Selective construction of dispiro[indoline-3,2'-quinoline-3',3''-indoline] and dispiro[indoline-3,2'-pyrrole-3',3''-indoline] via three-component reaction

• Ziying Xiao,
• Fengshun Xu,
• Jing Sun and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2023, 19, 1234–1242, doi:10.3762/bjoc.19.91

• nucleophiles, especially active methylene compounds, have attracted much attentions [36][37][38][39][40][41]. This kind of Michael adduct has more than one reactive site and could proceed domino reactions with various electrophiles [42][43][44][45][46][47][48][49]. In this respect, several elegant domino or

Radical ligand transfer: a general strategy for radical functionalization

• David T. Nemoto Jr,
• Kang-Jie Bian,
• Shih-Chieh Kao and
• Julian G. West

Beilstein J. Org. Chem. 2023, 19, 1225–1233, doi:10.3762/bjoc.19.90

• indicative of a carbocationic pathway are not observed, suggesting that RPC does not occur. Further, the inability of ATRA products to undergo SN2 with the added nucleophiles under our reaction conditions is inconsistent with a tandem ARTA/nucleophilic displacement alternative mechanism. Finally, a

Exploring the role of halogen bonding in iodonium ylides: insights into unexpected reactivity and reaction control

• Carlee A. Montgomery and
• Graham K. Murphy

Beilstein J. Org. Chem. 2023, 19, 1171–1190, doi:10.3762/bjoc.19.86

• ylides and Lewis basic nucleophiles in which halogen bonding has been specifically invoked. The reactions discussed herein are organized to enable the reader to build an understanding of how halogen bonding might impact yield and chemoselectivity outcomes in reactions of iodonium ylides. Areas of focus

• nucleophiles and iodonium ylides, where the nucleophile could halogen bond to either σ-hole, and that this could lead to distinct reductive elimination pathways (see Scheme 1) [101]. To probe this theory, they prepared a series β-dicarbonyl-derived iodonium ylides (76a–f) possessing a σ-hole-blocking ortho-t

• calculations for enaminone synthesis from iodonium ylides and thioamides. Crystal structures of 76c (top) and 76e (bottom) [101], (CCDC# 2104180 & 2104181) [143][144]. Outline of possible reaction pathways between iodonium ylides and Lewis basic nucleophiles (top); and, reaction between 6 and HCl to give 7, as

Photoredox catalysis harvesting multiple photon or electrochemical energies

• Mattia Lepori,
• Simon Schmid and
• Joshua P. Barham

Beilstein J. Org. Chem. 2023, 19, 1055–1145, doi:10.3762/bjoc.19.81

Aromatic C–H bond functionalization through organocatalyzed asymmetric intermolecular aza-Friedel–Crafts reaction: a recent update

• Anup Biswas

Beilstein J. Org. Chem. 2023, 19, 956–981, doi:10.3762/bjoc.19.72

• -substituted indoles having methyl or cycloalkyl substitutents of different ring sizes exclusively reacted as nucleophiles. Chiral phosphoric acid P16 mediated the asymmetric transformation to regulate the stereochemical output of the quaternary stereocenter with good to excellent enantioselectivities. A

• π-nucleophiles in combination with β,γ-alkynyl-α-imino esters 93 acting as the electrophilic reagent. Chiral phosphoric acid P16 was the catalytic agent to access a series of enantioenriched α-amino esters 94 containing 5-aminopyrazolyl and alkynyl substituents at the α-carbon. A library of products

• developed an aza-Friedel–Crafts reaction involving β-naphthols 119 as π-nucleophiles and benzothiazolimines 118 as electrophiles. Chiral squaramide S1-assisted this process affording enantioenriched 1-((benzothiazol-2-ylamino)methyl)naphthalen-2-ols 120 with high chemical yields. The activation of the

Clauson–Kaas pyrrole synthesis using diverse catalysts: a transition from conventional to greener approach

• Dileep Kumar Singh and
• Rajesh Kumar

Beilstein J. Org. Chem. 2023, 19, 928–955, doi:10.3762/bjoc.19.71

• of amine nucleophiles were examined in this method. As a result, it was found that nucleophiles with low pKa values, such as sulfonamides, reacted very well, while reactions with nucleophiles with high pKa values, such as benzylamine, did not work well. Compared with other classical methods, this

