C2-Selective, Functional-Group-Divergent Amination of Pyrimidines by Enthalpy-Controlled Nucleophilic Functionalization

Ham, Won Seok; Choi, Hoonchul; Zhang, Jianbo; Kim, Dongwook; Chang, Sukbok

doi:10.1021/jacs.1c13373

Cited by 23 publications

(19 citation statements)

References 101 publications

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“…Continuing our efforts to develop transition-metal-free amino group transfer reactions, − the designed amidation of phenylboronic acid 2a was commenced by first testing the compatibility of hydroxamates 1a and 1b (Scheme ). While N–O-type amino reagents have been established highly effective for the transition-metal-free C(aryl)–N bond formation by borate 1,2-aryl migration, , the amide versions are absent in the relevant mechanistic framework.…”

Section: Resultsmentioning

confidence: 99%

Photoinduced Transition-Metal-Free Chan–Evans–Lam-Type Coupling: Dual Photoexcitation Mode with Halide Anion Effect

et al. 2022

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Herein, we report a photoinduced transition-metal-free C(aryl)−N bond formation between 2,4,6-tri(aryl)boroxines or arylboronic acids as an aryl source and 1,4,2-dioxazol-5-ones (dioxazolones) as an amide coupling partner. Chloride anion, either generated in situ by photodissociation of chlorinated solvent molecules or added separately as an additive, was found to play a critical cooperative role, thereby giving convenient access to a wide range of synthetically versatile N-arylamides under mild photo conditions. The synthetic virtue of this transition-metalfree Chan−Evans−Lam-type coupling was demonstrated by large-scale reactions, synthesis of 15 N-labeled arylamides, and applicability toward biologically relevant compounds. On the basis of mechanistic investigations, two distinctive photoexcitations are proposed to function in the current process, in which the first excitation involving chloro-boron adduct facilitates the transition-metal-free activation of dioxazolones by single electron transfer (SET), and the second one enables the otherwise-inoperative 1,2-aryl migration of the thus-formed N-chloroamido-borate adduct.

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Section: Resultsmentioning

confidence: 99%

Photoinduced Transition-Metal-Free Chan–Evans–Lam-Type Coupling: Dual Photoexcitation Mode with Halide Anion Effect

et al. 2022

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“…The Chang laboratory developed an interesting method to selectively aminate the C–H bond at the 2-position of pyrimidines (Scheme A) . They converted pyrimidines into their corresponding N -oxides and then added Tf 2 O to form pyrimidinium N -OTf salts as activated Int 7 .…”

Section: Reactions Via Dearomatized Intermediatesmentioning

confidence: 99%

Late-Stage C–H Functionalization of Azines

2023

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Azines, such as pyridines, quinolines, pyrimidines, and pyridazines, are widespread components of pharmaceuticals. Their occurrence derives from a suite of physiochemical properties that match key criteria in drug design and is tunable by varying their substituents. Developments in synthetic chemistry, therefore, directly impact these efforts, and methods that can install various groups from azine C−H bonds are particularly valuable. Furthermore, there is a growing interest in late-stage functionalization (LSF) reactions that focus on advanced candidate compounds that are often complex structures with multiple heterocycles, functional groups, and reactive sites. Because of factors such as their electron-deficient nature and the effects of the Lewis basic N atom, azine C−H functionalization reactions are often distinct from their arene counterparts, and the application of these reactions in LSF contexts is difficult. However, there have been many significant advances in azine LSF reactions, and this review will describe this progress, much of which has occurred over the past decade. It is possible to categorize these reactions as radical addition processes, metal-catalyzed C−H activation reactions, and transformations occurring via dearomatized intermediates. Substantial variation in reaction design within each category indicates both the rich reactivity of these heterocycles and the creativity of the approaches involved.

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“…Recently, Chang and co‐workers described an efficient C−H amination of pyrimidines to access complex aminopyrimidines with high selectivity (Scheme 12). [34] The reaction process initiated with catalytic oxidation of pyrimidine to its N ‐oxide species and followed by activation with triflic anhydride to give N ‐triflyloxypyrimidinium intermediate, which reacted with the amination reagents could result in the formation of pyrimidine‐2‐iminium salts 51 or 52 . Various amine products were then achieved after treatment with different reagent.…”

Section: Electrophilic Activation Of Nitrogen‐containing Heterocycles...mentioning

confidence: 99%

Recent Applications of Trifluoromethanesulfonic Anhydride in Organic Synthesis

Cheng

Jiao

2023

Angewandte Chemie

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Trifluoromethanesulfonic anhydride has been widely used in synthetic organic chemistry, not only for the conversion of various oxygen‐containing compounds to the triflates, but also for the electrophilic activation and further conversion of amides, sulfoxides, and phosphorus oxides. In recent years, the utilization of Tf2O as an activator for nitrogen‐containing heterocycles, nitriles and nitro groups has become a promising tool for the development of new valuable methods with considerable success. In addition, Tf2O has been used as an efficient radical trifluoromethylation and trifluoromethylthiolation reagent due to the contained SO2CF3 fragment, and significant progress has been made in this area. This review summarizes the recent progress in the applications of Tf2O in the above two aspects, and aims to illustrate the role and potential application of this reagent in organic synthesis.

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C2-Selective, Functional-Group-Divergent Amination of Pyrimidines by Enthalpy-Controlled Nucleophilic Functionalization

Cited by 23 publications

References 101 publications

Photoinduced Transition-Metal-Free Chan–Evans–Lam-Type Coupling: Dual Photoexcitation Mode with Halide Anion Effect

Photoinduced Transition-Metal-Free Chan–Evans–Lam-Type Coupling: Dual Photoexcitation Mode with Halide Anion Effect

Late-Stage C–H Functionalization of Azines

Recent Applications of Trifluoromethanesulfonic Anhydride in Organic Synthesis

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