Periodic Reporting for period 1 - PHOTALLICA (1,2-Dicarbofunctionalization of Alkenes by Merging Photoredox and Transition-Metal Catalysis)
Reporting period: 2019-05-01 to 2021-04-30
Project 1: Catalytic radical generation of π-allylpalladium complexes, published in Nature Catalysis, Year 2020, Volume 3, Pages 393–400.
Project 2: Diastereodivergent synthesis of enantioenriched α,β-disubstituted γ-butyrolactones via cooperative N-heterocyclic carbene and Ir catalysis. Nature Catalysis, Year 2020, Volume 3, Pages 48–54.
A system based on two chiral catalysts working hand-in-hand was develop for the second project. The novel chemical transformation targeted the synthesis of all four stereoisomers of so-called α,β-disubstituted γ-butyrolactones, which are moieties present in numerous biologically-relevant molecules. The key to success was the use of a cooperative catalytic system based on an iridium catalyst and a N-heterocyclic carbene organocatalysts. The modularity of the catalytic system resulted in the selective production of one of the four stereoisomers of the product, depending on the reaction conditions, at will. Before this work, the field of dual metal/NHC organocatalysis was limited to the use of palladium as the transition-metal catalyst, limiting its applicability to certain starting materials. Now, by using iridium as the catalyst, new building blocks can be employed as starting point. The products formed in the reaction are highly valuable motifs that are present in the core of numerous natural products displaying a wide range of biological activities. For example pilocarpin, a drug used to treat glaucoma. It is foreseen that the work will aid in the discovery of pharmaeutical compounds and inspire the discovery of new dual catalytic systems based on organocatalysis and transition-metal cataylsis, as well as new stereodivergent asymmetric transformations.