A research team led by Prof KOH Ming Joo, from the Department of Chemistry, National University of Singapore in collaboration with Prof Osvaldo GUTIERREZ, from the University of Maryland, has conceived a tandem strategy that merges regiocontrolled Heck reaction and stereocontrolled C=C bond migration in a single step (see Figure). Mechanistic and computational studies showed that the reaction proceeds through a non-radical pathway, and that both the sizeable alkoxide base and N-heterocyclic carbene (NHC) ligand are crucial for the catalytic process.
Prof Koh said, “Our initial foray into this research area was to hypothetically ask how can we transform monosubstituted α-olefins, a highly abundant class of feedstock chemicals, to the more valuable but difficult-to-synthesize trisubstituted and tetrasubstituted analogues, in a single process. As it turns out, the solution to this was to design a tandem reaction that first reacts with the monosubstituted substrate, then isomerizes it to the desired product. A well-orchestrated control of regio- and stereoselectivity was paramount, which led us to discover the unique effectiveness of the NHC-ligated nickel catalysts.”
“We expect our new methodology to enhance the way in which many bioactive molecules are synthesized, and to serve as a blueprint for the design of catalytic tandem transformations to construct important building blocks from non-precious materials,” added Prof Koh.
The research team plans to exploit the insights obtained from this work to develop new tandem transformations to facilitate fine chemical synthesis.
Figure above: Schematic showing the development of a novel Ni-catalysed system that converts cheap and readily available monosubstituted olefins to high-value tri- and tetrasubstituted analogues, and its application to the synthesis of complex bioactive compounds. [Credit: Nature Catalysis]. Read the full story here.
