Tuning acylthiourea ligands in Ru(II) catalysts for altering the reactivity and chemoselectivity of transfer hydrogenation reactions, and synthesis of 3-isopropoxy-1H-indole through a new synthetic approach

doi:10.1016/j.jorganchem.2019.121087

Journal of Organometallic Chemistry

Volume 908, 15 February 2020, 121087

https://doi.org/10.1016/j.jorganchem.2019.121087 Get rights and content

Highlights

•
A new series of Ru(II)-p-cymene complexes containing pseudo-acylthiourea ligands was synthesized and characterized.
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The molecular structure of the ligands and one of the complexes was confirmed by XRD technique.
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The chemoselectivity and reactivity of TH reaction was altered by tuning the acylthiourea ligands in the Ru(II) catalyst.
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The catalyst was compatible with broad range of substrates and gram-scale synthesis was achieved for the bio-fuel.
•
One pot synthesis of 3-isopropoxy indole from 2-nitrocinnamaldehyde was achieved via a new synthetic route.

Abstract

Ru(II)-p-cymene complexes (1–3) containing picolyl based pseudo-acylthiourea ligands (L₁-L₃) were synthesized and characterized. The crystallographic study confirmed the molecular structures of all the ligands (L₁-L₃) and complex 3. The catalytic activity of the complexes was tested mainly towards TH of carbonyl compounds and nitroarenes. The influence of steric and electronic effects of the ligands on the chemoselectivity and reactivity were reported. The catalytic activity was enhanced and chemoselectivity was switched after tuning the ligands in the catalysts, compared to their corresponding unmodified Ru(II)-p-cymene complexes. The catalysis was extended to a broad range of substrates including some challenging systems like furfural, benzoylpyridine, benzoquinone, chromanone, etc. The strategy of tuning the bifunctional ligands in the catalysts for effective and selective catalysis worked nicely. Further, the catalysis was extended to one pot synthesis of 3-isopropoxyindole from 2-nitrocinnamaldehyde, the first synthetic route similar to Baeyer Emmerling indole synthesis. All the catalytic experiments exhibited high conversion and selectivity.

Graphical abstract

Introduction

Hydrogenation is the key step in many organic transformations. Many chemoselective homogeneous catalysts were reported for hydrogenation reactions so far [[1], [2], [3], [4]]. Transfer hydrogenation (TH) reactions are preferred over hydrogenation using H₂ gas due to their mild and sustainable reaction conditions. Notably, TH reactions gained prominence after the milestone discovery of bifunctional catalysts by Noyori and his co-workers. They explained the importance of N–H moiety for the bifunctional mechanism which enhances the rate of the TH reactions. This metal-ligand cooperation effect (N–H effect) led to the discovery of many bifunctional catalysts for the effective catalytic TH reactions. However, there is an ongoing search for a universal catalyst which can comply the needs of TH reactions like phosphine free, inexpensive, active with cheaper hydrogen donors, chemoselective and compatible with a broad range of substrates [[5], [6], [7]]. Chemoselective reactions have inherent advantage as they facilitate single step reactions by avoiding protection and deprotection steps. The controlled chemoselectivity is achieved mostly in homogeneous catalysis due to the extraordinary variability in the structure of molecular catalysts. The change in bulkiness, chirality, coordination mode and electronic property of the ligands on the metal center of the catalysts will influence their reactivity, stereoselectivity, regioselectivity and chemoselectivity. Hence, ligands play an important role in tuning the behavior of the catalysts [1,[8], [9], [10], [11], [12], [13], [14], [15], [16], [17], [18]]. In some cases, even pH of the reaction medium influences the chemoselectivity [19]. Sommer et al. reported the influence of coordination mode of azocarboxamide ligands in Ru(II)-arene complexes on base-free TH catalysis [20]. Recently, Malan et al. reported picolyl based Ru(II)–NHC complexes as catalysts for TH of ketones and oxidation of alcohols [21]. Hintermair et al. reported the influence of ancillary ligands in Ir(III)-Cp* catalyst towards TH reaction using 2-propanol as hydrogen source and KOH as base [22]. Although the literature seems to offer a variety of tuned catalysts, scope of the substrates and chemoselectivity aspect remain limited.

