Bifunctional Transition Metal-Based Molecular Catalysts for Asymmetric Syntheses

Abstract

The discovery and development of conceptually new chiral bifunctional molecular catalysts based on the metal/NH acid-base synergy effect are described. The chiral bifunctional molecular catalysis originally developed for asymmetric transfer hydrogenation of ketones is applicable in enantioselective hydrogenation of polar functionalities as well as practical oxidative reactions including aerobic oxidation of alcohols. The structural modification and electronic fine-tuning of the protic amine chelating ligands are crucial to develop unprecedented catalytic reactions. The present bifunctional transition metal-based molecular catalyst offers a great opportunity to open up new fundamentals for stereoselective molecular transformations.

Why Does Alkylation of the N–H Functionality within M/NH Bifunctional Noyori-Type Catalysts Lead to Turnover?

“…The latter is manifested in the methylation of the N–H functionality which led to a totally inactive catalyst . The discovery of the Noyori catalyst stimulated the development of a powerful field which became known as M/NH bifunctional catalysis . Hundreds of new ligands and catalysts, the key structural parameter of which is traditionally prescribed as a “deprotonatable” N–H functionality, were developed and synthesized for the hydrogenation of carbonyl functionalities over the past decade .…”

Metal–ligand cooperation by aromatization–dearomatization as a tool in single bond activation

“…Traditionally, catalysis by metal complexes has been based on the metal centre, whereas the ligands bound to it influence its reactivity electronically and/or sterically, but do not interact directly with incoming substrate molecules. However, there are classes of catalysts in chemical and biological processes in which the ligands can cooperate with the metal centre by jointly interacting with the substrate and undergoing reversible bond-making and -breaking processes during substrate activation and product formation [1][2][3]. For example, metal-ligand cooperation (MLC) between an amine ligand and an iron centre is thought to be involved in the catalytic mechanism of the enzyme hydrogenase [4].…”

Asymmetric Hydrogenation of β-Aryl Alkylidene Malonate Esters: Installing an Ester Group Significantly Increases the Efficiency

“…In this reaction model, the substrate receives a hydride from the metal center and a proton from the amino group of the ligand but does not coordinate with the metal center of the catalyst, so the activity of the catalyst is maintained . However, the reported metal-NH bifunctional catalysts, including Noyori’s Ru-BINAP-diamine catalyst, are effective only for the hydrogenation of highly polar double bonds such as the CO and CN bonds of ketones and imines . With this fact in mind, we speculated that introduction of an ester group at the α-position of α,β-unsaturated carboxylic esters would increase the polarity of the CC double bond, making the resulting alkylidene malonates suitable substrates for chiral metal-NH bifunctional catalysts (Scheme b).…”

“…DFT calculations were performed to study the stereochemistry-determining step, hydride/proton transfer, based on an outer-sphere mechanism to understand the origins of the stereochemistry of reaction. Accordingly, models of the interaction between the substrate 2a and catalyst ( R )- 1m based on the crystal structure of Ir-SpiroPAP were proposed (Figure ).…”

“…We have found that the chiral iridium complexes of spiro pyridine-aminophosphine ligands, Ir-SpiroPAP, are extremely efficient catalysts for the asymmetric hydrogenation of ketones with turnover numbers (TONs) exceeding 10 6 . The high efficiency of this type of metal-NH bifunctional catalyst is attributed to the hydrogenation proceeding via an outer-sphere six-membered-ring transition state . In this reaction model, the substrate receives a hydride from the metal center and a proton from the amino group of the ligand but does not coordinate with the metal center of the catalyst, so the activity of the catalyst is maintained .…”