Rh^III‐ and Ir^III‐Catalyzed Asymmetric Transfer Hydrogenation of Ketones in Water

Abstract

Asymmetric transfer hydrogenation (ATH) of ketones by formate in neat water is shown to be viable with Rh-TsDPEN and Ir-TsDPEN catalysts, derived in situ from [Cp*MCl2]2 (M=Rh, Ir) and TsDPEN. A variety of ketones were reduced, including nonfunctionalized aryl ketones, heteroaryl ketones, ketoesters, and unsaturated ketones. In comparison with Ir-TsDPEN and the related Ru II catalyst, the Rh III catalyst is most efficient in water, affording enantioselectivities of up to 99 % ee at substrate/catalyst (S/C) ratios of 100-1000 even without working under an inert atmosphere. The aqueous phase reduction is shown to be highly pH-dependent; the optimum pH windows for TOF greater than 50 mol mol(-1) h(-1) for Rh- and Ir-TsDPEN are 5.5-10.0 and 6.5-8.5, respectively. Outside the pH window, the reduction becomes slow or stagnant depending on the pH. However, the enantioselectivities erode only under acidic conditions. At a higher S/C ratio, the aqueous ATH by Rh-TsDPEN is shown to be product- as well as byproduct-inhibited; the product inhibition appears to stem at least partly from the reaction being reversible. The aqueous phase reduction is simple, efficient and environmentally benign, thus presenting a viable alternative for asymmetric reduction.

Enantioselective Synthesis of Alcohols and Amines by Iridium‐Catalyzed Hydrogenation, Transfer Hydrogenation, and Related Processes

“…in 24 h). [128] Moreover, and in contrast to the related [RuClA C H T U N G T R E N N U N G (p-cymene)A C H T U N G T R E N N U N G (TsDPEN)], the activity of the iridium catalyst was completely inhibited in the HCO 2 H/ NEt 3 azeotrope. The rate of reduction was strongly pH dependent, with the highest TOFs achieved within a 2-unit window around pH 7.5.…”

Application of Proline‐Functionalised 1,2‐Diphenylethane‐1,2‐diamine (DPEN) in Asymmetric Transfer Hydrogenation of Ketones

“…The combined organic extracts were combined, dried over magnesium sulfate and the organic solvent was removed under reduced pressure to leave the crude product as a pale yellow solid. The crude product was -2-(((1S,2S)-2-(4-methylphenylsulfonamido)-1,2diphenylethyl)-carbamoyl)pyrrolidine-1-carboxylate (19): N-tBoc-(L)-proline (500 mg, 2.33 mmol) and triethylamine (1.1 cm 3 ) were dissolved in anhydrous THF (11.7 cm 3 ) and cooled to 0 °C. Ethyl chloroformate (0.24 cm 3 , 2.5 mmol) was added and the mixture was stirred at 0 °C for 30 minutes.…”

“…[16e,i,j] The ATH of ketones in water [17] has been the subject of a number of studies. [18,19] In 2004 Xiao [20] found that the use of a ruthenium (pcymene) TsDPEN catalyst ((S,S)-1) in water exhibited good catalytic activity when using sodium formate as the hydrogen donor. [21,22] The pH of the reaction had a pivotal effect; at low pH, the nitrogen atom adjacent to the tosyl group protonates and becomes detached from the metal centre, thus reducing activity, whilst at higher pH the ligand-metal bonding remains intact.…”

Unexpectedly fast catalytic transfer hydrogenation of aldehydes by formate in 2-propanol–water mixtures under mild conditions

“…very often applying Ru(II)-based homogeneous catalysts. Excellent rates and selectivities were achieved by Noyori [37], Bäckvall [8], Xiao [38] and others in synthesis of secondary alcohols. In general, water is not well tolerated in such processes [38], and several studies showed that both the rates and selectivities decrease substantially with increasing water content of the 2-propanol-water mixtures even in those cases when watersoluble catalysts were applied.…”

“…Excellent rates and selectivities were achieved by Noyori [37], Bäckvall [8], Xiao [38] and others in synthesis of secondary alcohols. In general, water is not well tolerated in such processes [38], and several studies showed that both the rates and selectivities decrease substantially with increasing water content of the 2-propanol-water mixtures even in those cases when watersoluble catalysts were applied. Notable exceptions are the transfer hydrogenations of ketones studied by Williams et al [39,40] and by Ajjou and Pinet [11] where up to 51% (v/v) water could be applied beneficially.…”