One‐Pot Three‐Step Synthesis of Naphtho[2,3‐a]carbazole‐ 5,13‐diones using a Tandem Radical Alkylation–Cyclization– Aromatization Reaction Sequence

Abstract

A three-step, one-pot tandem reaction including radical nucleophilic alkylation/cyclization/ aromatization was developed using 0.3 equivalents of silver(I) acetate (AgOAc) as the catalyst and 2 equivalents of ammonium persulfate [(NH 4 ) 2 S 2 O 8 ] as the oxidant. This strategy is highly efficient for the assembly of pentacyclic complex carbazoles from aryl-fused bromobenzoquinones and indol-3-ylpropanoic acid acids in 52-72% overall yields (three steps). This new approach provides a significant improvement over the previously reported methods and would greatly facilitate analog library construction of pentacyclic complex carbazoles and benefit further biological evaluation of these compounds.

Evaluation of the anti-inflammatory effects of synthesised tanshinone I and isotanshinone I analogues in zebrafish

“…Reaction optimisation, through systematic variation of numerous reaction parameters using the unsubstituted 3-phenylpropionic acid 12, in a Design of Experiments (DoE) approach (further information provided in the S1 File), led to improved yields of around 40%, including a 42% yield of alkylation product 11. Throughout these studies, although formation of a small quantity (< 10%) of doubly-alkylated product was observed, none of the alternative mono-alkylated product (alkylated adjacent to the methoxide group) was seen, which was consistent with previous reports, and likely a directing effect due to the bromide substituent [66,68].…”

Catalytic Radical Domino Reactions in Organic Synthesis

“…34 These carbazoles are formed via a radical/radical/radical/oxidation/anionic/oxidation domino process. This transformation begins by oxidation of Ag(I) to Ag(II), which then oxidizes 90 to a carboxy radical ( 93 ).…”

Lewis Acid Mediated One‐Pot Synthesis of Aryl/Heteroaryl‐Fused Carbazoles Involving a Cascade Friedel–Crafts Alkylation/Electrocyclization/Aromatization Reaction Sequence

“…[11] A one-pot synthesis of carbazolonaphthoquinones was realized in a three-step tandem radical alkylation/cyclization/aromatization reaction sequence. [12] Very recently, highly efficient one-pot syntheses of carbazoles and dihydrobenzo [a]carbazoles were reported that involve Pd-mediated domino reactions. [13,14] The synthesis of annulated heterocycles 2 (Scheme 1) by domino reaction of benzylic bromo compounds 1 containing a malonylidene unit with arenes and heteroarenes in the presence of a Lewis acid has been reported by our laboratory.…”