The group is particularly interested in asymmetric catalysis, and our current aims encompass the design, preparation and application of new catalytic systems. Despite the remarkable progress in the development of asymmetric catalysts, this field still represents an exciting, and never-ending challenge for chemists. Criteria such as stereoselectivity, chemoselectivity, turnover number enhancements, rate, robustness, or recoverability are always amenable to improvement.
Two factors have contributed to the remarkable progress in the field. First and foremost, the use of ligands derived from enantiopure non-natural starting materials has broadened the structural diversity of available catalysts. Secondly, the modular nature of the ligands has facilitated the tuning of their performance by modifying the stereoelectronic properties of the different molecular fragments (modules). A reduced group of ligands, the so called “Priviliged Chiral Catalysts”, have gained prominence through their ability to effect a wide variety of unrelated transformations under very high enantiocontrol and in high yield.
The research group is pursuing two objectives in the field of asymmetric catalysis. In the first instance, it is aimed to develop new ligands with the potential, a priori at least, to be applied to several transformations of interest (Priviliged Chiral Catalysts). Secondly, we are developing a strategy to generate a set of supramolecular ligands which resemble a privileged structure yet at the same time offer a range of closely geometrically related active sites.
Phosphinooxazolines are privileged ligands which have found application in a wide variety of organic transformations. Following on from our work in the preparation and application of efficient asymmetric catalysts from non-natural enantiopure starting materials, phosphinooxazolines 1 incorporating a substituent at the C5 position of the oxazoline ring have been prepared from Sharpless epoxyalcohols in high yield. Highly efficient asymmetric catalysts for the allylic alkylation and amination reactions have subsequently been achieved.
The preparation of a library of new P-O-P ligands (phosphine-phosphinites 2 and phosphine-phosphites 3), easily available in two synthetic steps from enantiopure Sharpless epoxy-ethers has been achieved. Epoxide ring-opening with nucleophilic trivalent phosphorus derivatives has allowed the introduction of the phosphine functionality in the chiral skeleton and further derivatisation of the corresponding hydroxy phosphines with trivalent phosphorus electrophiles have rendered a library of P-O-P ligands 2 and 3 (Figure 1).
Figure 1. Chiral ligands for asymmetric transformations of interest.
The “lead” catalyst of the series (Figure 2) has shown to have outstanding catalytic properties in the rhodium catalysed asymmetric hydrogenation of a wide variety of functionalised alkenes. The remarkably good performance and modular nature of the catalyst makes it attractive for future applications. The strategy utilised to discover new chiral catalysts -tuning of the performance of the catalyst by modifying the stereoelectronic properties of the molecular fragments or modules- is based on a correct hypothesis. The results described show that the different parts of a given chiral catalyst can be optimised separately, so it is possible to achieve high levels of enantioselectivity even starting from a mediocre ligand. Work is in progress to discover new catalysts for asymmetric hydrogenation in still challenging fields (C=N, unfunctionalised C=C bonds and aromatic compounds).
We have developed an efficient epoxidation method for unfunctionalized alkenes mediated by 4 and involving Oxone in organoaqueous medium. The catalyst has shown to be more robust than the standard Shi’s catalyst, as high enantioselectivities have been obtained with a lower catalyst loading. The use of this catalyst for the preparation of new “chirons” for our P-O-P ligands is currently underway. A study of the stereoselective processes in the epoxidation has revealed several key aspects about the origin of the stereoinduction mediated by 4. This gain in the understanding of the reaction is currently being exploited to develop new epoxidation-related asymmetric transformations.
Figure 2. Complex between the «lead» P-O-P ligand and a prochiral alkene.
Catalysis has been one of the longstanding proposed applications of supramolecular chemistry, which has reached a level of development that allows the practitioner to achieve the design and construction of complex multicomponent assemblies with exquisite detail. Efficient supramolecular systems capable of recognition and catalysis have emerged in recent years, however, the application of supramolecular interactions to generate chiral catalysts is still in its infancy, and reports in the literature are scarce.
Our approach focuses on the generation of chiral ligands capable of exploiting supramolecular interactions, and is based on a self-assembly process between the chiral and catalytic components. During the self-assembly process, the chiral information will be transferred from the chiral unit to the catalytic unit and a new supramolecular entity will be formed which will assume the role of the ligand in the asymmetric transformation. In effect we are transferring the chirality from one component to the other via hydrogen-bonding and metal-ligand interactions. These processes are shown schematically in Figure 3.
Figure 3. Synthetic strategy to generate ligands for asymmetric catalysis using supramolecular interactions.
The novelty of this supramolecular approach to enantioselective catalysis, is that by understanding the interactions that dominate the assembly, it will be possible to design and prepare new ligands with minimum ‘synthetic effort’.
Furthermore, this process can be easily parallelised to rapidly generate ligand libraries, in which the ligands will preserve most the structural generalities of their predecessors, but it will incorporate “subtle” changes in their three-dimensional structure that will improve the catalytic properties of the assemblies. The use of appropriated computational methods for the calculation of the energies of the two possible final supramolecular assemblies, is helping us improve the design and optimise the catalytic outcomes.
Some examples of supramolecular chiral assemblies of biaryl ligands (i.e. BINOL, BINAP), whose synthesis is currently underway in the group, have been depicted in Figure 4 (three-dimensional models are computer generated structures).
Figure 4. Supramolecular catalysts for asymmetric catalysis.