Chiral N-Alkylfluorenyl-Substituted N-Heterocyclic Carbenes in the Gold(I)-Catalyzed Enantioselective Cycloisomerization of 1,6-Enynes

Abstract

A series of chiral ^A*Flu-NHC-gold(I) complexes, where ^A*Flu-NHC is an N-heterocyclic carbene (imidazolin-2-ylidene or benzimidazolin-2-ylidene) bearing a chiral 9-alkyl-9-fluorenyl N-substituent and a 2,6-diisopropylphenyl or benzyl N'-substituent, were straightforwardly prepared in few steps from readily available 2,6-diisopropylamine, imidazole or benzimidazole. The chirality of the N-substituent lies in the presence of a chiral alcoholic alkyl chain on the fluorenyl, which results from the opening of commercially available chiral styrene oxide, yielding to a 2-hydroxy-2-phenylethyl or a 2-hydroxy-1-phenylethyl group. Four [AuCl(^A*Flu-NHC)] complexes were tested as precatalysts in an enantioselective cycloisomerization of a 1,6-enyne. Notably, the best inductions were observed with the benzimidazolin-2-ylidene derivative bearing a 2-hydroxy-1-phenylethyl group on the fluorenyl ring, showing that a constrained rotation around the N-C_fluorenyl bond and a chiral center in α position of the fluorenyl ring are determining factors. Interestingly, a strong improvement of the induction with up to 72 % ee was observed using AgOTf as activator. The presence of a hydrogen bond between the hydroxyl group and OTf^- in the in situ generated active cationic gold(I) species probably stiffens its structure. This type of ligand-counteranion interaction represents a novel strategy for optimizing chirality transfer in asymmetric gold(I) catalysis.

Keywords: Asymmetric catalysis; Cycloisomerization; Gold; N-heterocyclic carbenes; Steric hindrance.