Natural Product-Oriented Photo-Induced Denitrogenative Annulations of 1-Alkenylbenzotriazoles.

The photo-induced denitrogenative annulations of a variety of 1-alkenylbenzotriazoles were investigated. By judiciously manipulating the structural variations of 1-alkenylbenzotriazoles, two characteristic polycyclic skeletons associated with monoterpene indole alkaloids were constructed through a diverted and controllable manner. The present work not only enriches the photochemistry of 1-alkenylbenzotriazoles, but also offers a unified approach to access skeletally diverse indole alkaloid scaffolds.

Transition-Metal-Catalyzed Denitrogenative Annulation to Access High-Valued N-Heterocycles.

Over the past few years, the development of efficient methods to construct high-valued N-heterocyclic molecules have received massive attention owing to their extensive application in the areas of medicinal chemistry, drug discovery, natural product synthesis and so on. To access those high-valued N-heterocycles, many methods have been developed. In this context, transition-metal-catalyzed denitrogenative annulation of 1,2,3-triazoles and 1,2,3,4-tetrazoles has appeared as a powerful synthetic tool because it offers a step- and atom-economical route for the preparation of the nitrogen-rich molecules. Compared with the denitrogenative annulation of various 1,2,3-triazole frameworks, annulation of 1,2,3,4-tetrazole remains more challenging due to the inertness of the tetrazole moiety. This Review summarizes the significant achievements made in the field of denitrogenative annulation of various 1,2,3-triazoles and 1,2,3,4-tetrazoles including some pioneering examples in this area of research. We anticipate that this denitrogenative annulation reaction will find broad applications in the pharmaceutical industry, drug discovery and other fields of medicinal chemistry.

Scope of tetrazolo[1,5-a]quinoxalines in CuAAC reactions for the synthesis of triazoloquinoxalines, imidazoloquinoxalines, and rhenium complexes thereof.

The conversion of tetrazolo[1,5-a]quinoxalines to 1,2,3-triazoloquinoxalines and triazoloimidazoquinoxalines under typical conditions of a CuAAC reaction has been investigated. Derivatives of the novel compound class of triazoloimidazoquinoxalines (TIQ) and rhenium(I) triazoloquinoxaline complexes as well as a new TIQ rhenium complex were synthesized. As a result, a small 1,2,3-triazoloquinoxaline library was obtained and the method could be expanded towards 4-substituted tetrazoloquinoxalines. The compatibility of various aliphatic and aromatic alkynes towards the reaction was investigated and the denitrogenative annulation towards imidazoloquinoxalines could be observed as a competing reaction depending on the alkyne concentration and the substitutions at the quinoxaline.

Iron-Catalyzed Radical Activation Mechanism for Denitrogenative Rearrangement Over C(sp3 )-H Amination.

An iron-catalyzed denitrogenative rearrangement of 1,2,3,4-tetrazole is developed over the competitive C(sp3 )-H amination. This catalytic rearrangement reaction follows an unprecedented metalloradical activation mechanism. Employing the developed method, a wide number of complex-N-heterocyclic product classes have been accessed. The synthetic utility of this radical activation method is showcased with the short synthesis of a bioactive molecule. Collectively, this discovery underlines the progress of radical activation strategy that should find wide application in the perspective of medicinal chemistry, drug discovery and natural product synthesis research.

Dual Reactivity of 1,2,3,4-Tetrazole: Manganese-Catalyzed Click Reaction and Denitrogenative Annulation.

A general catalytic method using a Mn-porphyrin-based catalytic system is reported that enables two different reactions (click reaction and denitrogenative annulation) and affords two different classes of nitrogen heterocycles, 1,5-disubstituted 1,2,3-triazoles (with a pyridyl motif) and 1,2,4-triazolo-pyridines. Mechanistic investigations suggest that although the click reaction likely proceeds through an ionic mechanism, which is different from the traditional click reaction, the denitrogenative annulation reaction likely proceeds via an electrophilic metallonitrene intermediate rather than a metalloradical intermediate. Collectively, this method is highly efficient and offers several advantages over other methods. For example, this method excludes a multi-step synthesis of the N-heterocyclic molecules described and produces only environmentally benign N2 gas a by-product.