Asymmetric Reductive Amination of α-Keto Acids Using Ir-Based Hydrogen Transfer Catalysts: An Access to Unprotected Unnatural α-Amino Acids.

A direct asymmetric reductive amination of α-keto acids catalyzed by Cp*Ir complexes bearing a chiral N-(2-picolyl)sulfonamidato ligand is described. The combined use of optically active 2-phenyglycinol as an aminating agent is effective for the chemo- and stereoselective transfer hydrogenation using formic acid. The subsequent elimination of the hydroxyethyl moiety by orthoperiodic acid can afford various unprotected α-amino acids in satisfactory isolated yields (20 examples) with excellent optical purities (up to >99% ee).

Asymmetric Transfer Hydrogenative Amination of Benzylic Ketones Catalyzed by Cp*Ir(III) Complexes Bearing a Chiral N-(2-Picolyl)sulfonamidato Ligand.

A convenient asymmetric reductive amination of benzylic ketones (α-arylated ketones) catalyzed by newly designed Cp*Ir complexes bearing a chiral N-(2-picolyl)sulfonamidato ligand was developed. Using readily available ß-amino alcohols as chiral aminating agents, a range of benzo-fused and acyclic ketones were successfully reduced with formic acid in methanol at 40 °C to afford amines with favorable chemo- and diastereoselectivities. The amino alcohol-derived chiral auxiliary was easily removed by mild periodic oxidants, leading to optically active primary ß-arylamines without erosion of the optical purity (up to 97% ee). The excellent catalytic performance was retained even upon lowering the amount of catalyst to a substrate/catalyst (S/C) ratio of 20,000, and the amination could be performed on a large scale exceeding 100 g. The precise hydride transfer to iminium species generated from the ketonic substrate and the chiral amine counterpart was suggested by the mechanistic studies on stoichiometric reactions of isolable hydridoiridium complexes and model intermediates such as N,O-acetal, enamine, and iminium compounds.

Asymmetric Catalysis Using Aromatic Aldehydes as Chiral α-Alkoxyalkyl Anions.

We have developed a new umpolung strategy for catalytically forming a chiral α-alkoxyalkyl anion from an aromatic aldehyde for use in asymmetric synthesis. The reaction between aromatic aldehydes and aryl or allyl electrophiles with a silylboronate utilizing a chiral copper-N-heterocyclic carbene catalyst and a palladium-bisphosphine catalyst in a synergistic manner occurred with high enantioselectivities to deliver the three-component coupling products, chiral silyl-protected secondary alcohol derivatives. Our method features the catalytic generation of enantioenriched chiral α-alkoxyalkylcopper(I) intermediates from aldehydes and their subsequent palladium-catalyzed stereospecific cross-coupling.

Synergistic palladium/copper-catalyzed Csp3-Csp2 cross-couplings using aldehydes as latent α-alkoxyalkyl anion equivalents.

The first Csp3-Csp2 cross-coupling using aldehydes as latent α-alkoxyalkyl anion equivalents has been achieved. The synergistic palladium/copper-catalyzed reaction of aromatic aldehydes and aryl bromides with a silylboronate afforded the three-component coupling products, silyl-protected benzhydrol derivatives. The reaction pathway involves the catalytic formation of a nucleophilic α-silyloxybenzylcopper(i) species followed by its palladium-catalyzed cross-coupling with aryl bromides.

Rhodium(I)-Catalyzed Cycloisomerization of Homopropargylallene-Alkynes through C(sp3 )-C(sp) Bond Activation.

Upon exposure to a catalytic amount of [RhCl(CO)2 ]2 in 1,4-dioxane, homopropargylallene-alkynes underwent a novel cycloisomerization accompanied by the migration of the alkyne moiety of the homopropargyl functional group to produce six/five/five tricyclic compounds in good yields. A plausible mechanism was proposed on the basis of an experiment with 13 C-labeled substrate. The resulting tricyclic derivatives were further converted into the corresponding bicyclo[3.3.0] skeletons with vicinal cis dihydroxy groups.