Lewis acid enhancement by hydrogen-bond donors for asymmetric catalysis.


Small-molecule dual hydrogen-bond (H-bond) donors such as ureas, thioureas, squaramides, and guanidinium ions enjoy widespread use as effective catalysts for promoting a variety of enantioselective reactions. However, these catalysts are only weakly acidic and therefore require highly reactive electrophilic substrates to be effective. We introduce here a mode of catalytic activity with chiral H-bond donors that enables enantioselective reactions of relatively unreactive electrophiles. Squaramides are shown to interact with silyl triflates by binding the triflate counterion to form a stable, yet highly Lewis acidic, complex. The silyl triflate-chiral squaramide combination promotes the generation of oxocarbenium intermediates from acetal substrates at low temperatures. Enantioselectivity in nucleophile additions to the cationic intermediates is then controlled through a network of noncovalent interactions between the squaramide catalyst and the oxocarbenium triflate.

DOI: 10.1126/science.aao5894

Cite this paper

@article{Banik2017LewisAE, title={Lewis acid enhancement by hydrogen-bond donors for asymmetric catalysis.}, author={Steven M Banik and Anna Levina and Alan M Hyde and Eric N Jacobsen}, journal={Science}, year={2017}, volume={358 6364}, pages={761-764} }