Evolutionary Catalyst Screening: Iridium‐Catalyzed Imine Hydrogenation

Abstract

A high throughput catalyst screening is presented employing an evolutionary approach. The method comprises the optimization of initial leads by subjecting the catalysts to iterative rounds of optimization, including structural elaboration of the ligands by creating new focused libraries. Highly modular supramolecular ligands, robotized synthesis combined by high throughput experimentation creates a platform for fast catalyst development. An illustrative example for the asymmetric hydrogenation of cyclic 2,3,3-trimethyl-3H-indole using iridium catalysts is presented. The kinetic investigation of the best catalyst yields an unusual second order in iridium, first order in hydrogen and zeroth order in substrate. Under optimized reaction conditions a TOF of 100 mol mol À1 h À1 with 96% ee could be obtained with the best catalyst. A full catalyst screening and kinetic study was conducted within a three-week time-frame.

Combinatorial Strategies to find New Catalysts for Asymmetric Hydrogenation Based on the Versatile Coordination Chemistry of METAMORPhos Ligands

“…Triethylammonium salts of METAMORPhos ligands Lan1 − – Lan5 − were synthesized in both enantiomeric forms by the simple condensation of 1,1′‐binaphthyl‐2,2′‐diyl phosphorochloridate (BINOL P‐Cl) with sulfonamide in the presence of triethylamine according to reported procedures . The electronic properties of the ligand were varied by changing the substituent on the S atom (from weakly electron‐withdrawing 4‐butylphenyl to strongly electron‐withdrawing trifluoromethyl) and the steric properties were tuned by introducing different groups on the 3,3′‐position of the BINOL moiety.…”

Transfer hydrogenation of N-benzylideneaniline catalyzed by ruthenium complexes with pincer-type phosphorus nitrogen ligands using propan-2-ol as the hydrogen source

“…For example, the NH moieties in organometallic catalysts can serve as coordination groups, hydrogen bonding donors, hydrogen bonding acceptors, and/or proton sources [6]. Although the hydrogenation of imines using transition metals as catalysts is usually conducted using molecular hydrogen, some authors prefer propan-2-ol acting as the hydrogen source [7][8][9][10]. In this regard, PNchelate ligands or NPN ligands have attracted considerable attention in both coordination chemistry and catalysis due to the unusual electronic properties and the pronounced hemilabile character that arises when two very different binding sites are present [11,12,13].…”

Comparison of a Molecular and an Immobilized Gadolinium(III)‐tris[(1R,4S)‐3‐heptafluorobutanoyl‐camphor] as Catalyst in the Asymmetric Danishefsky‐Hetero‐Diels‐Alder‐Reaction

“…In order to ensure efficient catalyst improvement a reliable and versatile screening setup, which could even be speeded up by a high-throughput approach, 27 is required to master the accumulating amount of data. [28][29][30][31][32][33] Thus, our intention of using immobilized catalysts is not only to recycle the material, but to create rapid screening platforms, 34 where catalysts are prepared by complexing metals to the immobilized ligand at an analytical level, which lowers costs in the highthroughput screening of new catalysts and reactions. [35][36][37][38][39]…”