Self-Adaptable Tropos Catalysts

Abstract

Conspectus Biological systems have often served as inspiration for the design of synthetic catalysts. The lock and key analogy put forward by Emil Fischer in 1894 to explain the high substrate specificity of enzymes has been used as a general guiding principle aimed at enhancing the selectivity of chemical processes by optimizing attractive and repulsive interactions in molecular recognition events. However, although a perfect fit of a substrate to a catalytic site may enhance the selectivity of a specific catalytic reaction, it inevitably leads to a narrow substrate scope, excluding substrates with different sizes and shapes from efficient binding. An ideal catalyst should instead be able to accommodate a wide range of substrates—it has indeed been recognized that enzymes also are often highly promiscuous as a result of their ability to change their conformation and shape in response to a substrate—and preferentially be useful in various types of processes. In biological adaptation, the process by which species become fitted to new environments is crucial for their ability to cope with changing environmental conditions. With this in mind, we have been exploring catalytic systems that can adapt their size and shape to the environment with the goal of developing synthetic catalysts with wide scope. In this Account, we describe our studies aimed at elucidating how metal catalysts with flexible structural units adapt their binding pockets to the reacting substrate. Throughout our studies, ligands equipped with tropos biaryl units have been explored, and the palladium-catalyzed allylic alkylation reaction has been used as a suitable probe to study the adaptability of the catalytic systems. The conformations of catalytically active metal complexes under different conditions have been studied by both experimental and theoretical methods. By the design of ligands incorporating two flexible units, the symmetry properties of metal complexes could be used to facilitate conformational analysis and thereby provide valuable insight into the structures of complexes involved in the catalytic cycle. The importance of flexibility was convincingly demonstrated when a phosphine group in a privileged ligand that is well-known for its versatility in a number of processes was exchanged for a tropos biaryl phosphite unit: the result was a truly self-adaptive ligand with dramatically increased scope.

Asymmetric Total Synthesis of (+)-Alstonlarsine A

“…Subsequently, catalytic asymmetric construction of cyclopentene 15 through an asymmetric allylic alkylation (AAA) reaction was investigated. Although the AAA reaction has been widely used as a key step in the total synthesis of natural products, it remains a major challenge for the reaction involving cyclic allyl alcohol-derived substrates. − In particular, Hamada found that the enantiomeric excess (ee) value was only 50% for the reaction of 2-methyl-2-cyclopentenyl carbonate ( 17 ) with dimethyl malonate . To the best of our knowledge, no reports have addressed the allylic substitution reactions of 2-substituted 2-cycloalkenyl carbonates (such as 17 ) with malonate derivatives (such as 16 ).…”

Self-Adaptive Dirhodium Complexes in a Metal–Organic Framework for Synthesis of N–H Aziridines

“…Moreover, these catalysts often provide an “anchor-like” immobilization where only one ligand is connected to the support, which usually distorts the coordination environment of Rh sites and thus affects the reactivity and reproducibility. , Furthermore, most of the supports used in the heterogenization process are rigid materials such as silica, in which three-dimensional active sites hardly adapt their molecular structures to a reacting substrate through noncovalent interaction, thereby limiting catalytic performances of heterogenized dirhodium catalysts . Therefore, the development of a facile way to obtain heterogenized dirhodium carboxylates in a flexible but nonstationary microenvironment with self-adaptive catalytic behaviors is urgently needed. − …”

Nonlinear Effects in Asymmetric Catalysis by Design: Concept, Synthesis, and Applications

“…Such a system represents a cofactor ligand, which is stereoselectively aligned upon interaction with a chiral anionic auxiliary. 48,49 It has been successfully demonstrated by Suginome and coworkers that dynamic helical polymer-based catalysts show nonlinear effects in asymmetric catalysis, their enantioselectivity can be switched, and the catalytic activity can be turned on or off. 50,51 We developed a different strategy using stereodynamically flexible biphenyls as the ligand core of the targeted catalysts.…”