  • A modular approach has been developed for the synthesis of chiral P,N,N ligands.

  • The ligands were used in the iridium-catalyzed hydrogenation of conjugated ketones.

  • The P,N and N,N bridge length strongly affected the activity and selectivity.

  • High activity, chemo- and enantioselectivity could be obtained.

  • The Ir-catalysts were active in methanol-water mixtures as solvents.

Abstract

A novel, highly modular approach has been developed for the synthesis of new chiral P,N,N ligands with the general formula Ph2P(CH3)CH(CH2)mCH(CH3)NHCH2CH2(CH2)nN(CH3)2 and Ph2P(CH3)CHCH2CH(CH3)NHCH2(CH2)n-2-Py (m, n = 0, 1). The systematic variation of their Psingle bondN and Nsingle bondN backbone led to the conclusion that the activity, chemo- and enantioselectivity in the hydrogenation of α,β-unsaturated ketones are highly dependent on the combination of the two bridge lengths. It has been found that a minor change in the ligand's structure, i. e. varying the value of m from 1 to 0, can switch the chemoselectivity of the reaction, from 80% Cdouble bondO to 97% Cdouble bondC selectivity.

Introduction

Transition metal catalyzed asymmetric hydrogenation of ketones is one of the simplest chemical transformations affording optically active secondary alcohols that serve as useful intermediates for the synthesis of biologically active compounds such as medicines, perfumes, and agrochemicals [[1], [2], [3], [4]]. Since the development of highly efficient chiral ruthenium-diphosphine/diamine complexes by Noyori et al. for the asymmetric hydrogenation of ketones in the 1990s [5], the design and synthesis of novel and even more efficient transition metal catalysts still represents a challenging direction in this research area [6,7]. Besides ruthenium-based systems, chiral iridium-complexes proved to be highly active, selective and robust catalysts in the asymmetric hydrogenation of a broad range of ketonic substrates. In this contribution, Ir-complexes modified by potentially tridentate P,N,N ligands constitute a unique class of chiral catalysts due to their extremely high activity and selectivity, structural modularity and high substrate tolerance (Fig. 1). Recently, Zhou and coworkers developed spiro pyridine-aminophosphine (SpiroPAP) based Ir-catalysts that were utilized in the asymmetric hydrogenation of simple [8] and functionalized ketones (ketoesters [[9], [10], [11]], ketoacids [12], α-amino-ketones [13]) with outstanding activities (eg. TOF > 100,000 h−1 for acetophenone) and enantioselectivities (>99% ee). To date the Ir-SpiroPAP system is the only Ir(P,N,N) catalyst used in the hydrogenation of α,β-unsaturated ketones toward enantioselective preparation of chiral 2-substituted acyclic allylic alcohols [14,15]. Zhang et al. synthesized Irsingle bondP,N,N catalysts containing ferrocene based aminophosphine-oxazoline type chiral ligands (f-Amphox) and sucessfully used them in the enantioselective hydrogenation of simple ketones [16], α-hydroxy- [17] and halogenated ketones [18] and β-ketoesters [19] with remarkably high enantioselectivity and activity. Another ferrocene-containing ligand family has been developed by the workgroups of Hu and Zhang and applied in the Ir-catalyzed hydrogenation of aromatic ketones [20,21] and β-ketoesters [22] as well as for the hydrogenation of α-alkyl-β-ketoesters [23] via dynamic kinetic resolution. In addition to these systems Hu et al. reported on the synthesis of an oxazoline-containing tridentate ligand that exhibited good performance in the hydrogenation of β-ketoesters [24]. It should be pointed out that all of these ligands include aromatic moieties in the backbone which might decrease the conformational flexibility of the chelate ring. The Ir-complexes of these ligands are capable of producing chiral secondary alcohols with the same efficiency as the corresponding Ru-based systems, and in several cases even outperform their catalytic efficiency in terms of both activity and enantioselectivity.

A key factor in an efficient catalyst design is the careful stereoelectronic fine tuning of the ligands structure. In asymmetric transition metal catalysis, the majority of reports on ligand modifications have followed systematic variation of the simple spatial demands of the catalyst, and/or substituent controlled electronic tuning of the chiral ligands. Indeed, this trend can nicely be recognized regarding the above examples, as the structural modifications, marked with red color in Fig. 1, involve (i) the alteration of the phosphorus substituents (PAr2), (ii) the modification of pendant side groups (R or X) or (iii) the variation of the relative configurations of the stereogenic elements.

Generally, less common are instances of the manipulation of the chelate ring size, despite the fact that such changes can be, in many cases, readily implemented resulting in steric and also electronic alteration and producing similarly dramatic improvements in catalytic activity and enantioselectivity [[25], [26], [27]]. Surprisingly, the variation of the ring size of potentially tridentate ligands in catalysis is very rare [[28], [29], [30], [31]] and to the best of our knowledge there is no such example concerning asymmetric catalytic transformations. However, as it was underlined by Crabtree and Peris, “this little studied area, analogous to bite angle effects in chelates, seems worth further efforts” [32].

In the present study we report on the development of a highly modular synthetic approach leading to a novel class of chiral P,N,N ligands based on two alkane-diyl backbones of different P,N and N,N tether lengths (Fig. 1). In order to compare the catalytic behavior of the new ligands, they were tested in the iridium catalyzed chemo- and enantioselective hydrogenation of enones, a challenging substrate class, with the intention to compare their activity, chemo- and enantioselectivity. Our primary aim was to vary the chelate ring size formed by the ligands and hence influence the bite angle and the conformational flexibility of the catalysts. Additionally, the effect of the reaction conditions and the substrate scope was carefully screened.

Section snippets

Synthesis of the ligands

The novel ligands were synthesized in two simple steps. At first, enantiomerically pure (4S,5S)-4,5-dimethyl-1,3,2-dioxathiolane 2,2-dioxide (1a) or (4R,6R)- or (4S,6S)-4,6-dimethyl-1,3,2-dioxathiane-2,2-dioxide (1b) and the corresponding diamine were mixed in THF leading to aminoalkyl sulfates 2a-f (Scheme 1). A remarkable feature of this methodology is that strong bases as deprotonating agents for the amines can be avoided. The addition of three equivalents of LiPPh2 in THF provided the

Declaration of Competing Interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Acknowledgements

We thank Mr. Béla Édes for skillful assistance in analytical measurements and synthetic experiments. The research was supported by the project NKFIH K128074. The research was also supported by the EU and co-financed by the European Regional Development Fund under the projects GINOP-2.3.2-15-2016-00008 and GINOP-2.3.3-15-2016-00004.

References (35)

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