多聚氮杂环的脱氮自由基转化:C−N键的构建研究进展

多聚氮杂环化合物在有机合成、药物化学以及材料化学等领域具有重要的作用.人们已经在多聚氮杂环的修饰和可控转换领域取得了诸多突破性的研究成果.在多种多聚氮杂环转换反应中,脱氮是一类重要反应,可以快速地构建其他氮杂环或者C?N键.通常而言,多聚氮杂环化合物更易于脱氮形成金属卡宾中间体,继而发生后续串联或环化反应,但涉及自由基中间体的多聚氮杂环脱氮反应尚未得到充分关注和研究.在过去几年中,得益于现代合成手段如有机光化学合成、有机电化学合成和有机光电合成等的革新,自由基化学得到快速发展,建立了很多多聚杂环脱氮自由基串联反应,为高度复杂的杂环骨架或具有复杂杂环体系的天然产物提供了一条通用且便捷的合成路径.光催化剂在有效地将可见光中的能量转移至非吸收化合物方面的应用越来越受到关注,该方法可温和而有效地生成自由基,以新的方式形成化学键.此外,啉钴与卟啉铁催化剂在多聚杂环的脱氮反应中亦展现出较好的催化性能.本文综述了多聚氮杂环的脱氮自由基转化(C?N键的构建)领域的最新进展,重点讨论了脱氮生成自由基的方法与串联模式和反应机理,分析了存在的挑战.本文还根据反应底物的类别从四个模块展开讨论:(1)苯并三嗪和苯并噻三嗪的自由基脱氮串联反应;(2)苯并三氮唑的自由基脱氮串联反应;(3)吡啶三氮唑与四氮唑的脱氮反应;(4)3-氨基吲唑的自由基脱氮反应.综上,研究者们通过多聚氮杂环的脱氮自由基转化(C?N键的构建)的方法合成了一些重要的药物分子及其前体,并证明了该方法具有潜在的应用价值.未来,将多聚氮杂环脱氮反应应用于活性天然产物合成与修饰是非常可行的.     

Synthetic applications of aryl radical building blocks for cyclisation onto azoles

2-(2-Bromophenyl)ethyl groups have been used as building blocks in radical cyclisation reactions onto azoles to synthesise tri- and tetra-cyclic heterocycles. 2-(2-Bromophenyl)ethyl methanesulfonate was used to alkylate azoles (imidazoles, pyrroles, indoles and pyrazoles) for the synthesis of the radical precursors. Cyclisations of the intermediate aryl radicals yield new 6-membered rings attached to the azoles. The aryl radicals undergo intramolecular homolytic aromatic substitution onto the azole rings. Tributylgermanium hydride has been used with success to replace the toxic and troublesome tributyltin hydride. Initial studies show that the protocol can be used on solid phase resins. The molecular and crystal structures of methyl 5,6-dihydroimidazo[5,1-a]iso-quinoline-1-carboxylate and methyl 5,6-dihydroimidazo[2,1-a]isoquinoline-3-carboxylate were determined by X-ray crystallography.     

Unprecedented aromatic homolytic substitutions and cyclization of amide-iminyl radicals: experimental and theoretical study

Amide-iminyl radicals are versatile and efficient intermediates in cascade radical cyclizations of N-acylcyanamides. They are easily trapped by alkenes or (hetero-)aromatic rings and cyclize into a series of new heterocyclic compounds which bear a pyrroloquinazoline moiety. As an illustration of the synthetic importance of these compounds, the total synthesis of the natural antitumor compound luotonin A was achieved through a tin-free radical cascade cyclization process. Not only do amide-iminyl radicals lead to new tetracyclic heterocycles but these nitrogen-centered radical species also react in aromatic homolytic substitutions. Indeed, the amide-iminyl radical moiety unprecedentedly displaces methyl, methoxy, and fluorine radicals from an aromatic carbon atom. This seminal reaction in the field of radical chemistry has been developed experimentally and its mechanism has additionally been investigated by a theoretical study.     

Stereoselective radical reactions

For many years, the reputed lack of selectivity in some free-radical reactions has resulted in this class of reaction being overlooked in the stereoselective synthesis of important target molecules. More recently, however, the situation has changed as new and milder methods of radical generation have been developed, which have helped researchers to gain a better understanding of the key factors that influence selectivity in radical transformations. As a consequence, the use of radicals in stereoselective synthesis is increasing and there are a number of important intra- and intermolecular additions, where high levels of stereoselectivity have been achieved in the formation of carbon-carbon bonds.     

