Trithioorthoester Exchange and Metathesis: New Tools for Dynamic Covalent Chemistry

Abstract

To expand the toolbox of dynamic covalent and systems chemistry, we investigated the acid-catalyzed exchange reaction of trithioorthoesters with thiols. We found that trithioorthoester exchange occurs readily in various solvents in the presence of stoichiometric amounts of strong Brønsted acids or catalytic amounts of certain Lewis acids. The scope of the exchange reaction was explored with various substrates, and conditions were identified that permit clean metathesis reactions between two different trithioorthoesters. One distinct advantage of S,S,S-orthoester exchange over O,O,O-orthoester exchange is that the exchange reaction can kinetically outcompete hydrolysis, thereby making the process less sensitive to residual moisture. We expect that the relatively high stability of the products might be beneficial in future supramolecular receptors or porous materials.

Sulfur in Dynamic Covalent Chemistry

“…Based on its tripodal geometry, exposure of one trithioorthoester to one thiol can result in three trithioorthoester products. The reported reaction conditions include the use of organic solvents, the presence of thiols, and preferably the exclusion of water [135] . The strength of the required acid is halfway in between that for orthoesters and that for dithioacetals, which is in line with their hydrolytic stability: trithioorthoesters are more robust towards hydrolysis than orthoesters but much less stable than the dithioacetal group.…”

Superchaotropic Boron Clusters as Membrane Carriers for the Transport of Hydrophilic Cargos

“…The reported reaction conditions include the use of organic solvents, the presence of thiols, and preferably the exclusion of water. [135] The strength of the required acid is halfway in between that for orthoesters and that for dithioacetals, which is in line with their hydrolytic stability: trithioorthoesters are more robust towards hydrolysis than orthoesters but much less stable than the dithioacetal group.…”

Teaching an Old Compound New Tricks: Reversible Transamidation in Maleamic Acids

“…Due to their ease of preparation and responsiveness to external triggers, dynamic combinatorial libraries (DCLs) based on this approach have found applications in a variety of fields, such as responsive systems and materials, [2][3][4][5][6] design of enzyme inhibitors, [7][8][9][10][11] cell recognition, [12] and self-replicating molecules. [13,14] These applications are restricted to the dynamic bonds that are available, [15][16][17][18][19][20][21][22] each of them with limitations in terms of experimental conditions and functional group compatibility. As the applications of DCC grow, there is also an increasing demand for the discovery of new dynamic bonds to expand its scope.…”