Ruthenium-catalysed asymmetric transfer hydrogenation of para-substituted α-fluoroacetophenones

Investigation into the enantioselection mechanism of ruthenium–arene–diamine transfer hydrogenation catalysts using fluorinated substrates

“…Each reduction was performed using four different ruthenium based catalysts IeIV, see Scheme 1. R = CH 3 (1,13), CH 2 F (2, 14),CHF 2 (3,15), CF 3 (4,16), Et (5,17), i-Pr (6,18), t-Bu (7,19) In order to reveal how structural variations affected the enantioselectivity, regression analysis was performed using the difference in Gibbs free energy for the reactions leading to the two enantiomers, D(DG), calculated from the ee-values and substituent constants. 28 The substituent constant evaluated includes parameters for size of groups: Taft's Es (Es), Charton volume (ESÀV), inductive parameters: s-para, s-para À , s-para þ , resonance: resonance effect (R), resonance delocalisation of negative charge (R À ), resonance delocalisation of positive charge (R þ ), group dipole, hydrophobicity, group electronegativity and molar refractivity.…”

“…15 Therefore, a comparison is useful in rationalising their enantioselection mechanisms. In the following sub-chapters their efficiency as catalysts in ATH in formic acid/triethylamine are discussed.…”

“…ATH of 1b, 2b, 3b and 4b in formic acid/triethylamine using catalyst I and III, R¼CH 3 (1, 13), CH 2 F (2, 14), CHF 2 (3,15), CF 3 (4, 16).…”

Enantioenriched 1-aryl-2-fluoroethylamines. Efficient lipase-catalysed resolution and limitations to the Mitsunobu inversion protocol

“…Based on our previous findings, 28 the fluoroalcohols (R)-4aeh were synthesised from the corresponding a-fluoroacetophenones 1aeh by asymmetric transfer hydrogenation catalysed by [RuCl 2 (mesitylene)] 2 complexed with (1S,2S)-N-p-tosyl-1,2-diphenylethylenediamine ((S,S)-TsDPEN). The alcohols (R)-4aee and (R)-4geh were synthesised in a formic acid/triethylamine (5/2 mol ratio) medium, while (R)-4f was prepared using water with sodium formate as hydrogen donor.…”

Catalytic asymmetric transfer hydrogenation of ketones: recent advances

“…Preparation of β-fluoro alcohols 87. 84 Iridium complexes 89 were efficient in the ATH of α-cyano phenones 88 using either formic acid (with or without triethylamine) or sodium formate in aqueous methanol as the hydrogen source, so the corresponding chiral β-hydroxy nitriles 90 were obtained with variable yields and enantioselectivities (Scheme 7).…”