The synthesis of cannabigerol—a cannabinoid with significant pharmaceutical potential—is described. The synthesis involves four stages. In the first step, (E)-non-3-en-2-one reacts with dimethyl malonate to yield a cyclic enone, which is subsequently oxidized with bromine to produce the olivetol ester. This ester then undergoes an alumina-catalyzed coupling reaction with geraniol, followed by ester hydrolysis to obtain cannabigerol. By modifying the chain length of the enone in the initial step and employing allylic alcohols other than geraniol, a range of cannabigerol derivatives can be synthesized, including the natural product cannabigerovarin.

Photocatalytic decarboxylation of carboxylic acids or their redox active esters has become an important strategy in organic chemistry. Using catalytic amounts of metal-based or organic photocatalysts, normally under visible light irradiation, these substrates generate carbon centered radicals, which have been applied to a broad range of C-C and C-heteroatom bond forming reactions. Addition reaction to electron-deficient alkenes, hydroalkylation of unsaturated C-C bonds and addition to C-heteroatom multiple bonds have been extensively studied. Cross-coupling reactions such as arylation, alkylation, allylation, vinylation, alkynylation, acylation, cyanation and C-H functionalization reactions are also successfully performed. In the case of C-heteroatom bond forming reactions, C-halogen, C-oxygen, C-sulfur, C-nitrogen, C-phosphorus, C-boron and C-silicon are fundamental functionalization processes. Hydro- and deuterodecarboxylation reactions allow the substitution of the carboxylic group by a hydrogen or a deuterium atom regioselectively. Finally, decarboxylative elimination reactions, such as olefination reactions for the synthesis of alkenes and decarboxylative C-C bond cleavage of cyclic carboxylic acids, give 1,n-dicarbonyl compounds. These photoredox transformations, a renaissance in organic chemistry, starting from readily accessible carboxylic acids widely available in Nature and the pharma industry with a great structural diversity occur under mild and simple reaction conditions with excellent efficiency and clean energy input.

The deacetylative reaction of 3-acetyl-3-fluoro-2-oxindoles with a mild base promotes the in situ generation of 3-fluoro-2-oxindole enolates which react with aliphatic N-tert-butanesulfinyl imines via the Mannich-type reaction generating alpha-fluoro beta-sulfinylamino oxindoles in a diastereoselective way. The orientation of the attack of the enolate to the imine was computationally investigated, and the analysis of the absolute configuration of the resulting products was performed according to vibrational circular dichroism.

The stereoselective synthesis of vicinal amino alcohols derivatives from 1-substituted cyclopropanols and chiral N-tert-butanesulfinyl imines is described. Cyclopropanols are easily prepared from carboxylic esters upon reaction with ethylmagnesium bromide in the presence of titanium tetraisopropoxide and undergo carbon-carbon bond cleavage by means of diethylzinc to produce, upon base deprotonation, enolized zinc homoenolates, which react with chiral sulfinyl imines in a highly regio- and stereoselective manner.

The asymmetric catalytic synthesis of 1,2-diamines has received considerable interest, especially in the last ten years, due to their presence in biologically active compounds and their applications for the development of synthetic building blocks, chiral ligands and organocatalysts. Synthetic strategies based on C-N bond-forming reactions involve mainly (a) ring opening of aziridines and azabenzonorbornadienes, (b) hydroamination of allylic amines, (c) hydroamination of enamines and (d) diamination of olefins. In the case of C-C bond-forming reactions are included (a) the aza-Mannich reaction of imino esters, imino nitriles, azlactones, isocyano acetates, and isothiocyanates with imines, (b) the aza-Henry reaction of nitroalkanes with imines, (c) imine-imine coupling reactions, and (d) reductive coupling of enamines with imines, and (e) [3+2] cycloaddition with imines. C-H bond forming reactions include hydrogenation of CN bonds and C-H amination reactions. Other catalytic methods include desymmetrization reactions of meso-diamines.

The pseudo-multicomponent reaction between propargyl amine, an aldehyde and an electron-deficient alkene is described. The C-H activation takes place thermally and allows the obtaining of cycloadducts in very good yields with high diastereoselectivities. The relative configuration is determined by X-ray diffraction analysis of the chiral molecule, obtained as a single diastereoisomer, using a chiral maleimide. A brief study of the stability of the possible ylides involved in the process is also mentioned, confirming the high diastereoselectivity observed. The high functional group density of these cycloadducts permits the synthesis of complex heterocycles. After allylation or propargylation of the pyrrolidine nitrogen atom, RCM-DA cycloaddition or cyclotrimerization with an alkyne is studied, respectively. In this last example, the resulting tetracyclic structures are of potential interest as drugs for the treatment of cystic fibrosis.