Advancements in the Synthesis and Applications of Cationic N‐Heterocycles through Transition Metal‐Catalyzed C−H Activation

Cationic N‐heterocycles are an important class of organic compounds largely present in natural and bioactive molecules. They are widely used as fluorescent dyes for biological studies, as well as in spectroscopic and microscopic methods. These compounds are key intermediates in many natural and pharmaceutical syntheses. They are also a potential candidate for organic light‐emitting diodes (OLEDs). Because of these useful applications, the development of new methods for the synthesis of cationic N‐heterocycles has received a lot of attention. In particular, many C?H activation methodologies that realize high step‐ and atom‐economies toward these compounds have been developed. In this review, recent advancements in the synthesis and applications of cationic N‐heterocycles through C?H activation reactions are summarized. The new C?H activation reactions described in this review are preferred over their classical analogs.     

Thiol mediated 8-endo-trig radical cyclization: an easy access to medium-sized cyclic ethers

An efficient new method for the synthesis of eight-membered heterocycles has been developed via a thiophenol mediated intramolecular 8-endo radical cyclization reaction. Alkenyl radicals are generated from easily available terminal alkynes and thiophenol.     

Taming the free radical shrew - learning to control homolytic reactions at higher heteroatoms

Free radical chemistry has come a long way in a relatively short period of time. Armed with mechanistic and rate constant data, the synthetic practitioner can now apply free radical chemistry to the synthesis of many different classes of target molecule with confidence. This Feature Article highlights progress made in the understanding and application of free radical reactions at main group higher heteroatoms and demonstrates how this knowledge can be used to construct interesting higher heterocycles, many of which exhibit biological activity, through the use of intramolecular homolytic substitution chemistry.     

Recent Advances in Minisci‐Type Reactions

Reactions that involve the addition of carbon‐centered radicals to basic heteroarenes, followed by formal hydrogen atom loss, have become widely known as Minisci‐type reactions. First developed into a useful synthetic tool in the late 1960s by Minisci, this reaction type has been in constant use over the last half century by chemists seeking to functionalize heterocycles in a rapid and direct manner, avoiding the need for de novo heterocycle synthesis. Whilst the originally developed protocols for radical generation remain in active use today, they have been joined in recent years by a new array of radical generation strategies that allow use of a wider variety of radical precursors that often operate under milder and more benign conditions. The recent surge of interest in new transformations based on free radical reactivity has meant that numerous choices are now available to a synthetic chemist looking to utilize a Minisci‐type reaction. Radical‐generation methods based on photoredox catalysis and electrochemistry have joined approaches which utilize thermal cleavage or the in situ generation of reactive radical precursors. This review will cover the remarkably large body of literature that has appeared on this topic over the last decade in an attempt to provide guidance to the synthetic chemist, as well as a perspective on both the challenges that have been overcome and those that still remain. As well as the logical classification of advances based on the nature of the radical precursor, with which most advances have been concerned, recent advances in control of various selectivity aspects associated with Minisci‐type reactions will also be discussed.     

Metal complexes of thiazyl radicals

A diverse variety of thiazyl radicals is known. Intense study of these heterocycles continues in the pursuit of molecule-based materials with novel, academically interesting, and technologically relevant properties. Coordination of these species to metal atoms and ions has focused primarily on the 1,2,3,5-dithiadiazolyl 2 and 1,3,2-dithiazolyl 6. The potential of these two heterocycles as ligand building-blocks has, by no means, been fully exploited. From the structural and electronic similarities between 2 and the verdazyl and nitronyl nitroxide radicals, it is apparent that similar radical ligand designs ought to be achievable. The sulfur atoms of 2 lend a unique feature to this radical that may yet be employed as a means of controlling intermolecular interactions or developing multi-metal species. The recent report of sulfur coordination to 6 demonstrates that there is yet more design flexibility available from this thiazyl as well. Coordination complexes of other radical thiazyls have begun appearing in the literature. This field is currently in its infancy and is starting to be recognized as an enormous source of untapped potential in the future development of molecule-based materials.     

