Photocatalytic Thiol-Yne Reactions of Alkynyl Sulfides.

Thiol-yne reactions typically employ thiols and terminal alkynes as the reaction partners. The thiol-yne reaction of alkynyl sulfides and thiols is possible when employing a nonmetal photocatalyst eosin Y, green LED irradiation, under an air atmosphere. Alkynyl sulfides were transformed in good overall yields (58-90% total yields, 11 examples) favoring the cis isomer. No addition to the α-position of the alkynyl sulfide is observed, and regioselectivity is believed to be controlled through the stabilization of radical intermediates by the adjacent sulfur atom. Furthermore, control experiments with "all-carbon" internal alkynes demonstrate that alkynyl sulfides possess improved reactivity and regioselectivity profiles during thiol-yne processes.

Synthesis and Diversification of Macrocyclic Alkynediyl Sulfide Peptides.

The synthesis of rare macrocyclic alkynediyl sulfides by a Cu-catalyzed Csp -S cross-coupling is presented. The catalytic protocol (Cu(MeCN)4 PF6 /dtbbpy) promotes macrocyclization of peptides, dipeptides and tripeptides at ambient temperature (14 examples, 23→73 % yields) via thiols and bromoalkynes, and is chemoselective with regards to terminal alkynes. Importantly, the underexplored alkynediyl sulfide functionality incorporates a rigidifying structural element and opens new opportunities for diversification of macrocyclic frameworks through S oxidation, halide addition and azide-alkyne cycloaddition chemistries to integrate sulfones, halides or valuable fluorophores (7 examples, 37→92 % yields).