Nucleophile-induced ring contraction in pyrrolo[2,1-c][1,4]benzothiazines: access to pyrrolo[2,1-b][1,3]benzothiazoles

• Ekaterina A. Lystsova,
• Maksim V. Dmitriev,
• Andrey N. Maslivets and
• Ekaterina E. Khramtsova

Beilstein J. Org. Chem. 2023, 19, 646–657, doi:10.3762/bjoc.19.46

• -containing heterocycles intensively studied in medicinal chemistry and pharmacology. In the present paper, a new synthetic approach to pyrrolobenzothiazoles is developed based on 1,4-thiazine ring contraction in 3-aroylpyrrolo[2,1-c][1,4]benzothiazine-1,2,4-triones under the action of nucleophiles. The

• dramatically depends on the nature of the heteroatom X in FPDs I, II, 1 [33][34]. It should be noted that the reactions of 5-aza- and 5-oxa-FPDs I and II with nucleophiles are studied rather well [33][34], and their reactivity did not give us any insights for the development of new approaches to PBTAs. However

• 1 (Scheme 5). Firstly, FPDs 1 bear a 1,4-benzothiazine moiety that is known to be prone to undergo a ring contraction reaction to afford the corresponding 1,3-benzothiazole derivatives under the action of nucleophiles [39][40][41][42], oxidizing agents [43][44][45][46][47][48] or ultraviolet

Enolates ambushed – asymmetric tandem conjugate addition and subsequent enolate trapping with conventional and less traditional electrophiles

• Péter Kisszékelyi and
• Radovan Šebesta

Beilstein J. Org. Chem. 2023, 19, 593–634, doi:10.3762/bjoc.19.44

• . These transformations combine several reactions into a sequence that uses functionalities generated in previous steps without isolating intermediates [1]. Stabilized carbon-based nucleophiles, or in other words, conjugate bases of weak C–H acids, are termed enolates, and they participate in a large

• building blocks providing an aminomethyl moiety upon adding nucleophiles. Protected formaldehyde aminals are useful synthetic equivalents to formaldehyde imines. The imine functionality can be unmasked (68) in the reaction medium by Lewis acids such as TiCl4. The formed Mg enolates 66 readily react with

Access to cyclopropanes with geminal trifluoromethyl and difluoromethylphosphonate groups

• Ita Hajdin,
• Romana Pajkert,
• Mira Keßler,
• Jianlin Han,
• Haibo Mei and
• Gerd-Volker Röschenthaler

Beilstein J. Org. Chem. 2023, 19, 541–549, doi:10.3762/bjoc.19.39

• obtained by the deoxofluorination of the corresponding dicarboxylic acids with sulfur tetrafluoride, thiophilic ring-opening reactions with nucleophiles or reactions of donor-substituted furans with bis(trifluoromethyl)-substituted ethylenes (Scheme 1D) [41][42][43]. The lack of application of highly

Transition-metal-catalyzed domino reactions of strained bicyclic alkenes

• Austin Pounder,
• Eric Neufeld,
• Peter Myler and
• William Tam

Beilstein J. Org. Chem. 2023, 19, 487–540, doi:10.3762/bjoc.19.38

• and Renaud expanded the scope of the photoredox/Ni dual-catalyzed coupling of alkyl nucleophiles 36 with heterobicyclic alkenes 30 to include α-amino radicals (Scheme 7) [40]. The authors noted the electron-rich oxabenzonorbornadiene derivatives provided the corresponding ring-opened adducts in good

• lab reported the Rh-catalyzed domino reaction of doubly bridgehead-substituted oxabicyclic alkenes 134 with secondary amine nucleophiles 135 for the synthesis of bicyclo[2.2.2]lactones 136 (Scheme 24) [70]. This reaction proceeded smoothly with a variety of secondary amine nucleophiles, including

• those with hydrocarbon, ether, acetal, and ester functionalities; although, aniline nucleophiles only resulted in the one step asymmetric ring-opening (ARO) product under the standard reaction conditions. Fortunately, the authors noted the addition of triethylamine allowed for aniline nucleophiles to

