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

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• 作者：Yong Liang ; Jennifer Gloudeman ; Stanislaw F. Wnuk
• 刊名：Journal of Organic Chemistry
• 出版年：2014
• 出版时间：May 2, 2014
• 年：2014
• 卷：79
• 期：9
• 页码：4094-4103
• 全文大小：415K
• 年卷期：v.79,no.9(May 2, 2014)
• ISSN：1520-6904

文摘

The 1-N-benzyl-5-iodo(or bromo)uracil undergoes Pd-catalyzed [Pd₂(dba)₃] direct arylation with benzene and other simple arenes in the presence of TBAF in DMF without the necessity of adding any ligands or additives to give 5-arylated uracil analogues. The TBAF-promoted coupling also occurs efficiently with electron rich heteroarenes at 100 掳C (1 h) even with only small excess of heteroarenes. The protocol avoids usage of the arylboronic acid or stannane precursors for the synthesis of 5-(2-furyl, or 2-thienyl, or 2-pyrrolyl)uracil nucleosides, which are used as important RNA and DNA fluorescent probes. The fact that 1-N-benzyl-3-N-methyl-5-iodouracil did not undergo the TBAF-promoted couplings with arenes or heteroarenes suggests that the C4-alkoxide (enol form of uracil) facilitates coupling by participation in the intramolecular processes of hydrogen abstraction from arenes. TBAF-promoted arylation was extended into the other enolizable heterocyclic systems such as 3-bromo-2-pyridone. The 蟺-excessive heteroarenes also coupled with 5-halouracils in the presence of Pd(OAc)₂/Cs₂CO₃/PivOH combination in DMF (100 掳C, 2 h) to yield 5-arylated uracils.