Palladium-catalyzed/copper-mediated carbon–carbon cross-coupling reaction for synthesis of 6-unsubstituted 2-aryldihydropyrimidines

Nishimura, Yoshio; Kubo, Takanori; Takayama, Saho; Yoshida, Hanako; Cho, Hidetsura

doi:10.1039/d2ra05155a

Cited by 1 publication

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“…18 We also reported a method for the synthesis of 6-unsubstituted 1-Boc 2-aryl-DPs by Pd-catalyzed/Cu-mediated 2-arylation reaction of 1-Boc 2-methylthio-DPs with arylstannane reagents as a Liebeskind–Srogl-type cross-coupling reaction. 19 20 In the previous study, 20 we also disclosed that pentasubstituted 2-methylthio-1,4-DP 3a and 1,6-DP 4a (R 1 , R 2 , R 3 = Me, R 4 = Et) could be used as precursors for the synthesis of hitherto unavailable fully substituted pentasubstituted 2-aryl-DPs. Based on the results, we investigated in this study the reaction in detail and realized the Pd(PPh 3 ) 4 -catalyzed/CuBr-mediated 2-arylation reaction of 3 and 4 with arylstannane reagents 7 to give 5 and 6 .…”

Section: Table 1 Optimization Of Palladium Catalysts [P...mentioning

confidence: 92%

Fully Substituted Dihydropyrimidines, Pentasubstituted 2-Aryldihydropyrimidines Synthesized by Palladium-Catalyzed/Copper-Mediated Cross-Coupling Reaction

et al. 2023

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Dihydropyrimidines (DPs) show a wide range of biological activities suitable for medicinal applications. Among DP derivatives, 2-aryl-DPs have been reported to display remarkable pharmacological properties. In this work, we describe a method of synthesizing hitherto unavailable fully substituted pentasubstituted 2-aryl-DPs as tautomeric mixture using a Pd(PPh3)4-catalyzed/CuBr-mediated 2-arylation reaction. The reaction using aryl tributylstannanes with various substituents such as MeO, Me, Ph, CF3, CO2Me, and NO2 groups efficiently afforded the corresponding 2-aryl-DPs in high yields. Heteroaryl tributylstannanes having 2-thienyl, 3-thienyl, or 2-pyridinyl groups were also suitable for the reaction. Regarding the substituents at the 4-, 5-, and 6-positions of DPs, the reactions of DPs bearing substituents such as Me, n-C3H7, n-C5H11, -(CH2)5- , phenyl and fluorenylidene groups proceeded smoothly to give the desired products. The synthetic method was also applied to a 2-thioxo-DP to give the 2-aryl-DP. Therefore, the reaction will help expand DP-based molecular diversity, which may impact biological and pharmacological studies.

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Section: Table 1 Optimization Of Palladium Catalysts [P...mentioning

confidence: 92%

Fully Substituted Dihydropyrimidines, Pentasubstituted 2-Aryldihydropyrimidines Synthesized by Palladium-Catalyzed/Copper-Mediated Cross-Coupling Reaction

et al. 2023

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Palladium-catalyzed/copper-mediated carbon–carbon cross-coupling reaction for synthesis of 6-unsubstituted 2-aryldihydropyrimidines

Abstract: This protocol enables the synthesis of 6-unsubstituted 2-aryldihydropyrimidines using various substituents at the 2- and 4-positions, which would impact dihydropyrimidine-based biological and pharmacological studies.

Cited by 1 publication

References 52 publications

Fully Substituted Dihydropyrimidines, Pentasubstituted 2-Aryldihydropyrimidines Synthesized by Palladium-Catalyzed/Copper-Mediated Cross-Coupling Reaction

Fully Substituted Dihydropyrimidines, Pentasubstituted 2-Aryldihydropyrimidines Synthesized by Palladium-Catalyzed/Copper-Mediated Cross-Coupling Reaction

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