Coupling Metaloid-Directed Self-Assembly and Dynamic Covalent Systems as a Route to Large Organic Cages and Cyclophanes.

Abstract

The synthesis of large cyclic and caged disulfide structures was achieved by pnictogen-assisted iodine oxidation starting from self-assembled pnictogen thiolate complexes. The directing behavior of pnictogen enables rapid and selective syntheses of many discrete disulfide assemblies over competing oligomers/polymers, ranging from structures that are small and strained to those that are large and multifaceted, including 3D cages. Traditional cyclization reactions carried out under kinetic control are generally low-yielding, which often results in the formation of insoluble oligomers and polymers as unwanted side products. The prospect of self-assembling organic structures efficiently under thermodynamic control adds an attractive tool for the synthesis of cyclophanes and other large cage compounds. This method of metaloid-directed self-assembly within a dynamic covalent system allows for the rapid and discriminant self-assembly of disulfide cyclophanes without the consequences sometimes seen in traditional cyclophane syntheses such as poor yields, long reaction times, low ring-closing selectivity, and extensive purifications. The present paper provides an overview of this approach, explores the role of the pnictogen additive and solvent in this reaction, begins to test the limits of this strategy in complex 3D molecule formation, and extends our strategy to include one-pot syntheses that do not require the use of a pnictogen additive. This Viewpoint also includes an extended introduction to serve as a minireview highlighting the utility of a self-assembly approach to create organic cage structures. From a practical standpoint, the cyclophanes isolated from this method can serve as precursors in the production of insulating plastics (e.g., through the widely used parylene polymerization process, which uses derivatives of paracyclophane as monomers) or as potential hosts for molecular separations or capture.