Nitrogen containing compounds are of great importance because of their interesting and diverse biological activities. The construction of the C-N bond is of significant importance as it opens avenues for the introduction of nitrogen in organic molecules. Despite significant advancements in this field, the construction of the C-N bond is still a major challenge for organic chemists, due to the involvement of harsh reaction conditions or the use of expensive catalysts in many cases. Thus, it is a challenge to develop alternative, milder and cheaper methodologies for the construction of C-N bonds. Herein, we have selected some prime literature reports that may serve this purpose.

In recent years, the transition-metal catalyzed three-component coupling of an aldehyde, an alkyne and an amine, commonly called A(3)-coupling, has been established as a convenient and general approach towards propargylamines. Furthermore, the A(3)-coupling has found a broad application as a key step in the construction of various nitrogen-containing heterocycles, biologically active compounds and natural products. Several interesting modifications of the A(3)-coupling as well as different tandem reactions involving A(3)-coupling have been developed. This tutorial review aims to highlight the current achievements in the field of A(3)-couplings and related transformations.

A microwave-assisted three-component reaction was used to prepare a series of 1,4-disubstituted-1,2,3-triazoles from corresponding alkyl halides, sodium azide, and alkynes. This procedure eliminates the need to handle organic azides, as they are generated in situ, making this already powerful click process even more user-friendly and safe.

First described almost a decade ago, "click" reactions such as the Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC) are widely used today in organic and medicinal chemistry, in the polymer and material science field, and in chemical biology. While most click reactions can be performed at room temperature there are instances where some form of process intensification is required. In this tutorial review, aimed at the synthetic chemistry community, examples of click chemistry carried out under non-classical reaction conditions, such as for example applying microwave heating or continuous flow processing will be highlighted.

The direct scalability of microwave-assisted organic synthesis (MAOS) in a prototype laboratory-scale multimode microwave batch reactor is investigated. Several different organic reactions have been scaled-up typically from 1 mmol to 100 mmol scale. The transformations include multicomponent chemistries (Biginelli dihydropyrimidine and Kindler thioamide synthesis), transition metal-catalyzed carbon-carbon cross-coupling protocols (Heck and Negishi reactions), solid-phase organic synthesis, and Diels-Alder cycloaddition reactions using gaseous reagents in prepressurized reaction vessels. A range of different solvents (high and low microwave absorbing), Pd catalysts (homogeneous and heterogeneous), and varying reaction times and temperatures have been explored in these investigations. In all cases, it was possible to achieve similar isolated product yields on going from a small scale (ca. 5 mL processing volume) to a larger scale (max 500 mL volume) without changing the previously optimized reaction conditions (direct scalability). The prototype, benchtop multimode microwave reactor used in the present study allows parallel processing in either quartz or PTFE-TFM vessels with maximum operating limits of 300 °C and 80 bar of pressure. The system features magnetic stirring in all vessels, complete on-line monitoring of temperature, pressure and microwave power, and the ability to maintain inert or reactive gas atmosphere.

Spiroindolines and spiroindoles are an important class of spirocyclic compounds present in a wide range of pharmaceuticals and biologically important natural alkaloids. Various spiroindolines and spiroindoles possess versatile reactivity which enables them to act as precursors for other privileged heterocycles. In view of the importance of this scaffold, many researchers focused their efforts to develop facile and mild synthetic methods for spirocyclization of indoles. However, the synthesis of spiroindolines and spiroindoles is known to be difficult due to rapid 1,2-migration to restore aromaticity. This review aims to briefly discuss the latest developments to access highly functionalized spiroindolines and spiroindoles to stimulate further research in the field to find new and efficient methodologies for accessing new spiroindolines and spiroindoles.

An efficient, microwave-assisted Cu(I)-catalyzed one-pot coupling of a ketone, an alkyne, and a primary amine (KA(2) coupling) is described, giving access to secondary propargylamines.

In recent years, reaction of inexpensive and abundantly available alcohols (C-OH) with unactivated nucleophilic coupling partners (C-H), leading to the construction of the C-C bond, has emerged as one of the vital strategies since it is an atom-economical and environmentally benign approach with water as the by-product. Various transition metal-catalyzed or metal-free approaches for the direct dehydrative coupling employing the C-OH bond (including in situ activation) have recently been devised. This review article aims to highlight advances in such waste-free C-C bond forming dehydrative strategies.