Potassium t-Butoxide Alone Can Promote the Biaryl Coupling of Electron-Deficient Nitrogen Heterocycles and Haloarenes

Abstract

The biaryl coupling of electron-deficient nitrogen heterocycles and haloarenes can be promoted by potassium t-butoxide alone, without the addition of any exogenous transition metal species. Electron-deficient nitrogen heterocycles such as pyridine, pyridazine, pyrimidine, pyrazine, and quinoxaline are arylated with haloarenes. Control experiments support a radical-based mechanism. Taking these findings into account, radical processes may be partially involved in the reported transition-metal-catalyzed arylation reactions employing t-butoxide bases and haloarenes under elevated temperatures or under microwave irradiation.

Reductive Cleavage of C—O Bond in Model Compounds of Lignin

“…[32][33][34] The KO t Bu-mediated reduction of diaryl ethers and alkyl aryl ethers by NaH in this work maybe follow the similar SET mechanism as well. To verify this hypothesis, several preliminary experiments were conducted.…”

Toward Ideal Arene Assembly: Catalytic C-H Bond Arylation of Aromatic Compounds

“…Finally, a quantitative elemental analysis of KOt Bu was conducted by ICP AES (Inductively Coupled Plasma Atomic Emission Spectrometry). 21 Though very low in concentration, the most abundant exogenous elements found to be present in the KOt Bu used in this study were Si (0.92 ppm), Al (0.38 ppm), and Ca (0.048 ppm). More importantly, no transition metal was present at over 0.50 ppm in the KOt Bu employed in our study.…”

“…Struck by the similarity of reactions employing dramatically distinct Ir sources, we carried out the coupling reaction in the absence of Ir and remarkably found that the coupling reaction proceeded to the same extent with KOt Bu as the sole reagent. 21 With these unexpected results in hand, we further examined the reaction conditions using pyrazine as a substrate (Scheme 9). 21 When a mixture of pyrazine (40 equiv), iodobenzene (1.0 equiv), and KOt Bu (1.5 equiv) was stirred in the dark at 120 for 13 h, C H bond phenylation took place to afford 2 phenylpyrazine in 79% yield.…”

“…21 With these unexpected results in hand, we further examined the reaction conditions using pyrazine as a substrate (Scheme 9). 21 When a mixture of pyrazine (40 equiv), iodobenzene (1.0 equiv), and KOt Bu (1.5 equiv) was stirred in the dark at 120 for 13 h, C H bond phenylation took place to afford 2 phenylpyrazine in 79% yield. Under microwave irradiation, a quantitative coupling occurred after 5 min at 50 .…”

“…24 While other mechanisms cannot be rigorously excluded, the radical nature of the present reaction was supported by control experiments performed in the presence of radical scavengers (Scheme 11). 21 For example, the addition of 2,2,6,6 tetramethylpiperidine 1 oxyl (TEMPO), galvinoxyl, or acrylonitrile to the reaction of pyrazine, iodobenzene, and KOt Bu completely shut down the otherwise effi cient biaryl coupling. Furthermore, we observed the formation of 2 cyclohexylpyrazine when the reaction was conducted in the presence of cyclohexane (Scheme 11).…”