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

Abstract

An electro-triggered cascade cyclization strategy was disclosed with concomitant phosphinylation and N-heterocycle construction. It provides a novel and environmentally friendly approach to access phosphinyl-substituted N-heterocycles with no external metal catalyst, oxidant, or heating. Mechanistic studies have revealed that anodic oxidation of H-phosphorus compounds occurs first to generate the key Pcentered radical directly and cathodic reduction leads to the concurrent release of molecular hydrogen or methane. This protocol features simple operation, broad substrate scope, clean and mild conditions, and atom and step economy to form heterocycle-containing organophosphorus scaffolds.

Synthetic Methods for Azaheterocyclic Phosphonates and Their Biological Activity: An Update 2004–2024

“…This methodology was applied with some modifications for the obtention of 2-phosphonylated isoquinolines 506 by using vinyl isocyanides 505, K 2 CO 3 as a base and a platinum electrode (Pt) in CH 3 CN. 248 Bestmann−Ohira reagents 507 are a class of α-diazoalkylphosphonates used for the synthesis of phosphonylated heterocycles. The group of Namboothiri developed the synthesis of phosphonylpyrazoles 509 by reaction with nitroalkenes 508.…”

“…This oxidant-free and metal catalyst-free cascade, developed by Zhu and co-workers, is carried out under electrochemical conditions (10 mA; anode, glassy carbon (GC); cathode, nickel foam (NF)) to generate the P-radicals from phosphorus oxides 503 in the presence of n -Bu 4 NPF 6 as an electrolyte in DMF at room temperature (Scheme ). This methodology was applied with some modifications for the obtention of 2-phosphonylated isoquinolines 506 by using vinyl isocyanides 505 , K 2 CO 3 as a base and a platinum electrode (Pt) in CH 3 CN …”

“…370 Through a radical phosphonylation with H-phosphites 670 in the presence of catalytic amounts of AgNO 3 , it is possible to perform the direct and regioselective Csp 2 −H functionalization of quinolinones 669 to afford the 3-phosphonylated derivatives 671 in moderate to good yields under mild conditions (Scheme 123). 371 Kamel studied the condensation between 3-phenyl 2,4benzoxazin-1-one 672 with different types of α-phosphonyl carbanions (673, 248,22) in the presence of an excess of LiH in DMF to access phosphono-quinolinones 675−676 and -indoles 677 and 678 in moderate yields (Scheme 124). 372 The mechanism to afford the different products is different, but all of them are initiated by an attack of phosphorus carbanions onto the C�O group in the oxazinones 672 with a subsequent ring-opening.…”

Silver-catalyzed P-centered anion nucleophilic addition to isocyanide: access to 2-phosphinoyl indoles/indol-3-ols

“…Phosphorus-functionalized heterocycles represent a valuable class of scaffolds, widely present in pharmaceuticals, agrochemicals, materials, and ligands. 1 Among these heterocycles, phosphinoylindoles have drawn considerable attention due to their interesting prospects as pharmaceuticals, materials, and ligands (Fig. 1).…”