Nitrogen-Containing Six-Membered Heterocycles: Solid-Phase Synthesis

Solid-phase organic synthesis is a rapidly expanding area of synthetic chemistry that is being widely exploited in the search for new medicinally important compounds using combinatorial techniques. In recent decades, a large number of reports related to solid-phase synthesis of heterocycles have appeared because of the wide variety of their biological activity. In this review, we report the important role of solid-phase synthesis in the synthesis of nitrogen containing six-membered ring heterocycles.     

Solid-Phase Synthetic Approach Toward the Synthesis of Oxygen-Containing Heterocycles

Solid-phase organic synthesis is a rapidly expanding area of synthetic chemistry which is being widely exploited in the search for new medicinally important compounds using combinatorial techniques. In recent decades, a large number of reports related to solid-phase synthesis of heterocycles have appeared because of the wide variety in their biological activity. In this review, we report the important role of solid-phase synthesis in the synthesis of oxygen-bearing heterocycles.     

Generation and cycloaddition of polymer-supported azomethine ylide by utilizing the characteristics of silicon: a facile route to pyrrolidines and pyrroles from α-silylimines bound to resin

The solid-phase synthesis of pyrrolidine and pyrrole derivatives using polymer-supported α-silylimines is described. Polymer-supported azomethine ylides were generated from the corresponding α-silylimine by thermal 1,2-silatropy onto the imino nitrogen or by treatment with a trifluorosilane as a quaternization and desilylation reagent, and the resulting species were then reacted with dipolarophiles to give five-membered heterocycles.     

An Oxidation-Labile Traceless Linker for Solid-Phase Synthesis

Traceless release of biaryls, acetylenes, alkenes, heterocycles, thioethers, and secondary amines from different solid supports can be achieved under very mild conditions by using a hydrazide group. This group, which is converted into an acyl diazene by oxidation and subsequently cleaved by a nucleophile (see scheme), is thus an attractive new linker for solid-phase synthesis and combinatorial chemistry.     

茂铁杂环化合物的绿色合成

综述了近年来含二茂铁杂环化合物绿色合成研究的新进展, 主要包括微波、超声波、固相合成、特殊催化剂的使用、绿色溶剂、光催化合成等新技术、新试剂在该类反应中的应用.     

Synthetic routes to seven and higher membered S-heterocycles by use of metal and nonmetal catalyzed reactions

Nitrogen, oxygen, and sulfur containing heterocycles have a wide range of biological activities. Metal and nonmetal catalysts are used in organic reactions with high activity. New strategies have been developed for the preparation of heterocycles in the last decades. The metal and nonmetal catalyzed synthesis of heterocycles is becoming an important and highly rewarding protocol in organic synthesis. In this review article, the synthesis of seven and higher-membered S-heterocycles is presented with the application of metal and nonmetal catalysts for the period from 1968 to 2018.     

聚合物支载合成杂环化合物的研究进展

聚合物支载的反应与传统的经典液相反应相比，具有独特的优点，广泛应用于 杂环化合物的合成。综述了近年来杂环化合物的固相和液相合成研究。     

氮杂Wittig反应的最近进展

综述了最近几年氮杂Wittig反应的研究进展,包括分子间氮杂Wittig反应、分子内氮杂wittig反应及串联的氮杂Wittig反应。讨论了氮杂Wittig反应在一些含氮杂环、稠杂环及天然产物合成中的应用。     

Copper catalyzed synthesis of seven and higher membered heterocycles

Nitrogen, oxygen, and sulfur-containing heterocycles have a wide range of biological activities. Metal catalysts are used in organic reactions with high activity. New methods have been explored for the synthesis of heterocyclic compounds in the past few years. The preparation of heterocycles with the assistance of metal catalyst is becoming a highly rewarding strategy in organic synthesis. In this review article, the synthesis of seven and higher-membered heterocycles is presented using copper as a catalyst.     

Annulation of primary amines to piperazines and diazaspirocycles utilizing alpha-methyl benzyl resin

The microwave-assisted solid-phase synthesis of piperazines, 3,9-diazaspiro[5.5]undecanes and 2,9-diazaspiro[5.5]undecanes is reported. The synthesis relies on the direct annulation of primary amines with resin-bound bismesylates. Critical to the success of this chemistry was the development of alpha-methyl benzyl carbamate resin linker. This resin permits the cleavage of the heterocycles under mildly acidic conditions, free of contaminating linker-derived N-alkylated byproducts.     

Synthesis of Five-Membered N,N,N- and N,N,N,N-Heterocyclic Compounds: Applications of Microwaves

The development of new strategies for the synthesis of small-sized heterocycles has remained a highly attractive but challenging proposition. An overview of the application of microwave irradiation to the synthesis of five-membered heterocyclic compounds containing three and four nitrogen atoms is presented, focusing on the developments in the past 5–10 years. This contribution covers the literature concerning the total synthesis of N,N,N- and N,N,N,N-heterocycles. The literature data are summarized based on the size and type of cycles.     

