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 PCNOx-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, (PCNOx)Ir(H)2, as the catalytically active intermediate, which can decay to a dimeric species (κ3-PCNOx)IrH(µ-H)2IrH(κ2-PCNOx) 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 (PCNOx)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.

Iridium-Catalyzed Asymmetric Transfer Hydrogenation of 1-Aryl-1-alkylethenes with Ethanol.

Asymmetric transfer hydrogenation of 1-aryl-1-alkylethenes with ethanol was developed with a chiral (PCN)Ir complex as the precatalyst, featuring high enantioselectivities, good functional group tolerance, and operational simplicity. The method is further applied to formal intramolecular asymmetric transfer hydrogenation of alkenols without an external H-donor, producing a tertiary stereocenter and remote ketone group simultaneously. The utility of the catalytic system was highlighted by gram scale synthesis and the synthesis of the key precursor of (R)-xanthorrhizol.

Chiral Iridium Complexes of Anionic NCP Pincer Ligand for Asymmetric Transfer Hydrogenation of 1,1-Diarylethenes with Ethanol.

Chiral iridium complexes ligated by anionic oxazoline-bearing NCP-type pincer ligands were developed and applied to the asymmetric transfer hydrogenation (ATH) of diarylethenes using environmentally benign ethanol as the hydrogen donor. High enantioselectivities could be achieved for substrates bearing ortho-Me, ortho-Cl, or ortho-Br substituents on one of the aryl groups. The ATH of ortho-Br-substituted diarylethenes is particularly attractive due to the propensity of the C(aryl)-Br bond to undergo various new bond-forming events.