Enantioselective Catalysis with Pyrrolidinyl Gold(I) Complexes: DFT and NEST Analysis of the Chiral Binding Pocket

• Published in: JACS Au Vol. 3; no. 6; pp. 1742 - 1754
• Main Authors: Zuccarello, Giuseppe, Nannini, Leonardo J., Arroyo-Bondía, Ana, Fincias, Nicolás, Arranz, Isabel, Pérez-Jimeno, Alba H., Peeters, Matthias, Martín-Torres, Inmaculada, Sadurní, Anna, García-Vázquez, Víctor, Wang, Yufei, Kirillova, Mariia S., Montesinos-Magraner, Marc, Caniparoli, Ulysse, Núñez, Gonzalo D., Maseras, Feliu, Besora, Maria, Escofet, Imma, Echavarren, Antonio M.
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 26.06.2023
• Subjects: NEST tool; gold catalysis; enynes; atroposelective cyclization; enantioselective catalysis; DFT calculations
• ISSN: 2691-3704; 2691-3704
• DOI: 10.1021/jacsau.3c00159

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.