NUS chemists have developed an efficient method to access enantioenriched drug-like compounds by cross-coupling multicomponent olefins using chiral nickel catalysts.
Chiral molecules containing enantioenriched tri- and tetra-substituted stereogenic centers are found among many natural products and medicines. The spatial arrangement of atoms around these centers often dictates the general shape of a molecule and influences its biological function or toxicity. Thus, the ability to generate enantiomerically pure compounds by asymmetric catalysis is vital in pharmaceutical and agrochemical research. However, related strategies that use non-precious metal-derived catalyst systems to promote enantioselective synthesis using cheap and abundant olefin feedstocks are often of limited scope. This limits their widespread adoption.
A research team led by Assistant Professor Koh Ming Joo, Department of Chemistry, National University of Singapore, has devised a new strategy that exploits widely available nickel catalysts containing hindered N-heterocyclic carbene (NHC) ligands , to fuse olefins with an organotrilate and a metal alkoxide as the hydride donor. The replacement of the metal alcoholate by an organometallic reagent allows the installation of two different carbogenic groups.
These multicomponent reactions provide a simplified route to chiral molecules bearing carbon-substituted tertiary or quaternary stereogenic centers or enantioenriched heteroatoms. This is a collaboration with Professor Shi-Liang Shi, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences. The findings were published in Natural catalysis.
Professor Koh said: “Through selective carbofunctionalisations, we can even access the opposite enantiomers of a chiral molecule using a single chiral catalyst antipode. This is difficult to achieve using alternative systems, demonstrating a unique advantage of our catalytic regime. We can now use this new protocol as a general platform to produce valuable chiral molecules with high stereochemical purity.”
“We believe that this methodology will greatly enrich the toolbox of asymmetric catalysis to facilitate countless applications in stereoselective synthesis of natural products and drug discovery,” added Professor Koh.
The research team is developing novel chiral NHC-nickel catalysts to promote cross-coupling transformations of olefins that can potentially solve other unsolved challenges in organic synthesis.
Chiral amines synthesized by nickel-catalyzed asymmetric reductive hydroalkylation
Chen-Fei Liu et al, Synthesis of tri- and tetra-substituted stereocenters by enantioselective nickel-catalyzed olefin cross-couplings, Natural catalysis (2022). DOI: 10.1038/s41929-022-00854-8
Provided by National University of Singapore
Quote: Chiral drug-like building blocks by nickel-catalyzed enantioselective olefin cross-coupling (2022, October 28) retrieved October 29, 2022 from https://phys.org/news/2022-10-chiral-drug-like- blocks-nickel-catalyzed-enantioselective.html
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