Practical Synthesis of Chiral Ferrocenenylphosphino-Gold(I) Cata-lysts and NEST Analysis of the Enantioinduction

The concise modular synthesis of a family of monodentate 1,2-disubstituted ferrocene ligands containing a diaryl phosphine and a 2-aryl indole is described. Their gold(I) complexes were applied to the enantioselective gold(I)-catalyzed formal [4+2] cycloaddition of 1,6-arylenynes, the enyne cyclization/nucleophile addition of N-tethered 1,6-enynes, and the methoxycyclization of 1,6-arylenyne with high levels of enantioselectivity in all cases. Crystallographic and computational studies highlight the relevant role of non-covalent interactions within the ligand scaffold and between ligand-substrate in the modes of enantioinduction in the cyclization of unsaturated substrates. Our recently developed open-source tool NEST was applied to analyze the chiral pockets of the new catalysts, which in combination with RDKit allowed to understand the enantioselectivity in these reactions, paving the way for a predictive-based approach towards the rational development of chiral ligands for enantioselective Au(I) catalysis.