Direct synthesis of acyl fluorides from carboxylic acids using benzothiazolium reagents

• Lilian M. Maas,
• Alex Haswell,
• Rory Hughes and
• Matthew N. Hopkinson

Beilstein J. Org. Chem. 2024, 20, 921–930, doi:10.3762/bjoc.20.82

• to acyl fluorides are inspiring greater interest in these compounds. Various synthetic approaches have been investigated with two main strategies being pursued: fluorine-transfer to acyl radicals and nucleophilic fluorination of acyl electrophiles [15]. The latter approach is the most intensively

Skeletal rearrangement of 6,8-dioxabicyclo[3.2.1]octan-4-ols promoted by thionyl chloride or Appel conditions

• Martyn Jevric,
• Julian Klepp,
• Johannes Puschnig,
• Oscar Lamb,
• Christopher J. Sumby and
• Ben W. Greatrex

Beilstein J. Org. Chem. 2024, 20, 823–829, doi:10.3762/bjoc.20.74

• small amounts of the C2 epimers. Oxidation of the hemiacetal 12a gave a moderate and unoptimised yield of 40% for lactone 24. The probable mechanism for the transformation with SOCl2 and under Appel conditions is shown in Figure 2. The reaction of alcohol 10 with the electrophiles gives the

Mechanisms for radical reactions initiating from N-hydroxyphthalimide esters

• Carlos R. Azpilcueta-Nicolas and
• Jean-Philip Lumb

Beilstein J. Org. Chem. 2024, 20, 346–378, doi:10.3762/bjoc.20.35

• catalytic cycle. Finally, the corresponding NiII complex 129 is reduced back to the corresponding Ni0 species by the stoichiometric reductant, initiating a new catalytic cycle. Weix and co-workers have developed a series of Ni-catalyzed couplings of NHPI esters with different electrophiles, including aryl

Nucleophilic functionalization of thianthrenium salts under basic conditions

• Xinting Fan,
• Duo Zhang,
• Xiangchuan Xiu,
• Bin Xu,
• Yu Yuan,
• Feng Chen and
• Pan Gao

Beilstein J. Org. Chem. 2024, 20, 257–263, doi:10.3762/bjoc.20.26

• . Therefore, developing a green method to functionalize alkylthianthrenium salts is still highly desirable. Considering the highly polarized C(sp3)–S bond in alkylthianthrenium salts, alkylthianthrenium salts have the potential to serve as alkyl electrophiles to react with nucleophiles directly in the absence

• % yield (Scheme 4). This operationally simple protocol enables the rapid development of novel thioetherification reactions using bench-stable alkylthianthrenium salts as the electrophiles. As is well known, alkyl trifluoromethanesulfonate (alkyl-OTf), serving as a potent electrophilic reagent, can also

Catalytic multi-step domino and one-pot reactions

• Svetlana B. Tsogoeva

Beilstein J. Org. Chem. 2024, 20, 254–256, doi:10.3762/bjoc.20.25

• stereocenters [7]. In the Review paper by Kisszékelyi and Šebesta, the diverse variety of chiral metal enolates obtained by asymmetric conjugate additions of organometallic reagents and the possibilities to engage metal enolates in tandem reactions with new electrophiles are presented [8]. A Perspective from X

Perspectives on push–pull chromophores derived from click-type [2 + 2] cycloaddition–retroelectrocyclization reactions of electron-rich alkynes and electron-deficient alkenes

• Michio Yamada

Beilstein J. Org. Chem. 2024, 20, 125–154, doi:10.3762/bjoc.20.13

• -order kinetics, indicating a bimolecular process. Furthermore, their findings elucidated a compelling linear free-energy relationship between the rate constants and electronic characteristics of the para-substituents of the DCV electrophiles, implying a dipolar, zwitterionic mechanism. The researchers

• generalizing the elucidated reaction mechanism to other [2 + 2] CA–RE reactions involving TCNE and TCNQ as electrophiles might be difficult. They emphasized the significance of considering a pre-equilibrium state of the charge-transfer complexes between the alkynes and alkenes and mentioned that the

• positioning of the [2 + 2] CA or RE step as the rate-determining step may depend upon the structural attributes of the electrophiles and nucleophiles. In 2023, Nielsen et al. conducted an exhaustive kinetic analysis of the [2 + 2] CA–RE reaction involving 4-trimethylsilylethynylaniline and TCNE by leveraging

Multi-redox indenofluorene chromophores incorporating dithiafulvene donor and ene/enediyne acceptor units

• Christina Schøttler,
• Kasper Lund-Rasmussen,
• Line Broløs,
• Philip Vinterberg,
• Ema Bazikova,
• Viktor B. R. Pedersen and
• Mogens Brøndsted Nielsen

