Enantioselective cyclization of bromoenynes: mechanistic understanding of gold(i)-catalyzed alkoxycyclizations

Abstract

The first enantioselective gold(I)-catalyzed alkoxycyclization of bromo-1,6-enynes has been achieved using a modified JohnPhos ligand bearing a distal C₂-chiral 2,5-diarylpyrrolidine unit. Using an achiral catalyst of the same family, the enantioselective cascade cyclization of bromo-1,5-enynes to form polycyclic scaffolds was also accomplished for the first time. Interestingly, performing the cyclization of bromo-1,6-enynes in the absence of an alcohol nucleophile led to the formation of nearly racemic cycloisomerization products. Control experiments and DFT calculations support a mechanism involving an in-cycle racemization process mediated by a 1,2-hydrogen shift, shedding new light on the mechanism of gold(I)-catalyzed alkoxycyclizations.