Current Organic Chemistry - Volume 25, Issue 18, 2021

The Pd^II-mediated cross-coupling of (hetero)arenes with alkenes may be an effective method for the formation of a C–C bond from two C–H bonds. This reaction was discovered by Fujiwara and his co-workers in 1967, which led to a number of reports that we first highlighted in 2011 (review with references till June 2010) and for which we retained the name “Dehydrogenative Heck Reaction” (DHR). The DHR of six-membered heteroarenes has been the subject of intensive research over the last ten years. The present review is limited to these dehydrogenative Heck reactions published since 2010, underlining the diversity of the procedures, mechanisms and intermediates that have been proposed along with some personal comments.

Selenium-containing heteroarenes consist of a synthetically valuable family of compounds that found applications in many different areas, such as organic synthesis, medicinal chemistry, supramolecular chemistry, and optoelectronic devices construction. Over the past decade, many advances have been achieved to the synthesis of these substances, and this review aims to cover a literature survey of the direct selenylation of heteroarenes under metal-free conditions, which represents one of the most powerful synthetic strategies for the preparation of those target molecules. The construction of new C-Se bonds through selective C-H functionalization reactions has become useful and atom-economical. The widespread adoption of metalfree approaches has emerged as a versatile, sustainable, and safe access to these organoselenium compounds. Among the features of these new protocols is the use of mild oxidants and A R T I C L E H I S T O R Y halogen-based catalysts, inorganic bases, as well as photo-induced reactions, and electrosynthesis.

The use of F-based decorations in drug discovery started from the development of fluorocorticoids and fluorochinolones (1950s and 1980s respectively) and it resulted in about 20% of approved drugs on the Market containing fluorine. From a medicinal chemistry perspective, the installation of F-based small groups (e.g. -CF3, -CF2H, -OCF3, -OCF2H, -SCF3, - SCF2H) necessarily impacts on physicochemical, pharmacokinetics, pharmacodynamics and toxicological properties of small molecules. Accordingly, a huge interest on this topic is constantly arising in the medicinal chemistry community. Focusing on heteroarenes, the synthetic access to these substitutions is guaranteed by a number of effective reactions, such as Miniscitype reaction, photochemistry or electrochemistry C-H activation. The aim of this work is to analyze the rational in using these groups in medicinal chemistry and to highlight the current available synthetic toolbox of C-H activation for their introduction on heteroarenes of pharmaceutical interest. A particular focus has been given to those procedures amenable at late-stage functionalisation process.

The functionalization of a Csp2-H bond of an heteroarene with an alkyne represent one of the most attractive procedure for the late-stage functionalization of the aromatic core, due to the structural characteristics and synthetic versatility given by a triple carbon-carbon bond. The aim of this review is to cover the most significant results reported in the literature regarding the synthesis of alkynyl-substituted five-membered heteroarenes by selective direct Csp2-H alkynylation with 1-haloalkynes and analogues, or by cross-dehydrogenative alkynylation (CDA) with terminal alkynes, without making use of directing groups.

Coumarin-based derivatives have easy modification and tunable properties and have been synthesized and applied in many areas including pro-drugs, biomedical materials, and chemical and biological sensing. In this review, recent advances of coumarin-based fluorescent probes for biosensing are reported for metal ion imaging. Metal detection in living cells are highlighted with representative examples together with fluorescence response mechanisms such as Photoinduced Electron Transfer (PET), Intramolecular Charge Transfer (ICT), and Fluorescence Resonance Energy Transfer (FRET). Some future perspectives are also briefly mentioned.