Heterocycles constitute the largest and the most diverse family of organic compounds Among them, aromatic heterocycles represent structural motifs found in a great number of biologically active natural and synthetic compounds, drugs, and agrochemicals Moreover, aromatic heterocycles are widely used for synthesis of dyes and polymeric materials of high value 1 There are numerous reports on employment of aromatic heterocycles as intermediates in organic synthesis 2

Although, a variety of highly efficient methodologies for synthesis of aromatic heterocycles and their derivatives have been reported in the past, the development of novel methodologies is in cuntinious demand Particlularly, development of new synthetic approaches toward heterocycles, aiming at achieving greater levels of molecular complexity and better functional group compatibilities in a convergent and atom economical fashions from readily accessible starting materials and under mild reaction conditions, is one of a major research endeavor in modern synthetic organic chemistry Transition metal-catalyzed transformations, which often help to meet the above criteria, are among the most attractive synthetic tools

Several excellent reviews dealing with transition metal-catalyzed synthesis of heterocyclic compounds have been published in literature during recent years Many of them highlighted the use of a particular transition metal, such as gold,3 silver,4 palladium,5 copper,6 cobalt,7 ruthenium,8 iron,9 mercury,10 rare-earth metals,11 and others Another array of reviews described the use of a specific kind of transformation, for instance, intramolecular nucleophilic attack of heteroatom at multiple C–C bonds,12 Sonogashira reaction,13 cycloaddition reactions,14 cycloisomerization reactions,15 C–H bond activation processes,16 metathesis reactions,17 etc Reviews devoted to an application of a particular type of starting materials have also been published Thus, for example, applications of isocyanides,18 diazocompounds,19 or azides20 have been discussed In addition, a significant attention was given to transition metal-catalyzed multicomponent syntheses of heterocycles21 Finally, syntheses of heterocycles featuring formation of intermediates, such as nitrenes,22 vinylidenes,23 carbenes, and carbenoids24 have also been reviewed

The main focus of the present review is a transition metal-catalyzed synthesis of aromatic monocyclic heterocycles The organization of the review is rather classical and is based on a heterocycle, categorized in the following order: (a) ring size of heterocycle, (b) number of heteroatoms, (c) type of heterocycle, and (d) a class of transformation involved A brief mechanistic discussion is given to provide information about a possible reaction pathway when necessary The review mostly discusses recent literature, starting from 200425 until the end of 2011, however, some earlier parent transformations are discussed when needed

Transition Metal-Mediated Synthesis of Monocyclic Aromatic Heterocycles

Environmentally benign synthesis of heterocyclic compounds by combined microwave-assisted heterogeneous catalytic approaches†

With the growing interest in renewable energy and global warming, it is important to minimize the usage of hazardous chemicals in both academic and industrial research, elimination of waste, and possibly recycle them to obtain better results in greener fashion. The studies under the area of mechanochemistry which cover the grinding chemistry to ball milling, sonication, etc. are certainly of interest to the researchers working on the development of green methodologies. In this review, a collection of examples on recent developments in organic bond formation reactions like carbon–carbon (C–C), carbon–nitrogen (C–N), carbon–oxygen (C–O), carbon–halogen (C–X), etc. is documented. Mechanochemical syntheses of heterocyclic rings, multicomponent reactions and organometallic molecules including their catalytic applications are also highlighted.

https://www.beilstein-journals.org/bjoc/content/pdf/1860-5397-13-186.pdf

Mechanochemical synthesis of small organic molecules.

A collection of smart multicomponent reactions (MCRs) with continuative post condensation cyclizations (PCCs) is presented to construct conventional three- to seven-membered heterocyclic compounds in diversity oriented syntheses (DOS). These will provide a high degree of applying economical and ecological advantages as well as of practicability. Water, ionic liquids, and solvent-less syntheses as well as use of various forms of energy as microwave and ultrasonic irradiation are examined and discussed.

/pdf/diversity-oriented-syntheses-of-conventional-heterocycles-by-36o11q2gyh.pdf

Diversity Oriented Syntheses of Conventional Heterocycles by Smart Multi Component Reactions (MCRs) of the Last Decade

Quinoline is one of the most widely investigated scaffolds by synthetic chemists because of its medicinal importance. A wide range of metal-catalyzed, metal-free, multi-step or domino one-pot protocols are reported in the literature for construction of this scaffold. Several reviews have appeared on synthetic aspects of this scaffold, however there is no focused review on metal-free domino one-pot protocols. Domino one-pot protocols offer an opportunity to access highly functionalized final products from simple starting materials. Because of this unique feature of domino protocols, in recent years their utility for generation of molecular libraries has been widely appreciated. In this review, all contributions till March 2015 are surveyed with particular emphasis on metal-free domino reactions for quinoline ring construction and are discussed herein along with mechanistic aspects.

Metal-free domino one-pot protocols for quinoline synthesis

Synthetic methodology for the synthesis of heterocycles is of continuous and high interest with applications in materials, catalysis, and medicines. Multicomponent reactions are suitable tools to efficiently generate chemically diverse sets of heterocycles with sufficient structural complexity. Especially isocyanides have proven to be particularly versatile building blocks in these one-pot processes. Due to their electronic structure, isocyanides are able to act sequentially or simultaneously as a nucleophile and an electrophile. Traditionally, isocyanides are therefore frequently used in multicomponent chemistry. In the recent literature, numerous reactions have been reported that involve formal cycloadditions of isocyanides with conjugated heterodienes. This Focus Review aims at mapping this reactivity and at providing insight into the relationship between the various reported reaction partners and the observed reactivity modes.

Synthesis of Heterocycles by Formal Cycloadditions of Isocyanides

Multicomponent reactions are valuable tools for the generation of diverse heterocycles. As in many fields or organic chemistry, microwave irradiation is rapidly replacing conventional heating methods in multicomponent chemistry. In this review, we present an overview of recent applications of the use of microwaves in multicomponent heterocycle synthesis.Where possible, the yield and chemo-, regio- and stereoselectivity of microwave-assisted reactions are compared with those using conventional heating. © 2011 Bentham Science Publishers Ltd.

Microwave-Assisted Multicomponent Synthesis of Heterocycles

https://pubs.acs.org/doi/pdf/10.1021/acs.orglett.8b01561

Hexafluoroisopropanol as the Acid Component in the Passerini Reaction: One-Pot Access to β-Amino Alcohols.

Non-fused 3,6-dihydro-2H-1,3-thiazine-2-thiones constitute a so far rather unexplored class of compounds, with the latest report dating back more than two decades. Thiazine-2-thiones contain an endocyclic dithiocarbamate group, which is often found in pesticides, in substrates for radical chemistry and in synthetic intermediates towards thioureas and amidines. We now report the multicomponent reaction (MCR) of in situ-generated 1-azadienes with carbon disulfide. With this reaction, a one-step protocol towards the potentially interesting 3,6-dihydro-2H-1,3-thiazine-2-thiones was established and a small library was synthesized.

/pdf/multicomponent-synthesis-of-3-6-dihydro-2h-1-3-thiazine-2-1ysj6bhrss.pdf

Art Kruithof

Papers

Synthesis of Heterocycles by Formal Cycloadditions of Isocyanides

Microwave-Assisted Multicomponent Synthesis of Heterocycles

Hexafluoroisopropanol as the Acid Component in the Passerini Reaction: One-Pot Access to β-Amino Alcohols.

Multicomponent synthesis of 3,6-dihydro-2H-1,3-thiazine-2-thiones.

Microwave-Assisted Multicomponent Synthesis of Heterocycles