Straightforward α-Amino Nitrile Synthesis Through Mo(CO) -Catalyzed Reductive Functionalization of Carboxamides.

The selective reduction of amides into an intermediate hemiaminal catalyzed by Mo(CO) together with the inexpensive and easy to handle TMDS (1,1,3,3-tetramethyldisiloxane) as reducing agent, followed by subsequent trapping of the hemiaminal with a cyanide source, allows for the straightforward synthesis of α-amino nitriles. The methodology presented here, displays high levels of chemoselectivity allowing for the reduction of amides in the presence of functional groups such as ketones, imines, aldehydes, and acids, which affords a simple route for the synthesis of α-amino nitriles with a broad scope of functionalities in high yields. Furthermore, the applicability of this methodology is demonstrated by scale up experiments and by derivatization of the target compounds into synthetically interesting products.

Mild Reductive Functionalization of Amides into -Sulfonylformamidines.

The development of a protocol for the reductive functionalization of amides into -sulfonylformamidines is reported. The one-pot procedure is based on a mild catalytic reduction of tertiary amides into the corresponding enamines by the use of Mo(CO) (molybdenum hexacarbonyl) and TMDS (1,1,3,3-tetramethyldisiloxane). The formed enamines were allowed to react with sulfonyl azides to give the target compounds in moderate to good yields.

Facile preparation of pyrimidinediones and thioacrylamides via reductive functionalization of amides.

The development of an efficient protocol for the reductive functionalization of amides into pyrimidinediones and amino-substituted thioacrylamides is presented. Enamines are generated in a highly chemoselective amide hydrosilylation reaction catalyzed by molybdenum hexacarbonyl in combination with 1,1,3,3-tetramethyldisiloxane. The direct addition of either isocyanate or isothiocyanate generates the corresponding pyrimidinediones and 3-aminothioacrylamides in high yields.

Mechanistic Elucidation of Zirconium-Catalyzed Direct Amidation.

The mechanism of the zirconium-catalyzed condensation of carboxylic acids and amines for direct formation of amides was studied using kinetics, NMR spectroscopy, and DFT calculations. The reaction is found to be first order with respect to the catalyst and has a positive rate dependence on amine concentration. A negative rate dependence on carboxylic acid concentration is observed along with S-shaped kinetic profiles under certain conditions, which is consistent with the formation of reversible off-cycle species.

Chemoselective reduction of carboxamides.

The reduction of amides gives access to a wide variety of important compounds such as amines, imines, enamines, nitriles, aldehydes and alcohols. The chemoselective transformation into these functional groups is challenging due to the intrinsic stability of the amide bond; nevertheless, the ability to reduce highly stable carboxamides selectively in the presence of sensitive functional groups is of high synthetic value for academic and industrial chemists. Hydride-based reagents such as LiAlH or diboranes are today the most commonly used compounds for amide reductions, and apart from the substantial amount of waste generated using these methods, they lack tolerance to most other functional groups.