Pd-catalyzed dehydrogenative cross-coupling of pyridine-N-oxides with uracils

Abstract

A highly efficient protocol for the regioselective dehydrogenative cross-coupling of pyridine-N-oxides with N,N-dialkyl uracils via 2-fold C-H activation has been developed. The resultant uracil substituted pyridine-N-oxide structural motifs is readily deoxygenated, making the present procedure a highly attractive route for the synthesis of 5pyridine substituted uracils.

Palladium-Catalyzed C8-Selective C–H Arylation of Quinoline N-Oxides: Insights into the Electronic, Steric, and Solvation Effects on the Site Selectivity by Mechanistic and DFT Computational Studies

“…8-Substituted quinolines are important structural motifs with applications in the areas of drug discovery, 5 materials science, 6 and catalysis. 7 A significant number of methods exist for catalytic functionalization of unsubstituted quinolines in the C2 position with Pd, 8 , 9 Cu, 10 Ni, 11 Rh, 12 Ru, 13 and Ag 14 as catalysts.…”

“…Since the first report by Fagnou, azine N -oxides have been employed as substrates for a variety of highly C2 selective C–H functionalizations. 9 The original method developed by Fagnou relied on the use of palladium complexes with sterically demanding phosphines (e.g., di- tert -butylphenylphosphine and tri- tert -butylphosphine) as catalysts. Initial mechanistic investigations supported the inner-sphere concerted metalation–deprotonation (CMD) pathway that did not involve precoordination of the N -oxide oxygen atom to palladium.…”

Palladium‐Catalyzed Regioselective Cross‐Dehydrogenative Coupling of Benzofurans with Uracils at Room Temperature

“…Although the mechanism of this reaction has not been established experimentally, on the basis of previous chemistry [12,14] and the high regioselectivity of the reaction (no byproduct resulting from activation of the uracil C6-H bond was observed), a plausible Pd 0 /Pd II mechanism for the cross-coupling reaction is proposed, as shown in Scheme 2. Initially, electrophilic C-H bond activation occurs preferentially at the C5 position of uracil, which leads to the formation of B.…”

“…Recently, we reported the Pd-catalyzed cross-dehydrogenative coupling of pyridine N-oxides with uracils. [12] As part of our ongoing interest in exploring C-C bond…”

Recent advances in the C–H-functionalization of the distal positions in pyridines and quinolines

“…1 However, with numerous C–H-bonds simultaneously available for activation, site-selective functionalization of complex molecules remains a significant challenge. 2 In pyridines, quinolines, and other structurally-related N -heterocycles, the C2 position can be readily functionalized using a variety of transition metal-catalyzed reactions with Pd, 3,4 Cu, 5 Ni, 6 Rh, 7 Ru, 8 Fe, 9 and Ag 10 as catalysts, as well as by means of non-catalytic approaches. 11 The facility of the C2–H-functionalization is due to the favourable electronic factors, e.g.…”