Microwave‐Promoted ortho‐C−H Bond (Hetero)arylation of Arylpyrimidines in Water Catalyzed by Ruthenium(II)−Carboxylate

Abstract

Efficient diarylation of ortho‐C−H bonds of 2‐arylpyrimidines was achieved by Ru(II)−carboxylate‐catalyzed reaction with aryl bromides in water, whereas meta‐substituted phenylpyrimidines selectively led to monoarylation. The reaction is strongly accelerated under microwave irradiation, and is compatible with various functional groups on both coupling partners. As established from Hammett plots, electron‐withdrawing groups on the pyrimidine substrates facilitate the arylation, while both, electron‐withdrawing and electron‐donating groups on the aryl bromides lead to a faster reaction. The C−H functionalization of 2‐arylpyrimidines with heteroaryl halides provides potential multidentate ligands.

Catalyst‐Free Synthesis of Few‐Layer Graphdiyne Using a Microwave‐Induced Temperature Gradient at a Solid/Liquid Interface

“…[ 34 ] Reaction rates and yields can be dramatically enhanced using microwave radiation as a heat source. [ 35 ] However, no catalyst was used in our approach, and the activation of the terminal CH bonds in the HEB monomers and the coupling of alkyne bonds between HEB molecules at the NaCl surfaces are both likely to be facilitated by microwaves.…”

Conformationally Driven Ru(II)-Catalyzed Multiple ortho-C–H Bond Activation in Diphenylpyrazine Derivatives in Water: Where Is the Limit?

“…We initiated our study by the reaction of 5,6-diphenyl-2,3-dihydropyrazine (1) with 4-bromoacetophenone as sterically non-demanding arylating agent, using the methodology for microwave-promoted Ru(II)-catalyzed arylation of 2-phenylpyrimidines in water developed within our group [37]. Due to the presence of the four ortho-C-H bonds in diphenylpyrazine 1, up to four arylations were expected.…”

“…Even though we intended to directly apply the previously established catalytic conditions [37] for the present arylation of dihydropyrazine substrate 1, the effect of base, solvent, ligands, and temperature was briefly investigated under conventional heating (see Supplementary Materials Supporting Information). The system comprising [RuCl 2 (p-cymene)] 2 /1-phenylcyclopentane-1-carboxylic acid (PCCA)/PPh 3 together with a large excess of K 3 PO 4 base has once again proven to be a catalyst system of choice, since quantitative conversions of 1 with four.equivalents of 4-bromoacetophenone into arylated pyrazine products in satisfactory diarylation selectivities were attained in water at 140 • C after 24 h. In order to shorten reaction times and to suppress aromatization of starting dihydropyrazine 1 and its arylated products, the reactions were performed in water under microwave (MW) heating conditions.…”

“…A great number of them are based on nitrogen as the metal-coordinating atom, the pyridine ring being prevalent, although other azaheterocycles, such as pyrazole, oxazoline, and quinoline have also been successfully employed in transition-metal-catalyzed ortho-C-H bond functionalization [33]. Požgan and co-workers have demonstrated that the quinazolinyl [34,35] and pyrimidinyl [36] groups efficiently allow regioselective ortho-arylations in the presence of Ru(II)-carboxylate catalyst, even in water as the solvent in some cases [37,38]. The success of Ru(II) catalysts is most likely ascribed to the easy formation of ruthenacyclic intermediate stable in water via C-H bond deprotonation with the assistance of directing groups [35,37,[39][40][41][42][43].…”

“…For these reasons, many synthetic methods for the construction of pyrazine derivatives have been developed [58][59][60][61][62][63], yet there is still great demand for the generation of novel pyrazine libraries. As a part of our ongoing interest in metal-catalyzed functionalization of (hetero)arenes via C-H bond activation [34][35][36][37][38], we reasoned that a pyrazine nucleus could direct cleavage and further functionalization of ortho-C-H bonds of the benzene ring in phenyl-substituted pyrazines. Moreover, by using 2,3-diphenylpyrazines as substrates, both nitrogen atoms could cooperate with the catalytic metal center to hypothetically promote four ortho-C-H bond activations, thus enabling the construction of highly functionalized, especially arylated or π-conjugated pyrazine derivatives.…”