The environmentally amiable route to carbon-heteroatom bond formation, described by Sharpless as 'click chemistry', has become known as a fast, efficient, and reliable approach to the synthesis of novel compounds with desired functionalities. Readily available starting materials must be used in this methodology and they should be essentially inert to most biological and organic conditions, including water and molecular oxygen. In this review, we cover reactions included in this label such as cycloadditions, nucleophilic ring-opening reactions of strained cycles, and amide synthesis, as well as their applications in organic synthesis, molecular biology, macromolecular chemistry and materials science. 1 Introduction 2 Click Synthesis of Epoxides and Aziridines 3 Nucleophilic Opening of Strained Rings: Epoxides and Aziridines 4 Huisgen 1,3-Dipolar Cycloadditions 4.1 Supramolecular Click Chemistry 4.2 Liquid Crystals 4.3 Self-Assembled Monolayers 4.4 Multicomponent Reactions 4.5 Creating Drug Candidates under Click Conditions 4.6 Click Chemistry with Peptides and Proteins 4.7 DNA as Participant in Click Reactions 5 Concluding Remarks

Multicomponent reactions are excellent tools to generate complex structures with broad chemical diversity and fluorescent properties. Herein we describe the adaptation of the fluorescent BODIPY scaffold to multicomponent reaction chemistry with the synthesis of BODIPY adducts with high fluorescence quantum yields and good cell permeability. From this library we identified one BODIPY derivative (PhagoGreen) as a low-pH sensing fluorescent probe that enabled imaging of phagosomal acidification in activated macrophages. The fluorescence emission of PhagoGreen was proportional to the degree of activation of macrophages and could be specifically blocked by bafilomycin A, an inhibitor of phagosomal acidification. PhagoGreen does not impair the normal functions of macrophages and can be used to image phagocytic macrophages in vivo.

The interaction of cyclic enol esters with diversely substituted anilines and ethyl glyoxalate yields, under Sc(OTf)3 catalysis, disubstituted N-aryl lactams in a multicomponent reaction. The protocol allows access to the trans stereoisomers after an epimerization of the initial mixture in which the cis isomers predominate. Vinyl acetate yields quinoline derivatives, whereas isopropenyl acetate leads to the corresponding Mannich adducts.

The reactions of azines (isoquinolines, pyridine) with TFAA and isocyanides in a new domino process yield mesoionic acid fluorides with an imidazo[1,2‐a]azine core. This multicomponent reaction has a general character, tolerating a wide range of substitution patterns on each component, and displays an unprecedented arrangement of reaction pathways. The protocol allows the incorporation of a fourth synthetic input by the reaction of a suitable nucleophile (alcohols, thiols, amines) with the acid fluoride moiety.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)