Alkenyl chlorides constitute a synthetically valuable yet historically underexplored class of organohalides. First prepared in 1868 by Charles Friedel – best known for the Friedel–Crafts reaction – via the reaction of ketones with phosphorus pentachloride, these compounds have steadily gained attention over the decades. In recent years, their distinct reactivity and potential in organic synthesis have been increasingly recognized. This review provides a comprehensive overview of the synthesis and application of alkenyl chlorides, with a focus on developments over the past four decades. By organizing this growing body of work, I aim to highlight key advances and help guide the design of new transformations involving this important and versatile functional group.

An atom- and step-economical electrochemical method for the synthesis of aliphatic nitro-NNO-azoxy compounds from the corresponding nitroso compounds was developed employing ammonium dinitramide, a prospective green oxidant for aerospace propulsion applications, as both electrolyte and source of a =NNO2 group. The developed method is green, practical, and scalable due to constant current electrolysis in an undivided cell at high current densities. Synthesized products demonstrated pronounced NO-donor activity and fungicidal activity against phytopathogenic fungi.

A novel route to the flavor enhancer ethylmaltol, a synthetic 4-pyrone, from naturally abundant maltol is disclosed. Two strategies were explored for the required C1 homologation. The most direct approach, C–C bond formation via methylation of a dianionic intermediate, proved unsuitable due to competing overalkylation and the necessity of sub-zero temperatures. In contrast, a transient protecting group approach enabled selective methylation under mild conditions. This culminated in a scalable, operationally simple one-pot synthesis of ethylmaltol from a renewable precursor.

The total synthesis of new members of prenylated indole alkaloids exhibiting α-glucosidase activity is described. Asperdinones B, C, D, and E are characterized by the presence of a (3R)-3-indolylmethylbenzodiazepine-2,5-dione unit at C-3 of C4–C7 prenylated indoles. Methods of direct and indirect prenylation of indole and tryptophan were explored. Different approaches were adopted for the functionalization of C4–C7 prenylindoles at C-3 using Negishi cross-coupling methods. The asperdinones are among the rare tryptophan-derived indole alkaloids which appear to have undergone epimerization due to genetic alteration of specific gene clusters that code for a (3R) configuration.

The use of 1,3-diamino-2-propanol with competitive N- and O-nucleophilic centers in a three-component cyclization with ethyl 4,4,4-trifluoroacetoacetate and methyl ketones enables the synthesis to be carried out for octahydropyrido[1,2-a]pyrimidin-6-ones and hexahydrooxazolo[3,2-a]pyridin-5-ones, the preferential formation of which depends on the substituent in the methyl ketone component. Dual acid–base catalysis of the reactions with alkyl methyl ketones increases the regioselectivity in the synthesis of octahydropyrido[1,2-a]pyrimidinones. The cyclization with acetophenone is characterized by the regiospecific generation of these bicycles. The presence of three chiral centers in the synthesized bicycles, depending on the alkyl substituent, causes the formation of two to four diastereomers, the structure of which has been determined with 1H, 19F, 13C, 2D 1H-13C HSQC/HMBC, 1H-1H COSY/NOESY NMR and X-ray diffraction analysis.

The synthesis of trifluoromethylated isothiazolium thiocyanates and 4-thiocyanato-2,5-dihydrofurans is presented through hydrothiocyanation/cyclization of CF3-iminopropargyl alcohols using NaSCN in AcOH/MeCN. The formation of the two products can be explained by different directions of cyclization of the primary adducts of thiocyanic acid at the triple bond – vinyl thiocyanates. This protocol features simple operating, readily prepared starting materials and occurs under relatively mild conditions.

In this paper, the mechanism of the hydroxy(tosyloxy)iodobenzene (HTIB)-mediated conversion of chalcones (α,β-unsaturated carbonyl compounds) to ditosyloxy ketones is investigated. Here, at β-carbon of the chalcone, an aryl group with a para-substituent is present. Our study focuses on investigating the effect of different nature of para-substituents on the reaction mechanism. The substituents considered in the study include -OCH3, -SCH3, -Cl and -NO2 groups. For these chalcones, different possible pathways at various steps during the reaction are investigated leading to formation of α,β-ditosyloxy ketones and β,β-ditosyloxy ketones. It is found that the mechanism for the formation of α,β-ditosyloxy ketone involves only electrophilic addition of HTIB, and the mechanism is the same for all studied chalcones, irrespective of whether an electron-donating or electron-withdrawing substituent is present on the aryl ring. However, the detailed mechanism for the formation of β,β-ditosyloxy ketones is different and depends on the nature of the substituent. Broadly, the formation of β,β-ditosyloxy ketones involves electrophilic addition followed by 1,2-aryl migration. Our study shows that the presence of an electron-donating group on the migrating aryl ring favours the formation of β,β-ditosyloxy ketones while in case of electron-withdrawing groups, there are nearly equal chances of the formation of α,β-ditosyloxy ketones and β,β-ditosyloxy ketones.

The Veratrum alkaloids constitute a class of natural products with particularly intricate polycyclic frameworks and dense stereochemistry and, thus, have stood long as benchmarks in chemical synthesis. Recently, these steroid alkaloids gained popularity as challenging targets in total synthesis, with a clear shift toward convergent strategies. Not only do these syntheses feature rapid assembly of their challenging cores through modular and strategic bond connections, but they also give a reflection on the advancement of modern synthetic methods and retrosynthetic logic. This review will cover recent syntheses, highlighting the convergence of modern strategic disconnections, stereocontrol, and late-stage functionalization for rapid access to these exceptional alkaloids, while also showcasing the evolution of the art of synthesis and its ability in meeting the demands posed by molecular complexity.

New tetra- and pentacyclic derivatives of the dibenzo[c,f][1,2]thiazepine ring system have been synthesized. The target compounds contain methylenedioxy or ethylenedioxy substituents linked to the benzene ring. The key step for the construction of the ring systems has been implemented by an intramolecular Friedel–Crafts cyclization. Altogether eight new ring systems are described here, five of them are also characterized by single-crystal X-ray diffraction.

Herein, we report a concise chemoenzymatic synthesis of the cardenolide rhodexin A in 9 steps and the first protecting-group-free synthesis of its aglycone sarmentogenin in 7 steps from 17-deoxycortisone. The synthesis features a scalable enzymatic C14–H α-hydroxylation, a Bestmann ylide-enabled one-step construction of the butenolide motif, a late stage Mukaiyama hydration, and a stereoselective C11 carbonyl reduction.