Photochemical Aminochlorination of Alkenes without the Use of an External Catalyst.

The niche field of photochemistry offers opportunities that are not found in "traditional" ground state chemical pathways. Aminochlorinated derivatives are an interesting family of 1,2-difunctionalised compounds that provide access to a variety of natural products and pharmaceutical active substances. A practical, catalyst-free chloroamination protocol is described herein, providing access to intermediates of great importance, utilising mild and photochemical reaction conditions (370 nm), where N-chlorosulfonamides are used as both nitrogen and chlorine sources. A wide variety of olefins, decorated with a plethora of functional groups, was tested providing excellent results (28 examples, 18-88 % yield). Mechanistic studies (UV-Vis, control experiments and quantum yield measurement) were also performed.

Cyrene: a bio-based solvent for the Mizoroki-Heck reaction of aryl iodides.

The development of greener and more sustainable methods, as well as the adaptation of already existing protocols to more environmentally friendly procedures, has become crucial for organic synthesis. The introduction and utilization of greener solvents is a very promising alternative, especially when they can replace toxic organic solvents in the known and widely used organic reactions. Cyrene has appeared to be an excellent alternative solvent for a number of organic reactions. In this work, the development of a new, greener and more economical protocol for the Mizoroki-Heck reaction is described, using Cyrene as the green solvent and Pd/C as the palladium catalyst source. A wide substrate scope for the coupling of aryl iodides with acrylamides, acrylates, acrylic acid, acrylonitrile and styrene was demonstrated. The recyclability of Cyrene and the leaching of palladium in the final product were examined in order to enhance the industrial applicability of this protocol. Furthermore, the synthesis of the natural product piperlotine A is reported.

A Unified Mechanism for the PhCOCOOH-mediated Photochemical Reactions: Revisiting its Action and Comparison to Known Photoinitiators.

Since 2014, we have introduced in literature the use of phenylglyoxylic acid (PhCOCOOH), a small and commercially available organic molecule, as a potent promoter in a variety of photochemical processes. Although PhCOCOOH has a broad scope of photochemical reactions that can promote, the understanding of its mode of action in our early contributions was moderate. Herein, we are restudying and revisiting the mechanism of action of PhCOCOOH in most of these early contributions, providing a unified mechanism of action. Furthermore, the understanding of its action as a photoinitiator opened a new comparison study with known and commercially available photoinitiators.

A sustainable photochemical aerobic sulfide oxidation: access to sulforaphane and modafinil.

Sulfoxide-containing molecules are an important class of compounds in the pharmaceutical industry and many efforts have been made to develop new and green protocols, targeting the chemoselective transformation of sulfides into sulfoxides. Photochemistry is a rapidly expanding research field employing light as the energy source. Photochemical aerobic processes possess additional advantages to photochemistry and may find applications in the chemical industries. Herein, a 370 nm catalyst-free aerobic protocol was developed, using 2-Me-THF as the green solvent. At the same time, two low-catalyst-loading anthraquinone-based processes (under a CFL lamp or 427 nm irradiation) in 2-Me-THF were developed. Furthermore, a broad range of substrates was tested. We also implemented our protocols towards the synthesis of the pharmaceutical active ingredients (APIs) sulforaphane and modafinil.

Thioxanthone: a powerful photocatalyst for organic reactions.

Photoorganocatalysis has been recognised by the organic chemistry community as an important part of photochemistry and catalysis. In general, aromatic ketones constitute key players in this type of catalysis as they are involved in a plethora of examples in the literature. Among the various aromatic ketones, thioxanthone (TX) seems to play a unique role in photochemistry. In comparison with other aromatic ketones, TX has a high triplet energy and a relatively long triplet lifetime, while it has the ability to participate successfully in merger reactions with metal complexes. In this review, we will discuss the photophysical properties of this small organic molecule, as well as the numerous examples of photochemical reactions, where it is employed as a mediator and more specifically in polymerisation reactions, and organic transformations.

Metal-catalyzed cycloisomerization as a powerful tool in the synthesis of complex sesquiterpenoids.

Covering: up to 2015Sesquiterpenoids are consistently attracting the interest of the scientific community due to their promising clinical profile as therapeutic agents. Cycloisomerization of enynes and dienes is a powerful tool in the hands of organic chemists to access them. In the last 20 years the field has witnessed remarkable advances, especially by revealing the capability of platinum and gold complexes to initiate such reactions. Nowadays, cycloisomerizations continue to enrich our knowledge with atom-economical routes and impressive cascades to reach more complex molecules. The current review covers the basic mechanistic aspects of metal catalysis in cycloisomerization reactions and their progress to the synthesis of selected complex sesquiterpenoids.

Organocatalytic activation of hydrogen peroxide: towards green and sustainable oxidations.

The advent of organocatalysis provided an additional option in every researcher's arsenal, towards the development of elegant and sustainable protocols for various organic transformations. Oxidation reactions are considered to be key in organic synthesis since oxygenated functionalities appear in many natural products. Hydrogen peroxide is categorized as a green oxidant, since its only by-product is water, offering novel opportunities for the development of green and sustainable protocols. In this review article, we intend to present recent developments in the field of the organocatalytic activation of hydrogen peroxide, providing useful insight into the applied oxidative protocols. At the same time, we will present some interesting mechanistic studies, providing information on the oxygen transfer processes.

Expanding the Use of Benzothioxanthene Imides to Photochemistry: Eco-Friendly Aerobic Oxidation of Sulfides to Sulfoxides.

