Jinhai Shen

A Metal-Free Multicomponent Cascade Reaction for the Regiospecific Synthesis of 1,5-Disubstituted 1,2,3-Triazoles†

The thermal Huisgen 1,3-dipolar cycloaddition of organic azides and alkynes to build 1,2,3-triazoles usually requires elevated temperatures and provides a mixture of regioisomers. The copper(I)-catalyzed azide–alkyne cycloaddition (CuAAC) and ruthenium(II)-catalyzed azide–alkyne cycloaddition (RuAAC) have been developed as powerful strategies for the regiospecific assembly of 1,4-disubstituted 1,2,3-triazoles and 1,5-disubstituted 1,2,3-triazoles, respectively. These reliable processes have quickly found many applications in organic synthesis, chemical biology, and materials science. Nevertheless, the contamination of heavy metals limits their potential application in the pharmaceutical industry. Several metal-free methods, including the azide–enamine cycloaddition, the condensation of azides with phosphonium ylides, and the addition of acetylide species to azides, have also been developed for the regiospecific synthesis of 1,2,3-triazoles. Considerable drawbacks, however, exist with these processes, such as poor functional-group tolerance or requiring functionalized substrates. Westermann recently reported an improved Sakai reaction to synthesize 1,4-disubstituted triazoles from primary amines and a,a-dichlorotosylhydrazones (Scheme 1a). This procedure is limited to the synthesis of 1,4-disubstituted regioisomers. Therefore, a general and metal-free procedure to synthesize 1,5-disubstituted triazoles from readily available substrates under mild reaction conditions is still of considerable interest. Herein we report the synthesis of the 1,5disubstituted triazoles 5 from a three-component reaction of aliphatic amines (1), propynones (2), and TsN3 by a Michael addition/deacylative diazo transfer/cyclization sequence (Scheme 1b). Theoretically, the enaminone compounds 4 may exist as three tautomers: the iminoenol 4a, iminoketone 4b, and ketoenamine 4c. The a-diazo iminoketone 7 and 1-tosyl triazole 8 could be obtained from the Regitz diazo transfer of 4b and 1,3-dipolar cycloaddition of 4c with TsN3, respectively. We assumed that, in the presence of suitable bases, 4a might react with TsN3 to give the a-diazoimine intermediate 6, which could further cyclize to afford the triazole 5 (Scheme 2).

Cleavage of the C–C triple bond of ketoalkynes: synthesis of 4(3H)-quinazolinones

A novel protocol for the synthesis of 4(3H)-quinazolinones via selective cleavage of the triple bond of ketoalkynes under oxidant-, metal-, and ligand-free conditions has been developed. Various 4(3H)-quinazolinones were obtained through fragmentation of the C–C triple bond and formation of two C–N bonds.

Palladium-Catalyzed Oxidative Cross-Coupling of N-Tosylhydrazones with Indoles: Synthesis of N-Vinylindoles

A general and efficient palladium-catalyzed oxidative cross-coupling reaction of N-tosylhydrazones with indoles providing N-vinylindoles has been developed. The reaction proceeds smoothly with various indoles and N-tosylhydrazones in a stereocontrolled manner, and a wide variety of N-vinylindoles were obtained up to 99% yields for 26 examples.

Base-Mediated Regiospecific Cascade Synthesis of N-(2-Pyridyl)pyrroles from N-Propargylic β-Enaminones

A KOH-promoted regiospecific synthesis of polysubstituted N-(2-pyridyl)pyrroles under transition metal-free conditions has been developed. The pyrrole and pyridine rings were simultaneously installed from acyclic enaminone precursors under mild conditions and generated 1 equiv. of H2O as the sole byproduct. A series of polysubstituted N-(2-pyridyl)pyrroles were provided in up to 91% yield for 21 examples.

Practical access to 1,3,5-triarylbenzenes from chalcones and DMSO

An unprecedented practical access to 1,3,5-triarylbenzenes has been developed from chalcones with DMSO as a reaction partner and solvent. This procedure involved a base-promoted addition of dimethyl sulfoxide anion to chalcones, followed by an aldol-type cyclization. The results of the isotopic labeling experiments indicated that one C of the central benzene ring was derived from DMSO. In comparison to the reported methods of preparing triarylbenzenes, this protocol could simultaneously provide C3-symmetric and C3-unsymmetric triarylbenzenes under obviously milder reaction conditions (60 °C, 5 h). The diverse functionalized triarylbenzenes were obtained in up to 82% yields for 24 examples.

A metal-free synthesis of diaryl-1,2-diketones by C–C triple bond cleavage of alkynones

A novel and environmentally benign protocol for diaryl-1,2-diketones was developed. Various diaryl-1,2-diketones were afforded in moderate to excellent yields by C–C triple bond cleavage of alkynones using molecular oxygen as an oxidant. A plausible reaction mechanism was proposed that accounts for all the experimental results. The products are important building blocks in organic synthesis and could be converted to various synthons via diverse transformations.

Carbon dots as fluorescent probes for detection of VB12 based on the inner filter effect

In this study, we constructed a new fluorescent sensing for VB12 and investigated the mechanism of vitamin B12 (VB12) quenching fluorescence of carbon dots (CDs). The fluorescence suppression is attributed to the inner filter effect (IFE) because of the overlap between UV-vis absorption spectrum of VB12 and emission/excitation spectra of CDs. This CDs-based sensor provides obvious advantages of simplicity, convenience, rapid response, high selectivity and sensitivity, which has potential application for the detection of VB12 in the medical and food industry.