Asymmetric Dearomatization of Phenols via Ligand‐Enabled Cooperative Gold Catalysis

Abstract

By employing a chiral bifunctional phosphine ligand, a gold(I)‐catalyzed efficient and highly enantioselective dearomatization of phenols is achieved via versatile metal‐ligand cooperation. The reaction is proven to be remarkably general in scope, permitting substitutions at all four remaining benzene positions, accommodating electron‐withdrawing groups including strongly deactivating nitro, and allowing carbon‐based groups of varying steric bulk including tert‐butyl at the alkyne terminus. Moreover, besides N‐(o‐hydroxyphenyl)alkynamides, the corresponding ynoates and ynones are all suitable substrates. Spirocyclohexadienone‐pyrrol‐2‐ones, spirocyclohexadienone‐butenolides, and spirocyclohexadenone‐cyclopentenones are formed in yields up to 99 % and with ee up to 99 %.

Asymmetric gold catalysis enabled by specially designed ligands

“…(Scheme 10B). 101 Among the ligands tested, the previously developed ligand L10A demonstrated the optimal performance for the 5-endo-dig cyclization of alkynes (10c). The gold(I) complex of this ligand successfully facilitated the production of spirocyclohexadienone derivatives (10d) with outstanding enantioselectivities (up to 99% ee) and high yields (up to 99%).…”

Chiral Bifunctional Phosphine Ligand Enables Asymmetric Trapping of Catalytic Vinyl Gold Carbene Species

“…For example, the addition of carboxylic acid to alkyne with the amide-functionalized WangPhos as the gold ligand is accelerated by >800 times over the reaction employing JohnPhos, in which there is no remote basic group . With these types of bifunctional ligands prepared from chiral binols (e.g., ( S )- L1 ), we have harnessed the accelerating phenomenon to achieve asymmetric allenol cyclization and dearomatization reactions with high levels of stereoselectivities. In all cases, the electrophilic site that is subjected to an accelerated nucleophilic attack is limited to gold-activated alkyne or allene moieties of substrates.…”

Gold-Catalyzed Homo/Heterodimerization of Terminal Alkynes Facilitated by Metal–Ligand Cooperation

“…To date, the nucleophilic group is limited to the HO group of a tethered alcohol or water and HN of in situ-generated HN 3 . Some related cases employ the carbonyl oxygen of carboxylic acid and the o- C­(sp 2 ) in phenols as the nucleophilic atom. It would represent a significant advance that a CH group could function like an OH group in this type of accelerated gold catalysis.…”