Synthesis of Multideuterated (Hetero)aryl Bromides by Ag(I)-Catalyzed H/D Exchange

Abstract

Deterium-labeled (hetero)­aryl bromide is one of the most widespread applicable motifs to achieve important deuterated architectures for various scientific applications. Traditionally, these deterium-labeled (hetero)­aryl bromides are commonly prepared via multistep syntheses. Herein, we disclose a direct H/D exchange protocol for deuteration of (hetero)­aryl bromides using Ag2CO3 as catalyst and D2O as deuterium source. This protocol is highly efficient, simply manipulated, and appliable for deuterium-labeling of over 55 (hetero)­aryl bromides including bioactive druglike molecules and key intermediates of functional materials. In addition, this method showed distinguishing site-selectivity toward the existing transition-metal-catalyzed HIE process, leading to multideuterated (hetero)­aryl bromides in one step.

Perdeuteration of Deactivated Aryl Halides by H/D Exchange under Superelectrophile Catalysis

“…Efficient transition-metal-catalyzed processes that overcome chemoselectivity issues (e.g., C­(sp 2 )–H versus C­(sp 2 )–F bond activation) have prospered in recent years (Scheme , top, upper reaction path) . While some procedures allow for distinct site-selective C–H isotope labeling, ,, the complete deuteration of arenes deactivated by more than one halogen substituent is usually difficult to achieve . Base-promoted HIE labeling provides an alternative route to deuterated aryl halides .…”

C–H Bond Functionalization of (Hetero)aryl Bromide Enabled Synthesis of Brominated Biaryl Compounds

“…Nevertheless, when compared with fluoride and chloride, the relatively lower electron-withdrawing feature of bromide leads to the lower reactivity of bromoarenes toward C–H activation via the CMD pathway, which is a great challenge for achieving C–H functionalization of bromoarenes. Recently, we reported an efficient H/D exchange reaction of bromoarenes with silver carbonate as catalyst, which indicated the ability of silver salt to promote direct C–H activation of bromoarenes . Herein, we disclose a palladium-catalyzed coupling reaction to construct brominated biaryl compounds from aryl bromide and aryl iodide, which is proposed to proceed via direct C–H arylation of aryl bromide.…”

“…In our previous work, we identified the combination of silver salt and phosphine ligand as a robust catalyst for the H/D exchange process . In addition, to achieve direct C–H arylation of brominated arenes, the oxidative addition between palladium catalyst and C–Br bond should be suppressed.…”

“…Recently, we reported an efficient H/D exchange reaction of bromoarenes with silver carbonate as catalyst, which indicated the ability of silver salt to promote direct C−H activation of bromoarenes. 12 Herein, we disclose a palladium-catalyzed coupling reaction to construct brominated biaryl compounds from aryl bromide and aryl iodide, which is proposed to proceed via direct C−H arylation of aryl bromide.…”

“…In our previous work, we identified the combination of silver salt and phosphine ligand as a robust catalyst for the H/D exchange process. 12 In addition, to achieve direct C−H arylation of brominated arenes, the oxidative addition between palladium catalyst and C−Br bond should be suppressed. Thus, we began our study with 1,4-dibromobenzene and 4iodoanisole as model substrates in the presence of silver salt and a phosphine ligand.…”