Recent advance in sulfur ylide and sulfonium salts chemistry

Abstract

Organosulfur compounds are ubiquitous in natural products and active pharmaceutical ingredients. They are also versatile scaffold that are widely applicable in material and food chemistry. The increasing demand indeed lead to a continuous progress in developing of new methodologies in organosulfur chemistry. Among them, sulfur ylides and sulfonium salts with unique reactivities have been employed to provide simple, effective, and often stereoselective methods to gain access to sulfur containing molecules. The essential goal of this review is to provide a comprehensive account of representative research progress on sulfonium salt and sulfur ylide chemistry in the past three years. Seminal reports on this topic are occasionally covered with the purpose of providing a brief research background. For the sake of convenience, this review is organized in three parts based on the role they played in organic reactions (synthetic intermediates, reagents and catalysts). In the first section, the development of new approaches for generate sulfur ylide or sulfonium salt intermediates were summarized. Electrophilic aryne species could be employed to react with sulfides or sulfoxides to form the desired sulfur intermediates, which could underwent a variety of interesting transformations. Moreover, recent progress in metal carbene-based sulfur ylide approaches have also been introduced. Both the progress in asymmetric catalysis variants and reactions in aqueous solution have been presented. The second section describes the transformations using stabilized sulfonium salts and sulfur ylides as bench-stable reactants. The extra stability of these species is accompanied by a compromise in the reactivity, which usually requires developing activation methods. With transition metal catalysts to activate sulfonium salts, they have been discovered as efficient coupling partners in carbon-carbon bond and carbon-heteroatom bond formation reactions. Stable sulfur ylides could also be utilized to install fluorine-containing groups in a large variety of transformations. The third section covers recent progress in employing sulfonium salts as catalysts in organic reactions. The acidity of the α C−H in sulfonium salt is relatively high than its nitrogen and phosphine analogues. Therefore, it could be easily removed to form the sulfur ylide, which have restricted its application as catalysts. On one hand, scientists took advantage of these properties and developed new cyclic sulfonium salts as hydrogen bonding catalysts. On the other hand, sulfonium salts could be used as stable phase transfer catalysts under base free conditions in order to avoid degradations. Finally, the review discussed the limitations of the known chemistry in this field as well as the future opportunities. Sulfur ylide and sulfonium salts have displayed many unique reactivities as summarized in this review. New reactivity will still be the central theme of research given the importance of organosulfur compounds. In addition, insights into the factors controlling the reactivity via mechanistic studies will be of great importance for further research and development. Moreover, the applications of sulfonium salts as organocatalysts are still limited to a relatively narrow range of transformations. Therefore, it remains to be an elusive task to unlock their full potential, and future research must include the development of scalable and cost-efficient methods, broadening of reaction scopes, and integration with other catalytic manifolds. We hope that this review will pique the interests of readers and deliver inspiration for future development in this interesting and promising field.