Direct Oxidative Coupling of N‐Acetyl Indoles and Phenols for the Synthesis of Benzofuroindolines Related to Phalarine

Abstract

Inspired by the biogenetic synthesis of benzofuroindoline-containing natural products, we designed an oxidative coupling between phenol and N-acetyl indoles. This straightforward and direct radical process, mediated by 2,3-dichloro-5,6-dicyano-1,4-benzoquinone and FeCl 3 allowed the regioselective synthesis of benzofuro[3,2-b]indolines, whose structure is found in the natural product phalarine. Scheme 4. Oxidative coupling between phenols and N-acetyl indoles leading to benzofuro[2,3-b]indolines. Scheme 5. Mechanistic considerations of the regioselectivity.

External oxidant-free electrooxidative [3 + 2] annulation between phenol and indole derivatives

“…Based on the experimental results and previous reports 10 , 48 , a plausible reaction mechanism between 1a and 2a is presented in Fig. 8 .…”

“…In 2014, Vincent and co-workers reported an oxidative [3 + 2] annulation between phenols and 3-substituted N -acetylindoles for the synthesis of benzofuro[3,2]indolines using excess amount of FeCl 3 and 2,3-dicyano-5,6-dichlorobenzoquinone, and the reaction yields ranged from 27 to 62% (Fig. 1a ) 48 . It is highly desirable to develop more efficient phenol–indole [3 + 2] annulation for the synthesis of benzofuro[3,2-b]indolines.…”

Electrochemical Dearomatization: Evolution from Chemicals to Traceless Electrons

“…In 2014, Vincent and co‐workers developed an FeCl 3 ‐mediated straightforward oxidative coupling of N ‐acetylindoles and phenols for the synthesis of benzofuroindolines in the presence of 2,3‐dichloro‐5,6‐dicyano‐1,4‐benzoquinone (DDQ) . Inspired by this elegant work, Lei and co‐workers in 2017 showcased the electrolytic version, namely, the dearomative reaction of 3‐ or 2‐substituted N ‐acetylindoles via anodically electrooxidative [3+2] annulation with electron‐rich phenols (Scheme ) .…”

“…Deprotonation furnished the final products. Compared with the previously reported chemical procedure, the need for an oxidant was obviated …”

Recent Advances in the Catalytic Functionalization of “Electrophilic” Indoles

“…In the present article, a collection of the more representative and recent methodologies for the realization of catalytic nucleophilic functionalization of indoles is proposed with the main purpose to emphasize working plans, scopes, limitations and mechanistic insights. We would like also to emphasize that remarkable progresses have been achieved recently in this field by means of stoichiometric additives or electrochemical tools, [8f] however, these elegant variants of nucleophilic manipulations of indoles can be considered out of the scope of the present selection.…”