Synthesis of Indolo[2,1‐a]isoquinolin‐6(5H)‐Ones Derivatives via Fe(OTf)₃‐Promoted Tandem Selenylation/Cyclization of 2‐Arylindoles

Abstract

A practical method for the synthesis of selenylsubstituted indolo[2,1‐a]isoquinolin‐6(5H)‐ones through Fe(OTf)3‐promoted tandem selenylation/cyclization of 2‐arylindoles was developed. In this transformation, new C−Se bond and C−C bond were constructed simultaneously under mild conditions.

Metal‐free and One‐pot for the Synthesis of Indolo[2,1‐a]isoquinoline Aldehyde via a Free Radical Cascade Pathway followed by Direct Hydrolyzation

“…Additionally, Mn‐promoted for the preparation of phosphoryl‐substituted indolo[2,1‐ a ]isoquinolin‐6(5 H )‐ones via tandem phosphinoylation/cyclization pathway was also reported by Li's group (Scheme 1a) [6] . Very recently, Xu's group revealed a synthetic approach for selenysubstituted indole[2,1‐ a ]isoquinolin‐6(5 H )‐ones through Fe(OTf) 3 ‐promoted tandem selenylation/cyclization (Scheme 1b) [7] …”

“…5-Fu was used as the positive control. [7][8] To our delight, compound 6 d exhibited some inhibitory activity against human glioma U-87MG after some screening (Figure 2). However, the compound 6 d was required to be further optimized to enhance its bioactivity, and this work was ongoing in our lab.…”

“…Besides above discussion, the biological activity of compound 6 d against human cancer cells were further carried out. 5‐Fu was used as the positive control [7‐8] . To our delight, compound 6 d exhibited some inhibitory activity against human glioma U‐87MG after some screening (Figure 2).…”

“…1 H NMR (400 MHz, CDCl 3 ) δ 9.43 (s, 1H), 8.32 (dd, J = 20.0, 10. 6 Hz,1H),1H),7.31 (s,1H),2H),7.16 (dd, J = 7.0, 2.0 Hz, 1H), 7.11 (t, J = 7.6 Hz, 1H), 6.95-6.85 (m, 1H), 3.75-3.44 (m, 1H), 3.36-3.13 (m, 1H), 2.35 (s, 3H), 1.54 (s, 3H).…”

“…13 C NMR (101 MHz, CDCl 3 ) δ 198.0, 171. 7,164.4,161.9,140.5,140.4,136.0,133.6,131.9,130.2,126.6,126.5,125.3,120.7,120.6,120.1,117.5,115.5,115.2,112.1,111.9,102.1,53.6,45.0,30.1. HRMS (ESI): Calcd for C 19 H 14 ClFNO 2 , [M + H] + 342.0698, find 342.0696.…”