Asymmetric DNA-based OrganoCatalysis

Asymmetric catalysis is arguable the most appealing way to prepare complex chiral scaffolds. In this context, metal-catalyzed transformations have been more widely used in comparison to metal-free strategies.

Nonetheless, the complexity involved with the transition metal catalysts, the toxicity often associated with the metals and the none-negligible amounts of waste produced during the reactions have caused significant drawbacks.

The advent of green and sustainable chemistry brought organocatalysis into prominence (2021 Nobel Prize in Chemistry), allowing the field to emerge as an effective alternative to classical metal-based asymmetric catalysis. Small Molecule Organocatalysts (SMOs) have been used in a plethora of different synthetic transformations.

Their stability to air excludes the need for inert conditions and ultra-dry solvents and thus minimizes overall research expenditure.

Among all the SMOs reported throughout the years, N-heterocyclic carbenes (NHCs) have shown great promise, offering interesting prospects for both academic and industrial applications.In the last decade, bio-hybrid DNA-based asymmetric catalysis (DAC) has appeared as an attractive tool providing excellent enantioselectivities on a broad range of reactions.

DNAOrgCat aims at combining, for the first time, asymmetric organocatalysis and bio-hybrid catalysis to develop new, highly enantioselective, scalable and sustainable organocatalytic processes.

To reach this goal, we will design, synthesize and ultimately evaluate a series of NHC-modified oligonucleotides on a model Stetter reaction.

We will also develop sustainable catalytic systems based on recyclable, solid-supported, modified oligonucleotides, which will ultimately be implemented to large-scale continuous flow processes.

By doing so, not only do we intend to expand the current frontiers of DNA-based asymmetric catalysis, we also wish to set a mind change and unquestionably place DNA-based catalysts in the chemists’ toolbox.