The synthesis of 4-arylthiazol-2(3H)-ones is reported employing a novel and mild methodology using benign solvents. In a second objective the multicomponent preparation of 5,5’-methylenebis[4-arylthiazol-2(3H)-ones] is described following the same strategy. The analysis of the mechanism is also studied and confirmed using chemical tests.

An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.

The N-tert-butanesulfinylimine group behaves as a suitable electron-withdrawing group in 1-azadienes, allowing the diastereoselective synthesis of densely substituted pyrrolidines by 1,3-dipolar cycloadditions (1,3-DCs) with azomethylene ylides. The use of Ag2CO3 as catalyst has allowed one to obtain a wide variety of proline derivatives with high regio- and diastereoselectivities. Subsequent efficient transformations provide valuable proline derivatives, some of which can be used as organocatalysts. The influence of the N-tert-butanesulfinyl group on the diastereoselectivity was studied by computational methods.

Enantioconvergent catalysis has expanded asymmetric synthesis to new methodologies able to convert racemic compounds into a single enantiomer. This review covers recent advances in transition-metal-catalyzed transformations, such as radical-based cross-coupling of racemic alkyl electrophiles with nucleophiles or racemic alkylmetals with electrophiles and reductive cross-coupling of two electrophiles mainly under Ni/bis(oxazoline) catalysis. C-H functionalization of racemic electrophiles or nucleophiles can be performed in an enantioconvergent manner. Hydroalkylation of alkenes, allenes, and acetylenes is an alternative to cross-coupling reactions. Hydrogen autotransfer has been applied to amination of racemic alcohols and C-C bond forming reactions (Guerbet reaction). Other metal-catalyzed reactions involve addition of racemic allylic systems to carbonyl compounds, propargylation of alcohols and phenols, amination of racemic 3-bromooxindoles, allenylation of carbonyl compounds with racemic allenolates or propargyl bromides, and hydroxylation of racemic 1,3-dicarbonyl compounds.

The stereocontrolled synthesis of 1-substituted homotropanones, using chiral N-tert-butanesulfinyl imines as reaction intermediates, is described. The reaction of organolithium and Grignard reagents with hydroxy Weinreb amides, chemoselective N-tert-butanesulfinyl aldimine formation from keto aldehydes, decarboxylative Mannich reaction with β-keto acids of these aldimines, and organocatalyzed L-proline intramolecular Mannich cyclization are key steps of this methodology. The utility of the method was demonstrated with a synthesis of the natural product (−)-adaline, and its enantiomer, (+)-adaline.

Alien species must adapt to new biogeographical regions to acclimatise and survive. We consider a species to have become invasive if it establishes negative interactions after acclimatisation. Xylella fastidiosa Wells, Raju et al., 1986 (XF) represents Italy's and Europe's most recent biological invasion. In Apulia (southern Italy), the XF-encountered Philaenus spumarius L. 1758 (Spittlebugs, Hemiptera: Auchenorrhyncha) can acquire and transmit the bacterium to Olea europaea L., 1753. The management of XF invasion involves various transmission control means, including inundative biological control using Zelus renardii (ZR) Kolenati, 1856 (Hemiptera: Reduviidae). ZR is an alien stenophagous predator of Xylella vectors, recently entered from the Nearctic and acclimated in Europe. Zelus spp. can secrete semiochemicals during interactions with conspecifics and prey, including volatile organic compounds (VOCs) that elicit conspecific defence behavioural responses. Our study describes ZR Brindley's glands, present in males and females of ZR, which can produce semiochemicals, eliciting conspecific behavioural responses. We scrutinised ZR secretion alone or interacting with P. spumarius. The ZR volatilome includes 2-methyl-propanoic acid, 2-methyl-butanoic acid, and 3-methyl-1-butanol, which are consistent for Z. renardii alone. Olfactometric tests show that these three VOCs, individually tested, generate an avoidance (alarm) response in Z. renardii. 3-Methyl-1-butanol elicited the highest significant repellence, followed by 2-methyl-butanoic and 2-methyl-propanoic acids. The concentrations of the VOCs of ZR decrease during the interaction with P. spumarius. We discuss the potential effects of VOC secretions on the interaction of Z. renardii with P. spumarius.

