Current Organic Synthesis - Volume 16, Issue 4, 2019

Background: Oxabenzonorbornadiene (OBD) is a useful synthetic intermediate capable of undergoing multiple types of transformations due to three key structural features: a free alkene, a bridged oxygen atom, and a highly strained ring system. Most notably, ring-opening reactions of OBD using transition metal catalysts and nucleophiles produce multiple stereocenters in a single step. The resulting dihydronaphthalene framework is found in many natural products, which have been shown to be biologically active. Objective: This review will provide an overview of transition metal-catalyzed reactions from the past couple of years including cobalt, copper, iridium, nickel, palladium and rhodium- catalyzed reactions. In addition, the recent derivatization of OBD to cyclopropanated oxabenzonorbornadiene and its reactivity will be discussed. Conclusion: It can be seen from the review, that the work done on this topic has employed the use of many different transition metal catalysts, with many different nucleophiles, to perform various transformations on the OBD molecule. Additionally, depending on the catalyst and ligand used, the stereo and regioselectivity of the product can be controlled, with proposed mechanisms to support the understanding of such reactions. The use of palladium has also generated a cyclopropanated OBD, with reactivity similar to that of OBD. An additional reactive site exists at the distal cyclopropane carbon, giving rise to three types of ring-opened products.

During the last few years, the preparation of bifunctional fluorescent probes, which exhibit differential response towards multiple analytes, has attracted considerable attention since they are cost-effective and highly desirable for real-time applications. This review focuses on the recent advances in the design principles, recognition mechanisms, and applications of multifunctional fluorescent probes for the differential detection of multiple guests.

Background: The inherent glycosidase inhibitory activity and potentially therapeutic value of the polyhydroxylated pyrrolizidine alkaloids containing a hydroxymethyl substituent at the C-3 position have been well documented. Belonging to this class, the naturally occurring hyacinthacine C-type alkaloids are of general interest among iminosugar researchers. Their selective micromolar α -glycosidase inhibitory ranges (10 – 100 μM) suggest that these azasugars are potential leads for treating type II diabetes. However, the structures of hyacinthacine C1, C3 and C4 are insecure with hyacinthacine C5 being recently corrected. Objective: This review presents the hyacinthacine C-type alkaloids: their first discovery to the most recent advancements on the structures, biological activities and total synthesis. Conclusion: The hyacinthacine C-type alkaloids are of exponentially increasing interest and will undoubtedly continue to be reported as synthetic targets. They represent a challenging but rewarding synthetic feat for the community of those interested in accessing biologically active iminosugars. Since 2009, ten total syntheses have been employed towards accessing similarly related products but only three have assessed the glycosidase inhibitory activity of the final products. This suggests the need for an accessible and universal glycosidase inhibitory assay so to accurately determine the structure-activity relationship of how the hyacinthacine C-type alkaloids inhibit specific glycosidases. Confirming the correct structures of the hyacinthacine C-type alkaloids as well as accessing various analogues continues to strengthen the foundation towards a marketable treatment for type II diabetes and other glycosidase related illnesses.

Background: The Hirao reaction discovered ca. 35 years ago is an important P–C coupling protocol between dialkyl phosphites and aryl halides in the presence of Pd(PPh3)4 as the catalyst and a base to provide aryl phosphonates. Then, the reaction was extended to other Preagents, such as secondary phosphine oxides and H-phosphinates and to other aryl and hetaryl derivatives to afford also phosphinic esters and tertiary phosphine oxides. Instead of the Pd(PPh3)4 catalyst, Pd(OAc)2 and Ni-salts were also applied as catalyst precursors together with a number of mono- and bidentate P-ligands. Objective: In our review, we undertook to summarize the target reaction with a special stress on the developments attained in the last 6 years, hence this paper is an update of our earlier reviews in a similar topic. Conclusions: “Greener” syntheses aimed at utilizing phase transfer catalytic and microwave-assisted approaches, even under “P-ligand-free. or even solvent-free conditions are the up-to date versions of the classical Hirao reaction. The mechanism of the reaction is also in the focus these days.

