One-Pot Access to a Library of Structurally Diverse Nicotinamide Derivatives via a Three-Component Formal Aza [3 + 3] Cycloaddition

Abstract

The three-component formal [3 + 3] aza-annulation between chalcones, β-ketoamides, and ammonium acetate in the presence of CAN as a Lewis acid affords good to excellent yields of highly substituted nicotinamides or their fused derivatives. This transformation leads to the formation of one C-C and two C-N bonds in a single synthetic operation and involves up to five individual steps.

Montmorillonite Clay-Promoted, Solvent-Free Cross-Aldol Condensations under Focused Microwave Irradiation

“…Since the catalytic affect of the clay can be attributed to the Lewis acid activity of its metallic centers (Scheme 2a), the good reactivity of the methoxy derivatives can be explained by accepting that coordination of the oxygen atom in the OMe group with cationic centers in the clay attenuates its electron-releasing effect (Scheme 2b) [40]. Another special case was that of nitrobenzaldehyde derivatives which, again unexpectedly, gave relatively low yields (entries 7,8,9,13,18,22,25,[30][31][32][33][34][35]. In this case, we propose that the lower reactivity is due to an increased activation energy associated to stabilizing interactions of the aldehyde with the clay by coordinating two of the cationic centers (Scheme 2c).…”

“…The need for this research became apparent in the course of our program on the use of aryl and heteroaryl trans-chalcones in heterocyclic synthesis [35][36][37][38], when we noticed the shortcomings of the currently available protocols for the synthesis of the required starting materials. Thus, we present here our studies on a solvent-free protocol for their synthesis under microwave irradiation conditions in the presence of a montmorillonite clay catalyst, its application to a large number of examples in order to establish its scope and a brief study of its subsequent generalization to other types of substrates.…”

Chlorophosphines as auxiliary ligands in ruthenium-catalyzed nitrile hydration reactions: application to the preparation of β-ketoamides

“…The outstanding performance of complex [RuCl 2 IJη 6 -pcymene){PIJ4-C 6 H 4 F) 2 Cl}] (2b) was further exploited in the catalytic synthesis of β-ketoamides by hydration of β-ketonitriles (Table 4). At this point, we would like to stress that β-ketoamides are versatile intermediates in the preparation of a large variety of heterocycles, such as lactams, 27 pyrans, 28 oxocyclohexenes, 29 isoquinolines, 30 pyrroloquinolines, 31 naphthyridines, 32 nicotinamides, 33 or 3-acyltetramic acids, 34 to name a few. In addition, they can also be easily converted, via a zinc-carbenoid mediated chain-extension, into their γ-keto homologues, which are compounds related with a number of biologically relevant systems.…”

Metal-Free Multicomponent Syntheses of Pyridines

“…In 2012, Tenti et al focusing on the regioselective access to functionalized nicotinamide derivatives described a CANcatalyzed related reaction. 168 Thus, an ethanol solution of a chalcone, a β-ketoamide, and ammonium acetate was heated at reflux with a catalytic amount of CAN, providing nicotinamides 185 in synthetically useful yields and great functional diversity (Scheme 91). Formation of pentasubstituted pyridines with this strategy seemed difficult.…”