Controllable Cycloadditions between 2H-(Thio)pyran-2-(thi)ones and Strained Alkynes: A Click-and-Release Strategy for
Qi Cui1, Tony W Pan1, Meg Shieh1
1Department of Chemistry, Brown University, Providence, Rhode Island 02912, United States.
Abstract:
In this work, we carried out computational studies to predict the cycloaddition efficiency of strained alkynes with 2H-pyran-2-one and its three sulfur-containing analogues: 2H-pyran-2-thione, 2H-thiopyran-2-one, and 2H-thiopyran-2-thione. It was predicted that the decreased aromaticity of the substrate would yield higher reactivity. Experimental studies confirmed the calculation results, and 2H-pyan-2-thiones were found to be the most reactive substrates. This reaction proceeded effectively in aqueous buffers and in cellular environments. It also produced COS as the byproduct, which could be converted into hydrogen sulfide (H2S) in the presence of carbonate anhydrase. This click-and-release approach may serve as a unique way to deliver COS/H2S to specific locations.
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