Enhancing Effects of Salt Formation on Catalytic Activity and Enantioselectivity for Asymmetric Hydrogenation of Isoquinolinium Salts by Dinuclear Halide‐Bridged Iridium Complexes Bearing Chiral Diphosphine Ligands

Abstract

Asymmetric hydrogenation of 1- and 3-substituted and 1,3-disubstituted isoquinolinium chlorides using triply halide-bridged dinuclear iridium complexes [{Ir(H)(diphosphine)}2 (μ-Cl)3 ]Cl has been achieved by the strategy of HCl salt formation of isoquinolines to afford the corresponding chiral 1,2,3,4-tetrahydroisoquinolines (THIQs) in high yields and with excellent enantioselectivities after simple basic work-up. The effects of salt formation have been investigated by time-course experiments, which revealed that the generation of isoquinolinium chlorides clearly prevented formation of the catalytically inactive dinuclear trihydride complex, which was readily generated in the catalytic reduction of salt-free isoquinoline substrates. Based on mechanistic investigations, including by (1) H and (31) P{(1) H} NMR studies and the isolation and characterization of several intermediates, the function of the chloride anion of the isoquinolinium chlorides has been elucidated, allowing us to propose a new outer-sphere mechanism involving coordination of the chloride anion of the substrates to an iridium dihydride species along with a hydrogen bond between the chloride ligand and the N-H proton of the substrate salt.

Strong Brønsted acid promoted asymmetric hydrogenation of isoquinolines and quinolines catalyzed by a Rh–thiourea chiral phosphine complex via anion binding

“…Strong experimental evidence was presented to favor an outer-sphere mechanism, in which hydrogen bonding between an Ir–Cl complex and N–H proton was proposed ( Scheme 3 , eqn (2)). 18 Both of these mechanism studies above were focused on hydrogenation of the halide salts of aromatic compounds. Similarly, the nature of protonated (iso)quinolines suggests that it seems not possible for the substrates to coordinate to the rhodium complex in this case, no matter if in a σ-bonding or a π-bonding manner.…”

Iridium‐Catalyzed Enantioselective Hydrogenation of 3‐Substituted Isoquinolinium Salts

“…Combined with the above results and related mechanistic research, [7,10] we proposed a possible pathways to THIQs from isoquinolinium salts catalyzed by the bromine‐bridged dimeric complex 1 b (Scheme 3a). Firstly, the hydrogenation underwent a 1,2 reduction to form the dihydroisoquinolinium salts 4 a ‐HCl.…”

Asymmetric Hydrogenation of Aryl Perfluoroalkyl Ketones Catalyzed by Rhodium(III) Monohydride Complexes Bearing Josiphos Ligands

“…This induction period is not observed, when the catalyst is stirred in the solvent under an argon atmosphere overnight before applying hydrogen pressure. Based on the previously reported mechanisms for the dinuclear iridium(III)‐catalyzed asymmetric C=N hydrogenations and investigations of alkene insertion into the Rh−H bond, we propose that a plausible mechanism could involve a similar catalytic cycle. Accordingly, the dinuclear rhodium species slowly dissociates to form mononuclear species possibly stabilized by the nitrile solvent.…”