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

Abstract

Reported herein is the catalytic asymmetric aminative dearomatization reaction of common phenols. As opposed to the well-studied indoles and naphthols, phenols are supposed to be challenging substrates for catalytic asymmetric dearomatization reactions in terms of their strong aromaticity and regioselectivity issues. Under the catalysis of a chiral phosphoric acid, the C4-regiospecific aminative dearomatization of phenols with azodicarboxylates readily occurred at ambient temperature, delivering an array of biologically and synthetically important aza-quaternary carbon cyclohexadieneones in good yields and with excellent enantioselectivities (29 examples, up to 98% yield, and >99% ee).

Pyrroloindoles as Therapeutically Invaluable Agents: A Review on their Diverse Synthetic Methodologies

“…Pyrroloindole and its derivatives are considered as a crucial structural motif within a diverse array of fused heterocycles, that hold considerable importance in the realm of natural compounds and bioactive molecules. [23] Further, they exhibit a wide range of pharmacological activities such as anti-inflammatory, cytotoxic, anti-nociceptive, [24] antimalarial, [25] blackwater fever and stomach disorder, [26] antifungal, [24] antibacterial, [27] antitumor and chemotherapeutic agents [28] and various applications in the fields of agrochemicals, materials and organic synthesis [29] along with unique electrical and optical properties. [30] Of particular interest, due to the structural versatility, this nucleus is of considerable interest for many researchers both chemically and biologically.…”

Dearomative spiroannulation of indoles enabled by the diaza-[1,2]-Wittig rearrangement

“…31 Very recently, Xiao developed synergistic scandium/gold-catalyzed dearomative spiroannulation for diastereoselective assembly of spiroindolenines. 32 Our group is highly interested in the dearomatization reaction of aromatics including indoles; 33–38 herein, our goal is to develop a novel DSA strategy for this highly underdeveloped field.…”

Enantioselective Dearomatization of Substituted Phenols via Organocatalyzed Electrophilic Amination

“…Despite the fact that a number of catalytic asymmetric aminative dearomatization methods have been disclosed for substituted naphthols and indoles, the corresponding method for phenols remains unreported. With our continuous interest in the asymmetric electrophilic aminations of azodicarboxylates enabled by chiral phosphoric acid (CPA) catalysis, herein we report on the CPA-catalyzed aminative dearomatization of phenols, which delivers a series of chiral 2,5-cyclohexadienones bearing 4-aza-quaternary stereocenters with excellent yields and enantioselectivities (Figure e).…”