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Catalytic Enantioselective 1,2-Rearrangements Using Lewis Base Catalysis

Carlsbergfondets internationaliseringsstipendier

What

The aim of the project is to develop an efficient organo-catalytic methodology for the enantioselective [1,2]-rearrangement of allylic ammonium ylides in the formation of amino acids. The project will involve the development of new catalysts to promote this transformation. Furthermore, once the method is optimized, the mechanism will be elucidated to give an even better insight into this important reaction.

Why

Amino acids are one of the fundamental building blocks of life. For this reason, they play an essential role in both medicine and science. This method allows for a straightforward synthesis of amino acids from simple starting materials, generating chiral centers and C-C bonds in the process. Moreover, it explores a significant and recognized challenge in organic chemistry. Contrary to the [1,2], the [2,3]-sigmatropic rearrangement is a well-known reaction. A challenge of this project will be to favor the [1,2]-rearrangement over the [2,3]-rearrangement, allowing for a much wider scope for these transformations.

How

The project will be carried out in collaboration with Prof. Andrew Smith from the University of St Andrews. Prof. Smith and his team are expert in organo-catalysis, using BTM as a catalyst. Building on previous results using BTM to promote the [2,3]-sigmatropic rearrangement of allylic ammonium ylides, BTM analogues will be synthesized and optimized for properties to promote the [1,2]-rearrangement. Furthermore, it will be investigated which structural motifs will bias towards the [1,2]-rearrangement. With this knowledge in hand, the reaction will be fine-tuned by applying meticulous optimization of temperature, reaction time, solvent, and additives. This in turn is expected to yield a well performing reaction of allylic ammonium ylides to amino acids by a [1,2]-rearrangement.

SSR

The amino acid structure is an essential motif for the chemical industry and research in general. By developing new and improved ways of synthesizing this motif we not only make it cheaper to produce medicine and other fine chemicals, but we also broaden the scope of what motifs are easily accessible, and therefore useful to the chemical industry. This in turn leads to a more sustainable industry and a medical/chemical industry with more possibilities when developing new medicine or fine chemicals. BTM is one of the few organo-catalysts that has found industrial application. By employing this catalyst, we hope to reduce the need for transition metal catalysts making a more environmentally friendly chemical industry a possibility.