Synthesis and reactivity of azole-based iodazinium salts

• Thomas J. Kuczmera,
• Annalena Dietz,
• Andreas Boelke and
• Boris J. Nachtsheim

Beilstein J. Org. Chem. 2023, 19, 317–324, doi:10.3762/bjoc.19.27

• phenotellurazine 7c were isolated in lower yields of 16% and 6%, likely due to undesired oxidations of selenium and tellurium [38]. Substitutions with nitrogen nucleophiles were performed, giving the N-phenylphenazine 8 in 26% yield [39][40] and the N-tosyl derivative 9 in 18% yield [41]. Anion exchange reactions

Continuous flow synthesis of 6-monoamino-6-monodeoxy-β-cyclodextrin

• János Máté Orosz,
• Dóra Ujj,
• Petr Kasal,
• Gábor Benkovics and
• Erika Bálint

Beilstein J. Org. Chem. 2023, 19, 294–302, doi:10.3762/bjoc.19.25

• in 69% yield and 98% purity according to the authors. Many nucleophiles can react with tosylated CDs to give the corresponding C-6-monofunctionalized CDs. However, alkaline bases cannot be used as nucleophiles due to the intramolecular substitution, resulting in a mono-3,6-anhydro product [13]. On

• readily reduced to mono(6-amino-6-deoxy)-CDs (NH2-CDs) opening the way for the preparation of amine, thioureido or amide-linked CD scaffolds [14]. Several other nucleophiles can react with mono-6-O-tosyl-CDs, such as iodide, dithiol, hydroxylamine, alkylamine or polyalkylamine to give iodo- [15], thio

Total synthesis of insect sex pheromones: recent improvements based on iron-mediated cross-coupling chemistry

• Eric Gayon,
• Guillaume Lefèvre,
• Olivier Guerret,
• Adrien Tintar and
• Pablo Chourreu

Beilstein J. Org. Chem. 2023, 19, 158–166, doi:10.3762/bjoc.19.15

• reactions, which witnessed considerable development in the last two decades [14], several cross-coupling methodologies involving soft nucleophiles, such as iron-mediated Suzuki–Miyaura cross-couplings, being reported [15]. The introduction of alkyl–alkenyl linkage by means of iron-catalyzed cross-coupling

• -coupling reactions between alkylmanganese nucleophiles AlkylMnX and thioesters RC(O)SEt using Fe(acac)3 as catalyst could act as a ligand to on-cycle organoiron(II) intermediates (Table 2, entry 3) [39]. This behaviour opens the door to interesting synthetic perspectives, since it suggests that leaving

1,4-Dithianes: attractive C2-building blocks for the synthesis of complex molecular architectures

• Bram Ryckaert,
• Ellen Demeyere,
• Frederick Degroote,
• Hilde Janssens and
• Johan M. Winne

Beilstein J. Org. Chem. 2023, 19, 115–132, doi:10.3762/bjoc.19.12

• cation in (3 + 2) cycloadditions: 5,6-dihydro-1,4-dithiin-2-methanol as a stabilized allyl cation Allyl cations are versatile electrophiles for the allylation of various nucleophiles, but can also act as C3-π-systems in a range of cycloaddition reactions (Scheme 13) [84][85][86][87][88]. When combined

• nucleophile to the putative sulfonium-type dithiin intermediates such as 134. It is noteworthy that these Pummerer rearrangement-generated sulfonium intermediates do not give the expected fully unsaturated dithiin rings, but can be captured by nucleophiles before elimination of a proton happens. Conclusion In

Revisiting the bromination of 3β-hydroxycholest-5-ene with CBr₄/PPh₃ and the subsequent azidolysis of the resulting bromide, disparity in stereochemical behavior

• Christian Schumacher,
• Jas S. Ward,
• Kari Rissanen,
• Carsten Bolm and
• Mohamed Ramadan El Sayed Aly

