The Hydrated Structure Factor in Additive Effect on Enantioselective Organocatalytic Transfer Hydrogenation Reactions with Hantzsch Esters

Abstract

Acid additives were frequently used in amine-catalyzed asymmetric catalysis as a practical strategy for the promotion of reaction activity/selectivity with a reduced amount of chiral catalyst. A fact is that the acid additives were discovered mostly by chance rather than by a logic prediction. Two bioinspired hydrated mechanisms for the organocatalytic transfer hydrogenation reactions were proposed in this work. And the proposed different acid-water-imine hydrated structures involved mechanism could well explain the additive effect supported by the reported experimental data. The new insight shows promise for assisting a logic acid additive screening in cationic imine-mediated asymmetric catalysis.

Planar Cationic Imine Radical Iodide Charge Transfer Complexes: Key Intermediates for Iodine-(co)catalyzed Homogenous Asymmetric Hydrogenation of N-Arylimines

“…The relatively short reaction time, ranging from 10 mins to 7 hrs in both catalytic systems 6,8 , suggests a Lewis acid catalyst role of molecule iodine in the imine formation step. For some aldimines from aromatic aldehydes with strong electron-deficient groups, a hydrated form [12][13][14] might form initially and the molecular iodine would likely play a role in dehydration due to its extremely low hydration capability, based on the recent study on hydrated imines 11 .…”

“…Hence, the underlying mechanisms of iodine activation of N-arylimine are still in debate and systematic investigations of experimental evidences cross-disciplinary beyond the homogenous catalysis area are highly desirable 10 to uncover the nature of the actual catalytic species, for future rational designs. Based on our recent work on the elucidation of sugar-NaCl-water complexes in NaCl solution 11 and the subsequent rational design of asymmetric catalysis with predictable electrostatic non-covalent interactions within chiral imine intermediates [12][13][14] , a hypothesis that the stereochemistry change of the N-arylimine moiety upon complexation with iodine could be a key for both the increase of the reactivity of the reaction, and the improvement of the enantioselectivity in previous reports, seems incredibly possible (Scheme 3B). A systematic investigation including early experimental evidences of the conformation of N-arylimines and the iodine N-arylimine complexes [15][16] , mechanisms in iodine catalysis [17][18][19] , and the structure evidences of iodine-poly(Schiff bases) complexes 20 , would be carried out in this work, to gain new insights on the mechanisms of iodine catalysis with N-arylimines.…”