Transition Metal Catalyzed Synthesis of Carboxylic Acids, Imines, and Biaryls

Dehydrogenative synthesis of carboxylic acids catalyzed by a ruthenium N- heterocycliccarbene complex. A new methodology for the synthesis of carboxylic acids from primary alcohols and hydroxide has been developed. The reaction is catalyzed by the ruthenium N-heterocycliccarbene complex [RuCl2(IiPr)(p-cymene)] where dihydrogen is generated as the only by-product (Scheme i).

The dehydrogenative reaction is performed in toluene, which allows for a simple isolation of the products by precipitation followed by extraction. Various substituted benzyl alcohols smoothly undergo the transformation. The fast conversion to the carboxylic acids can be explained by the involvement of a competing Cannizzaro reaction.

The scope of the dehydrogenation was further extended to linear and branched saturated aliphatic alcohols, although longer reaction times are necessary to ensure complete substrate conversions. The kinetic isotope effect of the reaction was determined to be 0.67 using 1-butanol as the substrate. A plausible catalytic cyclewas characterized by DFT/B3LYP-D3 and involved coordination of the alcohol tothe metal, β-hydride elimination, hydroxide attack on the coordinated aldehyde, and a second β-hydride elimination to furnish the carboxylate.  Manganese catalyzed radical Kumada-type reaction between aryl halidesand aryl Grignard reagents.

The reaction between aryl halides and aryl Grignard reagents catalyzed by MnCl2 has been extended to several methyl-substituted aryl iodide reagents byperforming the reaction at 120 ˚C in a microwave oven (Scheme ii). A limitation of the heterocoupling process is the concomitant dehalogenation of the aryl halide and homocoupling of the Grignard reagent leading low to moderate yields of the desired heterocoupling product.

The mechanism of the cross-coupling process was investigated by performing two radical trap experiments. The employment of radical scavengers such as 1,4-cyclohexadiene and 4-(2-bromophenyl)-but-1-enerevealed the presence of an aryl radical intermediate. This leads to the proposal of an SRN1 pathway for the coupling.  Study of the dehydrogenative synthesis of imines from primary alcohols and amines catalyzed by manganese complexes.

An initial study of the dehydrogenative synthesis of imines catalyzed by simple and commercially available manganese complexes has been conducted (Scheme iii). Originally the low valent CpMn(CO)3, Mn(CO)5Br, and Mn2(CO)10 complexes were employed for the coupling reaction between benzyl alcohol and cyclohexylamine, but these displayed only poor or no reactivity.

Surprisingly when the Jacobsen complex is used as the catalyst, the reaction between benzyl alcohol andvcyclohexylamine resulted in 77% yield of the corresponding imine. Moreover gas evolution confirmed that the reaction occurs by dehydrogenation.