Transition Metal‐Participated Synthesis and Utilization of N‐containing Heterocycles: Exploring for Nitrogen Sources

This account aims to describe our recent efforts on the synthesis and utilization of N‐containing heterocycles, where transition metals participate in the synthesis. A variety of nitrogen sources, including amines, amides, hydrazones, pyrimidines, isocyanides, and copper nitrate, have been disclosed for the synthesis of diverse bioactive and pharmacologically interesting N‐containing heterocycles under the participation of transition metals. The well‐known nitrogen sources, such as amines and amides, were used for the construction of indoles, isatins, and quinolones. Dihydrophthalazines, isoquinolines, indazoles, and pyrazoles were obtained from hydrazones, while various pyrimidine‐containing heterocycles were afforded through regioselective C?H functionalizations using pyrimidine as the directing group. Recent research has focused on the chemistry of isocyanides to achieve several kinds of heterocyclic compounds with high efficiency under the catalysis of transition metals (Pd, Rh, Mn, Cu), through oxidative cyanation reactions, sequential isocyanide insertions into C?H, N?H, or O?H bonds, and tandem radical annulation. More recently, an efficient route to isoxazolines has been reported using copper nitrate as a novel nitrogen source.     

Recent advances in azaborine chemistry

The chemistry of organoboron compounds has been primarily dominated by their use as powerful reagents in synthetic organic chemistry. Recently, the incorporation of boron as part of a functional target structure has emerged as a useful way to generate diversity in organic compounds. A commonly applied strategy is the replacement of a CC unit with its isoelectronic BN unit. In particular, the BN/CC isosterism of the ubiquitous arene motif has undergone a renaissance in the past decade. The parent molecule of the 1,2-dihydro-1,2-azaborine family has now been isolated. New mono- and polycyclic B,N heterocycles have been synthesized for potential use in biomedical and materials science applications. This review is a tribute to Dewar's first synthesis of a monocyclic 1,2-dihydro-1,2-azaborine 50 years ago and discusses recent advances in the synthesis and characterization of heterocycles that contain carbon, boron, and nitrogen.     

A New Method of Deoxygenation in the Synthesis of Taxanes by Hypophosphorous Acid

Based on the chemistry involved in the radical chain deoxygenation of alcohols by the Barton-McCombie reaction, numerous applications in the synthesis of taxanes were reported. [1] In the original Barton-McCombie method,tributyltin hydride was the hydrogen atom source and tributyltin radical generated from the hydride served as a chain carrier. [2] Although the method gave the good yield and found many applications, the problems associated with the price, toxicity and removal of tin residues prompted search for other hydrogen atom sources. Radical chain deoxygenation of alcohols can be carried out with phosphorus centered radicals, generated from hypophosphorous acid orits salts. [3]     

An easy access to pyrimidine-fused azocine derivatives by thiophenol-mediated radical cyclization via 8-endo-trig mode

An efficient route for the synthesis of eight-membered nitrogen heterocycles has been developed via a thiophenol-mediated intramolecular 8-endo-trig radical cyclization. The radical precursors were prepared using BF₃·Et₂O-catalyzed aza-Claisen rearrangement followed by the reaction with propargyl bromide. The alkenyl radicals are generated from thiophenol initiated by the benzoyl peroxide instead of commonly used AIBN for easy and facile isolation of the pure products.     

Synthesis of Heterocycles through Denitrogenative Cyclization of Triazoles and Benzotriazoles

During the past few decades, there has been considerable growth in the development of denitrogenative reactions of triazole skeletons to construct valuable cyclic compounds, particularly heterocycles. Despite the inherent difficulty of the ring-opening of triazole derivatives, many novel and efficient approaches have arisen in this area mainly with the use of transition metal (such as rhodium, palladium, silver, copper) catalysis, photolysis, or free radical mediated reactions. Generally, these procedures begin with the ring-opening of 1,2,3-triazoles or benzotriazoles followed by N₂ extrusion and subsequent diverse transformations, which enable the rapid synthesis of various heterocycles in a single step. To avoid overlap with other related reviews, this minireview covers the recent advances in the denitrogenative cyclization of 1,2,3-triazoles since 2016 and the denitrogenative cyclization of benzotriazoles since 2012.     

Isocyanides in the synthesis of nitrogen heterocycles

Isocyanides have long proved themselves to be irreplaceable building blocks in modern organic chemistry. The unique features of the isocyano group make isocyanides particularly useful for the synthesis of a number of important classes of nitrogen heterocycles, such as pyrroles, indoles, and quinolines. Several cocyclizations of isocyanides via zwitterions and radical intermediates as well as transition-metal-catalyzed syntheses of different types of heterocycles have recently been developed. Methods starting from isocyanides often have distinct advantages over alternative approaches to the same heterocycles because of their enhanced convergence, the great simplicity of most of the operations with them, and the great variety of isocyanides readily available for use. Isocyanides have also been used in some enantioselective syntheses of chiral heterocyclic compounds, including natural products as well as precursors thereof.     

