Brønsted acid–catalyzed asymmetric dearomatization for synthesis of chiral fused polycyclic enone and indoline scaffolds

Abstract

In the past two decades, substantial advances have been made on the asymmetric alkyne functionalization by the activation of inert alkynes. However, these asymmetric transformations have so far been mostly limited to transition metal catalysis, and chiral Brønsted acid–catalyzed examples are rarely explored. Here, we report a chiral Brønsted acid–catalyzed dearomatization reaction of phenol- and indole-tethered homopropargyl amines, allowing the practical and atom-economical synthesis of a diverse array of valuable fused polycyclic enones and indolines bearing a chiral quaternary carbon stereocenter and two contiguous stereogenic centers in moderate to good yields with excellent diastereoselectivities and generally excellent enantioselectivities (up to >99% enantiomeric excess). This protocol demonstrates Brønsted acid–catalyzed asymmetric dearomatizations via vinylidene–quinone methides.

Organocatalyzed double dearomatization reaction of non-functionalized phenols and propargylic alcohols: the important regulating effect of steric hindrance

“…6 Remarkably, this strategy efficiently circumvents the challenge resulting from the uncontrolled rearomatization process of the conventional Wheland intermediate by establishing a stable fully substituted carbon center on the aromatic nucleophilic partner, offering a reliable route to structurally and stereochemically complex dearomatized products. Utilizing such an expedient tactic, the dearomatization reactions of electron-rich arenes, such as phenols, 7 indoles 8 and pyrroles 9 have fruitfully been performed to access highly functionalized cyclic systems. However, despite the fact that considerable progress has been made in the field of dearomatization, the catalytic dearomatization reactions of electron-rich arenes bearing no substituent at their reactive site have rarely been reported.…”

Organocatalytic Asymmetric Dearomative Spirocyclization/Oxa-Michael Addition Sequence: Synthesis of Polycyclic Tetralones

“…For the synthesis of various enantiopure spirocarbocyclic compounds, transition-metal-catalyzed dearomatization of phenol and naphthol derivatives has received extensive study in recent years . In contrast, metal-free nonoxidative methods are less common . Also, most of the methods generate cyclohexadienone or napthalenone frameworks after the dearomatization reaction (Scheme A, types I and II).…”

Catalytic Asymmetric Synthesis of Aza-Quaternary Carbon Cyclohexadieneones Enabled by Aminative Dearomatization of Phenols

“…10π-Electron indoles and 2-naphthols are the typical substrates for CADA reactions to prepare partially dearomatized indolenines and naphthalenones by making use of the C3- and C1-nucleophilicity, respectively (Scheme a). , On the other hand, phenols are usually identified as challenging substrates because of the strong aromaticity (6π-electron) and potential regioselectivity issue over the C2- and C4-positions . To our knowledge, only a few successful cases of the CADA reactions of phenols have been reported, which were mainly limited to the construction of all-carbon quaternary carbon cyclohexadieneones via metal-catalyzed intramolecular allylation, arylation, and alkylation reactions (Scheme b). In sharp contrast, catalytic asymmetric aminative dearomatization of phenols remains elusive .…”