Strain-release driven reactivity of a chiral SuFEx reagent provides stereocontrolled access to sulfinamides, sulfonimidamides, and sulfoximines.

Efforts aimed at enriching the chemical and structural diversity of small molecules have invigorated synthetic exploration in the last two decades. Spatially defined molecular functionality serves as the foundation to construct unique chemical space to further advance discovery science. The chiral SuFEx reagent t-BuSF provides a modular platform for the stereocontrolled bifunctionalization of sulfur. Here we report a third functional feature of t-BuSF enabled by carbamoyl torsional strain-release that further expands the S(IV) and S(VI) chemical space accessible as showcased in over seventy examples, multiple applications in medicinal chemistry, organocatalysis, and diversity-oriented synthesis. The methods presented herein allow for rapid asymmetric diversification around a stereodefined sulfur center with readily available building blocks, improving upon the current state-of-the-art for sulfinyl and sulfonimidoyl synthesis.

Phosphine-mediated three-component bioconjugation of amino- and azidosaccharides in ionic liquids.

Bioconjugation of carbohydrates has been a challenging task because of their chemical, functional, and structural diversities, and no single chemical modification tool can be universally applicable to all the target substrates in different environments. In this report, we have developed a bioconjugation strategy for labeling of carbohydrate derivatives through a phosphine-mediated three-component coupling reaction in an ionic liquid medium.

An Ionic Liquid Medium Enables Development of a Phosphine-Mediated Amine-Azide Bioconjugation Method.

While a diverse set of design strategies have produced various chemical tools for biomolecule labeling in aqueous media, the development of nonaqueous, biomolecule-compatible media for bioconjugation has significantly lagged behind. In this report, we demonstrate that an aprotic ionic liquid serves as a novel reaction solvent for protein bioconjugation without noticeable loss of the biomolecule functions. The ionic liquid bioconjugation approach led to discovery of a novel triphenylphosphine-mediated amine-azide coupling reaction that forges a stable tetrazene linkage on unprotected peptides and proteins. This strategy of using untraditional media would provide untapped opportunities for expanding the scope of chemical approaches for bioconjugation.