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

Abstract

A regioselective Pd-catalyzed cross-dehydrogenative coupling between uracils and alkenes is reported. This protocol provides easy access to a variety of 5-alkenyluracil structural motifs.

Palladium-Catalyzed Direct Arylation of 5-Halouracils and 5-Halouracil Nucleosides with Arenes and Heteroarenes Promoted by TBAF

“…6 The arylation and heteroarylation of the uracil ring at the 5 position have been accomplished efficiently using Suzuki, 7 Stille, 8 and other coupling reactions. 1 The 5-(2-furyl)uridine and 5-(2-thienyl)-2′-deoxyuridine analogues, which were prepared in these ways, have been incorporated into RNA and DNA fragments using solid support and used as fluorescent probes.…”

2,3-Dihydropyridin-4(1H)-ones and 3-Aminocyclohex-2-enones: Synthesis, Functionalization, and Applications to Alkaloid Synthesis

“…34 Although C5 alkenylation had been reported previously in the context of biological investigations on uracil derivatives, preactivated uracils and metalated alkenes were used in most cases. 35,36 With the aim of streamlining these inefficient processes, we developed a direct dehydrogenative coupling, based on results from our enaminone chemistry.…”

“…The key additives were silver(I) acetate, which acts as an effective palladium oxidant, and pivalic acid, which presumably lowers the energy of the transition state and facilitates palladation of the uracil. 34 We examined the scope of this reaction with various olefins (Scheme 38) and various 1,3-disubstituted uracils 4.121 (Scheme 39).…”

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

“…[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. [18] Also, Pd-catalyzed cross-dehydrogenative coupling between uracils and alkenes has been reported recently [19] (Scheme 1). This protocol also includes a single example of a reaction between uracil and benzoquinone.…”

“…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].…”