Synthetic evolutions in the nucleophilic addition to alkynes

This short account describes our efforts to transform the simple nucleophilic addition of alkynes into a more efficient, selective and environmentally benign synthetic tool. We have circumvented the lack of regioselectivity in the gold-catalyzed triple bond addition of water through neighboring group participation and in the process we developed a ‘functionalized hydration’ (multiple bond formation and hydration in a one-pot process) using fluorine-engendered cationic gold catalysis. In addition, we have conducted the synthesis of O-heterocycles through a gold-catalyzed tandem addition/cycloisomerization sequence, the synthesis of N-heterocycles through a copper-catalyzed cyclization-triggered addition of alkynes, and a green synthesis of thioethers ‘on water’ without catalyst or initiator. These nucleophilic synthetic evolutions, catapulted by a simple addition to an alkyne, will surely contribute to provide a wider synthetic access to sophisticated biological targets.

Graphical abstractThis short account describes our efforts to transform the simple nucleophilic addition of alkynes into a more efficient, selective and environmentally benign synthetic tool through neighboring group participation and tandem/cascade reaction sequences.Figure optionsDownload full-size imageDownload as PowerPoint slideResearch highlights► Neighboring group participation. ► Fluorine-engendered cationic gold catalysis. ► Cyclization-triggered tandem additions. ► Synthesis ‘on water’.