Background: Transition metal-catalyzed reactions of alkynyl halides are a versatile means of synthesizing a wide array of products. Their use is of particular interest in cycloaddition reactions and in constructing new carbon-carbon and carbon-heteroatom bonds. Transition metal-catalyzed reactions of alkynyl halides have successfully been used in [4+2], [2+2], [2+2+2] and [3+2] cycloaddition reactions. Many carbon-carbon coupling reactions take advantage of metal-catalyzed reactions of alkynyl halides, including Cadiot-Chodkiewicz, Suzuki-Miyaura, Stille, Kumada-Corriu and Inverse Sonogashira reactions. All the methods of constructing carbon-nitrogen, carbon-oxygen, carbon-phosphorus, carbon-sulfur, carbon-silicon, carbon-selenium and carbon-tellurium bonds employed alkynyl halides. Objective: The purpose of this review is to highlight and summarize research conducted in transition metalcatalyzed reactions of alkynyl halides in recent years. The focus will be placed on cycloaddition and coupling reactions, and their scope and applicability to the synthesis of biologically important and industrially relevant compounds will be discussed. Conclusion: It can be seen from the review that the work done on this topic has employed the use of many different transition metal catalysts to perform various cycloadditions, cyclizations, and couplings using alkynyl halides. The reactions involving alkynyl halides were efficient in generating both carbon-carbon and carbonheteroatom bonds. Proposed mechanisms were included to support the understanding of such reactions. Many of these reactions face retention of the halide moiety, allowing additional functionalization of the products, with some new products being inaccessible using their standard alkyne counterparts.

Background: 5-Hydroxymethylfurfural (5-HMF) is a biomass-derived platform chemical, which can be produced from carbohydrates. In the past decades, 5- HMF has received tremendous attention because of its wide applications in the production of various value-added chemicals, materials and biofuels. The manufacture and the catalytic conversion of 5-HMF to simple industrially-important bulk chemicals have been well reviewed. However, employing 5-HMF as a building block in organic synthesis has never been summarized exclusively, despite the rapid development in this area. Objective: The aim of this review is to bring a fresh perspective on the use of 5-HMF in organic synthesis, to the exclusion of already well documented conversion of 5-HMF towards relatively simple molecules such as 2,5-furandicarboxylic acid, 2,5-dimethylfuran and so on notably used as monomers or biofuels. Conclusion: As it has been shown throughout this review, 5-HMF has been the object of numerous studies on its use in fine chemical synthesis. Thanks to the presence of different functional groups on this platform chemical, it proved to be an excellent starting material for the preparation of various fine chemicals. The use of this C-6 synthon in novel synthetic routes is appealing, as it allows the incorporation of renewable carbonsources into the final targets.

Recent advances in the application of environmentally benign acid catalysts in organic synthesis are reviewed. The work includes three main parts; (i) description of environmentally benign acid catalysts, (ii) synthesis with heterogeneous and (iii) homogeneous catalysts. The first part provides a brief overview of acid catalysts, both solid acids (metal oxides, zeolites, clays, ion-exchange resins, metal-organic framework based catalysts) and those that are soluble in green solvents (water, alcohols) and at the same time could be regenerated after reactions (metal triflates, heteropoly acids, acidic organocatalysts etc.). The synthesis sections review a broad array of the most common and practical reactions such as Friedel-Crafts and related reactions (acylation, alkylations, hydroxyalkylations, halogenations, nitrations etc.), multicomponent reactions, rearrangements and ring transformations (cyclizations, ring opening). Both the heterogeneous and homogeneous catalytic synthesis parts include an overview of asymmetric acid catalysis with chiral Lewis and Brønsted acids. Although a broad array of catalytic processes are discussed, emphasis is placed on applications with commercially available catalysts as well as those of sustainable nature; thus individual examples are critically reviewed regarding their contribution to sustainable synthesis.