Ruthenium-catalyzed asymmetric hydrogenation of aromatic and heteroaromatic ketones using cinchona alkaloid-derived NNP ligands

Abstract

A series of cinchona alkaloid-based NNP ligands including a new one has been employed for the asymmetric hydrogenation of ketones. By combining ruthenium complexes, various ketones were smoothly reacted with up to 99.9% ee.

Iridium-catalyzed asymmetric transfer hydrogenation of aromatic ketones with a cinchona alkaloid derived NNP ligand

“…These indicated the formation of iridium hydride complexes. According to these results, our previous research studies 36,37 and the literature, 2,6,38,39 the ATH of aromatic ketones catalyzed by [Ir(COD)Cl] 2 / L8 was proposed to follow the outer sphere hydride transfer mechanism as shown in Scheme 1. First, ligand L8 reacted with [Ir(COD)Cl] 2 in i -PrOH to generate the complex Ir( L8 )(COD)Cl.…”

“…1). All NNP ligands (synthesized according to a reported method 36,37 ) were tested employing acetophenone as the model substrate using i-PrONa as a base at 82 °C within 3 h and the outcomes are illustrated in Table 1. It could be seen that the reaction hardly proceeded in the absence of any ligands ( With the introduction of ligands, the catalyst was generated in situ from [Ir(COD)Cl] 2 and ligands, and the ATH products were also observed.…”

“…Recently, we designed and synthesized tridentate NNP ligands based on commercially available cinchona alkaloids in an extremely simple and versatile method for asymmetric hydrogenation of ketones. 36,37 Although excellent activity and enantioselectivity were achieved in the asymmetric hydrogenation of ketones, high hydrogen pressure was necessary. As a further advancement of the practical applications, we wish to report a convenient, efficient and safe method for asymmetric transfer hydrogenation of ketones, owing not only to high performance, but also to operational simplicity.…”

The Ir-Catalyzed Asymmetric Hydrogenation of α-Halogenated Ketones Utilizing Cinchona-Alkaloid-Derived NNP Ligand to Produce (R)- and (S)-Halohydrins

“…Recently, we have designed and synthesized a series of novel and easily accessed cinchona-alkaloid-based NNP ligands, which achieved excellent results in iridiumcatalyzed asymmetric hydrogenation of aromatic, heteroaryl, and alkyl ketones. 28,29 Prompted by these encouraging results, we herein realized Ir-catalyzed asymmetric hydrogenation of halogenated ketones such as α-chloroacetophenones, heterocyclic thienyl and furanyl substrates, and even bromoketones.…”

“…Despite many successful cases for asymmetric hydrogenation of halogenated ketones having been reported, expensive reagent and multistep complicated reactions were employed to synthesize most ligands, and it remained an unsolved challenge to obtain both enantioenriched ( R )- and ( S )-alcohols with one type of ligand in previous studies. Recently, we have designed and synthesized a series of novel and easily accessed cinchona-alkaloid-based NNP ligands, which achieved excellent results in iridium-catalyzed asymmetric hydrogenation of aromatic, heteroaryl, and alkyl ketones. , Prompted by these encouraging results, we herein realized Ir-catalyzed asymmetric hydrogenation of halogenated ketones such as α-chloroacetophenones, heterocyclic thienyl and furanyl substrates, and even bromoketones. To our delight, a preferential formation of the ( R ) and ( S ) product was observed in the presence of NNP ligands derived from quinidine and quinine, respectively.…”