Current Organic Chemistry - Volume 26, Issue 5, 2022

Chiral ligands are the footstones for asymmetric synthesis, constructing the enantioenriched molecules that are widely used in material and medicinal sciences. Naturally occurring compounds, such as proline analogues and cinchona alkaloids, are widely used as privileged ligands in asymmetric synthesis. Sparteine, a natural alkaloid firstly reported in 1968, was also employed in asymmetric synthesis, albeit with less satisfactory results. In this perspective, transition metal-involved asymmetric transformations using sparteine or family members as ligands are overviewed and discussed. The design and perspective of ligands with similar skeleton are also proposed.

This perspective highlights a new environmentally benign strategy for the introduction of phosphate functionality into organic substrates via activated cyclic oligometaphosphates. The use of these novel phosphorylating reagents greatly simplify the synthesis of nucleoside mono- and polyphosphates and provides a platform to access diverse phosphorylated amino acids, peptides, sugars, and other phosphorus-containing fine chemicals. The new phosphorylation protocol represents an advance in terms of atom-efficiency, regioselectivity, functional tolerance and safety for the environment.

Among the different synthetic procedures available where the reactivity of substances is exploited using solid-state chemistry, such as microwave irradiation, ultrasound (sonochemistry), photochemistry, and mechanochemistry, the latter stands out as a synthetic tool in various areas of chemistry and materials sciences, acquiring great relevance in recent years. Thus, mechanochemistry has been applied in different areas, such as organic synthesis, preparation of metal complexes, multicomponent pharmaceutical solid forms, catalysis, polymers, etc. However, despite the attractiveness of this sustainable technique, its application in the synthesis of coordination and organometallic compounds has been very incipient. On the other hand, pincer compounds have been a privileged ligand platform that has been profusely used for the synthesis of organometallic and coordination compounds for the last 20 years, finding applications in a large number of areas of chemistry, this being particularly true in the case of catalysis, being able to activate bonds difficult to activate, such as C-H bonds, due in part to their characteristic thermal robustness. Thus, on this perspective paper, we present the current state of mechanochemistry in the preparation of organometallic pincer compounds and discuss future perspectives for the synthesis of these foremost interesting species via mechanochemistry.

Coumarin derivatives occur widely in nature and are a part of both traditional and modern advancements in synthesis and application. To date, thousands of coumarin derivatives have been synthesized in lab or isolated from plant and marine life. These are essentially 2- pyrone core fused with a benzene ring and belong to the family of aromatic oxygen heterocycles. Coumarin in conjugation with various other heterocyclic systems has provided a robust framework for tuning the properties associated with the parent structure. The frequency of reports has increased for these biheterocyclic systems from the mid twentieth century. Biheterocyclic coumarins have also attracted the attention of many organic and pharmaceutical chemists as these systems serve as useful synthetic intermediates in the synthesis of analogs of existing drugs. Their application in the design of effective organocatalysts and chemosensors has further extended their versatility. Coumarin biheterocyclic core is utilized in the rational design and tuning of complex molecular entities in molecular recognition, analytical and material chemistry. This review highlights the advancements in the synthesis and applications of coumarin-linked nitrogen, oxygen, and sulfur heterocycles. It also provides an account of five-, six-, and seven-membered heterocyclic rings linked to coumarin core. Critical physicochemical properties coupled with their application will make this review useful for synthetic chemists and drug discovery labs. A comprehensive spectrum of literature in this review will facilitate further development of biheterocycles along with their promising applications in the future.

A pinacol rearrangement is a well-known reaction by which a 1,2-diol is converted to a carbonyl compound through acid-catalyzed dehydration followed by a 1,2-migration of one of the neighboring substituents. Due to the particular abilities in installing polycyclic skeletons, quaternary carbon centers, and spirocyclic cores, the pinacol rearrangement reaction is a powerful and effective means of forming carbonyl functional groups in a variety of different molecules. Moreover, the substrates with an alkene group, a furan ring or alkyl chain tethered between the two diols have also been investigated as the expansion of pinacol rearrangement. Benefiting from the continuous development of the catalysis methodologies, pinacol rearrangements demonstrate synthetic utility in the preparation of natural products, bioactive molecules, and other functionally useful compounds. In this review, we discuss recent advances in the development of pinacol rearrangement and extended pinacol rearrangement reactions catalyzed by Brønsted acid, Lewis acid, and heterogeneous catalysts. In addition, we summarize several examples use pinacol rearrangements used in the synthesis of natural products and other valuable molecules.

Diazomethane and trimethylsilyl diazomethane are common and versatile reagents in organic synthesis and they are unique as reactants in synthetic methodology. These reagents may be used in esterification, dipolar cycloaddition, epoxidation, aziridination, cyclopropanation, and carbonyl homologation. The lack of practical, scalable methods for the construction of cyclopropanes is a long-standing problem in industrial chemistry and diazomethane/ trimethylsilyl diazomethane has the potential to significantly reduce the cost of bringing new cyclopropane-bearing compounds to market. The transition metal-mediated reactions of diazomethane and trimethylsilyl diazomethane with alkenes, terminal alkynes and carbonyl compounds are being discussed in this article. The mechanism of different coupling, insertion and rearrangement reactions are also explored in this review article. The toxicity and explosive nature of diazomethane/ trimethylsilyl diazomethane are known to all, but concurrently, their efficacy and significant role as the reagents in synthetic transformation can’t be ignored. The untoward properties of diazomethane and trimethylsilyl diazomethane combined with its versatility, make the identification of safe protocols for its use. Considering the importance of these reagents, a concise review is needed. This article will highlight recent metalmediated reactions of diazomethane and trimethylsilyl diazomethane compounds that have been reported from 2000 until 2020.

Background: A direct synthesis of functionalized spiro[oxindole-3,3'-pyrrolines] is achieved via thermodynamic control (~60 oC), three-component 1,4-dipolar cycloaddition reaction involving 3-phenylimidazo[5,1-a]isoquinoline, dimethyl acetylenedicarboxylate, and N-alkylisatins. Methods: Conversely, this one-pot reaction furnished, upon conduction at 25-38 oC, the expected 1,3-oxazepino[7,6-b]indoles as the main kinetic control products. The calculated energy of the optimized molecular structures of model spiro-oxindole and its isomeric oxazepinoindole indicate that spiro-oxindole is more stable by 76.1 kJ/mol. Results: The structures of the synthesized spiro adducts were evidenced from NMR and MS spectral data and further confirmed by single-crystal X-ray diffraction. Characteristic features of the spiro-oxindoles are displaced in their ¹³C-spectra as diagnostic signals at ~53 and ~70 ppm assigned, respectively, to the spiro carbon-3 and sp3 CH-2' of the pyrroline ring. Conclusion: This unprecedented thermally induced pathway in 1,4-dipolar cycloaddition, utilizing imidazo[5,1- a]isoquinoline and related congeners, would serve as a new route towards the synthesis of spiro[oxindole-3,3'- pyrrolines], a class of diverse biological activities. An insight into the thermodynamic control pathway is presented.