Synthesis of Eight‐Membered Nitrogen Heterocycles via a Heterogeneous PtI₂‐Catalyzed Cascade Cycloaddition Reaction of δ‐Aminoalkynes with Electron‐Deficient Alkynes

Abstract

A novel heterogeneous PtI2‐catalyzed cascade reaction of δ‐aminoalkynes was developed for the synthesis of various eight‐membered nitrogen heterocycles in excellent yields. The reaction proceeds via a hydration of δ‐aminoalkynes and subsequent intramolecular cyclization and intermolecular addition as well as ring‐expansion cascade reaction with another electron‐deficient alkynes. This method has the advantages of simple operation and mild reaction conditions. And the simple PtI2 with no any supports could be readily recycled through simple centrifugation without substantial loss of activity in 1,2‐dichloroethane (DCE). The recyclability of PtI2 may be ascribed to its insolubility in DCE. The reaction constitutes a formal [6+2]‐cycloaddition.

Platinum Iodide-Catalyzed Formal Three-Component Cascade Cycloaddition Reactions between γ-Aminoalkynes and Electron-Deficient Alkynes

“…To ascertain the reactivity of the key intermediate 7aa for further transformation, we carried out additional comparative experiments through using similar structural seven- or eight-membered nitrogen heterocyclic compounds 10 and 11 synthesized by our group previously, but unfortunately, these two substrates failed to react with 2a with the compounds 10 and 11 remaining untouched in the presence of 10 mol % PtI 2 at 125 °C for 4 h (Scheme ). The reason might be ascribed to the relatively weak N nucleophilicity of 10 with no methyl group and relatively stable 11 with eight-membered N-heterocycle structure; thus, their reactivity was inferior to that of 7aa .…”

“…To determine whether intermediate 7aa could undergo additional transformations, we carried out some experiments with structurally similar seven- and eight-membered nitrogen heterocycles 10 and 11 , which had previously been synthesized by our group . Unfortunately, these two substrates failed to react with 2a upon treatment with 10 mol % PtI 2 at 125 °C for 4 h (Scheme ).…”

“…In previous work, we reported methods for intermolecular cascade cyclization reactions of β- and δ-aminoalkynes ( n = 1 and 3, respectively) with electron-deficient alkynes, which allowed us to efficiently synthesize pyrrolo- b -cyclobutenes and seven- and eight-membered nitrogen heterocycles, respectively (Scheme ). In an extension of that work, we investigated the reactivity of γ-aminoalkynes ( n = 2), and we herein report the unexpected development of a protocol for PtI 2 -catalyzed formal three-component cascade cyclization reactions between γ-aminoalkynes and electron-deficient alkynes (Scheme ). This cascade reaction mode is completely different from the reaction modes of other aminoalkynes, including other γ-aminoalkynes .…”

Recent advances in cascade reactions and their mechanistic insights: a concise strategy to synthesize complex natural products and organic scaffolds

“…Due to the highly strained skeleton and sterically bulky substituents, intermediate 182 was further easily transformed into the eight-membered nitrogen heterocycle 176 by ring expansion. 92–94 Notably, the highlighted point of this mechanism to showcase the possibility of 177 undergoing a direct intramolecular 6- exo-dig hydroamination cyclization to yield intermediate 179 (path b) cannot be ruled out. This highly efficient cascade reaction afforded a variety of eight-membered nitrogen heterocycles in excellent yields.…”

Catalyst- and Additive-Free Approach to Constructing Benzo-oxazine, Benzo-oxazepine, and Benzo-oxazocine: O Atom Transfer and C═O, C–N, and C–O Bond Formation at Room Temperature

“…Cui and co-workers reported the synthesis of benzo­[ b ]­[1,4]­oxazepines from easily accessible N -(2-haloaryl)­enaminones in which the intramolecular cyclization was promoted by the cesium carbonate and N -methylpyrrolidone. Liu and co-workers developed a heterogeneous PtI 2 -catalyzed cascade reaction of δ-aminoalkynes to afford N- and O-containing eight-membered nitrogen heterocycles. The reaction proceeded via hydration of δ-aminoalkynes followed by subsequent intramolecular cyclization, intermolecular addition, and then ring-expansion cascade reaction with electron-deficient alkynes.…”