This review covers the recent developments (since 2015) of enantioselective desymmetrization reactions using metal-catalyzed, organocatalyzed and enzymatic processes of prochiral and meso-compounds. This asymmetric strategy has been applied to a great number of organic compounds such as diarylalkanes, silanes, alcohols, amines and dibenzylmethylamines, as well as unsaturated compounds comprising dienes, diynes and cyclohexenes. The classical desymmetrization of 1,2-, 1,3-diols and other polyols by inter- and intramolecular acylation and alkylation reactions, but also by oxidation methods are important processes. Carbonyl compounds such as cycloalkanones, cyclohexadienones, cyclic and acyclic 1,3-diketones, cyclic 1,4-diketones are desymmetrized and applied to the synthesis of a wide range of natural products. In the case of dicarboxylic acid derivatives, diesters and lactones, anhydrides, diamides and dinitriles are mainly desymmetrized by intra- and intermolecular esterifications and hydrolysis. Small ring carbocycles such as cyclopropanes and cyclopropenes, cyclobutanes and cyclobutenes, and also cyclopentanes and cyclopentenes, cyclohexanes and cyclohexenes are considered. Heterocyclic systems such as small ring oxygen containing epoxides, oxetanes and oxabenzonorbornadienes as well as nitrogen containing aziridines, azetidines, azabenzonorbornadienes and diazanorbornenes are desymmetrized mainly by asymmetric ring opening reactions. The synthetic applications of these desymmetrization methodologies in the total synthesis of natural products and biologically active compounds are highlighted. (C) 2022 Published by Elsevier Ltd.

Indium-mediated allylation of N-tert-butanesulfinyl imines derived from indole-2 and 3-carbaldehydes 3 and 5 with allylic bromides 6, proceed with high diastereoselectivity. Homoallylic amide derivatives 13 and 14 are transformed into dihydropyridinones 15 and 16, upon successive desulfinylation, N-acylation with acryloyl chloride and ring-closing-metathesis. Desulfinylation of amine ester derivatives 17 and 18, obtained when ethyl 2-(bromomethyl)acrylate (6 b) is used as the allylating reagent, lead to the corresponding alpha-methylene-gamma-butyrolactams 19 and 20, in modest yields.

The synthesis of nitrogen-containing heterocycles, including natural alkaloids and other compounds presenting different types of biological activities have proved to be successful employing chiral sulfinyl imines derived from tert-butanesulfinamide. These imines are versatile chiral auxiliaries and have been extensively used as eletrophiles in a wide range of reactions. The electron-withdrawing sulfinyl group facilitates the nucleophilic addition of organometallic compounds to the iminic carbon with high diastereoisomeric excess and the free amines obtained after an easy removal of the tert-butanesulfinyl group can be transformed into enantioenriched nitrogen-containing heterocycles. The goal of this review is to the highlight enantioselective syntheses of heterocycles involving the use of chiral N-tert-butanesulfinyl imines as reaction intermediates, including the synthesis of several natural products. The synthesis of nitrogen-containing heterocycles in which the nitrogen atom is not provided by the chiral imine will not be considered in this review. The sections are organized according to the size of the heterocycles. The present work will comprehensively cover the most pertinent contributions to this research area from 2012 to 2020. We regret in advance that some contributions are excluded in order to maintain a concise format.

An efficient stereocontrolled preparation of 2-substituted pyrrolidines and 5-substituted indolizidin-7-ones, by using chiral N-tert-butanesulfinyl imines derived from 4-halobutanal as starting materials, is detailed. Addition of Grignard reagents and a decarboxylative Mannich reaction with.-keto acids involving these chiral imines proceeded with high diastereoselectivity. The synthesis of the pyrrolidinic alkaloids (-)-bgugaine, (+)-villatamine B, (-)-norhygrine, trans-dendrochrysanine, and (-)-ruspolinone demonstrated the utility of this methodology.

Tetracyclic benzocarbazoles are examples of nitrogen-containing heterocycles, which display interesting pharmacological activities and physicochemical properties. This chapter aims to bring some examples about the synthesis of bezocarbazoles, mostly benzo[a]carbazoles (including the dihydro and tetrahydro derivatives), with interesting properties. This chapter also includes aza-pterocarpans and aza-coumestans, which are structurally similar to benzo [a] carbazoles, although their analogous natural products are formed through different biosynthetic pathways. Being aware of the potential interest of these compounds, many efforts have been made for the development of new methodologies to carry out their synthesis and will be discussed below.

Transition metal-catalyzed reactions of N-sulfinyl imines with several substrates lead to the corresponding chiral amines with high yields and diastereo- or enantioselectivities. As metals, titanium, copper, ruthenium, rhodium, palladium and silver have been successfully used as catalysts in different carbon-carbon forming reactions as well as hydrogenations with molecular hydrogen or transfer hydrogenations with isopropanol as hydrogen source. (C) 2021 Elsevier Ltd. All rights reserved.

The addition of functionalized organolithium compounds derived from 5-chloro-2-methoxy-1-pentene and 6-chloro-2-methoxy-1-hexene to N-tert-butanesulfinyl aldimines imines, and a subsequent hydrolysis of the enol ether moiety, yielded different δ- and ε-amino ketone derivatives, respectively, in moderate yields and diastereoselectivities. The application of these compounds in organic synthesis was demonstrated by the preparation of 2-substituted 6-methylpiperidines in a stereoselective manner, among them natural alkaloids (+)- and (−)-isosolenopsin A.