Beilstein J. Org. Chem. 2023, 19, 91–99, doi:10.3762/bjoc.19.9

• nucleophiles were trimethylsilyl-based nucleophiles. TiCl4 and BF3·OEt2 served as activators. No reaction was observed with the 3α-mesyl analog and the cholestane congener. The 3β-azido derivative could also be obtained from 6β-azido-3α,5-cyclo-5α-cholestane [14] by treatment with a mixture of TMSN3 and BF3

Combining the best of both worlds: radical-based divergent total synthesis

• Kyriaki Gennaiou,
• Antonios Kelesidis,
• Maria Kourgiantaki and
• Alexandros L. Zografos

Beilstein J. Org. Chem. 2023, 19, 1–26, doi:10.3762/bjoc.19.1

• to the intermediate trans-218. In the presence of external nucleophiles (e.g., MeOH), the cation can be trapped, leading to substitution in the 7-position, while the radical is postulated to be oxidized to a cation, followed by a Friedel–Crafts reaction to the final product 222. When an excess of

• nucleophile is employed, radical 223 is favored, leading to either monosubstitution or disubstitution with external nucleophiles, depending on the presence of oxidant or reductant in the reaction mixture. Based on this plan, Zhu’s group managed to synthesize a rich number of lignans and congeners, such as

Synthetic study toward tridachiapyrone B

• Morgan Cormier,
• Florian Hernvann and
• Michaël De Paolis

Beilstein J. Org. Chem. 2022, 18, 1741–1748, doi:10.3762/bjoc.18.183

• -pyrone by desymmetrization of α,α’-dimethoxy-γ-pyrone 2 through the addition of hindered nucleophiles to construct the vicinal quaternary carbon. In a subsequent and potentially enantioselective desymmetrization step, compound 5 would be converted into trichiachiapyrone B by 1,4-addition of the side

• AlMe3 to 4,4-dimethyl-2,5-cyclohexadienone in the presence of a copper salt/chiral ligand and silylating reagent [37][38]. The racemic conjugate addition of nucleophiles to 5 was first investigated, starting with the Gilman reagent which was used in Takemoto and Iwata study (Scheme 6). In addition, a

• -cyclohexadienone followed by an oxidative anionic oxy-Cope rearrangement promoted by hydroxide of quaternary ammonium salt. Moreover, the coupling of lithiocyclopentadiene to α,α’-dimethoxy-γ-pyrone was demonstrated, enlarging the scope of nucleophiles grafted to the pharmaceutically relevant α’-methoxy-γ-pyrone

Redox-active molecules as organocatalysts for selective oxidative transformations – an unperceived organocatalysis field

• Elena R. Lopat’eva,
• Igor B. Krylov,
• Dmitry A. Lapshin and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2022, 18, 1672–1695, doi:10.3762/bjoc.18.179

• , organocatalysis by the modulation of redox properties of reagents has much in common with redox-neutral organocatalysis. With the exception of free-radical processes, the distinguishing feature of these organocatalyzed oxidations frequently lies in the involvement of peroxides as O-nucleophiles or O-electrophiles

• instead of corresponding C-nucleophiles or C-electrophiles in redox-neutral organocatalyzed reactions. Organocatalysis by redox-active organic molecules N-Oxyl radical catalysis Reactive N-oxyl radicals generated in situ from the corresponding N-hydroxy compounds have found numerous applications in CH

Preparation of β-cyclodextrin-based dimers with selectively methylated rims and their use for solubilization of tetracene

• Konstantin Lebedinskiy,
• Volodymyr Lobaz and
• Jindřich Jindřich

Beilstein J. Org. Chem. 2022, 18, 1596–1606, doi:10.3762/bjoc.18.170

• same conditions lead to a different product in CD chemistry [30]. In the absence of strong nucleophiles such as amines, the CD gives a dimer with a urea bridge instead of providing the isocyanate. The compound 5 was synthesized from 3 according to the standard procedure [30]. The synthesis of dimers

Functionalization of imidazole N-oxide: a recent discovery in organic transformations

• Koustav Singha,
• Imran Habib and
• Mossaraf Hossain

Beilstein J. Org. Chem. 2022, 18, 1575–1588, doi:10.3762/bjoc.18.168

• cyanoacetate to generate ethyl 2-cyano-2-(1,3-dihydro-2H-imidazole-2-ylidene)acetates in the presence of aldehyde catalyst through a [3 + 2] cycloaddition [16]. Here, imidazole N-oxides behaved as 1,3-dipoles and nucleophiles in Michael-type addition reactions. The optimized reaction conditions were estimated