Beilstein J. Org. Chem. 2024, 20, 59–73, doi:10.3762/bjoc.20.8

• could potentially after deprotonation be reacted with electrophiles as previously established [29] for the parent structure [30] without tert-butyl substituents. UV–vis absorption spectroscopy UV–vis absorption spectra of the known compound 4 [14] and new compounds 9–12 and 15 are depicted in Figure 3

Controlling the reactivity of La@C₈₂ by reduction: reaction of the La@C₈₂ anion with alkyl halide with high regioselectivity

• Yutaka Maeda,
• Saeka Akita,
• Mitsuaki Suzuki,
• Michio Yamada,
• Takeshi Akasaka,
• Kaoru Kobayashi and
• Shigeru Nagase

Beilstein J. Org. Chem. 2023, 19, 1858–1866, doi:10.3762/bjoc.19.138

• produced chemically or electrochemically. C602− is a strong electron donor and potential nucleophile that reacts with electrophiles [6][7][8][9][10][11]. The mechanism for the reaction of C602− with alkyl halides has been studied in detail by Fukuzumi et al., who found that the reaction occurs via electron

N-Sulfenylsuccinimide/phthalimide: an alternative sulfenylating reagent in organic transformations

• Fatemeh Doraghi,
• Seyedeh Pegah Aledavoud,
• Mehdi Ghanbarlou,
• Bagher Larijani and
• Mohammad Mahdavi

Beilstein J. Org. Chem. 2023, 19, 1471–1502, doi:10.3762/bjoc.19.106

• construction of 4-chalcogenylated pyrazoles 57 and 59 was carried out starting from α,β-alkynic hydrazones 55 (Scheme 24) [60]. In the procedure, α,β-alkynic hydrazones were subjected to S- or Se-electrophiles 56 and cyclization reaction. Additionally, NCS and ArSH produced the S-electrophile for the

α-(Aminomethyl)acrylates as acceptors in radical–polar crossover 1,4-additions of dialkylzincs: insights into enolate formation and trapping

• Angel Palillero-Cisneros,
• Paola G. Gordillo-Guerra,
• Fernando García-Alvarez,
• Olivier Jackowski,
• Franck Ferreira,
• Fabrice Chemla,
• Joel L. Terán and
• Alejandro Perez-Luna

Beilstein J. Org. Chem. 2023, 19, 1443–1451, doi:10.3762/bjoc.19.103

• atom to zinc enables this SH2 process which represents a rare example of alkylzinc-group transfer to a tertiary α-carbonyl radical. The zinc enolate thus formed readily undergoes β-fragmentation unless it is trapped by electrophiles in situ. Enolates of substrates having free N–H bonds undergo

• enolate with electrophiles in protocols wherein all the reactive partners can be introduced from the start, given that dialkylzinc reagents offer a large functional group tolerance; and 3) the radical character of the process allows for the use of alkyl iodides as alkyl source in multicomponent reactions

• interesting to note that the levels of induction for the 1,4-addition–aldol condensations are somewhat higher than those obtained for the 1,4-additions. Aldehydes also proved competent terminal electrophiles for the tandem sequence. Illustratively, adducts 23 and 24 were obtained from α-(aminomethyl)acrylates

Consecutive four-component synthesis of trisubstituted 3-iodoindoles by an alkynylation–cyclization–iodination–alkylation sequence

• Nadia Ledermann,
• Alae-Eddine Moubsit and
• Thomas J. J. Müller

Beilstein J. Org. Chem. 2023, 19, 1379–1385, doi:10.3762/bjoc.19.99

• summary the indole anion intermediate resulting from a one-pot alkynylation–cyclization sequence, which has been previously shown to be efficiently trapped by carbon electrophiles to give N-substituted indoles in a consecutive three-component synthesis, can be selectively iodinated in the 3-position with

Visible-light-induced nickel-catalyzed α-hydroxytrifluoroethylation of alkyl carboxylic acids: Access to trifluoromethyl alkyl acyloins

• Feng Chen,
• Xiu-Hua Xu,
• Zeng-Hao Chen,
• Yue Chen and
• Feng-Ling Qing

Beilstein J. Org. Chem. 2023, 19, 1372–1378, doi:10.3762/bjoc.19.98

• nickel-catalyzed coupling of aryl bromides with an α-hydroxytrifluoroethyl radical for the synthesis of trifluoromethyl aryl alcohols [39]. Encouraged by this work, we envisioned that the nickel-catalyzed coupling of carboxylic acids-derived acyl electrophiles with an α-hydroxytrifluoroethyl radical

