Enantioselective Cyclization of Bromoenynes: Mechanistic Understanding of Gold(I)-Catalyzed Alkoxycyclizations

Abstract

The first enantioselective gold(I)-catalyzed alkoxycyclization of bromo-1,6-enynes is achieved using a modified JohnPhos ligand with a distal C2-chiral 2,5-diarylpyrrolidine. By using a chiral catalyst of the same family, the enantioselective cascade cyclization of bromo-1,5-enynes to afford polycyclic scaffolds was also achieved for the first time. Performing the cyclization of bromo-1,6-enynes in absence of an alcohol as nucleophile leads to the formation of products of cycloisomerization, with lower enantiomeric excess than those of the alkoxycyclization. Control experiments and DFT calculations support the hypothesis of an in-cycle racemization process based on a 1,2-hydrogen shift, which sheds light on the mechanism of gold(I)-catalyzed alkoxycyclizations.