Nickel-Assisted Carbon-Fluorine Bond Activation of 2,4,6-Trifluoropyrimidine: Synthesis of New Pyrimidine and Pyrimidinone Derivatives

Abstract

Rapid and regioselective activation of the C-F bond of 2,4,6-trifluoropyrimidine occurs on reaction with [Ni(cod)(2)] (cod=1,5-cyclooctadiene) in the presence of PEt(3) to give 1, which can be converted into complex 2, containing a further N(3)-metalated pyrimidin-4-one unit. The novel pyrimidin-4-one 3 is released on protonation of 2.

Synthesis and reactivity of rhodium fluoro complexes

“…The 19 F NMR spectrum at 223 K shows two signals at characteristic chemical shifts at d À176.4 ppm for the distal fluorine and at d À278.3 ppm for the proximal fluorine (Fig. 3)[14,15,25,[32][33][34][35][36][37][38]. The latter signal reveals a coupling of %175 Hz to a phosphorus nucleus.…”

“…We have, for instance, been developing a route to nickel fluoro complexes by C-F activation of aromatic molecules [10,[22][23][24][25][26]. Some of these fluoro compounds exhibit a distinctively different reactivity compared with their chloro analogues [22,25,26]. Other typical routes to fluoro complexes involve direct fluorination reactions at hydroxo, chloro or hydrido precursors using appropriate fluorination reagents [1][2][3][4]8,[14][15][16][17][18][19][20][21].…”

“…However, the sometimes exceptional chemistry [1][2][3][4][10][11][12][13][14] of coordination compounds bearing fluoro ligands implies, in turn, the requirement of innovative synthetic methods for their preparation [1][2][3][4]8,[13][14][15][16][17][18][19][20][21]. We have, for instance, been developing a route to nickel fluoro complexes by C-F activation of aromatic molecules [10,[22][23][24][25][26]. Some of these fluoro compounds exhibit a distinctively different reactivity compared with their chloro analogues [22,25,26].…”

“…The distal fluorine appears as a broad doublet of doublets with a coupling J FF ¼ 116 Hz and J FH ¼ 386 Hz. The latter value indicates a comparable HF interaction as in the vinylidene compound trans-[Rh(FHF)(¼C¼CHPh)(PiPr 3 ) 2 ] and other bifluoride complexes of Ni, Pd, Pt and W, which possess a more loosely bound HF molecule at the metal-fluoride[14,15,25,[32][33][34][35][36][37][38]. In contrast, ruthenium bifluoride compounds exhibit a stronger interaction within the bifluoride ligand[35][36][37].Treatment of a solution of [RhF(PEt 3 ) 3 ] (5) with hydrogen affords the oxidative addition product cis-mer-[Rh(H) 2 -F(PEt 3 ) 3 ]…”

Palladium mediated activation of C–F bonds in 2,4,6-trifluoropyrimidine: Synthesis and structure of palladium pyrimidyloxy and pyrimidinone derivatives

“…In an alternative reaction pathway the generated HF gives fluoro complexes [7]. At nickel the transformation of a carbon-fluorine bond of a fluorinated pyrimidine into a carbon-oxygen bond yielding a nickel pyrimidinone derivative has been reported [8]. Remarkably, the conversion provides access to a fluorinated pyrimidinone, which cannot be prepared selectively by any other means.…”