New phosphine-diamine and phosphine-amino-alcohol tridentate ligands for ruthenium catalysed enantioselective hydrogenation of ketones and a concise lactone synthesis enabled by asymmetric reduction of cyano-ketones

Abstract

Enantioselective hydrogenation of ketones is a key reaction in organic chemistry. In the past, we have attempted to deal with some unsolved challenges in this arena by introducing chiral tridentate phosphine-diamine/Ru catalysts. New catalysts and new applications are presented here, including the synthesis of phosphine-amino-alcohol P,N,OH ligands derived from (R,S)-1-amino-2-indanol, (S,S)-1-amino-2-indanol and a new chiral P,N,N ligand derived from (R,R)-1,2-diphenylethylenediamine. Ruthenium pre-catalysts of type [RuCl2(L)(DMSO)] were isolated and then examined in the hydrogenation of ketones. While the new P,N,OH ligand based catalysts are poor, the new P,N,N system gives up to 98% e.e. on substrates that do not react at all with most catalysts. A preliminary attempt at realising a new delta lactone synthesis by organocatalytic Michael addition between acetophenone and acrylonitrile, followed by asymmetric hydrogenation of the nitrile functionalised ketone is challenging in part due to the Michael addition chemistry, but also since Noyori pressure hydrogenation catalysts gave massively reduced reactivity relative to their performance for other acetophenone derivatives. The Ru phosphine-diamine system allowed quantitative conversion and around 50% e.e. The product can be converted into a delta lactone by treatment with KOH with complete retention of enantiomeric excess. This approach potentially offers access to this class of chiral molecules in three steps from the extremely cheap building blocks acrylonitrile and methyl-ketones; we encourage researchers to improve on our efforts in this potentially useful but currently flawed process.

Novel Biobased Furanic Diols as Potential Alternatives to BPA: Synthesis and Endocrine Activity Screening

“…The products were extensively characterized by spectroscopic techniques (SI). Compound 6f has been previously reported in the literature …”

“…Compound 6f has been previously reported in the literature. 28 Synthesis of a Tertiary Diol. Another chemical from cellulosic biomass which has become a feedstock compound is 2,5-furandicarboxylic acid (FDCA).…”

Chiral Tridentate Ligands in Transition Metal-Catalyzed Asymmetric Hydrogenation

“…Despite the precedent reports that PNO-type ligands tend to bind Ru in a ratio of 2:1, The Clarke group developed cyclohexane-based tridentate ligand PNO-L5 and successfully separated its ruthenium complex with a 1:1 ligand/metal ratio. 94,130 Employing this complex in ADH of ketones gave slightly higher enantioselectivity than its PNN analogue (PNN-L2).…”

“…PNO-Ru-6 was also tested in ADH of acetophenone and gave 51% ee and 98% conversion. 130 In the same year, Kuriyama developed PNP-Ru-1 for highly efficient ADH of acetophe- none. 151 The reaction was conducted with 0.005 mol % PNP-Ru-1 and 0.05 mol % t BuOK under 3 MPa H 2 at 40 °C.…”

Chiral Tridentate-Based Ligands

“…The same team also developed 5.8 (analogue of 5.6) based on the t-stilbenediamine scaffold (see Scheme 5.11), which also proved to be efficient in the enantioselective ruthenium-catalyzed ketone hydrogenation (ee up to 80% in the hydrogenation of phenyl tert-butyl ketone). 66 More recently, ligand 5.6 with X = H was used in the iridium-catalyzed alkyl aryl ketone hydrogenation and transfer hydrogenation. 67 Good enatioselectivities were, in particular, obtained when the alkyl group was 4-piperidyl (in the 75-96% range) or cyclohexyl (up to 98%).…”