TMSBr-Promoted Cascade Cyclization of ortho-Propynol Phenyl Azides for the Synthesis of 4-Bromo Quinolines and Its Applications

Abstract

Difficult-to-access 4-bromo quinolines are constructed directly from easily prepared ortho-propynol phenyl azides using TMSBr as acid-promoter. The cascade transformation performs smoothly to generate desired products in moderate to excellent yields with good functional groups compatibility. Notably, TMSBr not only acted as an acid-promoter to initiate the reaction, and also as a nucleophile. In addition, 4-bromo quinolines as key intermediates could further undergo the coupling reactions or nucleophilic reactions to provide a variety of functionalized compounds with molecular diversity at C4 position of quinolines.

Recent Advances in the Synthesis of Heterocyclics via Cascade Cyclization of Propargylic Alcohols

“…This cascade cyclization proceeded smoothly in moderate to excellent yields with a wide variety of functional groups under mild conditions. Moreover, the corresponding 4‐bromo and 4‐iodo quinolines were also obtained in good yields in the presence of TMSBr and TMSI, respectively [93] . Notably, the obtained 4‐halo quinolines could be further derived to various other functionalized quinolines through palladium‐catalyzed cross‐couplings and nucleophilic substitutions.…”

Synthesis of Six-Membered Spiro Azacyclic Oxindole Derivatives via a One-Pot Process of Umpolung Allylation/Aza-Prins Cyclization

“…Finally, the intermediates I and I ′ transform into the desired products II and II ′ through aza-Prins cyclization in the presence of H 2 O and TMSBr. Remarkably, water does not react with intermediates I and I ′ as a nucleophile; thus, we assume that water either solubilizes the iminium bromide generated from DBU to prevent whatever hampers the reaction or activates TMSBr to accelerate aza-Prins cyclization . Furthermore, preliminary studies have shown that chiral phosphine ligands, such as ( R )-BINAP, affect the desymmetrization of 1a with promising levels of enantioselectivity (Scheme b, 19% enantiomeric excess (ee)).…”

“…Remarkably, water does not react with intermediates I and I′ as a nucleophile; thus, we assume that water either solubilizes the iminium bromide generated from DBU to prevent whatever hampers the reaction 22 or activates TMSBr to accelerate aza-Prins cyclization. 23 Furthermore, preliminary studies have shown that chiral phosphine ligands, such as (R)-BINAP, affect the desymmetrization of 1a with promising levels of enantioselectivity (Scheme 4b, 19% enantiomeric excess (ee)). This result suggests that umpolung allylation/aza-Prins cyclization is amenable to an asymmetric catalysis system, and this research is underway.…”

Modern Strategies for Heterocycle Synthesis

“…A publication on a TMSBr-promoted cascade cyclization of ortho-propynol phenyl azides for the synthesis of 4-bromo quinolines is reported by Xiao and his group [18]. Moreover, a variety of functionalized compounds with molecular diversity at C4 position of quinolines are obtained through the subsequent coupling or nucleophilic reactions.…”