Preparation of Pincer 4-Functionalized 2-Aminomethylbenzo[h]quinoline Ruthenium Catalysts for Ketone Reduction

Reaction of 1-naphthylamine with ethyl benzoylacetate gives the corresponding benzoyl acetamide derivative 1, which undergoes cyclization to 4-phenylbenzo[ h ]quinolin-2(1 H )-one ( 2 ) in the presence of H 2 SO 4 . Bromination with POBr 3, followed by reaction with n -BuLi and DMF, gives 4-phenylbenzo[ h ]quinoline-2-carbaldehyde ( 4 ), which is converted to the corresponding oxime hydrochloride 5 with NH 2 OH·HCl. Hydrogenation of 5 catalyzed by 10% Pd/C (type 338) leads to 4-phenyl-2-aminomethylbenzo[ h ]quinoline hydrochloride (HCNN Ph ·HCl, 6 ) isolated in high yield. Similarly, the 4-methyl-2-aminomethylbenzo[ h ]quinoline derivative (HCNN Me ·HCl, 12 ) is prepared starting from 1-naphthylamine and 2,2,6-trimethyl-4 H -1,3-dioxin-4-one, following the route for 6 . Reaction of RuCl 2 (PPh 3 ) 3 with a diphosphine (PP), the HCl salt 6, and NEt 3 in 2-propanol leads to the pincer complexes RuCl(CNN Ph )(PP) (PP = Ph 2 P(CH 2 ) 3 PPh 2, 13; Ph 2 P(CH 2 ) 4 PPh 2, 14; 1,1′-bis(diphenylphosphino)ferrocene, 15 ). The methyl derivatives RuCl(CNN Me )(PP) (PP = Ph 2 P(CH 2 ) 3 PPh 2, 16; Ph 2 P(CH 2 ) 4 PPh 2, 17; 1,1′-bis(diphenylphosphino)ferrocene, 18 ) are obtained in a similar way using 12 in place of 6 . Treatment of [RuCl 2 ( p -cymene)] 2 with rac- BINAP, 6, and NEt 3 affords RuCl(CNN Ph )(BINAP) ( 19 ), isolated as a mixture of two diastereoisomers (3:4 molar ratio). The chiral RuCl(CNN Ph )[( S,R )-JOSIPHOS] ( 20 ) is obtained as a single isomer from [RuCl 2 ( p -cymene)] 2, ( S,R )-JOSIPHOS, and 6 . Complexes 13 – 20 efficiently catalyze the transfer hydrogenation of acetophenone in 2-propanol at reflux in the presence of NaO i Pr (2 mol%) with S/C = 5000–20 000 and at high rate (TOF up to 6.7 × 10 3 min –1 ). With complexes 13, 15, 17, and 18 several ketones of commercial-grade purity have been reduced to alcohols, including the bulky RCO( t Bu) (R = Me, Ph) substrates. With 20 acetophenone is reduced to ( S )-1-phenylethanol with 85% ee. The pincer complexes 13 – 15 and 18 are also found highly active in the hydrogenation of ketones at 40 °C with an S/C = 10 000, under 5 bar of dihydrogen in methanol and in the presence of 2 mol % of a base (NaOH, KOH, NaOMe).