Electrochemical Tri‐ and Difluoromethylation‐Triggered Cyclization Accompanied by the Oxidative Cleavage of Indole Derivatives

Abstract

Considering their unique roles in organic synthesis, and pharmaceutical and agrochemical applications, the development of fluoroalkylation, cyclization, and indole oxidative cleavage are important topics. Herein, an unprecedented electrochemical tri‐ and difluoromethylation/cyclization/indole oxidative cleavage process occurring in an undivided cell is presented. The protocol employs a readily prepared Langlois reagent as the fluoroalkyl source, affording a series of tri‐ or difluoromethylated 2‐(2‐acetylphenyl)isoquinoline‐1,3‐diones in good yields with excellent stereoselectivity. It is worth noting that this new methodology merges the fluoroalkylation/cyclization of N‐substituted acrylamide alkenes with the oxidative cleavage of an indole C(2)=C(3) bond under external oxidant‐free conditions.

Electro-Triggered Cascade Cyclization to Access Phosphinyl-Substituted N-Containing Heterocycles

“…11d A colorless liquid, (90 mg, 31% yield). 1 H NMR (500 MHz, CDCl 3 ) δ 8.15 (d, J = 10.0 Hz, 1H), 7.95 (d,J = 5.0 Hz,1H),4H),2H),4H), 2.66−2.62 (m, 4H), 1.19 (t, J = 5.0 Hz, J = 10.0 Hz, 6H). 13 C{ 1 H} NMR (126 MHz, CDCl 3 ) δ 167.5 (d,J = 126.0 Hz),155.5 (d,J = 12.6 Hz),149.4,136.9,133.2 (d,J = 12.6 Hz),128.5,128.4 (d,J = 12.6 Hz),127.6,126.7 (d,J = 12.6 Hz),124.8,122.2,29.1,15.2.…”

“…1 H NMR (500 MHz, CDCl 3 ) δ 8.15 (d, J = 10.0 Hz, 1H), 7.99 (d,J = 5.0 Hz,1H),2H),2H),7.10 (d,J = 5.0 Hz, 1H), 7.00 (d, J = 5.0 Hz, 1H), 2.48 (s, 6H), 2.32 (s, 6H). 13 C{ 1 H} NMR (126 MHz, CDCl 3 ) δ 168.5 (d,J = 126.0 Hz),155.3 (d,J = 25.2 Hz),137.4,126.8,126.0,124.9,122.2,22.7 (d,J = 3.8 Hz), 21.6. 31 P NMR (202 MHz, CDCl 3 ) δ 28.00 (s).…”

“…7d A white solid, (71 mg, 34% yield). 1 H NMR (500 MHz, CDCl 3 ) δ 9.59 (d, J = 5.0 Hz, 1H), 8.17 (d,J = 10.0 Hz,1H),4H),2H),6H),2H), 2.90 (s, 3H), 1.38 (t, J = 10.0 Hz, J = 5.0 Hz, 3H).…”

Progress in the Electrochemical Reactions of Sulfonyl Compounds

“…Many previously inactive electron-deficient substrates afforded corresponding cyclization products smoothly (Scheme 14b, products 92 a, 94 a, and 96 a). Very recently, Yuan et al [78] extended this cascade by oxidative cleavage of indoles (Scheme 14c). Both trifluoromethylation and difluoromethylation were available in this reaction, except for 20 mol% MnCl 2 •H 2 O being needed for difluoromethylation reaction.…”

“…Many previously inactive electron‐deficient substrates afforded corresponding cyclization products smoothly (Scheme 14b, products 92 a , 94 a , and 96 a ). Very recently, Yuan et al [78] . extended this cascade by oxidative cleavage of indoles (Scheme 14c).…”