Solid-Phase-Supported Chemoenzymatic Synthesis of a Light-Activatable tRNA Derivative

Herein, we present a multi-cycle chemoenzymatic synthesis of modified RNA with simplified solid-phase handling to overcome size limitations of RNA synthesis. It combines the advantages of classical chemical solid-phase synthesis and enzymatic synthesis using magnetic streptavidin beads and biotinylated RNA. Successful introduction of light-controllable RNA nucleotides into the tRNA^Met sequence was confirmed by gel electrophoresis and mass spectrometry. The methods tolerate modifications in the RNA phosphodiester backbone and allow introductions of photocaged and photoswitchable nucleotides as well as photocleavable strand breaks and fluorophores.     

Synthesis of five-membered N-heterocycles using Rh based metal catalysts

Abstract

One of the highly emerging and an important aspect of organic chemistry is the metal catalyzed synthesis of heterocycles. The methodologies used earlier for their synthesis were less approachable to the organic chemist because of their high cost, highly specified instrumentation, and inconvenient methods. For both the stereoselective and regioselective synthesis of five-membered nitrogen containing heterocycles, cyclic reactions that are Rh-catalyzed have known to be very efficient. The present review covers the varied applications of Rh as a catalyst and its importance in the formation of five-membered nitrogen containing heterocycles. The fascinating research that has been done in this area is enclosed in this review.     

Cu-assisted C–N bond formations in six-membered N-heterocycle synthesis

Abstract

One of the highly emerging and important aspect of organic chemistry is the metal-catalyzed synthesis of the heterocycles. The methodologies used earlier for its synthesis were less approachable to the organic chemist because of their high cost, highly specified instrumentation and inconvenient methods. For both the stereoselective and regioselective synthesis of six-membered nitrogen-containing heterocycles, cyclic reactions that are Cu-catalyzed have known to be very efficient. The presented review covers the varied applications of Cu as a catalyst and its importance in the formation of six-membered nitrogen-containing heterocycles. The fascinating research that has been done in this area is also enclosed in this review.     

Photochemical generation of nitrosocarbonyl intermediates on solid phase: synthons toward hetero Diels-Alder and Ene adducts through photocleavage

The synthesis of 1,2,4-oxadiazole-4-oxides on polystyrenic solid phase docked at the position 3 of the heterocyclic ring has been performed through the cycloaddition of stable supported nitrile oxides to amidoximes. The photochemical cycloreversion of these heterocycles afforded the free nitrosocarbonyl intermediates that were trapped by suitable dienes or enes. The method is proposed as a clean and environmental friendly approach to the fleeting nitrosocarbonyl intermediates, which afford valuable adducts for various synthetic applications. The isomeric heterocycles docked at the position 5 of the ring have also been obtained by cycloaddition of nitrile oxides to supported amidoximes. Their photolysis afforded resin-bound nitrosocarbonyls that were trapped with dienes affording valuable supported adducts suitable for further elaboration on solid-phase chemistry.     

Strained heterocycles in radical chemistry

Over the last few decades the use of radicals in synthesis has witnessed an explosive growth through introduction of efficient chain and electron-transfer reactions. Strained heterocycles, in particular, have emerged as a highly versatile and readily available class of radical precursors. The generation of carbinyl radicals of heterocycles has resulted in many elegant applications of heteroatom-centered radicals, such as beta fragmentations, cyclizations, and intramolecular hydrogen atom abstractions. Direct electron transfer to strained heterocycles has been realized through the use of arene radical anions. The method combines the virtues of radical and organometallic chemistry to yield useful functionalized organolithium compounds. Epoxides have been opened with high regioselectivity by titanocene(III) reagents in either stoichiometric or catalytic quantities to yield beta-titanoxy radicals. This development has resulted in many new applications in natural product synthesis.     

烯胺酮(酯)类化合物合成研究进展

本文综述了目前国内外烯胺酮(酯)类化合物的主要合成方法。从采用缩合、加成、取代及杂环分解等不同的反应类型,采用路易斯酸、无机酸等不同的催化剂体系,以及采用微波或超声波促进,利用离子液体作为反应介质等几个方面展开讨论。     

Efficient and improved synthesis of triazole-linked DNA (DNA) oligomers

A method for the synthesis of triazole-linked DNA oligomers has been revisited to incorporate a reliable protective group and linker for solid-phase synthesis. The new solid-phase synthesis allowed the preparation of oligomers with the efficiency of elongation reaching over 90%.     

Solid-phase and microwave-assisted syntheses of 2,5-diketopiperazines: small molecules with great potential

Diketopiperazines (DKPs) are a well-known class of heterocycles that have recently emerged as a promising biologically active scaffold. Solid-phase organic synthesis has become an important tool in the combinatorial exploration of these privileged structures, expediting the synthesis and, therefore, the discovery of active compounds. To date, certain DKPs have shown potent activities against a range of diseases and biological phenomena, including bacterial infections, various cancers, asthma, infertility, premature labor, and HIV. Recent applications of solid-phase DKP synthesis, with a particular focus on cyclative cleavage and microwave-assisted reactions, are highlighted herein.     

卤素盐参与下有机电合成含氮杂环化合物的研究进展

含氮杂环化合物广泛存在于医药、农药及天然产物中,是许多具有生理活性的化合物和药物的基本骨架.开发高效、绿色的含氮杂环化合物的构建方法具有重要意义.近年来,卤素盐参与下有机电合成含氮杂环化合物取得了诸多进展.该类反应具有操作简单、绿色环保等特点.综述了有机电化学合成反应中,卤素盐作媒介,含氮杂环化合物的合成研究新进展.