AMVN-initiated expedient synthesis of biaryls by the coupling reaction of unactivated arenes and heteroarenes with aryl iodides

Abstract

The role of radical initiators AMVN and AIBN has been studied in the potassium tert-butoxide mediated biaryl coupling reaction of aryl iodides with unactivated arenes. Radical initiator AMVN promoted carbon-carbon bond formation expeditiously from aryl iodide having various groups such as amino, methoxy, fluoro, methyl, and trifluoromethyl and arenes in the presence of potassium tert-butoxide (4 equiv.) at 110 1C in 2-5 h. Substituted arenes such as toluene, xylene, anisole, and fluorobenzene also proceeded to form biaryls under AMVN-initiated reaction conditions. Moreover naphthalene, pyridine, pyrimidine, and pyridazine also coupled with aryl iodides and produced biaryls in 41-82% yields.It seems that AMVN initiates the formation of the aryl radical, which enters the radical chain reaction.The generated aryl radical may combine with the arene leading to a biaryl radical, which upon protonation gives the biphenyl radical anion and tert-butanol. The biphenyl radical anion finally reacts with the aryl iodide generating the aryl radical and thus completes the radical chain reaction with concomitant release of biphenyl.

Enantiospecific Synthesis and Biological Investigations of a Nuphar Alkaloid: Proposed Structure of a Castoreum Component

“…Furthermore, the AMVN ‐initiated reaction of pyridazine ( 60 ) with 4‐iodotoluene gave 4‐( p‐ tolyl)pyridazine in 68% yield together with a trace amount of the 3‐arylated derivative 41. Notably, the direct arylation of the six‐membered heteroarenes 2 , 3 , 38 , 59 and 60 allowed the efficient cross‐coupling of unactivated arenes with aryl iodides and for the latter reactions spectroscopic evidence suggesting the involvement of radical intermediates was obtained 41…”

“…A further protocol for the metal‐free direct arylation of pyridine and other six‐membered nitrogen heteroarenes with aryl iodides was recently described by Sanjit Kumar and co‐workers 41. They reported that the radical initiator ( E )‐2,2′‐azobis(2,4‐dimethylvaleronitrile) ( AMVN ) (Figure 7) is able to efficiently promote the direct arylation of pyridine ( 2 ), pyrimidine ( 3 ), 4‐methoxypyridine ( 38 ), 3‐methylpyridine ( 59 ), and pyridazine ( 60 ) with both electron‐neutral and electron‐rich aryl iodides in the presence of KO‐ t‐ Bu at 110 °C.…”

Green synthesis of new chiral 1-(arylamino)imidazo[2,1-a]isoindole-2,5-diones from the corresponding α-amino acid arylhydrazides in aqueous medium

“…(iii) This clean method afforded compounds 5a – m without the need of additional purification such as column chromatography or recrystallization. (iv) The use of a sealed tube [ 36 – 43 ] obeys to four out of the twelve green chemistry principles: a cleaner and eco-friendly reaction profile with minimum of waste, solvent without negative environmental impact, shorter reaction time and safely work with a pressure tube canning prevent fires and emissions of hazardous compounds and toxic gas. (v) The reaction described in this work occurred with high atom efficiency (atom economy of 90%) and produced only stoichiometric H 2 O as waste (E-factor of 0.1).…”

Tetramethylammonium Fluoride Tetrahydrate-Mediated Transition Metal-Free Coupling of Aryl Iodides with Unactivated Arenes in Air

“…As a pioneering work of biaryl synthesis via radical pathway, in 2008, Itami and colleagues presented a t-BuOK-mediated biaryl coupling of aryl halides and electron-deficient heterocycles involving base-promoted homolytic aromatic substitution (BHAS), in which strong bases acted as a single electron donor to haloarenes, resulting in the generation of aryl radicals. 29) The subsequent works reported that some additives, such as 1,10-phenanthroline, 30,32,40,50) 1,2-dimethylethylenediamine, 31) proline, 37) alcohols, 42,49) p-tolylsulfonyl hydrazide, 44) and urea 51) etc. were effective in the coupling reaction in the presence of an inorganic base (t-BuOK or t-BuONa).…”