Acetaldehyde in the Enders triple cascade reaction via acetaldehyde dimethyl acetal

• Alessandro Brusa,
• Debora Iapadre,
• Maria Edith Casacchia,
• Alessio Carioscia,
• Giuliana Giorgianni,
• Giandomenico Magagnano,
• Fabio Pesciaioli and
• Armando Carlone

Beilstein J. Org. Chem. 2023, 19, 1243–1250, doi:10.3762/bjoc.19.92

• process. The ingenious crafting of the reaction lies in the selection of the reactivity of the different nucleophiles and electrophiles present in the mixture, both as reagents and as intermediates. First, the chiral aminocatalyst 1 activates the saturated aldehyde 2 via enamine intermediate A, which

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

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

• enantioselective aza-Friedel–Crafts addition. In the first step, the DDQ-promoted oxidation of 3-indolinonecarboxylate 22 generated indolenines that performed as the potential electrophiles towards indoles 4. The chiral catalyst effectively assembled the reacting partners in a chiral transition state through H

• of indole 9 through aza-Friedel–Crafts reaction with aryl-α-ketimino esters 26/29. They also utilized unsubstituted and 2,3-disubstituted pyrroles 9 as π-nucleophile towards the same electrophiles to incorporate an amine-substituted quaternary stereocenter at the C2’ position (Scheme 8b) [33]. In

• 2019, Inokuma, Yamada and co-workers reported the C3–H bond functionalization of indoles 4 through aza-Friedel–Crafts reaction utilizing N-o-nitrophenylsulfenyl (Nps)-iminophosphonates 32 as electrophiles. The chiral phosphoric acid P11 was used as H-bonding catalyst to impart stereoselectivities into

Asymmetric tandem conjugate addition and reaction with carbocations on acylimidazole Michael acceptors

• Brigita Mudráková,
• Renata Marcia de Figueiredo,
• Jean-Marc Campagne and
• Radovan Šebesta

Beilstein J. Org. Chem. 2023, 19, 881–888, doi:10.3762/bjoc.19.65

• , because of their particular chemical and physical properties [15]. In addition to ester/amide synthesis, enoyl imidazolides were developed as excellent Michael acceptors. Acylimidazoles are unique electrophiles that demonstrate moderate reactivity, relatively high stability, chemical selectivity, and high

• ]. These non-traditional electrophiles allow access to structurally highly interesting motifs. In addition, they are amenable to valuable synthetic transformations such as oxidative ring contraction of the cycloheptatrienyl ring or reduction of the benzodithiolyl group. In this context, we decided to study

Pyridine C(sp²)–H bond functionalization under transition-metal and rare earth metal catalysis

• Haritha Sindhe,
• Malladi Mounika Reddy,
• Karthikeyan Rajkumar,
• Akshay Kamble,
• Amardeep Singh,
• Anand Kumar and
• Satyasheel Sharma

Beilstein J. Org. Chem. 2023, 19, 820–863, doi:10.3762/bjoc.19.62

• with 1° alkyl electrophiles has been known in the past, however, the C–H alkylation with nonactivated secondary (2°) alkyl electrophiles and tertiary alkyl electrophiles was little known. In this context, in 2013, Fu and co-workers came across an unexpected finding with Pd-catalyzed C–H activation/C–C

• cross-coupling of pyridine N-oxides with nonactivated secondary (2°) alkyl bromides [51]. The cross-coupling is difficult to achieve as the Pd-catalyzed SN2 process is sensitive towards the steric bulk of the secondary or tertiary alkyl electrophiles. The optimized conditions for the ortho-alkylation of

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

• years of development. The effort of our group to broaden possibilities to engage metal enolates in reactions with new electrophiles is described. The material is divided according to the organometallic reagent employed in the conjugate addition step, and thus to the particular metal enolate formed

• stereogenic information, thus leading to chiral products. Enolate species are uniquely positioned for reactivity with a broad array of electrophiles and thus allowing quick and efficient construction of highly complex structures from readily available starting materials. Various polar organometallic reagents

• nucleophile (R3Zn−) to the ketone with moderate yields but still good stereoselectivities (Scheme 9B). In 2018, Wang and co-workers extended the group of applicable electrophiles for the zinc enolate-based tandem reactions. Following the conjugate addition of Et2Zn to acyclic α,β-unsaturated ketones 41, they

A new oxidatively stable ligand for the chiral functionalization of amino acids in Ni(II)–Schiff base complexes

• Alena V. Dmitrieva,
• Oleg A. Levitskiy,
• Yuri K. Grishin and
• Tatiana V. Magdesieva

