Switching the Regioselectivity of Direct C–H Arylation of 1,3‐Dimethyluracil

Abstract

An interesting dichotomy in the regioselectivity and mechanism of direct C–H arylation of 1,3‐dimethyluracil was observed. Its Pd‐catalyzed reactions with diverse aryl halides in the absence of CuI lead preferentially to 5‐aryluracils, while reactions in the presence of CuI give 6‐aryl derivatives as the major products. Cu‐mediated reactions (in the absence of a Pd catalyst) proceed with lower efficiency but give exclusively 6‐aryluracil derivatives. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)

Dehydrogenative alkenylation of uracils via palladium-catalyzed regioselective C–H activation

“…11 Direct C–H arylation, 12 acetoxylation, 13 trifluoromethylation, 14 and dimerization 15 of uracils have been reported by Pd-catalysis. In contrast, C–H alkenylation of uracils has been typically achieved using stoichiometric amounts of Pd.…”

Modification of Purine and Pyrimidine Nucleosides by Direct C-H Bond Activation

“…Thus, arylation in the presence of Pd(OAc) 2 and Cs 2 CO 3 mainly formed the 5-arylated uracil analogues 66 , while coupling in the presence of Pd catalyst and CuI (3 equiv.) preferentially formed the 6-arylated derivatives 67 (Scheme 22) [57,58]. Interestingly, Cu-mediated arylation in the absence of Pd catalyst gave exclusively 6-aryluracils 67 albeit in lower yields.…”

“…In order to prepare the unprotected uracil derivatives, these protocols were also applied to N -benzyl protected uracil derivatives. Subsequent debenzylation (e.g., 67 , R = Bn) afforded efficiently 5- or 6-aryled uracil derivatives [57,58]. The experimental results indicated that different mechanisms are involved in these diverse arylation reactions [57,58].…”

Pd-Catalyzed Dehydrogenative Cross-Coupling of 1,4-Quinones with N,N′-Dialkyluracils

“…Pd-catalyzed and/or Cu-mediated direct C-H arylations of 1,3-dimethyluracil with diverse electron-rich aryl halides was reported in 2009. [16] Synthesis of 5-and 6-aryluracil bases based on direct C-H arylations of diverse 1,3-protected uracils was reported by Hocek et al in 2011. [17] Direct alkenylation of 4H-pyrido [1,2-a]pyrimidin-4-ones via palladium-catalyzed C-H activation was developed by Cao and co-workers.…”

“…Ethyl acetate gave the best yield while solvents such as 1,4-dioxane, acetonitrile, and toluene afforded moderate yields of the product. NMP, DMAc, and t-amyl alcohol (t-AmOH) afforded poor results (Table 1, entries [13][14][15][16][17][18][19][20][21][22][23][24].…”