C–H Bonds as Ubiquitous Functionality: Preparation of Multiple Regioisomers of Arylated 1,2,4-Triazoles via C–H Arylation

We describe a general approach for the synthesis of complex aryl 1,2,4-triazoles. The electronic character of the C–H bonds and the triazole ring allows for the regioselective C–H arylation of 1-alkyl- and 4-alkyltriazoles under catalytic conditions. We have also developed the SEM and THP switch as well as trans-<i>N</i>-alkylation, which enable sequential arylation of the triazole ring to prepare 3,5-diaryltriazoles. This new strategy provides rapid access to a variety of arylated 1,2,4-triazoles and well complements existing cyclization methods

Direct C–H Alkenylation of Functionalized Pyrazoles

We have developed inter- and intramolecular C–H alkenylation reactions of pyrazoles. The catalyst, derived from Pd­(OAc)₂ and pyridine, enabled the oxidative alkenylation of pyrazoles containing a variety of functional groups at the C4 position. Activated alkenes, including acrylate, acrylamide, and styrene derivatives, and enamides could be installed in this process. The sequential C–H alkenylation and cyclization reactions gave rise to fused bicyclic pyrazoles, providing a new strategy to annulate readily available pyrazole compounds

Catalytic C–H Allylation and Benzylation of Pyrazoles

We describe a general approach for the synthesis of allylated and benzylated pyrazoles. An electron-withdrawing substituent, such as nitro, chloro, and ester groups, at C4 renders the Lewis basic nitrogen atom to be less basic and the C–H bond more acidic than the ones of the parent ring, enabling Pd-catalyzed C–H allylation and benzylation reactions of pyrazoles. The new method expanding the scope of the C–H functionalization of pyrazoles beyond arylation reactions provides a rapid access to complex pyrazole compounds

Synthesis of Fluorescent Indazoles by Palladium-Catalyzed Benzannulation of Pyrazoles with Alkynes

The synthesis of indazoles from pyrazoles and internal alkynes is described. Instead of complex benzenoid compounds, readily available pyrazoles were used for the preparation of indazoles by reaction of the C–H bonds of the heterocyclic ring. Oxidative benzannulation was also applied to imidazoles, providing benzimidazoles. This convergent strategy enabled alteration of the photochemical properties of benzo-fused diazoles by varying the substituents at the benzene ring, thus leading to the development of tetraarylindazoles as new fluorophores

Immunosensor Employing Stable, Solid 1‑Amino-2-naphthyl Phosphate and Ammonia-Borane toward Ultrasensitive and Simple Point-of-Care Testing

Biosensors for ultrasensitive point-of-care testing require dried reagents with long-term stability and a high signal-to-background ratio. Although ortho-substituted diaromatic dihydroxy and aminohydroxy compounds undergo fast redox reactions, they are not used as electrochemical signaling species because they are readily oxidized and polymerized by dissolved oxygen. In this report, stable, solid 1-amino-2-naphthyl phosphate (1A2N-P) and ammonia-borane (H₃N-BH₃) are respectively employed as a substrate for alkaline phosphatase (ALP) and a reductant for electrochemical-chemical (EC) redox cycling. ALP converts 1A2N-P to 1-amino-2-naphthol (1A2N), which is then employed in EC redox cycling using H₃N-BH₃. The oxidation and polymerization of 1A2N by dissolved oxygen is significantly prevented in the presence of H₃N-BH₃. The electrochemical measurement is performed without modification of indium–tin oxide (ITO) electrodes with electrocatalytic materials. For comparison, nine aromatic dihydroxy and aminohydroxy compounds, including 1A2N, are evaluated to achieve fast EC redox cycling, and four strong reductants, including H₃N-BH₃, are evaluated to achieve a low background level. The combination of 1A2N and H₃N-BH₃ allows the achievement of a very high signal-to-background ratio. When the newly developed combination is applied to the detection of creatine kinase-MB (CK-MB), the detection limit for CK-MB is ∼80 fg/mL, indicating that the combination allows ultrasensitive detection. The concentrations of CK-MB in clinical serum samples, determined using the developed system, are in good agreement with the concentrations obtained using a commercial instrument. Thus, the use of stable, solid 1A2N-P and H₃N-BH₃ along with bare ITO electrodes is highly promising for ultrasensitive and simple point-of-care testing