Regioselective C3‐Phosphonation of Free Indoles via Transition‐Metal‐Free Radical/Hydrolysis Cascade

Abstract

The selectivity is of great importance for the preparation of molecules in organic chemistry. Herein, a novel method to enable the highly regioselective C3‐phosphonation of free indoles has been developed. This transformation involves a radical and a hydrolysis procedure, and tolerates a range of functional groups, which gives an efficient route toward the 1H‐indol‐3 – ylphosphonic acid monoesters in one step.

Recent Advances in the Construction of Phosphorus‐Substituted Heterocycles, 2009–2019

“…The Cai group reported a transition metal‐free direct C‐3 phosphonation of indoles 275 , which provided the mono‐ester phosphonated indoles 276 from substituted N ‐free, N ‐methyl‐, or N ‐phenylindoles and trialkyl phosphites via a one‐pot radical/hydrolysis process (Scheme ) . Based on control experiments, the author proposed a plausible mechanism where trialkyl phosphites reacted with iodine to give phosphoriodidate species 277 and R−I.…”

Nickel-catalyzed reductive coupling of nitroarenes and phosphine oxides to access phosphinic amides

“…Therefore, there is still a need for the synthesis of phosphinic amides using stable, simple, and readily available starting materials. 3 a ,5 Based on our ongoing studies on organic phosphorus, 6 we hypothesize that nitroarenes, which are widely used and stable chemicals (often as aniline precursors), can be reduced to azobenzenes under reductive conditions. These azobenzenes could then couple with phosphine oxides in the presence of transition metal catalysts to form phosphinic amides.…”

Palladium‐Catalyzed Remote C−H Phosphonylation of Indoles at the C4 and C6 Positions by a Radical Approach

“…[12] Nevertheless, to the best of our knowledge, there is still no method for the phosphonylation onto indole benzenoid core, while the catalytic systems for C2-and C3-positions are wellestablished. [13] In this context, selective installation of phosphorous substituents onto the benzenoid core of indoles would thus be of significant utility. Herein, we report a palladium-catalyzed remote C4-H phosphonylation of indoles with di-tert-butylphosphinoyl as an effective directing group (DG).…”

“…The control experiments revealed that the cooperation between Ag 3 PO 4 and K 2 S 2 O 8 was essential for this transformation (Table 1, entries 10,11). Also, Pd(OPiv) 2 plays an important role in switching selectivity to obtain 4phosphonylated product 3 a as the major regioisomer (Table 1, entries 12,13).…”