Hirohito Ooka

Asymmetric Hydrogenation of Aromatic Ketones Catalyzed by the TolBINAP/DMAPEN−Ruthenium(II) Complex: A Significant Effect of N-Substituents of Chiral 1,2-Diamine Ligands on Enantioselectivity

Asymmetric hydrogenation of acetophenone in the presence of Ru(II) catalysts coordinated by TolBINAP and a series of chiral 1,2-diamines was studied. The sense and degree of enantioselectivity were highly dependent on the N-substituents of the diamine ligands. The N-substituent effect was discussed in detail. Among these catalysts, the (S)-TolBINAP/(R)-DMAPEN-Ru(II) complex showed the highest enantioselectivity. The mode of enantioface selection was interpreted by using transition state models based on the X-ray structure of the catalyst precursor. The chiral catalyst effected the hydrogenation of alkyl aryl ketones and arylglyoxal dialkyl acetals to afford the chiral alcohol in >99% ee in the best cases. Hydrogenation of racemic benzoin methyl ether with the chiral catalyst through dynamic kinetic resolution gave the anti-alcohol (syn:anti = 3:97) in 98% ee, while the reaction of alpha-amidopropiophenones resulted in the syn-alcohols (syn:anti = 96:4 to >99:1) in >98% ee.

Asymmetric Hydrogenation of Bicyclic Ketones Catalyzed by BINAP/IPHAN−Ru(II) Complex

Hydrogenation of 3-quinuclidinone and bicyclo[2.2.2]octan-2-one with a combined catalyst system of RuCl(2)[(S)-binap][(R)-iphan] and t-C(4)H(9)OK in 2-propanol afforded the chiral alcohols in 97-98% ee. 2-Diphenylmethyl-3-quinuclidinone was hydrogenated with the same catalyst to the cis alcohol with perfect diastereo- and enantioselectivity. The reaction of unsymmetrical ketones with a bicyclo[2.2.1] or -[2.2.2] skeleton gave the corresponding alcohols with high stereoselectivity.

Kinetic resolution of racemic α-tert-alkyl-α-hydroxy esters by enantiomer-selective carbamoylation.

Kinetic resolution of sterically hindered racemic α-tert-alkyl-α-hydroxy esters is performed by enantiomer-selective carbamoylation with the t-Bu-Box-Cu(II) catalyst (Box = bis(oxazoline)). The reaction with 0.5 equiv of n-C(3)H(7)NCO is carried out with a substrate-to-catalyst molar ratio of 500-5000 at -20 to 25 °C. The high enantiomer-discrimination ability of the catalyst achieves an excellent stereoselectivity factor (s = k(fast)/k(slow)) of 261 in the best case. A catalytic cycle for this reaction is proposed.