The sulfoxide moiety is one of the most commonly utilized groups in pharmaceutical and industrial chemistry. The need for sustainability and easy accessibility to sulfoxide moieties is deemed necessary, due to its ubiquity in natural products and potentially pharmaceutically active compounds. In this context, we report herein a sustainable, aerobic and environmentally friendly photochemical protocol based on the use of a benzothioxathene imide as the photocatalyst to selectively oxidize sulfides under mild irradiation (456 nm), in very low catalyst loading (0.01 mol %) and on water. In addition, to demonstrate the compatibility of our protocol with wide scope of substrates, the latter was successfully applied to the synthesis of the biologically-active Sulforaphane and Modafinil.

Aerobic Photocatalysis: Oxidation of Sulfides to Sulfoxides.

Sulfoxides constitute one of the most important functional groups in organic chemistry found in numerous pharmaceuticals and natural products. Sulfoxides are usually obtained from the oxidation of the corresponding sulfides. Among various oxidants, oxygen or air are considered the greenest and most sustainable reagent. Photochemistry and photocatalysis is increasingly applied in new, as well as traditional, yet demanding, reaction, like the aerobic oxidation of sulfides to sulfoxides, since photocatalysis has provided the means to access them in mild and effective ways. In this review, we will summarize the photochemical protocols that have been developed for the oxidation of sulfides to sulfoxides, employing air or oxygen as the oxidant. The aim of this review is to present: i) a historical overview, ii) the key mechanistic studies and proposed mechanisms and iii) categorize the different catalytic systems in literature.

Hexafluoroisopropanol-Promoted or Brønsted Acid-Mediated Photochemical [2+2] Cycloadditions of Alkynes with Maleimides.

Although the use of light stimulating organic transformations has been known for more than a century, there is an increasing research interest on expanding the established knowledge. While [2+2] cycloadditions are promoted photochemically, literature precedent on the reaction between alkynes and maleimides is limited and only a handful of examples exist, focusing mainly on N-aliphatic maleimides. Herein, the differences in reactivity between N-alkyl and N-aryl maleimides were identified, and the use of hexafluoroisopropanol (HFIP) or trifluoroacetic acid (TFA) as viable solutions was proposed in order to achieve high yields. In the case of N-alkyl maleimides, both HFIP-mediated or TFA-promoted reactions were established using LED 370 nm irradiation, without the use of an external photocatalyst. In the case of N-aryl maleimides, thioxanthone (THX) was employed as the energy transfer photocatalyst along with LED 427 nm irradiation and HFIP. Mechanistic studies were performed, supporting the pivotal role of HFIP or TFA, in acquiring good to high yields in both classes of maleimides.

Synthesis of novel thiopurine pyranonucleosides: evaluation of their bioactivity.

We report the synthesis of novel thiopurine pyranonucleosides. Direct coupling of silylated 6-mercaptopurine and 6-thioguanine with the appropriate pyranoses 1a-e via Vorbrüggen nucleosidation, gave the N-9 linked mercaptopurine 2a-e and thioguanine 4a-e nucleosides, while their N-7 substituted congeners 10a-e and 7a-e, were obtained through condensation of the same acetates with 6-chloro and 2-amino-6-chloropurines, followed by subsequent thionation. Nucleosides 3a-e, 5a-e, 8a-e, and 11a-e were evaluated for their cytostatic activity in three different tumor cell proliferative assays.

N-substituted pyrrole-based scaffolds as potential anticancer and antiviral lead structures.

Undoubtedly, efficient cancer treatment has been a significant challenge for the scientific community over the last decades. Despite tremendous progress made towards this direction, there are still efforts needed to discover new anticancer drugs. In this work, a series of N-substituted pyrrolebased scaffolds have been synthesized and evaluated for antiproliferative activity against a panel of cancer cell lines (L1210, CEM and HeLa). Furthermore, in order to discover new scaffolds as antiviral agents, all the examined compounds were evaluated for activity against different types of DNA and RNA viruses. The key feature of the above structures is the existence of an aromatic ring with at least one hydrogen-bonding donor and acceptor group. Results have shown noteworthy cytostatic activity for three of the synthesized compounds (1, 3 and 9). Especially, compound 1, containing a tropolone ring, proved to be the most promising scaffold (IC50:10-14 µM) for the development of novel potential anticancer agents. In addition, compound 1 has shown modest anti-HSV-1, -HSV2 activity in HEL cell cultures (EC50: 27-40 µM).

Stereoselective facile synthesis of 2'-spiro pyrimidine pyranonucleosides via their key intermediate 2'-C-cyano analogues. Evaluation of their bioactivity.

A novel series of 2'-spiro pyrimidine pyranonucleosides has been designed and synthesized. Their precursors, 2'-C-cyano nucleosides 5a,b and 6a,b, were obtained by subjecting 1a,b to the sequence of selective protection of the primary hydroxyl group, acetalation, oxidation, and finally treatment with sodium cyanide. Deoxygenation at the 2'-position of cyanohydrins 5a,b or 6a,b led to the 2'-deoxy derivatives 9a,b. Fully deprotection of 5a,b, 6a,b, and 9a,b gave the desired 2'-C-cyano 7a,b, 8a,b, and 2'-C-cyano-2'-deoxy pyranonucleosides 10a,b, respectively. Mesylation of the corresponding cyanohydrins 5a,b and 6a,b afforded compounds 11a,b and 12a,b which after base treatment and subsequent deprotection furnished the spiro nucleosides 15a,b and 16a. The new analogues were evaluated for their potential cytostatic activities in cell culture.