3 Ruthenium-Catalyzed Azide–Alkyne Cycloaddition (RuAAC)

Under ruthenium catalysis, 1,5-disubstituted 1,2,3-triazoles can be accessed with high selectivity from terminal alkynes and organic azides via a ruthenium-catalyzed azide–alkyne cycloaddition (RuAAC) reaction. These conditions also allow the use of internal alkynes, providing access to 1,4,5-trisubstituted 1,2,3-triazoles. This chapter reviews the scope and limitations of the RuAAC reaction, as well as selected applications. A brief mention of azide–alkyne cycloaddition reactions catalyzed by other metals is also included.

2.1 Introduction to CuAAC

The basic principles of the copper-catalyzed azide–alkyne cycloaddition reaction (CuAAC), widely considered to be the first click reaction, are described. This involves amongst others the concept of click reactions, the mechanism of CuAAC, the synthesis and reactivity of organic azides and acetylenes, an overview of most commonly used copper(I) catalysts and ligands, the properties of 1,2,3-triazoles and their resemblance to amides, and a general overview of the scope and limitations of this reaction.

Unsymmetrical Growth Synthesis of Nontraditional Dendrimers

Developing highly complex molecules is of great significance in science and technology. Here we present an unprecedented type of dendrimer assembled from linear ABB-type monomer. The construction of this nontraditional ramified architecture was facilely achieved through one simple convergent strategy established on the iridium-catalyzed cycloaddition of organic azides with internal 1-thioalkynes (IrAAC). By virtue of the unsymmetrically growing fashion in this process, diverse functional groups could be conveniently distributed on both of its exterior and interior layers. Syntheses of two dendrons from the cooperation of one linear alkyne motif with different azides were presented to demonstrate the efficiency and fidelity of this protocol. Post-modifications on their core or periphery were further conducted, resulting in diverse newly functionalized dendrimers with up to ~16.0 kDa molecular weight. The identity and purity of these unsymmetrical dendritic macromolecules were well confirmed by 1H NMR, MS and SEC analysis.

4-Alkyl-3-azidomethyl-2-ethoxy-2,5-dihydro-5H-1,2-oxaphosphole 2-Oxides: Synthesis and 1,3-Cycloaddition

Starting from phosphorylated allenes, a three-steps synthesis of a new class of organic azides with a 1,2-oxaphospholene carbon skeleton has been developed. The series of obtained 4-alkyl-3-azidomethyl-2-ethoxy-2,5-dihydro-5H-1,2-oxaphosphole 2-oxides were utilized in the 1,3-cycloaddition with alkyl 2-[1-(propyn-2-yl)-1H-indol-3-yl]-2-oxoacetates for the synthesis of conjugates, which are potentially active cytostatics.

Recent Advances in Cross-Couplings of Functionalized Organozinc Reagents

Cross-couplings involving organozinc reagents require usually a Pd-catalysis (Negishi cross-coupling), however, uncatalyzed cross-couplings of zinc organometallics proceed well in the absence of transition-metal catalysts with reactive electrophiles such as benzal 1,1-diacetates, benzhydryl acetates, and iminium trifluoroacetates. Also, organozinc compounds undergo C-N bond formations with O-benzoylhydroxylamines or organic azides in the presence of cobalt- or iron-catalysts. Besides, highly diastereoselective and enantioselective cross-couplings can be readily performed with room-temperature configurationally stable alkylzinc species producing diastereoselectively and enantiomerically enriched products. Finally, highly regioselective magnesiations of functionalized arenes and heteroarenes undergo Negishi (after transmetalation with ZnCl2) or Cu-catalyzed cross-couplings. 1 Introduction 2 Uncatalyzed Cross-Couplings of Organozinc Reagents with Highly Electrophilic Partners 3 Iron- and Cobalt-catalyzed Aminations Using Organozinc Reagents 4 Stereo- and Regioselective Cross-couplings of Organozinc Reagents 5 Conclusion