On the gold(I)-catalyzed enantioselective addition of indole to diphenylallene via anion-binding catalysis

Abstract

Neutral dual hydrogen bond donors (HBDs) are effective catalysts that enhance the electrophilicity of substrates or the Lewis/Brønsted acidity of reagents through an anion-binding mechanism. Despite their success in various enantioselective organocatalytic reactions, their application to transition metal catalysis remains rare. Herein, we report the activation of gold(I) precatalysts by chiral ureas, leading to enantioselective hydroarylation of allenes with indoles. Experimental and computational studies support an anion-binding mechanism for gold(I) precatalyst activation. Noncovalent interactions were identified as the source of enantiodifferentiation, providing insights into the cooperativity between achiral phosphine ligands and chiral ureas.

Keywords: Anion-binding catalysis; Asymmetric catalysis; Gold catalysis; Non-covalent interaction.

Fig. 1.

Strategies of asymmetric anion-binding catalysis. (A) representative example of enhanced electrophilicity of organic substrates by chiral HBDs; (B) representative example of enhanced reactivity of silicon-based Lewis acids by chiral HBDs; (C) activation of transition-metal precatalysts by chiral HBDs.

Fig. 2.

Proposed mechanism of gold(I)-catalyzed hydroarylation reaction.

Fig. 3.

Optimized structures of transition states TS-S and TS-R. TS-S involves indole addition to the (R)-allene–Au complex, leading to the (S)-hydroarylation product, whereas TS-R involves indole addition to the (S)-allene–Au complex, leading to the (R)-hydroarylation product. All Gibbs free energies and enthalpies are in kcal/mol relative to the reactant complex RC. Dispersion energies (ΔE_disp) of the π/π and C─H/π interactions were computed using DFT-D4 are in kcal/mol.

Fig. 4.

Correlation between experimental and calculated ΔΔG^‡ values between the enantiodetermining transition states with various para-substituted triarylphosphine ligands (ΔΔG^‡ = ΔG^‡(TS-S) − ΔG^‡(TS-R)).

Fig. 5.

Ion mobility mass spectrometry of three cationic adducts of 4d (with H⁺, Na⁺, and Ph₃PAu⁺).

Scheme 1.

Reaction of 1 (a) or Me-1 (b) under the optimized conditions.

Scheme 2.

Gold(I)-catalyzed hydroarylation of enantioenriched allene with indole. (a) Reaction of (S)-2 without chiral urea; (b) reaction of (S)-2 with chiral urea 4d; (c) reaction of (R)-2 with chiral urea 4d.