Electrochemical Oxidation Dearomatization of Anisol Derivatives toward Spiropyrrolidines and Spirolactones

Abstract

Spiro compounds are widely existed in biological activities and natural products. However, developing new strategies for their efficient synthesis and derivatization is still faced with challenge. Outstanding progresses have been made in the synthesis of spiro compounds through dearomatization of aromatic compounds, which were mainly mediated by the hypervalent iodine reagents. Herein, we reported a method of anodic oxidation spiroamination and spirolactonization of anisole derivatives, with concomitant cathodic reduction of protons in the absence of hypervalent iodine reagents. A wide variety of spiropyrrolidines and spirolactones with diverse functional groups were applicable scaffolds in this transformation, with yields up to 97%. Moreover, hectogram-scale synthesis could supply target products with 83% yields in flow electrochemical cell using carbon paper as anode, nickel plate as cathode, which showed the potential application of this method.

Nickel-catalyzed para-selective carboxylation of phenols with CBr4/MeOH

“…Free radicals directly react with arenes to provide a straightforward approach for constructing modified synthetic units. 7,8 For example, Cl, 8 a NO 2 , 8 b etc . can be introduced into phenol derivatives via a free radical pathway under photocatalytic conditions.…”

Electrochemical Mn-Promoted Radical Selenylation of Boronic Acids with Diselenide Reagents

“…Organic electrosynthesis is a versatile method for establishing green and sustainable processes, because dangerous and toxic oxidizers and reductants are replaced by electric current, and the overall energy consumption is reduced . Over the past decade, electrochemical methods have attracted widespread attention and are widely used in many chemical transformations.…”

Electrochemical oxidative dearomatization of 2-arylthiophenes

“…Dearomatization of aromatic compounds has been experiencing a dynamic resurgence in recent decades both in natural product synthesis 1 and medicinal chemistry, 2 owing to its unique capability to transform the fundamental and abundant aromatic molecules into functionalized products with interesting functional and structural diversity. To this end, many dearomatization strategies, such as enzymatic dearomatization, 3 transition-metal catalyzed dearomatization, 4 organo-catalyzed dearomatization, 5 and electrochemical dearomatization, 6 even including their asymmetric versions, 7 have been developed. Though every aromatic compound, in principle, may undergo a dearomative process, the high resonance stabilization energy of thiophene makes its dearomatization 8 much challenging when compared to other heteroaromatics, such as furan 9 and pyrrole (Scheme 1A).…”