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

A new generation of chiralgold(I) catalysts based on variations of complexes with JohnPhos-typeligands with a remote C (2)-symmetric 2,5-diarylpyrrolidinehave been synthesized with different substitutions at the top andbottom aryl rings: from replacing the phosphine by a N-heterocyclic carbene (NHC) to increasing the steric hindrance withbis- or tris-biphenylphosphine scaffolds, or by directly attachingthe C (2)-chiral pyrrolidine in the ortho-positionof the dialkylphenyl phosphine. The new chiral gold(I) catalysts havebeen tested in the intramolecular [4+2] cycloaddition of arylalkyneswith 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 phosphineled to the formation of opposite enantiomers. The chiral binding pocketsof the new catalysts have been analyzed by DFT calculations. As revealedby non-covalent interaction plots, attractive non-covalent interactionsbetween substrates and catalysts direct specific enantioselectivefolding. Furthermore, we have introduced the open-source tool NEST,specifically designed to account for steric effects in cylindrical-shapedcomplexes, which allows predicting experimental enantioselectivitiesin our systems.

Automated summary

A new generation of chiragold(I) catalysts based on variations of complexes with JohnPhos-type ligands have been synthesized and tested in various reactions. The chiral binding pockets of the catalysts have been analyzed by DFT calculations and attractive non-covalent interactions between substrates and catalysts have been identified. Additionally, an open-source tool called NEST has been introduced for predicting experimental enantioselectivities in these systems.