Iridium-Catalyzed Enantioselective Transfer Hydrogenation of 1,1-Dialkylethenes with Ethanol: Scope and Mechanism

Despite half a century’s advance in the field of transition-metal-catalyzed asymmetric alkene hydrogenation, the enantioselective hydrogenation of purely alkyl-substituted 1,1-dialkylethenes has remained an unmet challenge. Herein, we describe a chiral PCN_Ox-pincer iridium complex for asymmetric transfer hydrogenation of this alkene class with ethanol, furnishing all-alkyl-substituted tertiary stereocenters. High levels of enantioselectivity can be achieved in the reactions of substrates with secondary/primary and primary/primary alkyl combinations. The catalyst is further applied to the redox isomerization of disubstituted alkenols, producing a tertiary stereocenter remote to the resulting carbonyl group. Mechanistic studies reveal a dihydride species, (PCN_Ox)Ir(H)₂, as the catalytically active intermediate, which can decay to a dimeric species (κ³-PCN_Ox)IrH(μ-H)₂IrH(κ²-PCN_Ox) via a ligand-remetalation pathway. The catalyst deactivation under the hydrogenation conditions with H₂ is much faster than that under the transfer hydrogenation conditions with EtOH, which explains why the (PCN_Ox)Ir catalyst is effective for the transfer hydrogenation but ineffective for the hydrogenation. The suppression of di-to-trisubstituted alkene isomerization by regioselective 1,2-insertion is partly responsible for the success of this system, underscoring the critical role played by the pincer ligand in enantioselective transfer hydrogenation of 1,1-dialkylethenes. Moreover, computational studies elucidate the significant influence of the London dispersion interaction between the ligand and the substrate on enantioselectivity control, as illustrated by the complete reversal of stereochemistry through cyclohexyl-to-cyclopropyl group substitution in the alkene substrates.