Enantioselective Catalysis with Pyrrolidinyl Gold(I) Complexes: DFT and NEST Analysis of the Chiral Binding Pocket
Giuseppe Zuccarello, Leonardo J. Nannini, Ana Arroyo‐Bondía, Nicolás Fincias, Isabel Arranz, Alba H. Pérez-Jimeno, Matthias Peeters, Inmaculada Martín‐Torres, Anna Sadurní, Víctor García‐Vázquez, Yufei Wang, Mariia S. Kirillova, Marc Montesinos‐Magraner, Ulysse Caniparoli, Gonzalo D. Núñez, Feliu Maseras, María Besora, Imma Escofet, Antonio M. Echavarren
Abstract
High Resolution Image Download MS PowerPoint Slide A new generation of chiral gold(I) catalysts based on variations of complexes with JohnPhos-type ligands with a remote C 2 -symmetric 2,5-diarylpyrrolidine have been synthesized with different substitutions at the top and bottom aryl rings: from replacing the phosphine by a N -heterocyclic carbene (NHC) to increasing the steric hindrance with bis- or tris-biphenylphosphine scaffolds, or by directly attaching the C 2 -chiral pyrrolidine in the ortho-position of the dialkylphenyl phosphine. The new chiral gold(I) catalysts have been tested in the intramolecular [4+2] cycloaddition of arylalkynes with alkenes and in the atroposelective synthesis of 2-arylindoles. Interestingly, simpler catalysts with the C 2 -chiral pyrrolidine in the ortho-position of the dialkylphenyl phosphine led to the formation of opposite enantiomers. The chiral binding pockets of the new catalysts have been analyzed by DFT calculations. As revealed by non-covalent interaction plots, attractive non-covalent interactions between substrates and catalysts direct specific enantioselective folding. Furthermore, we have introduced the open-source tool NEST, specifically designed to account for steric effects in cylindrical-shaped complexes, which allows predicting experimental enantioselectivities in our systems.