Synthesis of Indolo- and Benzothieno[2,3-b]quinolines by a Cascade Cyclization of o-Alkynylisocyanobenzene Derivatives

Abstract

A new synthetic approach for the synthesis of indolo­[2,3-b]­quinolines and benzothieno­[2,3-b]­quinolines has been developed by employing the freshly prepared o-alkynylisocyanobenzenes derived from o-alkynylformamide derivatives as substrates. The synthetic transformations involved chloride-ion-triggered 6-endo cyclization of o-alkynylisocyanobenzenes to generate 2-chloroquinolines in situ, which further cyclized intramolecularly with nitrogen or sulfur atom via a cascade process to provide the corresponding indolo­[2,3-b]­quinolines and benzothieno­[2,3-b]­quinolines, respectively, in moderate to excellent yields.

Applications of Ethynylanilines as Substrates for Construction of Indoles and Indole‐Substituted Derivatives

“…Variety of 2-ethynylaniles 113 with different substituents were checked for the reaction scope. [59] The reaction proceeds smoothly and afford the chiral indolines derivatives 114 with excellent yields and enantioselectivities. The reaction is not sensitive to the length of the alkyl side chain and better reactivity was observed.…”

“…Yong-Ming Zhu et al [38] described a novel Pd(II) catalyzed one pot synthesis of N-imidoyl-(1H)-indoles 86 (scheme 28) from 2-(phenylethynyl)-anilines 83 arylboronic acids 84, and isonitriles 85. [59] Herein, 2-(phenylethynyl)-anilines 83 arylboronic acids 84, and isonitriles 85 undergo palladium catalysed oxidative insertion with Cu (OAc) 2 as oxidant, DMF as solvent at 100°C to give desired indole derivative. In the reaction optimization DPPE i. e., bidentate ligands found suitable for the total conversion of the substrates to the product.…”

“…Chutima Kuhakarn et al [59] developed intermolecular cyclization/6-endo dig cyclization strategy for synthesis for indolo [2, 3-b] quinolines 130 from o-alkynyl-isocyanobenzenes 128 (scheme 45) promoted by chloride ion in moderate to good yields. [57] This reaction proceeds through the formation of unstable nitrile intermediate 129 and which upon subsequent double cyclization gives fused indolo[2,3-b] quinolines 130.…”

Recent Advances in the Synthesis of Thienoquinolines (Quinoline‐fused heterocycle)

“…[10] (Scheme 18) Initially, acetanilide is reacted with Vilsmeier-Haack reagent (DMF and POCl 3 ) under reflux to obtain 2-chloroquinoline-3-carbaldehyde, (a) which treated with hydroxylamine hydrochloride to provide oxime, under the addition of thionyl chloride, further extended to obtain 2-chloroquinoline-3-cyano derivative, (b) which underwent sulfhydrylation in the presence of thiourea to afford 2- In 2019, Kuhakarn and co-workers successfully accomplished a metal-free synthesis of benzothieno[2,3-b]quinolines 59 from N-(2-((2-(methylthio)phenyl)ethynyl)phenyl)formamides 58 via cascade cyclization. [41] (Scheme 19a) Initially, in the step-1, methylthio-formamide is treated with POCl 3 and N,Ndiisopropylethylamine under the cold condition for 1 h to access o-alkynyl-isocyanobenzene intermediate. In Recently, we reported the synthesis of 2-acyl-thieno[2,3-b] quinolines 61 using 2-halo-quinolineketones 60 via Cu-TEMPO radical catalyzed dehydrogenative thiolation using elemental sulfur.…”

“…In 2019, Kuhakarn and co‐workers successfully accomplished a metal‐free synthesis of benzothieno[2,3‐ b ]quinolines 59 from N‐(2‐((2‐(methylthio)phenyl)ethynyl)phenyl)formamides 58 via cascade cyclization [41] . (Scheme 19a) Initially, in the step‐1, methylthio‐formamide is treated with POCl 3 and N,N‐diisopropylethylamine under the cold condition for 1 h to access o ‐alkynyl‐isocyanobenzene intermediate.…”