Beilstein J. Org. Chem. 2023, 19, 566–574, doi:10.3762/bjoc.19.41

• thermodynamically controlled stereoselectivity as compared to the parent Belokon complex. Additionally, functionalization with the tert-butyl group significantly enhances the reactivity of the deprotonated glycine complex towards electrophiles as compared to the anionic species formed from the original Belokon

• chemical transformations. The oxidation potential value of the deprotonated glycine complex correlates with the reactivity of the α-carbanionic species towards electrophiles [37]. Therefore, the electrochemical approach is very convenient and informative for the estimation of the relative reactivity of the

• determined previously for the parent Belokon complex (GlyNi)L1 (−0.32 V vs Ag/AgCl/KCl(sat.) [37]) and (GlyNi)L4 (−0.22 V [37]) showed that the nucleophilic equivalent of (GlyNi)L7 (Eox = −0.41 V, see Table 4) should be much more reactive towards electrophiles than the deprotonated (GlyNi)L1 and (GlyNi)L4

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

• intercepted by an electrophile to generate the difunctionalized system. This methodology has been applied several times to strained bicyclic alkenes with a variety of electrophiles. In 2015, Hirano and Miura developed a Cu-catalyzed aminoboration of bicyclic alkenes 1 with bis(pinacolato)diboron (B2pin2) (53

Group 13 exchange and transborylation in catalysis

• Dominic R. Willcox and
• Stephen P. Thomas

Beilstein J. Org. Chem. 2023, 19, 325–348, doi:10.3762/bjoc.19.28

• transborylation with HBpin, to give the thioBpin 77 product and regenerate the amine-borane catalyst 73 (Scheme 17). Yamamoto reported the borane-catalysed hydroalumination of alkenes and allenes (Scheme 18) [80][81][82][83] in which the organoaluminium products were reacted in situ with various electrophiles to

Investigation of cationic ring-opening polymerization of 2-oxazolines in the “green” solvent dihydrolevoglucosenone

• Solomiia Borova and
• Robert Luxenhofer

Beilstein J. Org. Chem. 2023, 19, 217–230, doi:10.3762/bjoc.19.21

• polymerization (CROP) of the respective 2-substituted 2-oxazoline (Figure 1) initiated with various electrophiles [18][19][20][21]; most commonly alkyl tosylates or triflates are applied [21][22][23][24]. The use of suitable solvents plays a significant role in obtaining well-defined polymers with a narrow molar

• NMR spectra (Figure S6), indicating no interaction between the solvent and the monomer. Polymerization of 2-ethyl-2-oxazoline Six different electrophiles, acetyl chloride (AcCl), propionyl chloride (PrCl), benzyl bromide (BnBr), MeOTf, MeOTs, and EtOxMeOTf, were examined as initiators for the EtOx

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

• could afford satisfying coupling yields by a suitable variation of the nature of the leaving group. In 2008, Cahiez reported an iron-catalyzed alkenylation of organomagnesium reagents with enol phosphates as electrophiles, instead of alkenyl halides [19]. In this case, when reactive enol phosphates

• ) as a co-solvent. Nevertheless, capitalizing on these results, Cahiez further developed this iron-catalyzed cross coupling reaction with dienol phosphates as electrophiles, which are thermally more stable than dienyl halides [20]. It was found that when dienol phosphates were used as electrophiles

• 1 by the M2i Company. Magnesium alkoxides used as additives Although it can lead to efficient NMP-free cross-coupling procedures, the use of enol phosphates as coupling electrophiles also brings several issues for efficient and sustainable procedures meant to be carried out at large scales. First

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

• highly reactive electrophiles. The homologous 1,4-dithianes or 1,4-dioxanes are readily available as simple building blocks, but also undergo a swift β-elimination following the metalation of one of their ring carbons, again limiting their appeal as building blocks [16][17]. In his landmark synthesis of

• expected fragmentation (Scheme 6e) [42]. The metalated dihydrodithiins can thus also be reacted with less activated electrophiles, including secondary alkylating agents. As we shall discuss in chapter 4, this makes 5,6-dihydro-1,4-dithiins the most suitable building blocks for Corey–Seebach-type

• opens up options for Corey–Seebach-type alkylation reactivity with a wider range of electrophiles. The method is demonstrated by the smooth lithiation and subsequent alkylation of the acetophenone-derived dithiin 50 (Scheme 10a) [42]. Palumbo’s elegant overall approach to dihydrodithiin-mediated

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

• enolate was treated with 4-nitrobenzaldehyde to promote the aldolization reaction but the corresponding alcohol was not observed, which confirmed the reluctance of 6a·Li to react with other electrophiles than protons. Unable to form the quaternary carbon of the target from this intermediate, the pathway