Periodic Reporting for period 4 - SEC (Stereoretentive-Enantioconvergent Catalysis: A New Concept in Asymmetric Synthesis)
Reporting period: 2022-05-01 to 2023-04-30
The objective of this project is to experimentally establish a new concept in asymmetric synthesis: stereoretentive-enantioconvergent catalysis. The ability to synthesise chiral molecules in enantiopure form is vitally important, most recognisably for the pharmaceutical industry. This is because the molecules of life are chiral (e.g. D-sugars and L-amino acids) and enantiomers often interact very differently with living organisms. Classically, asymmetric synthesis utilising racemic substrates is limited to achieving a maximum yield of 50% (e.g. kinetic resolutions). Enantioconvergent catalysis avoids this limitation with both enantiomers of the starting material being converted into a single enantioenriched product, thanks to complex stereoablative or stereomutative de-racemisation processes. Stereoretentive-enantioconvergent catalysis will represent a completely new method for accessing enantiopure materials starting from racemic substrates and will therefore impact all areas of synthetic chemistry.
The overall objective of this project is to establish a conceptually new stereoretentive-dimerisation approach that results in both enantiomers of the starting material being incorporated into the product with no de-racemisation required. This new concept will prove highly valuable for the synthesis of small enantiopure building blocks, which will be of high value in many areas of synthesis, and also for more complex late-stage transformations in complex molecule synthesis. Several approaches will be pursued to demonstrate proof-of-principle, and applications in the synthesis of complex natural and unnatural products will then be used to demonstrate the potential of stereoretentive-enantioconvergent catalysis in target-orientated synthesis.
The overall objective of this project is to establish a conceptually new stereoretentive-dimerisation approach that results in both enantiomers of the starting material being incorporated into the product with no de-racemisation required. This new concept will prove highly valuable for the synthesis of small enantiopure building blocks, which will be of high value in many areas of synthesis, and also for more complex late-stage transformations in complex molecule synthesis. Several approaches will be pursued to demonstrate proof-of-principle, and applications in the synthesis of complex natural and unnatural products will then be used to demonstrate the potential of stereoretentive-enantioconvergent catalysis in target-orientated synthesis.
Work was performed on developing the very first stereoretentive-enantioconvergent reactions, which represents an entirely new approach to achieving asymmetric synthesis. This involved the synthesis of multiple chemical substrates, chiral catalysts and various chiral reagents. The inherent reactivity and selectivity of these different reactions was investigated in great detail. Several of these reactions were determined to be unsuitable for further investigation. The reactions found to be suitable were then focused on and several stereoretentive-enantioconvergent reactions were successfully developed. All the key milestones were reached, which allowed us to provide the first proof-of-principle results for stereoretentive-enantioconvergent catalysis. Our results with several different reactions were combined into a single manuscript, which has been posted on the preprint journal ChemRxiv and has recently been accepted for publication in Nature Chemistry. Other results obtained through this work have also reseltued in three other publications.
This project successfuly developed a fundamentally new concept in the field of asymmetric synthesis, which represent a signifcant advancement for the field of synthetic chemistry.