Selective Asymmetric Transfer Hydrogenation of α‐Substituted Acetophenones with Bifunctional Oxo‐Tethered Ruthenium(II) Catalysts

Abstract

A practical method for the asymmetric transfer hydrogenation of a-substituted ketones was developed utilizing oxo-tethered N-sulfonyldiamine-ruthenium complexes. Reduction by HCO 2 H and HCO 2 K in a mixed solvent of EtOAc/H 2 O allowed for the selective synthesis of halohydrins from 2-bromoacetophenone (98%) and 2-chloroacetophenone (> 99%), leading to suppressed undesired side reactions stemming from formylation under the typical reaction conditions using an azeotropic 5:2 mixture of HCO 2 H and Et 3 N. A range of functional groups, such as halogens, methoxy, nitro, dimethylamino, and ester groups, were well tolerated, highlighting the potential of this method. Nearly complete selectivity with a preferable ee was maintained even with a substrate/ catalyst (S/C) ratio of 5000. This catalyst system was also effective for the asymmetric reduction of a-sulfonated ketones without eroding the leaving group.

Highly selective hydrogenation of acetophenone over supported amorphous alloy catalyst

“…Hitherto, various catalysts, including Raney Ni and noble‐metal catalysts (e.g., Pt, Pd, Ru, Rh), have been developed for hypnone hydrogenation. However, the Raney Ni catalyst, which is commonly used in industries for hypnone hydrogenation, not only has a low selectivity (approximately 82%), but also produces a large amount of aluminum, which is an environmental pollutant.…”

Bifunctional Homogeneous Catalysts Based on Ruthenium, Rhodium and Iridium in Asymmetric Hydrogenation

“…The excellent activity and selectivity were preserved even with a substrate/catalyst ratio of 5000. 123 Interestingly, while optimizing an industrial flow process, Touge and co-workers applied this method to the asymmetric transfer hydrogenation/dynamic kinetic resolution of an -amido -keto ester, as a suitable alternative to the previously used asymmetric hydrogenation/hydroxyl inversion on the same substrate (Scheme 21). By using the oxo-tethered catalyst, they accessed the anti diastereomer of a key intermediate in the synthesis of the D-erythro-CER[NDS] ceramide at an 80 kg production scale (96% yield, 69% de, 97% ee).…”

Ru‐TsDPEN catalysts and derivatives in asymmetric transfer hydrogenation reactions

“…These modified Ru-oxy-tethered catalysts are used in effective enantioselective reduction process of α-substituted acetophenones like α-bromo acetophenones (Compound 43). 53 Practical approach for ATH process of α-substituted ketones is explained in this work by application of oxo-tethered N-sulfonyl diamine ruthenium complexes for selective synthesis of halohydrins from When Cat. 2, Cat.…”