Asymmetric Transfer Hydrogenation of 1,3-Alkoxy/Aryloxy Propanones Using Tethered Arene/Ru(II)/TsDPEN Complexes

Abstract

A series of propanones containing combinations of aryloxy and alkoxy substituents at the 1- and 3-positions were reduced to the alcohols via asymmetric transfer hydrogenation using a tethered Ru(II)/TsDPEN catalyst. The enantioselectivities of the reductions reveal a complex pattern of electronic and steric effects which, when used in a matched combination, can lead to the formation of products of up to 68% ee (84:16 er) from this highly challenging class of substrate.

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

“…ATH of a dissymmetric propanone and trichloromethyl ketones. [109][110] The C3-tethered catalyst could also reduce efficiently trichloromethyl ketones, as reported by Fox and co-workers (7 substrates, up to 98% ee). 110 The corresponding optically enriched alcohols were converted into amino-amides via stereospecific Jocic-type reactions (Scheme 17b).…”

“…using substituted aryloxy substituents) did not allow to improve the enantiomeric excesses. 109 Scheme 17. ATH of a dissymmetric propanone and trichloromethyl ketones.…”

Prediction of the enantiomeric excess value for asymmetric transfer hydrogenation based on machine learning

“…The dataset we curated from the literature contained approximately 380 reactions. 1,14–34 This is not a very large dataset for ML. Currently, very popular deep learning algorithms cannot be applied in this work.…”

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

“…6–8 Based on the catalytic system, tethered catalysts imparting increased selectivity and stability compared to untethered analogues were designed and synthesized by Wills and co-workers. 9–15 Subsequently, an ether-tethered complex was first introduced by Ikariya, 16 which exhibited excellent catalytic performance for both ATH and H 2 hydrogenation. Of the ATH catalysts, Gao and co-workers synthesized [PNNP], 17–19 [PN], 20 [P 2 N 4 ], 21 [P 3 N 4 ], 22 [ONNO] 23 and other chiral ligands for ATH of ketones exhibiting excellent catalytic activity and enantioselectivity.…”