Indole as a Versatile Building Block in Cycloaddition Reactions: Synthesis of Diverse Heterocyclic Frameworks.

Indole, a ubiquitous and structurally versatile aromatic compound, has emerged as a key player in the synthesis of diverse heterocyclic frameworks via cycloaddition reactions. These reactions are completely atom-economical and, hence, are considered as green reactions. This review article provides a comprehensive overview of the pivotal role played by indole in the construction of complex and biologically relevant heterocyclic compounds. Here we explore the chemistry of indole-based cycloadditions, highlighting their synthetic utility in accessing a wide array of heterocyclic architectures, including cyclohepta[b]indoles, tetrahydrocarbazoles, tetrahydroindolo[3,2-c]quinoline, and indolines, among others. Additionally, we discuss the mechanistic insights that underpin these transformations, emphasizing the strategic importance of indole as a building block. The content of this article will certainly encourage the readers to explore more work in this area.

Copper-catalysed dehydrogenative self-coupling/cyclization of 5-aminopyrazoles: synthesis and photophysical study of pyridazines.

An interesting self-coupling/cyclization of 5-aminopyrazoles is revealed, which provides a variety of pyridazine cores in reasonable yields. In this reaction, C(sp2)-C(sp2) and N-N bond formation occurs simultaneously in one reaction vessel. The photophysical properties of the synthesized compounds were also studied and some of them exhibited fluorescence properties with good quantum yields. A radical mediated reaction mechanism is proposed with the help of control experiments.

Strategies Toward the Catalyst-Free α-C-H Functionalizations of Tertiary Amines.

α-C-H functionalization of tertiary amines has been a highly studied field for the past two decades because several important nitrogen containing heterocycles or compounds can be synthesized through this strategy. Though transition metal catalysts and some metal-free catalysts are mainly used for these reactions, a few catalyst-free reactions have recently been efficiently performed. Catalyst-free reactions are cost-effective, less sensitive to air/moisture, easier to operate, have a simple purification process, and are relatively environment-friendly. In this article, we have summarized all the α-C-H functionalization reactions of tertiary amines performed without using any external catalysts. The content of this article will undoubtedly encourage readers to do more work in this area.

Metal-Free Catalysis in C-C Single-Bond Cleavage: Achievements and Prospects.

This review article emphasizes the C-C bond cleavage in organic synthesis via metal-free approach. Conventional organic synthesis mainly deals with the reactive π bonds and polar σ bonds. In contrast, the ubiquitous C-C single bonds are inherently stable and are less reactive, which poses a challenge to synthetic chemists. Although inert, such C-C single-bond cleavage reactions have gained attention amongst synthetic chemists, as they provide unique and more straightforward routes, with significantly fewer steps. Several review articles have been reported regarding the activation and cleavage of C-C bonds using different transition metals. However, given the high cost and toxicity of many of these metals, the development of strategies under metal-free conditions is of utmost importance. Though many research articles have been published in this area, no review article has been reported so far. Herein, we discuss the reactions in a more concise way from the year 2012 to today, with emphasis on important reactions. Mechanisms of all the reactions are also well addressed. We believe that this review will be beneficial for the readers who work in this field.

Ten Years of Glory in the α-Functionalizations of Acetophenones: Progress Through Kornblum Oxidation and C-H Functionalization.

This review article focuses on the α-functionalization of acetophenones involving Kornblum oxidation and C-H functionalizations. Although various other strategies, such as classical approaches, enamine approaches and umpolung strategy are also known for this functionalization, here we discuss mainly the Kornblum oxidation approach and C-H functionalization strategy as they have advantages over the others. In Kornblum oxidation, the reaction uses iodine and dimethylsulfoxide and proceeds through the formation of arylglyoxal as the key intermediate. In C-H functionalization, the reaction requires metal, or metal-free catalyst, and generates radical intermediate in most cases. α-Functionalization of acetophenones is very important because of their huge applications in the synthesis of various natural products and pharmaceuticals and, therefore, a number of research articles have been published in this area. However, no review articles are available so far. In this article, we present a succinct discussion of various important and novel reactions, along with their mechanisms, published since 2012 to date. We believe that this first review article in this field will give readers one-stop information on this topic and encourage further intriguing work in this area.

