Iridium‐Catalyzed Enantioselective Hydrogenation of Oxocarbenium Ions: A Case of Ionic Hydrogenation

Abstract

Ionic hydrogenation has not been extensively explored, but is advantageous for challenging substrates such as unsaturated intermediates. Reported here is an iridium‐catalyzed hydrogenation of oxocarbenium ions to afford chiral isochromans with high enantioselectivities. A variety of functionalities are compatible with this catalytic system. In the presence of a catalytic amount of the Brønsted acid HCl, an α‐chloroether is generated in situ and subsequentially reduced. Kinetic studies suggest first‐order kinetics in the substrate and half‐order kinetics in the catalyst. A positive nonlinear effect, together with the half kinetic order, revealed a dimerization of the catalyst. Possible reaction pathways based on the monomeric iridium catalyst were proposed and DFT computational studies revealed an ionic hydrogenation pathway. Chloride abstraction and the cleavage of dihydrogen occur in the same step.

Recent Developments in Enantioselective Transition Metal Catalysis Featuring Attractive Noncovalent Interactions between Ligand and Substrate

“…This strategy has since proven to be successful for enantioselective hydrogenation of a wide range of imine-type substrates. 203 − 206 …”

Asymmetric Hydrogenation of Cationic Intermediates for the Synthesis of Chiral N,O‐Acetals

“…Our curiosity was then drawn by the enantioinduction model for this chemical transformation. Previous mechanistic studies revealed an ionic hydrogenation model . DFT calculations revealed the structure of the catalytic iridium species that would deliver hydride to the cationic sp 2 carbon atom (Figure a).…”

“…Our curiosity was then drawn by the enantioinduction model for this chemical transformation.P revious mechanistic studies revealed an ionic hydrogenation model. [21] DFT calculations revealed the structure of the catalytic iridium speciest hat would deliver hydridet ot he cationic sp 2 carbon atom (Figure3a). In this iridium dihydride complex, the sulfur atom of the thiourea moiety is prone to coordinate the metal center, to form ac onformationally stable chiral pocket.…”

Catalytic Reductive Alcohol Etherifications with Carbonyl‐Based Compounds or CO2 and Related Transformations for the Synthesis of Ether Derivatives

“…Finally, the asymmetric hydrogenation of the in‐situ generated oxocarbenium ion produces the chiral isochroman with excellent yield and enantioselectivity. Interestingly, isotope‐labeling experiments with deuterated solvents demonstrated a fast equilibrium between the oxocarbenium ion and the enol ether intermediate, suggesting a “S N 1‐like” hydrogenation mechanism (Scheme 15B) [39j] …”

“…Finally, Lin, Wen and co‐workers described last year a very interesting acid‐mediated strategy for the enantioselective hydrogenation of ketals into chiral isochromans via ionic reduction of the in‐situ formed oxocarbenium ions (Scheme 15 B). [39j] [Ir(COD)Cl] 2 complex in combination with a bifunctional thiourea‐based chiral diphosphine [( S , R )‐ZhaoPhos] was employed as highly efficient catalyst (TON up to 8600). Using this system at 25 °C and H 2 (10 bar), and in the presence of HCl (0.5 equiv.…”