New development of synthesis and reactivity of seleno- and tellurophenes

Due to the many new and remarkable findings and applications that have been published in recent years in seleno- and tellurophene chemistry, this review revisits the different aspects of this chemistry, including synthesis, reactivity and applications in the field of heterocycles.     

Synthesis of seven and higher membered nitrogen containing heterocycles using photochemical irradiation

Photochemical reactions have been applied for the synthesis of complex targets in many examples recently. In many cases, these processes provide access to unique modes of reactivity or offer unrivaled increases in molecular complexity. The key-features of photochemical reactions include increased selectivity, conversion, and yield and are beneficial for industrial and “green” processes. Despite these advantages, however, photochemical reactions in chemical production or R and D processes are rare. Most technical processes are limited to commodity chemicals and have been developed decades ago. The application of photochemical reactions for the synthesis of fine chemicals, natural products, and pharmaceutically active compounds, has become very popular. Photochemical reactions are used for organic synthesis and this review article highlighted the syntheses of heterocycles. Photochemistry is particularly fascinating and afforded an exotic charm due to its unconventional nature. In this review, I have given a clear idea of applicability of photochemical irradiations for the synthesis of a number of seven and higher membered N-heterocycles.     

Synthesis of Highly Functionalized Polycyclic Quinoxaline Derivatives Using Visible‐Light Photoredox Catalysis

A mild and facile method for preparing highly functionalized pyrrolo[1,2‐a]quinoxalines and other nitrogen‐rich heterocycles, each containing a quinoxaline core or an analogue thereof, has been developed. The novel method features a visible‐light‐induced decarboxylative radical coupling of ortho‐substituted arylisocyanides and radicals generated from phenyliodine(III) dicarboxylate reagents and exhibits excellent functional group compatibility. A wide range of quinoxaline heterocycles have been prepared. Finally, a telescoped preparation of these polycyclic compounds by integration of the in‐line isocyanide formation and photochemical cyclization has been established in a three‐step continuous‐flow system.     

Effects of silver nanoparticles on seed germination and seedling growth: A review

The advancement in nanotechnology, nanoparticles are reported to have applications in various fields. Their positive role in the environment, especially in plant ecosystem, is extensively studied nowadays. Among the metal nanoparticles, the silver nanoparticles (AgNPs) are receiving special attention because of their ability to increase the growth and yield in many crops. Although many studies are found that shows the toxic effects of AgNPs, the perspective of the present review is to collect the information about their positive roles in growth and yield enhancement of crops. During this overview, there are many methods of synthesizing silver AgNPs nanoparticles discussed, including chemical, bacterial-induced, fungal-derived and plant-mediated synthesis. There are numerous approaches towards the synthesis of AgNPs, including biological and chemical methods. Because of the use of reducing agents such as sodium borohydride in the synthesis of AgNPs, conventional methods have opened a path that threatens environmental sustainability. The chemical synthesis of silver colloids is the consequence of increased aggregation as storage time increases. AgNPs possess unique properties which has many applications such as antimicrobial and anticancer activities. It was concluded that cautious and sensible use of nanotechnology can warrant food security through boosting agricultural production. This review is aimed at providing an insight into the syntheses of AgNPs, its significant applications in various fields, and characterization techniques involved.     

Synthesis and applications of thiosulfonates and selenosulfonates as free-radical reagents

Chalcogenative sulfones (thiosulfonates and selenosulfonates), as reactants for organic transformations, are widely used and interesting because of their potential to react with nucleophiles, electrophiles, and free radicals. As stable radical reagents, the synthesis and applications of chalcogenative sulfones have opened up a novel pathway to synthesize many kinds of compounds containing sulfur or selenium motifs. However, despite the numerous recent works on the synthesis and applications of thiosulfonates and selenosulfonates as radical reagents, no review has yet provided a summary of the literature. In this paper, we aim to review the synthesis and applications strategies of chalcogenative sulfones as radical reagents reported over the past several decades. Different types of catalysis are discussed in this review: (i) metal catalysis; (ii) visible-light catalysis; (iii) synergistic catalysis; and (iiii) other types. Concurrently, in visible-light catalysis and metallaphotoredox catalysis sections, we highlight that developing relatively environmentally friendly synthetic methods in this area is always a great challenge, but also a persistent pursuit. Finally, the scopes, limitations, mechanisms, and existing problems of some reactions are described briefly.