Cu‐Catalyzed Hydrophosphonylation of 2‐(2‐Enynyl)pyridines: Easy Access to Indolizine‐Containing Diarylmethylphosphonates

Abstract

A competent method for the synthesis of indolizine‐based diarylmethylphosphonates is described. This protocol involves a metal‐catalyzed 5‐endo‐dig‐cyclization of 2‐(2‐enynyl)pyridine derivatives followed by a remote addition of diarylphosphites to provide indolizine‐containing diarylmethylphosphonates in good yields.

Synthesis of Indolizine‐Containing Diaryl‐ and Triarylmethanes through a Cu‐Catalyzed Domino Cyclization of 2‐(2‐Enynyl)pyridines

“…Based on the outcome of the reaction and our previous observation, a plausible mechanism for this transformation has been proposed (Scheme ). Initially, the alkyne moiety of 5 a is activated by Cu, and the subsequent 5‐ endo ‐ dig cyclization of complex I leads to intermediate II, which, on abstraction of a proton from the nucleophile (Hantzsch ester or 2‐naphthol) generates intermediate III.…”

“…Another interesting protocol, involving a metal‐catalyzed 5‐ endo ‐ dig cyclization of 2‐(2‐enynyl)pyridines, has been developed for the synthesis of substituted indolizines . A similar strategy has been recently adopted by our group for the synthesis of diarylmethylphosphonates, through a Cu‐catalyzed 5‐ endo ‐ dig cyclization of 2‐(2‐enynyl)pyridines followed by the remote addition of diarylphosphites …”

Heteroarene‐tethered Functionalized Alkyne Metamorphosis

“…Later in 2017, Anand and Mahesh reported a very similar synthesis of diarylmethylphosphonate containing indolizines 607 by using 10 mol % CuI in DCE at 70 °C (Scheme 153). [176] Very recently Anand and co‐workers summarized Ag‐catalyzed sequential double cyclization‐nucleophilic addition cascade synthesis of triaryl methane derivatives. Starting with 2‐alkynylanile, in situ generation of indole followed by Ag‐catalyzed indolizine formation and nucleophilic indole addition yielded the desired product [177] …”

Facile synthesis of indolizines using layered double hydroxides@poly(p‐phenylenediamine) as a catalyst with a green tool (neat technology)

“…In the work reported here, we aimed at synthesizing LDHs@PpPDA catalyst (Figure ) using the emulsion polymerization method and also investigating the formation of indolizine compounds. The importance and strong demand for these heterocycles are because of their versatile photochemical features and biological activities . The activation of indolizine in many natural and synthetic pharmaceutically active compounds is considered as a special heterocyclic nucleus .…”

“…The importance and strong demand for these heterocycles are because of their versatile photochemical features and biological activities. [28][29][30][31][32] The activation of indolizine in many natural and synthetic pharmaceutically active compounds is considered as a special heterocyclic nucleus. [33,34] Indolizines, as a vital class of N-heterocycles with 10 π-delocalized electrons, have received much attention due to their molecular structure and important biological activities.…”