A Bioinspired Gold–Chalcogen Bonding Synergistic Catalysis Platform: Switchable Activation and Dynamic Functional Group Sampling

Abstract

Enzymes achieve exceptional catalytic efficiency by leveraging proximity effects and cooperative interactions, inspiring the design of artificial catalysis systems. However, mimicking this concept has been constrained by rigid activation modes and limited functional group interactions. Inspired by chalcogen-bonding metalloenzymes, we report the design and application of a synergistic gold–chalcogen bonding catalysis platform featuring switchable activation centers and dynamic functional group sampling. This platform employs a rationally designed bifunctional gold–chalcogen bonding catalyst, in which the activation center switches between chalcogen and gold sites, while the complementary moiety provides proximity effect. Chalcogen bonding enables dynamic functional group sampling that allows the catalyst to orthogonally interact with various functional groups, including similar ones such as alkenes and alkynes, thereby triggering unique reactivity. Proof-of-concept studies demonstrate that this platform enables the direct synthesis of sterically hindered ethers via alcohol addition to multisubstituted alkenes, including fully substituted variants. Moreover, this strategy extends to new polymerization reactions of tryptamine and alkyne derivatives via a cyclization pathway. Control experiments confirm that none of these transformations proceed under gold or chalcogen bonding catalysis alone, underscoring the unique and synergistic nature of this platform. Given its high activity and broad potential, the concept of chalcogen-bonding metal synergistic catalysis is expected to find broad applications in developing diverse reactions.