Role of the NH₂ functionality and solvent in terdentate CNN alkoxide ruthenium complexes for the fast transfer hydrogenation of ketones in 2-propanol

The reaction of [RuCl- (CNN)(dppb)] (1; HCNN = 6-(4-methylphenyl)-2- pyridylmethylamine) with NaOiPr in 2-propanol/C₆D₆ affords the alcohol adduct alkoxide [Ru(OiPr)(CNN)(dppb)]·n iPrOH (5), containing the Ru-NH₂ linkage. The alkoxide [Ru(OiPr)(CNN)(dppb)] (4) is formed by treatment of the hydride [Ru(H)(CNN)(dppb)] (2) with acetone in C₆D₆. Complex 5 in 2-propanol/C₆D₆ equilibrates quickly with hydride 2 and acetone with an exchange rate of (5.4 ± 0.2) s^-1 at 25°C, higher than that found between 4 and 2 ((2.9±0.4)s^-1). This fast process, involving a β-hydrogen elimination versus ketone insertion into the Ru-H bond, occurs within a hydrogen-bonding network favored by the Ru-NH₂ motif. The cationic alcohol complex [Ru(CNN)(dppb)(iPrOH)](BAr^f₄) (6; Ar^f = 3,5-C₆H₃-(CF₃)₂), obtained from 1, Na[BAr^f₄], and 2-propanol, reacts with NaOiPr to afford 5. Complex 5 reacts with either 4,4′-difluorobenzophenone through hydride 2 or with 4,4′-difluorobenzhydrol through protonation, affording the alkoxide [Ru[OCH(4-C₆H₄F) ₂}(CNN)(dppb)] (7) in 90 and 85% yield of the isolated product. The chiral CNN-ruthenium compound [RuCl(CNN)-{(S,S)-Skewphos}] (8), obtained by the reaction of [RuCl₂(PPh₃)₃] with (S,S)-Skewphos and orthometalation of HCNN in the presence of NEt₃, is a highly active catalyst for the enantioselective transfer hydrogenation of methylaryl ketones (turnover frequencies (TOFs) of up to 1.4 × 10⁶h ^-1 at reflux were obtained) with up to 89% ee. Also the ketone CF₃CO(4-C₆H₄F), containing the strong electron-withdrawing CF₃ group, is reduced to the R alcohol with 64% ee and a TOF of 1.5 × 10⁴ h^-1. The chiral alkoxide [Ru(OiPr)(CNN)-((S,S)-Skewphos)]·n iPrOH (9), obtained from 8 and NaO(Pr in the presence of 2-propanol, reacts with CF₃CO-(4-C ₆H₄F) to afford a mixture of the diastereomer alkoxides [Ru(OCH-(CF₃)(4-C₆H₄F)}(CNN){(S,S)-Skewphosj] (10/11; 74% yield) with 67% de. This value is very close to the enantiomeric excess of the alcohol (R)CF₃CH(OH)(4-C₆H₄F) formed in catalysis, thus suggesting that diastereoisomeric alkoxides with the Ru-NH₂ linkage are key species in the catalytic asymmetric transfer hydrogenation reaction.