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

Abstract

Ru(II)/carboxylate/PPh3 catalyst system enabled the preparation of highly conjugated pyrazine derivatives in water under microwave irradiation. Both nitrogen atoms efficiently dictated cleavage of the ortho-C–H bonds in both benzene rings of 2,3-diphenylpyrazine substrates through chelation assistance. In conformationally more flexible diphenyldihydropyrazine 1, the arylation of four ortho-C–H bonds was possible, while in the aromatic analog 2, the triarylation was the limit.

Carbon–Carbon Bond Forming Reactions in Diazines via Transition-Metal-Catalyzed C–H Bond Activation

“…On the other hand, since diazine motifs are important building blocks in a variety of fields, it is of high interest and urgency to further develop technologies to circumvent the poor reactivity encountered not to mention to address selectivity issues when multiple C-H sites are available for reaction. Interestingly, as diazines are also used as directing groups for C-H functionalizations, [58][59][60][61][62][63][64][65][66][67][68][69][70][71][72][73][74] examples merging this strategy with direct C-H functionalization at the diazine core in a one-pot or cascade manner might be appealing to undertake. 75 With this review, we hope to stimulate the scientific community to developing efficient tools to tackle C-H functionalizations of diazines en route to complex structures.…”

Palladium−Ruthenium Catalyst Complementarity Strengthens Ortho‐Directed C−H Bond Arylation of 2‐Arylpyrazines

“…13 C NMR (101 MHz, CDCl 3 ) δ 154.5, 145. 9,145.7,144.2,142.5,139.3,136.1,132.2,131.0,130.6,130.4,129.8,129.1,118.7,111.1. MS (EI,70 eV) 2'-(3,5'-Bis(trifluoromethyl)-[1,1'-biphenyl]-2-yl)pyrazine 13: Following general Procedure B using 2-phenylpyrazine (234 mg, 1.5 mmol) and 1-bromo-3,5-bis(trifluoromethyl)benzene (293 mg, 1 mmol), the residue was purified by flash chromatography on aluminium oxide (Heptane-EtOAc, 90-10) to afford the desired compound 13 (261 mg, 71 %) as a pale white solid (Mp = 134-136°C): 1 H NMR (400 MHz, CDCl 3 ) δ 8.53 (dd, J = 2.4, 1.6 Hz, 1H), 8.43 (d, J = 2.5 Hz, 1H), 8.30 (d, J = 1.3 Hz, 1H), 7.76 (s, 1H), 7.74-7.69 (m, 1H), 7.63 -7.57 (m, 4H), 7.54-7.49 (m, 1H).…”

“…13 C NMR (101 MHz, CDCl 3 ) δ 158. 9,155.4,152.7,142.3,141.3,140.7,137.5,133.0,130.4,130.0,129.9,129.2,127.3,113.8,55.2,22.0. MS (EI,70 eV) 4, 152.7, 150.1, 142.3, 141.3, 141.0, 137.6, 137.5, 130.1, 130.0, 129.2, 129.0, 127.4, 125.2, 34.5, 31.4, 22.…”

“…In contrast to previously employed directing groups, quinoxaline only promotes ortho mono‐arylation affording the (hetero)biaryl products in moderate to good yields without the formation of bis‐arylated products. In 2020, Požgan and co‐workers described only one example of direct polyarylation of 2,3‐diphenylpyrazine using Ru(II)/carboxylate/PPh 3 as the catalytic system in water under microwave irradiation (Figure 2b) [9] . However, their work focused only on multiple C−H bond functionalizations using a large excess of the aryl bromide (4‐bromoacetophenone).…”

“…In 2020, Požgan and coworkers described only one example of direct polyarylation of 2,3-diphenylpyrazine using Ru(II)/carboxylate/PPh 3 as the catalytic system in water under microwave irradiation ( Figure 2b). [9] However, their work focused only on multiple CÀ H bond functionalizations using a large excess of the aryl bromide (4bromoacetophenone). The reaction was not selective and a mixture of diarylated and tetraarylated products was produced in poor yields.…”