Regio‐ and Enantioselective Hydroamination of Dienes by Gold(I)/Menthol Cooperative Catalysis

Abstract

Alcohol is key: Regio‐ and enantioselective hydroamination of 1,3‐dienes has been achieved with the dinuclear catalyst (R)‐DTBM‐SEGPHOS. The rate and selectivity of the reaction are enhanced by alcohol additives like menthol, which coordinates the cationic gold(I) to generate a Brønsted acid that can participate in catalysis. Mbs=p‐methoxybenzenesulfonyl.

Transition‐Metal‐Catalyzed Hydroamination Reactions

“…Such substrates are prone to proton-mediated reactivity profiles, as discussed earlier, and generation of an acidic species has been postulated for catalytic turnover in Au(I)-catalyzed reactions [300]. Using menthol as a chiral Brønsted acid source, upon the Lewis acid activation with the Au(I) center, cooperative catalysis was achieved to prepare substituted pyrrolidine heterocycles with excellent enantiomeric excesses (Scheme 15.83) [300]. These important contributions in Au(I)-catalyzed intramolecular hydroamination of protected amines demonstrate their usefulness in realizing highly sought after reactivity.…”

“…Protecting groups explored in this transformation focused on carbamates and sulfonylamides. In an effort to extend this reactivity to alkenes from allenes, the Toste group [300] performed the cyclohydroamination reaction with their preferred gold catalyst systems using diene-substituted sulfonylamides. Such substrates are prone to proton-mediated reactivity profiles, as discussed earlier, and generation of an acidic species has been postulated for catalytic turnover in Au(I)-catalyzed reactions [300].…”

“…In an effort to extend this reactivity to alkenes from allenes, the Toste group [300] performed the cyclohydroamination reaction with their preferred gold catalyst systems using diene-substituted sulfonylamides. Such substrates are prone to proton-mediated reactivity profiles, as discussed earlier, and generation of an acidic species has been postulated for catalytic turnover in Au(I)-catalyzed reactions [300]. Using menthol as a chiral Brønsted acid source, upon the Lewis acid activation with the Au(I) center, cooperative catalysis was achieved to prepare substituted pyrrolidine heterocycles with excellent enantiomeric excesses (Scheme 15.83) [300].…”

Enantioselective Gold-Catalyzed Synthesis of Heterocyclic Compounds

“…One example of an asymmetric diene hydroamination was reported by Toste et al in 2011 [56]. The authors showed that an alcohol solvent or additive significantly accelerated the rate of substrate conversion, resulting in formation of two products (Scheme 10); enantiomer match/mismatch of the alcohol and ligand was also important.…”

Advances toward the Synthesis of Functionalized γ-Lactams

“…25 Gold promotes the nucleophilic addition of amines and amides to inactivated alkenes in the presence of a proton sponge such as (¡)-menthol. Diene 67 was treated with catalyst (R)-(C)-5,5 0 -bis[di-3,5-terbutyl-4-methoxyphenyl)phosphine] 4,4 0 -bi1,3-benzodioxole gold chloride [DBTM-SEGPHOS (AuCl) 2 ], silver tetrafluoroborate (AgBF 4 ) and (¡)-menthol to provide compound 68 in modest yield, but excellent enantiomeric excess (Scheme 15).…”