The thermodynamically unfavorable anaerobic dehydrogenative alcohol activation to aldehydes and hydridometal species is found to be the bottleneck in metal-catalyzed N-alkylations due to a general and unnoticed catalyst deactivation by amines/amides. Thus, different from the anaerobic dehydrogenation process in borrowing hydrogen or hydrogen autotransfer reactions that require noble metal complexes or addition of capricious ligands for catalyst activation, the water-producing, exothermic, metal-catalyzed aerobic alcohol oxidation is thermodynamically more favorable and the most effective and advantageous aldehyde generation protocol. This leads to a general and advantageous air-promoted metal-catalyzed aerobic N-alkylation methodology that effectively uses many simpler, less expensive, more available, and ligand-free metal catalysts that were inactive under typical anaerobic borrowing hydrogen conditions, avoiding the use of preformed metal complexes and activating ligands and the exclusive requirement of inert atmosphere protection. This aerobic method is quite general in substrate scope and tolerates various amides, amines, and alcohols, revealing its potentially broad utilities and interests in academy and industry. In contrast to the commonly accepted borrowing hydrogen mechanism, based on a thorough mechanistic study and supported by the related literature background, a new mechanism analogous to the relay race game that has never been proposed in metal-catalyzed N-alkylation reactions is presented.

By simply running the reactions under air and solvent-free conditions using catalytic amounts of manganese dioxide, a practical and efficient N-alkylation method for a variety of sulfonamides and amines using alcohols as green alkylating reagents was developed.

Manganese Dioxide Catalyzed N-Alkylation of Sulfonamides and Amines with Alcohols under Air. -(YU, X.; LIU, C.; JIANG, L.; XU*, Q.; Org. Lett. 13 (2011) 23, 6184-6187, http://dx.doi.org/10.1021/ol202582c ; Coll. Chem. Mater. Eng., Wenzhou Univ., Wenzhou, Zhejiang 325035, Peop. Rep. China; Eng.) -R. Staver 13-049

The reaction allows convenient, efficient and environmentally friendly access to a wide range of secondary amines, amides, and sulfonamides. The mechanism is discussed. -(LIU, C.; LIAO, S.; LI, Q.; FENG, S.; YU*, X.; XU, Q.; J. Org. Chem. 76 (2011) 14, 5759-5773, http://dx.doi.org/10.1021/jo200862p ; Coll. Chem. Mater. Eng., Wenzhou Univ., Wenzhou, Zhejiang 325035, Peop. Rep. China; Eng.) -Jannicke 48-037

Optimized conditions are elaborated for each type of substrates to afford a broad spectrum of title compounds including fluoro derivatives with biological significance. -(LIU, C.; ZANG, X.; YU, B.; YU*, X.; XU, Q.; Synlett 2011, 8, 1143-1148, http://dx.doi.org/10.1055/s-0030-1259959 ; Coll. Chem. Mater. Eng., Wenzhou Univ., Wenzhou, Zhejiang 325035, Peop. Rep. China; Eng.) -Mais 37-074