Asymmetric reduction of ketones via whole cell bioconversions and transfer hydrogenation: complementary approaches

Dysprosium(III)-Mediated Carboxylate Formation from a Schiff Base

Noyori-Ikariya-type ruthenium(II)-catalysts for asymmetric transfer hydrogenation (ATH) have been known for 25 years and have proved as a well-behaved and user-friendly platform for the synthesis of chiral secondary alcohols. A progress has been made in the past five years in understanding the asymmetric reduction of complex ketones, where up to four stereocenters can be controlled in a single chemical transformation. Intriguing multi-chiral molecular architectures are therefore available in few well understood and robust synthetic steps from commercially available building blocks and possess handles for additional functionalization. The aim of this Review is to showcase the availability of three-dimensional scaffolds and homochiral lead-like compounds via ATH and inspire their direct use in drug discovery endeavors. Basic mechanistic insights are provided to demystify the stereo-chemical outcomes, as well as examples of diastereoselective transformations of enantiopure alcohols to give a feeling of how these rigid non-planar molecules can be further elaborated.

The asymmetric reduction of ketones and imines by transfer of hydrogen from isopropanol as the solvent catalyzed by metal complexes is a very useful method for preparing valuable enantioenriched alcohols and amines. Described here is the development of three generations of progressively more active iron catalysts for this transformation. Key features of this process of discovery involved the realization that one carbonyl ligand was needed (as in hydrogenases), the synthesis of modular ligands templated by iron, the elucidation of the mechanisms of catalyst activation and action, as well as the rational synthesis of precursors that lead directly and easily to the species in the catalytic cycle. The discovery that iron, an abundant element that is essential to life, can form catalysts of these hydrogenation reactions is a contribution to green chemistry.

Supported Noyori-Ikariya catalysts for asymmetric transfer hydrogenations and related tandem reactions

Asymmetric transfer hydrogenation of ketones is an important chemical reaction. In aqueous solution, Ru(p-cymene)[TsDPEN] is an efficient catalyst for asymmetric transfer hydrogenation via a metal–ligand bifunctional mechanism with either 2-propanol or formate as hydrogen donors. Here, we provide novel insight for two key steps in the catalytic cycle of transfer hydrogenation cycle, using a computational model of Ru(p-cymene)[TsDPEN] with an explicit aqueous solvent. Employing ab initio molecular dynamics simulations, we model the hydride transfer between formate and the protonated and deprotonated catalyst, and the dissociation of the ruthenium-formato complex. It is shown that the aqueous solvent provides a significant contribution to the reaction barriers, increasing the hydride transfer barrier, while decreasing the dissociation barrier for ruthenium-formato complex, when compared with a gas-phase model. These effects can be attributed to hydrogen-bond structure around the formate, which favors the fo...

The common use of NHC complexes in transition‐metal mediated C–C coupling and metathesis reactions in recent decades has established N‐heterocyclic carbenes as a new class of ligand for catalysis. The field of asymmetric catalysis with complexes bearing NHC‐containing chiral ligands is dominated by mixed carbene/oxazoline or carbene/phosphane chelating ligands. In contrast, applications of complexes with chiral, chelating bis(NHC) ligands are rare. In the present work new chiral iridium(I) bis(NHC) complexes and their application in the asymmetric transfer hydrogenation of ketones are described. A series of chiral bis(azolium) salts have been prepared following a synthetic pathway, starting from L‐valinol and the modular buildup allows the structural variation of the ligand precursors. The iridium complexes were formed via a one‐pot transmetallation procedure. The prepared complexes were applied as catalysts in the asymmetric transfer hydrogenation of various prochiral ketones, affording the corresponding chiral alcohols in high yields and moderate to good enantioselectivities of up to 68%. The enantioselectivities of the catalysts were strongly affected by the various, terminal N‐substituents of the chelating bis(NHC) ligands. The results presented in this work indicate the potential of bis‐carbenes as stereodirecting ligands for asymmetric catalysis and are offering a base for further developments. Copyright © 2010 John Wiley & Sons, Ltd.

Chiral Ionic Liquids (CILs) of amino acid amide were synthesized and used as novel organo catalyst for Asymmetric Transfer Hydrogenation (ATH) of acetophenone at room temperature. The developed CILs show very high yield and excellent enantio‐selectivity in transfer hydrogenation of acetophenone.

A series of polymeric chiral diamine ligands are developedby diboron-templatedasymmetric reductive couplings, and their iridium complexes Ir–polydiaminesare efficient and recyclable catalysts for asymmetric transfer hydrogenation(ATH) of functionalized ketones, affording a series of optically activesecondary alcohols in excellent enantioselectivities (up to 99% ee)and unprecedentedly high total TONs (12,000, six cycles). Ir–polydiaminecatalysts with longer chains offered higher reactivities, providinga plausible deactivation mechanism and practical solutions of ATHfor vitamin B5 and phenylephrine.

Newly developed oxo-tethered Ru amido complexes (R,R)-1 and their HCl adducts (R,R)-2 exhibited excellent catalytic performance for both asymmetric transfer hydrogenation and the hydrogenation of ketonic substrates under neutral conditions without any cocatalysts to give chiral secondary alcohols with high levels of enantioselectivity.

Newly developed oxo-tethered Ru amido complexes (R,R)-1 and their HCl adducts (R,R)-2 exhibited excellent catalytic performance for both asymmetric transfer hydrogenation and the hydrogenation of ketonic substrates under neutral conditions without any cocatalysts to give chiral secondary alcohols with high levels of enantioselectivity.

Chiral Ir(I) complex supported on external surface passivated SBA-15 as heterogeneous catalyst for asymmetric transfer hydrogenation of aromatic ketones

Dendritic catalysts for asymmetric transfer hydrogenation based (1 S,2 R)-norephedrine derived ligands

Ruthenium complexes, prepared by mixing potassium salt of α-amino acids and [RuCl2(arene)]2, acted as catalysts for asymmetric transfer hydrogenation of ketones from 2-propanol in the presence of KOH, and enantiomeric excesses of the products reached 92%.

Insight into the role of fluorinated dendrimers in ruthenium(II) catalyst for asymmetric transfer hydrogenation: The stabilizing effects from experimental and DFT approach

[reaction: see text] A rhodium(III) catalyst for asymmetric transfer hydrogenation of ketones has been designed. The incorporation of a tethering group between the diamino group and the cyclopentadienyl unit provides extra stereochemical rigidity. The catalyst is capable of enantioselective reduction of a range of ketones in excellent ee using formic acid/triethylamine as both the solvent and the reducing agent.