Accounts of Chemical Research最新文献

ConspectusDuring the past few years, the interest among organic synthesis practitioners in the use of sulfonium salts has exponentially growth. This can arguably be attributed to a series of specific factors: (a) The recent development of more direct and efficient protocols for the synthesis of these species, which make sulfonium reagents of a wide structural variety easily available in multigram scale. (b) The recognition that the reactivity of these salts resembles that of hypervalent iodine compounds, and therefore, they can be used as effective replacement of such species in most of their applications. (c) Their intrinsic thermal stability and tolerance to air and moisture, which clearly surpass that of I(III)-reagents of analogue reactivity, and facilitate their purification, isolation as well-defined species, storage, and safely handling on larger scale. (d) Finally, the possibility to further functionalize sulfonium salts once the sulfur-containing platform has been incorporated. Specifically, this last synthetic approach is not trivial when working with hypervalent I(III)-species and facilitates the access to sulfonium salts with no counterpart in the I(III) realm.This renewed interest in sulfonium salts has led to the improvement of already existing transformations as well as to the discovery of unprecedented ones; in particular, by the development of protocols that incorporate sulfonium salts as partners in traditional cross-coupling and C-H activation steps or combine them with more modern technologies such as photocatalysis or electrosynthesis. In this Account, the reactivity of a series of sulfonium salts originally prepared in our laboratory will be outlined and compared to their I(III)-counterparts. Some of these reagents are now commercially available, and their use has started to spread widely across the synthetic chemistry community, helping to speed the process of identification of potentially bioactive products or new functionaliced materials. However, challenges still remain. The development of sulfonium reagents characterized by an optimal balance between reactivity and site-selectivity, or showing broader compatibility toward sensitive functional groups is still a need. In addition, the intrinsic stability of sulfonium salts often makes necessary the use of (sophisticated) catalysts that activate the latent reactivity hidden in their structures. Although a priori one can see this fact as a disadvantage, it might actually be decisive to harvest the full synthetic potential of sulfonium salts because their thermal stability will surely facilitate the preparation of operational reagents with no counterpart in the context of I(III)-chemistry. If this becomes true, sulfonium salts may contribute to the expediting of retrosynthetic disconnections that, to date, are impossible.

Boronic acids (BAs) are one of the most important classes of reagents in modern synthesis, enabling a wide range of powerful transformations that facilitate the formation of key carbon–carbon and carbon–heteroatom bonds. While their success as reagents is well-known, their remarkable potential as building blocks for creating functional molecules is often overlooked.

At the core of BAs’ uniqueness is their ability to form reversible covalent bonds, thanks to the interconversion of the boron atom between its uncharged trigonal planar structure and an anionic sp³-hybridized form. This coordination chemistry has paved the way for exciting developments in fields such as medicinal chemistry and chemical biology. In recent years, BAs have been used to create a wide variety of materials, including small-molecule drugs, bioconjugates, drug delivery vehicles, polymeric nanomaterials, sensors, and even photosensitizers. What makes this strategy particularly unique is the structural diversity that can be achieved by functionalizing the BA coordination sphere, along with the possibility of incorporating stimuli-responsive mechanisms. This reactivity is further enhanced by the well-known oxidation of BAs in the presence of reactive oxygen species (ROS).

A detailed understanding of the mechanisms governing the dynamic nature of BAs enables the engineering of sophisticated materials that can respond to specific molecular stimuli, such as changes in pH, carbohydrate or glutathione concentrations, and hydrogen peroxide. These stimuli are often key indicators of diseases such as cancer, inflammation, and neurodegeneration, placing BAs at the forefront of tools for designing materials that can potentially influence the mechanisms behind these diseases.

In this Account, we draw on our group’s expertise to explore the exciting potential of BAs in the design of functional materials. The focus is on the response of different boron complexes to biologically relevant stimuli. We describe the preparation of boronated esters (BEs), BA–salicylhydroxamic acid (BA–SHA) complexes, iminoboronates, diazaborines, and boronated thiazolidines and discuss how these chemotypes respond to disease-relevant triggers. Given the growing importance of using external stimuli to control the efficacy of modern drugs, we also explore how some of these compounds respond to specific chemicals. While this Account is not meant to be an exhaustive survey of every example of BA stimulus-responsiveness, we aim to integrate existing chemotypes and their chemical triggers. Our goal is to provide an overview of the mechanisms enabled by BAs for designing functional materials that could one day lead to innovative therapeutic options for human diseases.