Weiming Chen

An unprecedented nickel-catalyzed tandem reaction involving alkyne hydrocyanation and sequential Thorpe reaction has been developed. By employing readily available and less toxic Zn(CN)2 as the cyanide source, both selective alkyne hydrocyanation and tandem cyclization are achieved in a substrate-controlled manner. Mechanistic studies and DFT calculations confirm that the alkenyl nitrile serves as a key intermediate, and hydrogen transfer is identified as the rate-determining step in the Thorpe reaction. This work offers a novel strategy for the construction of α-cyano-β-naphthylamine via a cascade reaction mode.

Pyridine derivatives are prepared via the dehydrogenative aromatization of 1,4-dihydropyridines (1,4-DHPs). Among these methods, stoichiometric catalysis with high waste and electrochemical oxidation with less productivity are limited in their use. Notably, methyl groups and nitrogen atoms may impose limitations on oxidation. We revealed the efficient strategy via recyclable Lindqvist-type polyoxometalate (POM) (n-Bu₄N)₂[Mo₆O₁₉] and 2,2,6,6-tetramethylpiperidin-1-oxyl (TEMPO) as co-catalysts using the green and economical oxidant hydrogen peroxide. The method applied to the aromatization of a large amount of 1,4-dihydropyridines (1,4-DHPs) incorporating multiple oxidation-prone groups to pyridines with a high conversation rate and selectivity. The Lindqvist-type POM/TEMPO/H₂O₂ ternary catalytic system was verified on a larger scale; meanwhile, after being recycled for six times, the Lindqvist-type POM catalyst could be used for the oxidation without obvious loss in reaction time and isolated yield (up to 90%). The mechanism of the ternary catalytic system was proposed by the control experiments.

A novel metal-free ortho-C–H borylation of 2,5-bis(phenylselanyl)pyridines using BBr3 has been developed. This method affords diverse bis(selenium)boronates with excellent site-selectivity in moderate to excellent yields. Furthermore, the downstream transformation of the resulting boronates provides a convenient route to access functionalized organoseleniums. Given the importance of organoseleniums and the limited availability of existing methods for synthesizing organoselenium boronates, the protocol holds significant value in both synthetic chemistry and medicinal chemistry.

A facile method for the synthesis of stereochemically well-defined ketonyl cysteine compounds has been established. This was achieved via an N-phenylphenothiazine-photocatalyzed, radical-based desulfurative addition, using the in situ-generated tetrafluoropyridyl cysteine derivative from the thiol as a key precursor, which ensures high retention of configuration. Notably, this method features simple operation: the phenothiazine photosensitizer employed in the reaction is inexpensive and readily available in comparison with costly iridium catalysts. It also boasts the advantages of easily accessible starting materials, mild reaction conditions, excellent functional group tolerance, high stereoretention, and good yields, thus exhibiting broad applicability in the modification of complex peptide molecules.

A novel strategy for boron-mediated C-H hydroxylation of 1-phenyl-1H-pyrazoles is presented. The protocol exhibits high efficiency and site exclusivity, offering the corresponding phenols in moderate to excellent yields with wide functional group tolerance under simple and metal-free conditions. Moreover, the hydroxylated products show good derivatization applications. This route provides a convenient and practical way to obtain functionalized 1-phenyl-1H-pyrazoles.

A novel metal-free chemoselective C-H hydroxylation and borylation of N-phenylbenzamides using BBr₃ is described. The protocol generates the corresponding phenols and arylboronic esters in moderate to excellent yields under mild conditions with brilliant chemoselectivity. Additionally, this strategy can be realized in one pot, and several potential bioactive derivatives can be synthesized efficiently. Density functional theory calculations certify that the preferred pathway for this metal-free C-H hydroxylation process is the formation of a five-membered boracycle.

In this study, the key intermediate N¹, N³-disubstituted 1,3,5-triazone of ensitrelvir fumaric acid, approved in Japan for the treatment of SARS-CoV-2 infection under the emergency regulatory approval system, was produced from S-ethylisothiourea hydrobromide and aminomethyl triazole with CDI by four-step telescoped strategy including CDI-activated, condensation, CDI-cyclization, and N¹-alkylation. The strategy with simple conditions and operations had a total yield of 53% on a gram scale. The strategy for synthesizing the key N¹, N³-disubstituted 1,3,5-triazone intermediate of ensitrelvir might provide a new avenue for further research and development of ensitrelvir analogs.