Indium-Mediated Microwave-Assisted One-Pot Synthesis of α,β-Unsaturated Amides

Abstract

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.

Synthesis of Novel Triazole Derivatives of Methyl 3-Oxocholanate Using Microwave Irradiation

“…It possesses useful attributes, such as ease of manipulation, enhanced reaction rates, clean reaction outcomes and high yields. [18][19][20][21][22][23] To the best of our knowledge, no work has been published on the synthesis and physicochemical properties of triazole derivatives obtained from methyl 3-oxocholanate. In view of this, we now report a simple, efficient and rapid synthetic method for preparing steroidal triazoles based on methyl 3-oxocholanate by condensation of the steroidal ketone with the 4-amino-3-substituted-1H-1,2,4-triazole-5-thione under microwave irradiation.…”