C(sp2)-H functionalization in non-aromatic azomethine-based heterocycles

Direct C(sp2)-H functionalization of the endocyclic azomethine and aldonitrone moieties in non-aromatic azaheterocycles has established itself as a promising methodology over the last decade. Transition metal-catalyzed cross-coupling reactions, α-metalation-electrophile quenching protocols, and (metal-free) nucleophilic substitution of hydrogen reactions (SNH) are the major routes applied on cyclic imines and their derivatives. In this overview, we show the tangible progress made in this area during the period from 2008 to 2020. This journal is © The Royal Society of Chemistry.The research was financially supported by the Russian Science Foundation (Project No. 20-43-01004), a bilateral Russian Science Foundation (RSF) – Fund for Scientific Research Flanders (FWO) project, and the Francqui Foundation

C-H FUNCTIONALIZATION IN THE SYNTHESIS OF CARBORANE-BASED POLYAZAHATEROCYCLIC HYDROCARBONS

Among the versatile organic fluorophores, special attention is known to be paid to photoactive organoboron compounds, in particular heterocyclic derivatives of carborane. According to numerous studies, the ortho-carborane scaffold is considered to be an “element-block” for preparing solid state luminescent materials due to its excellent suppression of aggregation-caused quenching (ACQ). Carborane-based materials also currently find an application in catalysis, medicine, supramolecular chemistry and photovoltaics.The research was financially supported by the Russian Science Foundation (Project no. 20-43-01004), a bilateral Russian Science Foundation (RSF) – Fund for Scientific Research Flanders (FWO) project, and the Francqui Foundation

Synthesis of Functionalized Pyrazin-2(1 H)-ones via Tele-Nucleophilic Substitution of Hydrogen Involving Grignard Reactants and Electrophiles

The reaction of 6-chloro-1-methylpyrazin-2(1H)-one with Grignard reactants followed by quenching with different electrophiles gave access to a variety of 3,6-difunctionalized 1-methylpyrazin-2(1H)-ones. This regioselective three-component reaction represents the first example of a tele-nucleophilic substitution of hydrogen (S N H ) in which the anionic σ H adduct is quenched by electrophiles (other than a proton) before elimination takes place. Quenching the reaction with iodine (I 2 ) or bromine (Br 2 ) provides an alternative reaction pathway, yielding a 3-functionalized 6-chloro-1-methylpyrazin-2(1H)-one or 5-bromo-6-chloro-1-methylpyrazin-2(1H)-one, respectively. The halogens present offer opportunities for further selective transformations. Copyright © 2019 American Chemical Society

Multicomponent Synthesis of 4-Aminophthalazin-1(2H)-ones by Palladium-Catalyzed Isocyanide Insertion

4-Aminophthalazin-1(2H)-ones (APOs) are underexplored heterocyclic compounds with promising and diverse biological activities. The classical synthesis of these compounds is tedious and does not allow the regioselective introduction of substituents. Here, we present our full studies on the Pd-catalyzed cross-coupling of substituted o-(pseudo)halobenzoates and hydrazines with isocyanide insertion allowing straightforward access to diversely substituted APOs. We illustrate the advantages of this method compared to other approaches and describe solutions for the limitations we encountered. In addition, we have developed efficient diversifications of this heterocyclic scaffold that allow access to more diverse APOs as well as novel heterocyclic scaffolds. © 2013 American Chemical Society

Transition metal-catalysed carbene- and nitrene transfer to carbon monoxide and isocyanides

Transition metal-catalysed carbene- and nitrene transfer to the C1-building blocks carbon monoxide and isocyanides provides heteroallenes (i.e. ketenes, isocyanates, ketenimines and carbodiimides). These are versatile and reactive compounds allowing in situ transformation towards numerous functional groups and organic compounds, including heterocycles. Both one-pot and tandem processes have been developed providing valuable synthetic methods for the organic chemistry toolbox. This review discusses all known transition metal-catalysed carbene- and nitrene transfer reactions towards carbon monoxide and isocyanides and in situ transformation of the heteroallenes hereby obtained, with a special focus on the general mechanistic considerations

An evaluation of credentials of a multicomponent reaction for the synthesis of isothioureas through the use of a holistic CHEM21 green metrics toolkit

Multicomponent reactions (MCRs) are considered green and material efficient methods for the synthesis of organic compounds, however very few studies have investigated the metrics of the upstream processes involved to achieve the starting materials used in these reactions. A novel MCR-approach for the synthesis of N-cyclohexyl-S-methyl-N′-phenylisothiourea from S-methyl methanethiosulfonate, cyclohexyl isocyanide and aniline was appraised in terms of its green metrics using the CHEM21 green metrics toolkit and compared with those of the state of the art approach. The upstream process leading to the component starting materials for both approaches were also appraised to gain an insight into how the greenness of both methods translate from the raw materials to the final product

Synthesis of Heterocycles via Aerobic Ni-Catalyzed Imidoylation of Aromatic 1,2-Bis-nucleophiles with Isocyanides

o-Phenylene N-substituted iminocarbonates have been obtained by aerobic Ni-catalyzed reaction of readily available catechols and isocyanides. The choice of oxidant and absence of base proved crucial to avoid competitive catechol oxidation into (semi)quinone, leading to degradation. The developed protocol is generally applicable on other oxidation-sensitive aromatic 1,2-bisnucleophiles, generating a variety of important bicyclic heterocycles from readily available building blocks, hitherto only accessible via aerobic noble metal catalysis. Experimental studies suggest involvement of a Ni (H) -catecholate complex, which has been supported by density functional theory of the catalytic cycle. o-Phenylene N-substituted iminocarbonates demonstrated to be interesting platform molecules providing access to dialkyl N-substituted iminocarbonates, dialkyl N-substituted dithioiminocarbonates, and N,N',N ''-trialkyl guanidines via reaction with respectively alcohols, thiols, and amines. The catechol, which is concomitantly produced as a byproduct in these substitution reactions, can be recycled. 'When 4-propylcatechol, accessible from pine and clove tree feedstock, is applied, the leaving group is also biorenewable

Event report: SynBio Workshop (Paris 2012) - Risk assessment challenges of Synthetic Biology

In Europe and beyond, several advisory bodies have been monitoring the developments in the field of Synthetic Biology. Reports have been sent to national governments for information on the developments and possible regulatory and risk assessment questions raised by this field. To put the issues in a broader perspective, four national biosafety advisory bodies (the French High Council for Biotechnology, the German Central Committee on Biological Safety, the Netherlands Commission on Genetic Modification and the Belgian Scientific Institute of Public Health (Biosafety and Biotechnology Unit)) decided to join forces and organize an international scientific workshop to review some of the latest scientific insights and look into possible challenges in the risk assessment of Synthetic Biology. The SynBio Workshop (Paris 2012) - Risk assessment challenges of Synthetic Biology took place on the 12th of December 2012 and gathered scientists from biosafety advisory bodies from fifteen European countries, from the European Food Safety Authority as well as representatives of the European Commission, together with research scientists selected for their excellence in the field. The workshop was divided into two sessions: the first session gave an overview of four major fields in Synthetic Biology. The second session was set up for discussion with a scientific panel and the audience to identify and address relevant questions for risk assessment raised by recent and future developments of Synthetic Biology. An overview of the workshop and the discussion points put forward during the day are discussed in this document.</p