Solid-Supported Tetrahydropyran-Based Hybrid Dipeptide Catalysts for Michael Addition of Aldehydes to Nitrostyrenes

The scarcity of resources and the continued popularization of the concept of sustainability as a promising approach for the effective and efficient utilization of available resources have recently found their way into the field of chemistry. One common concept of sustainability is the recovery and reuse/recycling of resources. In chemistry, especially in catalysis, the recovery and reuse of catalysts remain a big challenge despite its potential usefulness towards sustainable chemistry.

Presently, catalyst immobilization onto solid support insoluble in the reaction medium is a common method for recovering and reusing catalysts. This approach is relatively efficient, cost-effective, and has a low environmental impact. Several approaches have been developed to immobilize various catalysts. Among them, those based on organocatalysts have drawn significant research attention because it lacks common problems associated with the immobilization of catalysts, such as leaching and sensitivity-induced instability.

The recovery and reuse of immobilized organocatalysts is limited by two main factors. On the one hand, most of them exhibit decreased efficiency regarding homogeneous phase catalysts due to the interference of the catalyst by the solid support. Overcoming this limitation requires a suitable linker for binding the catalyst to the solid support. On the other hand, organocatalyst deactivation reduces the number of catalytic cycles, thus limiting its reuse. Deactivation could also trigger chemical modification that could interfere with the active sites of the catalysts. Additionally, most organocatalytic systems require the addition of additives that require additional steps to yield pure products.

Using bifunctional organocatalysts has emerged as a promising approach to overcoming these challenges. Although bifunctional dipeptide organocatalysts have high catalytic activity in the homogeneous phase, their performance when immobilized on a solid support is underexplored. To this note, Spanish scientists: Dr. Irma García-Monzón, Dr. Jorge Borges-González and led by Dr. Tomás Martín from the Institute of Natural Products and Agrobiology (IPNA) of the Spanish Council for Scientific Research (CSIC) prepared a series of polymer-supported tetrahydropyran-based immobilized hybrid dipeptides catalysts. Their research work is currently published in the research journal, Advanced Synthesis and Catalysis.

In their approach, the supported catalysts were designed considering the optimal position and orientation between the solid support and the catalyst. Copper-catalyzed alkyne azide cycloaddition reaction was used to immobilize the organocatalysts onto a solid support. The effects of the orientation, anchor position, and linker length on the catalytic activity of these catalysts in the Michael addition of aldehydes to β-nitrostyrenes was investigated.

The research team observed that the catalysts facilitated the transformation of various substrates with a yield ranging from 76 to 98% and enantiomeric excess between 94 – 97%. The resulting catalysts exhibited several advantages. Their bifunctional property rendered the use of additives during reaction unnecessary. As such, a simple filtration followed by solvent evaporation could be used to obtain the final product with high purity. Compared to others, these catalysts consumed less energy as they were operated at room temperature. Furthermore, optimal conditions were achieved in a single aprotic solvent, allowing more comprehensive access to structural complexity by facilitating an effective combination with other catalytic systems.

In summary, Dr. Tomás Martín and co-workers reported for the first time the successful fabrication of reusable polymers with catalytic activity for enantioselective Michael addition of aldehydes to β-nitrostyrenes that operate efficiently at room temperature. Further studies on the immobilized catalyst deactivation provided helpful information for increasing the catalytic activity and lifespan of such immobilized catalysts. In a statement to Advances in Engineering, lead author Dr. Tomás Martín noted that their study would expand the rational design of organocatalyst immobilization, an essential step towards sustainable chemistry.

Tomás Martín graduated in chemistry at the University of La Laguna, Tenerife, Spain in 1991, and obtained his Ph.D. in 1996 at the same University, working on the enantioselective synthesis of γ-lactones under the guidance of Dr. C. M. Rodríguez and Professor Víctor S. Martín. Later, he became a postdoctoral fellow of the Spanish Ministry of Education and Science (MEC) at the Scripps Research Institute from January 1997 to December 1998; where his research was focused on molecular recognition under the supervision of Professor Julius Rebek, Jr. In 1999, with a reincorporation contract from the Spanish MEC, he returned to the Canary Islands and joined Victor S. Martín´s group. In 2002, he was awarded a Ramón y Cajal (RyC) contract. With the RyC program he initiated a research project based on Supramolecular Chemistry. In 2005, he became Tenured Scientist at the Instituto de Productos Naturales y Agrobiología-CSIC, creating the “Molecular Recognition and Supramolecular Chemistry” group in 2008. In 2018, he was promoted to Research Scientist. At the moment, his research interests focus on supramolecular chemistry, organocatalysis, and total synthesis of bioactive natural products.


García‐Monzón, I., Borges‐González, J., & Martín, T. (2022). Solid‐supported tetrahydropyran‐based hybrid dipeptide catalysts for Michael addition of aldehydes to nitrostyrenesAdvanced Synthesis and Catalysis, 364(16), 2822–2829.


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