pH‐Regulated Asymmetric Transfer Hydrogenation of Quinolines in Water

Abstract

,4-Tetrahydroquinolines exist as key structural elements in many natural products and have found broad commercial application.[1] In particular, optically pure tetrahydroquinolines are commonly present in alkaloids and are required in pharmaceutical and agrochemical synthesis. Representative examples include the bioactive alkaloids (+)-galipinine [2] and (À)-augustureine, [2b, 3] and the antibacterial drug (S)-flumequine.[2b]The most convenient route to chiral tetrahydroquinolines is the asymmetric reduction of quinolines. Successful examples of their hydrogenation by H 2 with organometallic catalysts have been reported.[4] However, although enantioselectivities of up to 99 % ee have been demonstrated, these catalysts usually require a high hydrogen pressure. In recently reported organocatalytic asymmetric reduction reactions of quinolines with the Hantzsch ester as the hydrogen source, excellent enantioselectivities were observed for 2-aryl substituted quinolines.[5] Surprisingly, there have been no reports of the asymmetric transfer hydrogenation (ATH) of quinolines with metal catalysts, although economical and environmentally benign hydrogen sources, such as isopropanol or formate, are generally used for ATH reactions, and ATH is operationally simpler than hydrogenation. [6,7] Herein we describe the ATH of quinolines [8] in water. The reactions were carried out in air, and excellent enantioselectivities were observed for a wide range of substrates (Scheme 1). The use of water as a reaction medium has been under intense investigation.[9] Apart from potential economic and ecological gains, water can offer new reactivity and selectivity patterns. [9,10] In this context, we and other research groups have reported successful ATH reactions of ketones and imines in neat water. [6g, 11-13] In particular, a combination of the unmodified Noyori ligand Ts-dpen (Ts-dpen = N-(p-toluenesulfonyl)-1,2-diphenylethylenediamine) [14] and [{RuCl 2 (pcymene)} 2 ] or [(Cp*MCl 2 ) 2 ] (M = Rh, Ir) led to the efficient reduction of aryl ketones with HCOONa in water. Among these catalysts, the Rh-Ts-dpen catalyst showed the highest activity and selectivity. [11c] We chose to use presynthesized Rh-Ts-dpen as the catalyst [15] and began our study of quinoline reduction by examining the ATH of a model substrate, 2-methylquinoline (1 a: R = H, R' = 2-CH 3 ), with HCOONa in water (Scheme 1). Disappointingly, only 17 % conversion was observed at 40 8C in 12 h with a substrate/catalyst (S/C) ratio of 100:1 (1 a: 0.5 mmol, HCOONa: 10 equiv, water: 5 mL). However, the enantioselectivity was excellent: the product was obtained with 96 % ee.In our previous study on the ATH of ketones in water, the pH value of the solution was found to have a critical effect on the reaction rate. [11b,c] In the present quinoline reduction, the initial pH value of the solution was approximately 8. However, recent studies on asymmetric hydrogenation suggest that quinoline is hydrogenated through an ionic mechanism in its protonated form (Scheme 1). [4g, 5a, ...

Adventure in Asymmetric Hydrogenation: Synthesis of Chiral Phosphorus Ligands and Asymmetric Hydrogenation of Heteroaromatics

“…Iridium complexes with this type of chiral diamine as ligands were also found to be effective, with up to 99% ee [81]. In 2009, Xiao and coworkers reported the first Rh-catalyzed asymmetric transfer hydrogenation of quinolines in an aqueous formate solution with excellent enantioselectivities [80].…”

“…In addition, ruthenium and rhodium complexes were successively introduced to the asymmetric hydrogenation of quinolines by Fan [78,79] and Xiao [80] groups with phosphine-free ligands, and the catalysts were air stable (Fig. 11).…”

Low Pressure Asymmetric Hydrogenation of Quinolines using an Annulated Planar Chiral N‐Ferrocenyl NHC‐Iridium Complex

“…Them inor isomerw as found to convert to the major isomer in CH 2 Cl 2 solution after 16 ha tr oom temperature to afford 12 as ac rystalline oranges olid;y ield:1 94 mg (57%); R f = 0. 25 …”

“…[a] (À)-(S)-2-Methyl-l,2,3,4-tetrahydroquinoline (20a) [25,26] Av ial containingasolution of 2-methylquinoline 19a (0.07 mL, 0.51 mmol), triphenylphosphine (1.3 mg, 1mol%) and iridiumc omplex 13 (6 mg,1mol%) in toluene( 2mL) was sealed in aP arr bomb.T he vessel was evacuated and back-filled with hydrogen three times,t hen pressurized to 5atm. Them ixture wass tirred at room temperature for 6h, after which the pressure was carefully released.…”

Asymmetric cascade reaction of 2-nitrophenylpyruvates over chirally modified platinum catalyst

“…The asymmetric catalytic methods developed for preparing chiral hydroquinolines [12] are based on enantioselective catalytic hydrogenations of quinoline derivatives [13][14][15][16][17][18] or the assembly of the chiral heterocyclic ring using enantioselective catalytic cyclization [19][20][21][22].…”