Simple synthesis of multi-halogenated alkenes from 2-bromo-2-chloro-1,1,1-trifluoroethane (halothane)

• Yukiko Karuo,
• Atsushi Tarui,
• Kazuyuki Sato,
• Kentaro Kawai and
• Masaaki Omote

Beilstein J. Org. Chem. 2022, 18, 1567–1574, doi:10.3762/bjoc.18.167

• highly halogenated carbon centers, which enable halothane to participate in various reactions such as homolysis of carbon–halogen bonds and deprotonation. Multi-fluorinated compounds such as HCFC-133a (CF3CH2Cl) and HFC-134a (CF3CH2F) have been widely used in reactions with a variety of nucleophiles to

Efficient synthesis of aziridinecyclooctanediol and 3-aminocyclooctanetriol

• Emine Salamci and
• Ayse Kilic Lafzi

Beilstein J. Org. Chem. 2022, 18, 1539–1543, doi:10.3762/bjoc.18.163

• antibiotic activities. Therefore, synthetic methodologies for the preparation of the aziridinyl system have attracted attention in recent decades. Opening of the aziridine ring by using different nucleophiles gives the corresponding amino alcohols, amino esters, azido amines, amines, and other derivatives [9

Mechanochemical synthesis of unsymmetrical salens for the preparation of Co–salen complexes and their evaluation as catalysts for the synthesis of α-aryloxy alcohols via asymmetric phenolic kinetic resolution of terminal epoxides

• Shengli Zuo,
• Shuxiang Zheng,
• Jianjun Liu and
• Ang Zuo

Beilstein J. Org. Chem. 2022, 18, 1416–1423, doi:10.3762/bjoc.18.147

• metals have been explored to optimize the catalytic properties of chiral metal–salens, such as Cr [7], Co [8], Fe [9], Ti [10], Al [11], Y [12], and Mn [13] and investigated with numerous nucleophiles to afford chiral molecules. In addition to the variation of metals, salen ligands have also been studied

• ]. Since their discovery, researchers have investigated several Co–salen complexes for the KR of epoxides with phenols as nucleophiles (Figure 1) [18][19]. Kim et al. described a catalytic system of a chiral Co–salen immobilized on meso/macroporous silica monoliths for the ring opening of epoxides [20

Modular synthesis of 2-furyl carbinols from 3-benzyldimethylsilylfurfural platforms relying on oxygen-assisted C–Si bond functionalization

• Sebastien Curpanen,
• Per Reichert,
• Gabriele Lupidi,
• Giovanni Poli,
• Julie Oble and
• Alejandro Perez-Luna

Beilstein J. Org. Chem. 2022, 18, 1256–1263, doi:10.3762/bjoc.18.131

• Achmatowicz rearrangement [18]. Addition reactions of nucleophiles to the C–O double bond of furfurals represent an obvious synthetic approach to 2-furyl carbinols. We reasoned that for carbinols derived from C3-triorganosilyl-substituted furfurals, the OH unit could be exploited to assist C–Si bond

Reductive opening of a cyclopropane ring in the Ni(II) coordination environment: a route to functionalized dehydroalanine and cysteine derivatives

• Oleg A. Levitskiy,
• Olga I. Aglamazova,
• Yuri K. Grishin and
• Tatiana V. Magdesieva

Beilstein J. Org. Chem. 2022, 18, 1166–1176, doi:10.3762/bjoc.18.121

• cases, the targeted cysteine derivatives were isolated in practical yields. It should be noted that there is no need to separate the isomeric alkene complexes formed after the cyclopropane ring opening, they can be involved in the follow-up reaction with nucleophiles in the form of a mixture. This

• simplifies the synthetic procedure; the multistep process can be performed in an electrochemical cell, with the potential switching off prior to the addition of nucleophiles (thiols in our case). Complexes 10–12 were obtained as pure diastereomers (a set of signals corresponding to the individual compound is