Ruthenium-arene based catalysts with potential ligands are well known for TH reactions [4,5,23]. Acylthiourea ligands are one such ligands with a variety of coordination modes and having a huge space for tuning the electronic environment, which pave the way for the control of stereoselectivity, chemoselectivity and reactivity [[24], [25], [26], [27]]. Picolylamine based compounds are also potential ligands for TH of carbonyl compounds [28,29]. Our group has previously reported various chiral acylthiourea based Ru(II)-arene complexes as bifunctional catalysts for asymmetric TH reactions. These ligands are bound to the ruthenium center via monodentate neutral sulphur coordination. Generally, high conversions and excellent enantioselectivities were achieved, and mechanism was similar to Noyori’s bifunctional outer sphere mechanism [24,[30], [31], [32]]. We have also reported Ru(II)-p-cymene catalysts containing picolyl based acylthiourea ligands for the TH of nitroarenes and carbonyl compounds, wherein the chemoselectivity was observed towards nitroarenes [33]. Srinivas et al. reported thiopseudourea (modified acylthiourea) based Pd(II) complexes as versatile and efficient catalysts for C–C coupling reactions [34]. Herein we report the change in chemoselectivity of TH by tuning the bulkiness and coordination mode of acylthiourea based ligands present in the Ru(II)-p-cymene complexes. Scope of the substrates was broadly explored. Some challenging substrates like furfural, benzoyl pyridine, benzoquinone and chromanone were successfully tested.

One pot synthesis of biologically active heterocyclic motifs like indoles, quinolines etc. via TH followed by cyclization is an important area of research. Achieving this through hydrogen borrowing strategy is an active field of current research [35,36]. Interestingly, we have devised a novel one pot method for the synthesis of 3-isopropoxy-1H-indole from 2-nitrocinnamaldehyde.

Section snippets

Synthesis of the ligands (L₁-L₃)

The pyridine based acylthiourea precursors were prepared by following our previously reported procedure [33]. Benzyl bromide (1.5 mmol) was added to the solution of acylthiourea (1 mmol) and sodium hydride (3 mmol) in dry THF (20 mL). After stirring the reaction mixture under inert atmosphere for 5 h at 0 °C, it was neutralized with 10% aqueous ammonium chloride solution. Then, THF was removed using rotary evaporator, and product was extracted with ethyl acetate, dried over anhydrous sodium

Synthesis of the ligands and complexes

The pyridine based acylthiourea precursors were synthesized as per our own literature [32]. The ligands (L₁-L₃) were synthesized by reacting the corresponding precursors with benzyl bromide and sodium hydride in dry THF at 0 °C. The complexes [RuCl(η⁶-p-cymene)L]Cl were prepared from the reactions between [RuCl₂(η⁶-p-cymene)]₂ and L in toluene (Scheme 1). All the ligands and complexes were stable in air and soluble in CH₃CN, CHCl₃, CH₃OH, CH₂Cl₂, C₂H₅OH, DMSO, DMF and DMAc.

Characterization of the ligands and complexes

Electronic spectra of

Conclusions

The objective of the work was to tune the chemoselectivity and reaction rate by engineering the ligand in the catalyst. Hence, our previous Ru(II)-p-cymene catalyst containing monodentate acylthiourea ligand was tuned by protecting S atom of the ligand. This made bidentate coordination of resulting pseudo-acylthiourea feasible with ruthenium ion. Thus, the first Ru(II)-p-cymene complexes containing pseudo-acylthiourea ligand were synthesized and characterized by spectral techniques. 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

P·N.S. thanks NIT, Trichy and MHRD for the fellowship.

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Citation Excerpt :
Notably, substrates with electron-donating functional groups were found to be less reactive than that of electron-withdrawing groups due to the presence of excess electron density in the nitro/carbonyl group. These authors further used a similar class of acylthiourea ligands, L32-L34, for the preparation of their Ru(II) complexes 32-34 (Fig. 15) [72]. The corresponding Ru(II) complexes were synthesized by using [RuCl2(p-cymene)2]2.
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Tuning acylthiourea ligands in Ru(II) catalysts for altering the reactivity and chemoselectivity of transfer hydrogenation reactions, and synthesis of 3-isopropoxy-1H-indole through a new synthetic approach

Highlights

Abstract

Graphical abstract

Introduction

Section snippets

Synthesis of the ligands (L1-L3)

Synthesis of the ligands and complexes

Characterization of the ligands and complexes

Conclusions

Declaration of competing interest

Acknowledgements

Org. Lett.

Coord. Chem. Rev.

Org. Lett.

Organometallics

Organometallics

Organometallics

Org. Lett.

J. Organomet. Chem.

J. Organomet. Chem.

Organometallics

Organometallics

Chin. J. Catal.

Appl. Catal. A Gen.

Mol. Catal.

Catal. Today

Org. Process Res. Dev.

Appl. Catal. B Environ.

J. Mol. Catal. A Chem.

ACS Catal.

ACS Catal.

Hydrogen Transfer Reactions: Reductions and beyond in Topics in Current Chemistry Collections

Chem. Rev.

Chem. Rev.

Angew. Chem. Int. Ed.

Acc. Chem. Res.

Chem. Rev.

Chem. Rev.

Synthesis of the ligands (L₁-L₃)