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.

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

A stereoselective synthesis of α,β-unsaturated-N,N-diethyl amides was achieved by a one-pot reaction of triphenylphosphine, an aromatic aldehyde, and N,N-diethyl chloroacetamide in the presence of indium under microwave-assisted and solvent-free condition.Keywords: indium, microwave irradiation, α,β-unsaturated amide, solvent-free α,β-Unsaturated amides are a significant group of compounds found in many natural products, 1,2 and are useful substrates for many reactions such as conjugate additions with copper 3-4 and Grignard 5 reagents, and other transforamtions. 6-8 Indiummediated or -catalysed reactions have attracted considerable attention since the discovery of its remarkable reactivity in organic or aqueous media. 9-11 Indium has also shown great potential for reactions such as Reformatsky reaction, 12 Michael addition reactions, 13-15 Barbier type alkylations, 16 allylations, 17 and cross-coupling reactions. [18][19][20][21] Compared with other metals such as zinc and iron, indium appears to be the metal of choice due to its lack of requirement for activation, fewer side reactions, and higher regio-and stereoselectivites. Microwave irradiation has also been employed in various reactions, as an effective method for reducing the reaction time, such as in Michael 22 and Diels-Alder reactions 23 As part of an ongoing study into the synthesis of α,β-unsaturated amides, 24 we report here a convenient, efficient, and selective indium-mediated, one-pot method starting from triphenylphosphine, an aromatic aldehyde, and N,N-diethyl chloroacetamide (1) under microwave-assisted and solvent-free conditions.The study was initially carried out with the reaction of 1 and benzaldehyde (2a) to identify the optimal condition (Scheme 1). Factors that influenced the yield of the α,β-unsaturated amide 3a, such as solvent effects, temperature, time, and microwave power, are summarised in Table 1. The results showed that the reactions carried out under solvent-free condition (entry 7) generally afforded much higher yields than those run in solvents (entries 1-6). Thus, solvent-free conditions were employed in the following reactions. Temperature (entries 7-10) and microwave power (entries 11 and 12) screening showed that 150 °C (entry 9) and 1000 W (entry 12) were the best. It was also found that reaction time could be reduced to only 5 minutes (entry 14). The conditions employed above did not affect the E/Z ratio in the product 3a which were usually as high as 92/8.Having identified the optimal reaction conditions, the scope of the reaction was then investigated. Various aldehydes 2 were reacted with N,N-diethyl chloroacetamide 1, triphenylphosphine, and indium under the optimal condition (Scheme 2). The results are summarised in Table 2. It was found that aromatic and heterocyclic aldehydes all reacted quickly to form the target α,β-unsaturated amides in moderate to high yield with high E/Z selectivities (entries 1-11). Acetophenone (entry * Correspondent.

A general method for the synthesis of a,b-unsaturated primary amides was achieved by an one-pot, triphenylphosphine-and zinc powder-promoted Wittig reaction of bromoacetamide and aldehydes under solvent-free conditions.

Zinc-Mediated Facile Synthesis of α,β-Unsaturated Primary Amides. -An economic, convenient, and environmentally friendly one-pot method for the title synthesis is presented. It is not possible to separate the isomers (III) and (IV) by column chromatography. -(FENG, S.; ZHANG, Z.; JIANG, S.; YU*, X.; J. Chem. Res. 34 (2010) 7, 382-384, http://dx.doi.org/10.3184/030823410X520741 ; Coll. Chem. Mater. Eng.,