Simple 1,3-diamines and their application as ligands in ruthenium(ii) catalysts for asymmetric transfer hydrogenation of aryl ketones

Abstract

In this research work simple unsymmetrical 1,3-diamines were studied. The synthesis of the diamines started from non-commercial available compounds. S-5a and S,S-5c were obtained by biocatalysis with non conventional yeast, Rhodotorula rubra MIM 147, with excellent 99% e.e. and d.e. up to 90%. Different approaches of synthesis were applied to the same backbone to study both the steric and electronic effects of the ligands. The reactivity of the corresponding ruthenium complexes was evaluated in the asymmetric hydrogen transfer reduction of acetophenone as a standard substrate and of other different aryl ketones, highlighting the flexibility of the six membered chelating ring. A screening of the reaction conditions indicated aqueous media in the presence of HCOONa as a hydrogen donor to be the best system for overcoming the lack of stereocontrol thus allowing us to obtain 56% e.e. in the reduction of acetophenone with the complex in which the ligand was diamine 1, revealed as the best in terms of reactivity and stereoselectivity also in the reduction of the other different aryl ketones, in particular for a-tetralone, i (63% e.e.).

The Golden Age of Transfer Hydrogenation

“…Half-sandwich ruthenium complexes containing pincer skeletons with P−N, bipyridine, α-amino-oximes, amino alcohol, Schiff base, thioamide backbones, and 1,3-diamines 352 have been recently described with applications in TH (Scheme 30). The ruthenium−arene complexes containing 4,4′-dimethoxy-2,2′-bipyridine (74) showed catalytic activity in the reduction of water-soluble and -insoluble ketones with the use of HCOONa as the hydrogen donor at pH 4.…”

Evaluation of Chemical Diversity of Biotinylated Chiral 1,3‐Diamines as a Catalytic Moiety in Artificial Imine Reductase

“…Based on the biotin–streptavidin technology studied in depth by the Ward group, we synthesized six different biotinylated ligands starting from simple chiral 1,3‐diamines, previously reported by our group, which are able to be used as ligands in Ru II complexes for the asymmetric transfer hydrogenation (ATH) of ketones with interesting results regarding the differences in reactivity, especially with respect to different types of reaction media …”

“…The synthesis of the starting amino alcohols was achieved as previously reported . The reaction of para‐ , meta ‐, or ortho ‐nitrobenzenesulfonyl chloride in the presence of triethylamine (TEA) produced the corresponding nitrobenzenesulfonamides.…”

“…After 10 h, the conversion was complete but only 5–6 % enantioselectivity was achieved. As shown previously for reactions catalyzed by ruthenium(II) complexes, the conformational freedom of the chelating six‐membered ring might negatively affect enantioselectivity. However, by inserting a bulky substituent at the 3‐position and introducing these complexes in a rigid supramolecular system (Sav/biotinylated metal complex), we expect to increase the energy barrier for conformational change.…”

Efficient methodology to produce a duloxetine precursor using whole cells of Rhodotorula rubra

“…As reported in our previous work 25 for substrate 12, after 48 h the biotransformations were realized using a substrate concentration of 1 g L À1 for all employed substrates. In all cases the enantiomeric excess for the anti-diastereomers was very high (95-98%) although the diastereomeric excess was influenced by the different aryl group in a position to the carbonyl.…”