Xiuling Cui

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).

Pd-Catalyzed Direct C–H Bond Sulfonylation of Azobenzenes with Arylsulfonyl Chlorides

Pd(II)-catalyzed C-H sulfonylation of azobenzenes with arylsulfonyl chlorides has been developed. The sulfonylazobenzenes were obtained in moderate to excellent yields for 28 examples. This protocol features high efficiency, wide functional group tolerance, and atom economy.

Base-Promoted N-Pyridylation of Heteroarenes Using N-Propargyl Enaminones as Equivalents of Pyridine Scaffolds

N-Pyridylation of various N-heteroarenes, including N-heteroarene-containing peptides, was achieved using N-propargyl enaminones (isolated or generated in situ from propargyl amine and propynones) as masked polysubstituted pyridine cores. This metal-free procedure proceeds under mild reaction conditions and generates 1 equiv of H2O as the sole byproduct.

Rhodium(III)-Catalyzed C–H Activation/Alkyne Annulation by Weak Coordination of Peresters with O–O Bond as an Internal Oxidant

A redox-economic strategy has been developed, involved in an efficient Rh(III)-catalyzed oxidative C-H activation and alkyne annulation with perester as the oxidizing directing group. In this process, the cleavage of an oxidizing O-O bond as an internal oxidant is described for the first time. This reaction could be carried out under mild conditions and exhibits excellent regioselectivity and wide functional groups tolerance.

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.

Efficient Approach to 4-Sulfonamidoquinolines via Copper(I)-Catalyzed Cascade Reaction of Sulfonyl Azides with Alkynyl Imines‡

A novel and efficient approach to 4-sulfonamidoquinolines via copper-catalyzed cascade reaction of sulfonyl azides with alkynyl imines has been developed in which a 1,3-dipole cycloaddition/ketenimine formation/6π-electrocyclization/[1,3]-H shift cascade reaction was involved. Various 4-sulfonamidoquinolines were afforded in up to 84% yield for 19 examples. This synthetic strategy features with atom economy, concise steps, easy operation, and mild reaction conditions.

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.

Iridium-Catalyzed Direct C–H Sulfamidation of Aryl Nitrones with Sulfonyl Azides at Room Temperature

Ir(III)-catalyzed direct C-H sulfamidation of aryl nitrones has been developed to synthesize various sulfamidated nitrones in moderate to excellent yields with excellent regioselectivity and broad functional group tolerance. This transformation could proceed smoothly at room temperature with low catalyst loading in the absence of external oxidants, acids, or bases. Molecular nitrogen was released as the sole byproduct, thus providing an environmentally benign sulfamidation process. And this protocol could efficiently apply to synthesize the substituted benzisoxazoline via one-step transformation from the product.

Copper-Catalyzed Synthesis of 2-Arylquinazolinones from 2-Arylindoles with Amines or Ammoniums.

A novel copper-catalyzed synthesis of quinazolinones from easily available 2-arylindoles and amines or ammoniums has been developed, which provided various quinazolinones in up to 99% yields for 43 examples. This strategy features tolerance of a wide range of functional groups, easily available starting materials, simple operation, mild reaction conditions, and environmental friendliness.

Access to C4-Functionalized Quinolines via Copper-Catalyzed Tandem Annulation of Alkynyl Imines with Diazo Compounds

An efficient synthesis of C4-functionalized quinolines through copper-catalyzed tandem annulation of alkynyl imines with diazo compounds is described. This transformation involves an in situ formation of allene and intramolecular electrocyclization, which features high efficiency, mild reaction conditions, easy operation, and broad functional-group tolerance. A wide variety of C4-functionalized quinolines were provided in up to 92% yield for 33 examples.