Alkynes are among the most versatile and derivatized functional groups in organic synthesis. They can be directly substituted by a heteroatom (N, O, P, S), but heteroatom-substituted alkynes have yet to be fully exploited in synthesis. The limited use of these compounds is mostly due to the underdeveloped methods to access them. In recent years, however, copper-catalyzed procedures have been developed to construct nitrogen-substituted alkynes (ynamines and ynamides), which have shown considerable utility in modern synthesis. In contrast, less progress has been made toward the formation of sulfur-substituted alkynes, despite the prominence of sulfur-carbon bonds in biomolecules and drugs.<br/><br/>We have recently developed a visible-light-mediated continuous-flow synthesis of alkynyl sulfides that employs an organic fluorophore and nickel(II) catalyst system. Highly chemoselective C-S coupling of aryl bromoalkynes with thiols can be achieved under mild reaction conditions. The rapid continuous-flow process displays excellent functional group tolerance, as well as high reproducibility from small to large scale synthesis. In addition, we have reported the first application of photoredox/nickel dual catalysis towards macrocyclization, as well as the first example of the incorporation of an alkynyl sulfide functional group into a macrocyclic scaffold. Our method provides the first photochemical route to C(sp)-S bond architectures, and should complement existing photochemical functionalizations as the thiol-ene (C(sp3)-S bond) and thiol-yne (C(sp2)-S bond) reactions, which have been established as important tools in the chemical sciences.

Photochemical dual-catalytic synthesis of alkynyl sulfides

255th National Meeting (2018)

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