BORONDYKAT · VINYL AND HETEROARYL BORONIC ACIDS AS NON-STABILIZED NUCLEOPHILES IN RHODIUM-CATALYZED DYNAMIC KINETIC TRANSFORMATIONS

VINYL AND HETEROARYL BORONIC ACIDS AS NON-STABILIZED NUCLEOPHILES IN RHODIUM-CATALYZED DYNAMIC KINETIC TRANSFORMATIONS

The development of new chemical reactions allows to prepare substances with scientific relevance and useful properties more efficiently and in a selective manner. The ability to make carbon-based compounds holds a great importance in the synthesis of medicines, fragrances, polymers, materials, catalysts and the study of biological and physical properties. Among these compounds, chiral molecules represent an additional challenge. Chiral molecules are those which are non-superimposable on its mirror image. The mirror images of a chiral molecule are called enantiomers, and the chemical properties of each enantiomer of a given chiral molecule can be very different, therefore reactions that allow the preparation of one single enantiomer are of paramount importance. Asymmetric carbon-carbon bond forming reactions generate single enantiomers of chiral molecules at the same time as the molecular framework is assembled and is therefore a very powerful strategy in organic synthesis. Two strategies for generating single enantiomer compounds using enantioselective catalysis have become widely embraced: the first generates a chiral product by a reaction which introduces asymmetry to a prochiral substrate. This prochiral approach has proven important in the development of catalytic asymmetric reactions, despite the rather limited availability of prochiral substrates when compared to chiral substrates. The second widely used approach is to start from a racemic mixture (this is a 1:1 mixture of the two enantiomers of a chiral molecule). Here the catalyst selectively reacts with one of the two enantiomers allowing differentiation (or resolution) of the enantiomers, but the yield is necessarily limited to 50%, as the undesired enantiomer remains as starting material. An efficient variation of this second strategy is to couple enantiomer differentiation with interconversion of the enantiomers. This strategy allows yields over 50% from chiral starting materials while still producing highly enantiomerically enriched products. Despite the usefulness of this approach, it remains underdeveloped in contrast with the more traditional strategies mentioned above. Professor Fletcher research group has contributed to this field with the development of new dynamic kinetic asymmetric transformations (DYKATs) that employ racemic mixtures of cyclic allyl halides as electrophiles in combination with alkenes or boronic acids as nucleophiles to achieve enantiopure products in yields over 50%. The overall objectives of this project were the expansion of the scope of the DYKAT processes previously developed by the group. Thus, examination of new nucleophiles that can be used in combination with racemic mixtures of allyl halides has been carried out. The use of biologically-relevant heterocyclic scaffolds as electrophiles was also studied in combination with the successful new nucleophiles. Additionally, the study of alternative DYKAT procedures that relay on the use of more abundant or stable starting materials has also been carried out.

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