Rhenium-Loaded TiO2 : A Highly Versatile and Chemoselective Catalyst for the Hydrogenation of Carboxylic Acid Derivatives and the N-Methylation of Amines Using H2 and CO2.

Herein, we report a heterogeneous TiO2 -supported Re catalyst (Re/TiO2 ) that promotes various selective hydrogenation reactions, which includes the hydrogenation of esters to alcohols, the hydrogenation of amides to amines, and the N-methylation of amines, by using H2 and CO2 . Initially, Re/TiO2 was evaluated in the context of the selective hydrogenation of 3-phenylpropionic acid methyl ester to afford 3-phenylpropanol (pH2 =5 MPa, T=180 °C), which revealed a superior performance over other catalysts that we tested in this study. In contrast to other typical heterogeneous catalysts, hydrogenation reactions with Re/TiO2 did not produce dearomatized byproducts. DFT studies suggested that the high selectivity for the formation of alcohols in favor of the hydrogenation of aromatic rings is ascribed to the higher affinity of Re towards the COOCH3 group than to the benzene ring. Moreover, Re/TiO2 showed a wide substrate scope for the hydrogenation reaction (19 examples). Subsequently, this Re/TiO2 catalyst was applied to the hydrogenation of amides, the N-methylation of amines, and the N-alkylation of amines with carboxylic acids or esters.

TiO2 -Supported Re as a General and Chemoselective Heterogeneous Catalyst for Hydrogenation of Carboxylic Acids to Alcohols.

TiO2 -supported Re, Re/TiO2 , was found to promote selective hydrogenation of carboxylic acids having aromatic and aliphatic moieties to the corresponding alcohols. Re/TiO2 showed superior results compared to other transition-metal-loaded TiO2 and supported Re catalysts for selective hydrogenation of 3-phenylpropionic acid. 3-phenylpropanol was produced in 97 % yield under mild conditions (5 MPa H2 at 140 °C). Contrary to typical heterogeneous catalysts, Re/TiO2 does not lead to the formation of dearomatized byproducts. The catalyst is recyclable and shows a wide substrate scope in the synthesis of alcohols (22 examples; up to 97 % isolated yield).

Solvent-controlled stereoselective formation of a cyclic ether in the lewis acid-mediated allylation of an alpha-chloroacetoxy acyclic ether. Very high stereoselectivity in CH3CN vs low stereoselectivity in CH2Cl2.

The MgBr2.OEt2-mediated intramolecular allylation of a 4:1 diastereoisomeric mixture of the alpha-chloroacetoxyl ether 1a bearing the A-G/JK ring system of brevetoxin B in CH2Cl2 gave a 1:1 diastereoisomeric mixture of the trans- and cis-cyclization products 4a and 5a having the A-G/I-K ring system, while that in CH3CN afforded the trans-isomer 4a nearly as the single product. To help clarify a reason for this marked solvent effect in the cyclization of the brevetoxin B precursor, DFT computations for the starting materials, intermediates, transition states, and products were carried out. The cyclization would proceed through a carbocation intermediate 3a having sp2 flat structure (SN1 type mechanism) in CH2Cl2, in which the activation energies leading to both diastereoisomers are approximately identical, while in CH3CN alkylnitrilium salts 6a would be formed through the coordination of CH3CN to the carbocation leading to an sp3-type intermediate in which sever steric hindrance takes place in the transition state leading to the undesired diastereoisomer. The scope of this novel solvent-controlled stereoselectivity was tested for simple compounds. In small model compounds the marked solvent dependence was absent, but the model bearing two consecutive cyclic ether rings 1b exhibited a remarkable solvent effect similar to that observed in the brevetoxin B system.