Catalyst-free and additive-free reactions enabling C-C bond formation: a journey towards a sustainable future.

This review focuses on the catalyst- and additive-free C-C bond forming reactions reported mostly from the year 2005 to date. C-C bond forming reactions are highly important as large and complex organic molecules can be derived from simpler ones via these reactions. On the other hand, catalyst- and additive-free reactions are economical, environmentally friendly and less sensitive to air/moisture, allow easy separation of products and are operationally simple. Hence, a large number of research articles have been published in this area. Though a few reviews are available on the catalyst-free organic reactions, most of them were published a few years ago. The current review excludes catalysts as well as additives and is specific to only C-C bond formation. Besides many organic name reactions, catalyst/additive-free C-H functionalizations, coupling reactions and UV-visible-light-promoted reactions are also discussed. Undoubtedly, the contents of this review will motivate readers to do more novel work in this area which will accelerate the journey towards a sustainable future.

L-Proline-catalyzed regioselective C1 arylation of tetrahydroisoquinolines through a multicomponent reaction under solvent-free conditions.

Here we disclose the C1 arylation of tetrahydroisoquinolines (THIQ) through regioselective C(sp3)-H functionalization using a multicomponent reaction. The reaction was performed by reacting THIQ, aldehydes and aminopyrazoles or indoles under neat conditions with l-proline as a catalyst. The regioselectivity of the products was confirmed by X-ray analysis and spectroscopic data. The formation of an azomethine ylide intermediate is crucial for obtaining the regioselectivity.

Recent Advances on the C2-Functionalization of Indole via Umpolung.

Heterocyclic compounds having a nitrogen atom in the ring exhibit very interesting biological activities. Indole is the core structure of many bioactive compounds owing to its high affinity to bind with most biological targets. Indole is an electron-rich compound and generally prefers electrophilic rather than nucleophilic substitution. Hence, many important indole derivatives are difficult to synthesize through the conventional reactivity of indole. This limitation can be avoided by using the umpolung, from the German word meaning polarity inversion. In umpolung, the indole molecule, especially the C2 and C3 positions, behave as an electrophile. As C2-functionalized indoles have substantial importance in synthetic and pharmaceutical chemistry, this review focuses on the C2 umpolung of indoles via the indirect approach which is less explored. Unlike direct approaches of indole umpolung, indirect methods have several advantages and therefore a number of research articles have been published in this field. But no review is available up till now. This is the first review on this topic and we believe that it will surely motivate the readers to work in this area further.

Multi-component synthesis of 3-substituted indoles and their cyclisation to α-carbolines via I2-promoted intramolecular C2 oxidative amination/aromatisation at room temperature.

Condensation of indoles, aldehydes and pyrazol-5-amine in the presence of ceric ammonium nitrate gives 3-substituted indoles. These then cyclise to α-carbolines at room temperature through I2-promoted intramolecular C2 amination and aromatisation in open air. A plausible mechanism is proposed based on some controlled experiments.

Introducing tetramethylurea as a new methylene precursor: a microwave-assisted RuCl3-catalyzed cross dehydrogenative coupling approach to bis(indolyl)methanes.

Herein we report a microwave assisted Ru(iii)/TBHP-mediated reaction of indoles with tetramethylurea (TMU) synthesizing symmetrical as well as unsymmetrical bis(indolyl)methanes, where TMU acts as a methylenating agent. This is the first report where TMU is used as a methylene source. Moreover, the synthesis of unsymmetrical bis(indolyl)methanes by using a carbon precursor is also reported herein for the first time. Various substituted indoles are used for the reaction. The reaction is high yielding and takes a much shorter time to accomplish compared to the existing methods.

Synthesis of some novel annulated pyrido[2,3-d]pyrimidines via stereoselective intramolecular hetero Diels-Alder reactions of 1-oxa-1,3-butadienes.

Some novel annulated pyrido[2,3-d]pyrimidines 6 and 7 were synthesized stereoselectively by intramolecular hetero Diels-Alder reactions involving 1-oxa-1,3-butadienes.