Gold Catalysis in (Supra)Molecular Cages to Control Reactivity and Selectivity.

Gold catalysis has experienced a tremendous development over the past decades, and is nowadays widely used in organic synthesis to perform chemical transformations of π-bond-containing molecules. Catalyst development has been based mostly on ligand development and counter-ion strategies. More recently, the encapsulation of gold catalysts in (supra)molecular cages was explored as a new way to control selectivity and reactivity of gold catalysts. In this review, we describe the cages that have been employed as hosts for gold complexes, along with their impact on the catalytic performance. Covalent and supramolecular approaches to encapsulate single metal complexes will be described and the impact on the catalytic performance will be discussed. Also, recent strategies to pre-organize multiple metal centers will be discussed.

Rational Optimization of Supramolecular Catalysts for the Rhodium-Catalyzed Asymmetric Hydrogenation Reaction.

Rational design of catalysts for asymmetric transformations is a longstanding challenge in the field of catalysis. In the current contribution we report a catalyst in which a hydrogen bond between the substrate and the catalyst plays a crucial role in determining the selectivity and the rate of the catalytic hydrogenation reaction, as is evident from a combination of experiments and DFT calculations. Detailed insight allowed in silico mutation of the catalyst such that only this hydrogen bond interaction is stronger, predicting that the new catalyst is faster. Indeed, we experimentally confirmed that optimization of the catalyst can be realized by increasing the hydrogen bond strength of this interaction by going from a urea to phosphine oxide H-bond acceptor on the ligand.

A Switchable Gold Catalyst by Encapsulation in a Self-Assembled Cage.

Dinuclear gold complexes have the ability to interact with one or more substrates in a dual-activation mode, leading to different reactivity and selectivity than their mononuclear relatives. In this contribution, this difference was used to control the catalytic properties of a gold-based catalytic system by site-isolation of mononuclear gold complexes by selective encapsulation. The typical dual-activation mode is prohibited by this catalyst encapsulation, leading to typical behavior as a result of mononuclear activation. This strategy can be used as a switch (on/off) for a catalytic reaction and also permits reversible control over the product distribution during the course of a reaction.

Well-Defined Dinuclear Gold Complexes for Preorganization-Induced Selective Dual Gold Catalysis.

The synthesis, reactivity, and potential of well-defined dinuclear gold complexes as precursors for dual gold catalysis are explored. Using the preorganizing abilities of the ditopic PN(H) P(iPr) (L(H) ) ligand, dinuclear Au(I) -Au(I) complex 1 and mixed-valent Au(I) -Au(III) complex 2 provide access to structurally characterized chlorido-bridged cationic species 3 and 4 upon halide abstraction. For 2, this transformation involves unprecedented two-electron oxidation of the redox-active ligand, generating a highly rigidified environment for the Au2 core. Facile reaction with phenylacetylene affords the σ,π-activated phenylacetylide complex 5. When applied in the dual gold heterocycloaddition of a urea-functionalized alkyne, well-defined precatalyst 3 provides high regioselectivities for the anti-Markovnikov product, even at low catalyst loadings, and outperforms common mononuclear Au(I) systems. This proof-of-concept demonstrates the benefit of preorganization of two gold centers to enforce selective non-classical σ,π-activation with bifunctional substrates.