A 2-pyridone ring is a frequently occurring subunit in natural products, biologically active compounds, and pharmaceutical targets. Thus, the selective synthesis of substituted 2-pyridone derivatives ...through decoration and/or formation of pyridone rings has been one of the important longstanding subjects in organic synthetic chemistry. This minireview focuses on recent advances in site-selective C-H functionalization on 2-pyridone. The reported procedures are categorized according to the site selectivity that is achieved, and the substrate scope, limitations, mechanism, and controlling factors are briefly summarized.
This minireview focuses on recent advances in site-selective C-H functionalization on 2-pyridone which is an important heterocyclic motif in medicinal and pharmaceutical chemistry.
A Cu-catalyzed intramolecular C–H amination for the synthesis of carbazoles has been developed. The key to success is the installation of the picolinamide-based directing group, which is ...spontaneously removed after the coupling event. The Cu catalysis proceeded smoothly under Pd- and I(III)-free conditions, and its mild oxidation aptitude enables the rapid and concise construction of heteroatom-incorporated carbazole core π-systems.
Indoles and their analogues have been one of the most ubiquitous heterocycles during the past century, and extensive studies have been conducted to establish practical synthetic methods for their ...derivatives. In particular, selective functionalization of the poorly reactive benzenoid core over the pyrrole ring has been a great challenge. Reported herein is an iridium‐catalyzed direct alkynylation of the indole C4‐ and C7‐positions with the assistance of sulfur directing groups. This transformation shows a wide range of functional‐group tolerance with exceptional site selectivity. The directing group can be either easily removed or transformed after catalysis. The synthetic utility of the alkyne fragment is demonstrated by the derivatization into the core structure of natural indole alkaloids.
S‐directed: An iridium‐catalyzed direct alkynylation for the indole C4‐ and C7‐positions was achieved with the assistance of sulfur directing groups. The transformation shows broad functional‐group tolerance with complete site selectivity, and the directing group can be either easily removed or transformed after the reaction.
Hot couple: A precious‐metal‐free copper‐mediated intermolecular direct biaryl coupling of benzoic acid derivatives and 1,3‐azoles has been developed. The key to success is the installation of an ...amide‐based bidentate coordinating group, which is easily removed and transformed into the parent ester groups after the coupling reaction. Kinetic studies indicate that the rate‐limiting step is the aromatic CH bond cleavage of benzoic acid derivatives.
The iridium-catalyzed dehydrogenative cyclization of 2-aminobiphenyls proceeds smoothly in the presence of a copper cocatalyst under air as a terminal oxidant through intramolecular direct C–H ...amination to produce N-H carbazoles. A similar iridium/copper system can also catalyze the unprecedented dimerization reaction of 2-aminobiphenyl involving 2-fold C–H/N–H couplings.
Benzophosphole construction was achieved through the AgI‐mediated dehydrogenative annulation of phenylphosphine oxides with internal alkynes in a process involving CC and CP bond formation. A wide ...range of asymmetrical phenylacetylenes could be employed and the reactions proceeded with perfect regioselectivity. Moreover, the annulation could be conducted even at room temperature when a MnIII promoter was used in place of AgI.
A Lewis base catalyst Trip-SMe (Trip = triptycenyl) for electrophilic aromatic halogenation using N-halosuccinimides (NXS) is introduced. In the presence of an appropriate activator (as a ...noncoordinating-anion source), a series of unactivated aromatic compounds were halogenated at ambient temperature using NXS. This catalytic system was applicable to transformations that are currently unachievable except for the use of Br2 or Cl2: e.g., multihalogenation of naphthalene, regioselective bromination of BINOL, etc. Controlled experiments revealed that the triptycenyl substituent exerts a crucial role for the catalytic activity, and kinetic experiments implied the occurrence of a sulfonium salt Trip-S(Me)BrSbF6 as an active species. Compared to simple dialkyl sulfides, Trip-SMe exhibited a significant charge-separated ion pair character within the halonium complex whose structural information was obtained by the single-crystal X-ray analysis. A preliminary computational study disclosed that the π system of the triptycenyl functionality is a key motif to consolidate the enhancement of electrophilicity.
A new bronze age: The described copper‐mediated cross‐coupling with double CH activation can provide a convergent access to indole‐containing biheteroaryls that are of high interest in ...pharmaceutical and medicinal chemistry. In this strategy an easily attachable and detachable 2‐pyrimidyl directing group is used. Moreover, a variant that is catalytic in copper is achieved by using atmospheric oxygen as an ideal co‐oxidant (see scheme).
A metal-free electrophilic phosphination reaction has been developed. Electrophilic phosphorus species generated in situ from secondary phosphine oxides and Tf2O smoothly couple with alkynes ...possessing pendant nucleophiles to afford the corresponding phosphinated cyclization products in good yield. Preliminary NMR studies show that phosphirenium species may be involved as intermediates of the cyclization reactions.
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