Preparation Methods for Unsymmetrical Disulfides

Disulfides play pivotal roles in diverse scientific domains, ranging from protein folding and cellular redox homeostasis to advanced materials development and pharmaceutical innovation. While various synthetic methodologies have been established, the efficient and selective construction of unsymmetrical disulfides continues to present significant synthetic challenges. This review highlights innovative approaches for synthesizing unsymmetrical disulfides utilizing different sulfur sources, including thiols (or thiophenols), disulfurating reagents, and symmetrical disulfides as sulfur sources, demonstrating broad substrate applicability and functional group tolerance under mild conditions. These innovative methodologies demonstrate significant advantages in substrate diversity, functional group compatibility, and reaction efficiency under mild conditions, marking substantial progress over conventional methods. The synthetic protocols can be further enhanced through strategic optimization of reaction parameters, such as catalyst selection, substrate modification, and condition adjustment, to achieve the desired unsymmetrical disulfides. Beyond summarizing current achievements, this review outlines promising directions for future research, emphasizing the development of more sustainable and selective synthetic pathways. These advancements are anticipated to significantly contribute to the progress of pharmaceutical sciences, materials engineering, and related interdisciplinary fields, ultimately driving innovation in both fundamental research and practical applications.